J Nucl Med. 2024 May 16:jnumed.124.267497. doi: 10.2967/jnumed.124.267497. Online ahead of print.
NO ABSTRACT
PMID:38754958 | DOI:10.2967/jnumed.124.267497
19371 items (19371 unread) in 74 feeds
J Nucl Med. 2024 May 16:jnumed.124.267497. doi: 10.2967/jnumed.124.267497. Online ahead of print.
NO ABSTRACT
PMID:38754958 | DOI:10.2967/jnumed.124.267497
J Neuroendocrinol. 2024 May 16:e13412. doi: 10.1111/jne.13412. Online ahead of print.
ABSTRACT
Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.
PMID:38754956 | DOI:10.1111/jne.13412
J Immunother Cancer. 2024 May 15;12(5):e008659. doi: 10.1136/jitc-2023-008659.
ABSTRACT
BACKGROUND: Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.
METHODS: We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.
RESULTS: We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.
CONCLUSIONS: This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.
TRIAL REGISTRATION NUMBER: ACTRN12613000198729.
PMID:38754916 | DOI:10.1136/jitc-2023-008659
BMJ Open. 2024 May 15;14(5):e082045. doi: 10.1136/bmjopen-2023-082045.
ABSTRACT
INTRODUCTION: Reunion Island, a French overseas department, is located in the southern hemisphere, close to the Capricorn tropic. This island has a multicultural and multiethnic population of 860 000 inhabitants, a quarter of whom are at high risk of developing skin cancer due to intense ultraviolet radiation. Melanoma is responsible for the majority of skin cancer deaths. The early prevention of melanoma is based on sun protection in childhood, but French regulations are not adapted to the environmental conditions of this tropical region.The main objective of our study is to evaluate the effectiveness of three sun protection programs conducted in Reunionese primary schools through a pupil knowledge questionnaire.
METHODS AND ANALYSIS: PRESOLRE is an interventional, open-label, cluster-randomised controlled trial, in four parallel arms, that is being conducted throughout 2022-2023 on Reunion Island. The trial design assumes an escalation interventional effect using: first, a control arm without proposed intervention (arm 1); second, an arm whose classes are encouraged to use the validated educational programme 'Living With the Sun' (LWS) (arm 2); third, an arm whose classes are encouraged to use both 'LWS' combined with 'Mission Soleil Réunion's sun protection awareness programme (arm 3); fourth, an arm benefiting from an intervention similar to arm 3, combined with the distribution of hats, sunglasses and sun creams (arm 4). In all, 1780 pupils from 18 classes of 20 pupils, on average, will be included. Randomisation applies to the classes of pupils (so defined as clusters). The primary outcome is based on the proportion of correct answers to the knowledge questions after the awareness programme, compared between the four arms using a linear mixed model with random intercept.
ETHICS AND DISSEMINATION: The study obtained ethics approval in 2022 (ID: 2022-A00350-43). Results will be published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER: NCT05367180.
PMID:38754877 | DOI:10.1136/bmjopen-2023-082045
Sci Rep. 2024 May 16;14(1):11244. doi: 10.1038/s41598-024-61150-y.
ABSTRACT
We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10-7.67, Cox P = 2.63e-05) and PFS (HR = 3.72, 95% CI 2.06-6.73, Cox P = 1.38e-05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24-6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16-3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2-3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08-3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.
PMID:38755213 | DOI:10.1038/s41598-024-61150-y
Interdiscip Cardiovasc Thorac Surg. 2024 May 16:ivae103. doi: 10.1093/icvts/ivae103. Online ahead of print.
ABSTRACT
A 42-year-old man was referred to psychiatry with acute onset of confusion and agitation. His screening computed tomography showed middle mediastinal tumors. Preoperative cerebrospinal fluid analysis was positive for anti-contactin-associated protein-like 2 antibody, and possible paraneoplastic limbic encephalitis was diagnosed. Tumour resection was performed. Pathological examination showed thymic neuroendocrine tumour, stage IV. Postoperatively, the patient was treated with everolimus for adjuvant therapy, with complete improvement of encephalitis symptoms. The patient remained well without tumour recurrence or exacerbation of psychiatric disorders for 14 months after surgery.
PMID:38754121 | DOI:10.1093/icvts/ivae103
N Z Med J. 2024 May 17;137(1595):9-12. doi: 10.26635/6965.e1595.
NO ABSTRACT
PMID:38754110 | DOI:10.26635/6965.e1595
JCO Precis Oncol. 2024 May;8:e2300622. doi: 10.1200/PO.23.00622.
ABSTRACT
PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers.
MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation.
RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation.
CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.
PMID:38754058 | DOI:10.1200/PO.23.00622
Cancer J. 2024 May-Jun 01;30(3):185-193. doi: 10.1097/PPO.0000000000000723.
ABSTRACT
Neuroendocrine tumors (NETs) are rare tumors that develop from cells of the neuroendocrine system and can originate in multiple organs and tissues such as the bowels, pancreas, adrenal glands, ganglia, thyroid, and lungs. This review will focus on gastroenteropancreatic NETs (more commonly called NETs) characterized by frequent somatostatin receptor (SSTR) overexpression and pheochromocytomas/paragangliomas (PPGLs), which typically overexpress norepinephrine transporter. Advancements in SSTR-targeted imaging and treatment have revolutionized the management of patients with NETs. This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration-approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.
PMID:38753753 | DOI:10.1097/PPO.0000000000000723
Dis Colon Rectum. 2024 May 16. doi: 10.1097/DCR.0000000000003387. Online ahead of print.
NO ABSTRACT
PMID:38752658 | DOI:10.1097/DCR.0000000000003387
Dis Colon Rectum. 2024 May 16. doi: 10.1097/DCR.0000000000003309. Online ahead of print.
NO ABSTRACT
PMID:38752652 | DOI:10.1097/DCR.0000000000003309
J Neurol Surg Rep. 2024 May 15;85(2):e66-e73. doi: 10.1055/s-0044-1786740. eCollection 2024 Apr.
ABSTRACT
Introduction Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom severity, the use of dopamine agonists remains a first-line treatment. While bromocriptine has been found to increase tumor fibrosis, the effect of cabergoline on collagen deposition has been disputed. The aim of this article is to understand the influence of cabergoline on tumor fibrosis prior to resection. Case Presentations Four male patients who underwent prolactinoma resection were included in this report. The average age was 39.8 years (range: 26-52 years). Pre-treatment prolactin levels ranged from 957.8 to 16,487.4 ng/mL. Three patients received cabergoline for at least 1 month prior to surgery (treatment range: 1-6 months). One patient had surgery without prior cabergoline use. Pathology reports confirmed each tumor to be of lactotroph origin. For each sample, Masson's trichrome staining was performed and the percentage of sample fibrosis was quantified using an artificial intelligence imaging software. Among those who received preoperative cabergoline, the extent of tumor fibrosis was in the range of 50 to 70%. In contrast, specimen fibrosis was approximately 15% without cabergoline use. Conclusion This report demonstrates that a short duration of preoperative cabergoline can cause significant prolactinoma fibrosis. Understanding the effect of cabergoline on tumor consistency prior to surgery is essential as increased fibrosis can lead to more difficult tumor removal, reduce the extent of resection, and increase surgical complications. Considering these effects, further studies regarding the use of surgery prior to cabergoline for prolactinoma management are warranted.
PMID:38751869 | PMC:PMC11095984 | DOI:10.1055/s-0044-1786740
Case Rep Oncol. 2024 May 15;17(1):581-586. doi: 10.1159/000538796. eCollection 2024 Jan-Dec.
ABSTRACT
INTRODUCTION: Lung neuroendocrine tumors (NETs) are a rare type of pulmonary tumor and represent approximately 2% of all lung cancers. The prevalence of lung NETs is increasing, which may be due to improved diagnostic techniques for asymptomatic tumors. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare and underdiagnosed disease that falls under the spectrum of NETs.
CASE PRESENTATION: We presented a case of a 59-year-old male who presented with severe coughing spells, flushing, and diarrhea. His computed tomography scan showed innumerable pulmonary nodules and irregular nodular opacities throughout the lungs. He underwent a left upper lobe wedge resection and was eventually diagnosed with neuroendocrine tumorlets via immunohistochemical stains. He was started on a trial of octreotide and reported significant improvement in symptoms after 1 month.
CONCLUSION: DIPNECH is a rare preinvasive lesion characterized by the abnormal proliferation of pulmonary neuroendocrine cells. Patients with DIPNECH can present initially with respiratory symptoms, while other cases are discovered incidentally during the workup of different conditions. Definitive diagnosis of DIPNECH requires histopathological examination of lung tissue. There is limited evidence on DIPNECH management, and an individualized approach is currently advised.
PMID:38751830 | PMC:PMC11095596 | DOI:10.1159/000538796
Cancer Control. 2024 Jan-Dec;31:10732748241251572. doi: 10.1177/10732748241251572.
ABSTRACT
OBJECTIVES: • Gather a panel of Latin American experts in testing and treating BRAF-melanoma. • Describe the current landscape of BRAF-mutated melanoma in Latin America. • Outline the current gaps in testing and recommend improvements for testing and treating BRAF-mutated melanoma in the region.
INTRODUCTION: Melanoma prevalence in Latin America is lower than in high- and middle-income countries. However, recent data indicate that the region's incidence and mortality are rising, with more stage IV patients being diagnosed. According to international clinical practice guidelines, conducting BRAF-mutation testing in patients with stage III or stage IV melanoma and high-risk resected disease is imperative. Still, BRAF-mutation testing and targeted therapies are inconsistently available in the region.
METHODS: Americas Health Foundation convened a meeting of Latin American experts on BRAF-mutated melanoma to develop guidelines and recommendations for diagnosis through treatment.
RESULTS AND CONCLUSIONS: Some recommendations for improving diagnostics through improving access and reducing the cost of BRAF-mutation testing, enhancing efficiency in pathology laboratories, and creating country-specific local guidelines. The panel also gave treatment recommendations for neo-adjuvant therapy, adjuvant therapy, and therapy for patients with metastatic disease in Latin America.
PMID:38751033 | DOI:10.1177/10732748241251572
Commun Biol. 2024 May 15;7(1):574. doi: 10.1038/s42003-024-06261-y.
ABSTRACT
Metastases are the major cause of cancer-related death, yet, molecular weaknesses that could be exploited to prevent tumor cells spreading are poorly known. Here, we found that perturbing hydrolase transport to lysosomes by blocking either the expression of IGF2R, the main receptor responsible for their trafficking, or GNPT, a transferase involved in the addition of the specific tag recognized by IGF2R, reduces melanoma invasiveness potential. Mechanistically, we demonstrate that the perturbation of this traffic, leads to a compensatory lysosome neo-biogenesis devoided of degradative enzymes. This regulatory loop relies on the stimulation of TFEB transcription factor expression. Interestingly, the inhibition of this transcription factor playing a key role of lysosome production, restores melanomas' invasive potential in the absence of hydrolase transport. These data implicate that targeting hydrolase transport in melanoma could serve to develop new therapies aiming to prevent metastasis by triggering a physiological response stimulating TFEB expression in melanoma.
PMID:38750105 | DOI:10.1038/s42003-024-06261-y
NPJ Syst Biol Appl. 2024 May 15;10(1):51. doi: 10.1038/s41540-024-00379-9.
ABSTRACT
In vertical inhibition treatment strategies, multiple components of an intracellular pathway are simultaneously inhibited. Vertical inhibition of the BRAFV600E-MEK-ERK signalling pathway is a standard of care for treating BRAFV600E-mutated melanoma where two targeted cancer drugs, a BRAFV600E-inhibitor, and a MEK inhibitor, are administered in combination. Targeted therapies have been linked to early onsets of drug resistance, and thus treatment strategies of higher complexities and lower doses have been proposed as alternatives to current clinical strategies. However, finding optimal complex, low-dose treatment strategies is a challenge, as it is possible to design more treatment strategies than are feasibly testable in experimental settings. To quantitatively address this challenge, we develop a mathematical model of BRAFV600E-MEK-ERK signalling dynamics in response to combinations of the BRAFV600E-inhibitor dabrafenib (DBF), the MEK inhibitor trametinib (TMT), and the ERK-inhibitor SCH772984 (SCH). From a model of the BRAFV600E-MEK-ERK pathway, and a set of molecular-level drug-protein interactions, we extract a system of chemical reactions that is parameterised by in vitro data and converted to a system of ordinary differential equations (ODEs) using the law of mass action. The ODEs are solved numerically to produce simulations of how pathway-component concentrations change over time in response to different treatment strategies, i.e., inhibitor combinations and doses. The model can thus be used to limit the search space for effective treatment strategies that target the BRAFV600E-MEK-ERK pathway and warrant further experimental investigation. The results demonstrate that DBF and DBF-TMT-SCH therapies show marked sensitivity to BRAFV600E concentrations in silico, whilst TMT and SCH monotherapies do not.
PMID:38750040 | DOI:10.1038/s41540-024-00379-9
J Clin Pathol. 2024 May 15:jcp-2024-209507. doi: 10.1136/jcp-2024-209507. Online ahead of print.
ABSTRACT
AIMS: Cytological classification systems provide a standardised interpretation framework for reporting cytological specimens. Three well-known classification systems can be applied when reporting pancreatic cytology. This study aimed to compare the accuracy of these classification systems (C1-C5 system, the Papanicolaou system and the WHO classification) for the assessment of pancreatic neuroendocrine lesions.
METHODS: We analysed 73 pancreatic neuroendocrine tumour resections, 49 of which had corroborative cytology available, reported over a 12-year period, at a single UK tertiary referral centre. Each cytology case was classified using the aforementioned systems. The final tumour grade allocated at resection was used to assess and compare the accuracy of each cytological classification system.
RESULTS: Cytological assessment accurately reported 77.6% of neuroendocrine lesions as category IVB (neoplastic - other) on Papanicolaou grading, 77.6% as C5 (malignant) lesions and 85.7% as VII (malignant) on WHO grading. 74.3% of resected tumours were grade 1, 17.1% grade 2 and 8.6% grade 3. Complete resection was achieved in 80.8% of cases.
CONCLUSIONS: The results demonstrated that the WHO classification appeared to provide reduced ambiguity when compared with both 'C' and Papanicolaou classification systems; with a lower proportion of cases being classified as suspicious of malignancy as opposed to malignant. The Papanicolaou system was able to supersede the other two systems through its ability to distinguish neuroendocrine tumours from more aggressive entities such as pancreatic adenocarcinoma, thus, offering flexibility in management while still retaining a similar level of accuracy to the WHO classification system in distinguishing benign from malignant lesions.
PMID:38749664 | DOI:10.1136/jcp-2024-209507
PLoS One. 2024 May 15;19(5):e0298824. doi: 10.1371/journal.pone.0298824. eCollection 2024.
ABSTRACT
Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.
PMID:38748739 | DOI:10.1371/journal.pone.0298824
J Cell Mol Med. 2024 May;28(9):e18372. doi: 10.1111/jcmm.18372.
ABSTRACT
Multicellular organisms have dense affinity with the coordination of cellular activities, which severely depend on communication across diverse cell types. Cell-cell communication (CCC) is often mediated via ligand-receptor interactions (LRIs). Existing CCC inference methods are limited to known LRIs. To address this problem, we developed a comprehensive CCC analysis tool SEnSCA by integrating single cell RNA sequencing and proteome data. SEnSCA mainly contains potential LRI acquisition and CCC strength evaluation. For acquiring potential LRIs, it first extracts LRI features and reduces the feature dimension, subsequently constructs negative LRI samples through K-means clustering, finally acquires potential LRIs based on Stacking ensemble comprising support vector machine, 1D-convolutional neural networks and multi-head attention mechanism. During CCC strength evaluation, SEnSCA conducts LRI filtering and then infers CCC by combining the three-point estimation approach and single cell RNA sequencing data. SEnSCA computed better precision, recall, accuracy, F1 score, AUC and AUPR under most of conditions when predicting possible LRIs. To better illustrate the inferred CCC network, SEnSCA provided three visualization options: heatmap, bubble diagram and network diagram. Its application on human melanoma tissue demonstrated its reliability in CCC detection. In summary, SEnSCA offers a useful CCC inference tool and is freely available at [https:]
PMID:38747737 | PMC:PMC11095317 | DOI:10.1111/jcmm.18372
Pol Arch Intern Med. 2024 May 13:16748. doi: 10.20452/pamw.16748. Online ahead of print.
NO ABSTRACT
PMID:38747359 | DOI:10.20452/pamw.16748
Oncoimmunology. 2024 May 10;13(1):2349347. doi: 10.1080/2162402X.2024.2349347. eCollection 2024.
ABSTRACT
The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.
PMID:38746870 | PMC:PMC11093043 | DOI:10.1080/2162402X.2024.2349347
ACG Case Rep J. 2024 May 13;11(5):e01350. doi: 10.14309/crj.0000000000001350. eCollection 2024 May.
ABSTRACT
Insulinomas are rare neuroendocrine tumors characterized by episodic hypoglycemia. Typically, insulinomas are benign, solitary, intrapancreatic, and measure less than 2 cm in diameter. When insulinomas are multicenter or recurrent, they are often associated with genetic conditions such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, or von Hippel-Lindau disease. Most insulinomas can be resolved with surgery. Multicenter and recurrent insulinomas, known as insulinomatosis, may require additional medical and surgical management. We report a distinctive case involving recurrent multicenter insulinomatosis devoid of any identified genetic familial predisposition. The patient's complex medical history spans nearly 2 decades, marked by unsuccessful attempts at resolution through surgical enucleation and noninvasive medical management, culminating in the decision for total pancreatectomy.
PMID:38746622 | PMC:PMC11093572 | DOI:10.14309/crj.0000000000001350
Acta Otorhinolaryngol Ital. 2024 May;44(Suppl. 1):S86-S93. doi: 10.14639/0392-100X-suppl.1-44-2024-N2900.
NO ABSTRACT
PMID:38745520 | DOI:10.14639/0392-100X-suppl.1-44-2024-N2900
Nucl Med Commun. 2024 May 15. doi: 10.1097/MNM.0000000000001861. Online ahead of print.
ABSTRACT
OBJECTIVE: We aimed to compare different segmentation methods used to calculate prognostically valuable volumetric parameters, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), measured by 68Ga-DOTATATE PET/CT and to find the optimal segmentation method to predict prognosis.
PATIENTS AND METHODS: Images of 34 patients diagnosed with gastroenteropancreatic neuroendocrine tumor (GEPNET) who underwent 68Ga-DOTATATE PET/CT imaging were reanalyzed. Four different threshold-based methods (fixed relative threshold method, normal liver background threshold method, fixed absolute standardized uptake value (SUV) threshold method, and adaptive threshold method) were used to calculate SRETV and TLSRE values. SRETV of all lesions of a patient was summarized as whole body SRETV (WB-SRETV) and TLSRE of all lesions of a patient was computed as whole body TLSRE (WB-TLSRE).
RESULTS: WB-SRETVs calculated with all segmentation methods were statistically significantly associated with progression-free survival except WB-SRETVat which was calculated using adaptive threshold method. The fixed relative threshold methods calculated by using 45% (WB-SRETV45%) and 60% (WB-SRETV60%) of the SUV value as threshold respectively, were found to have statistically significant highest prognostic value (C-index = 0.704, CI = 0.622-0.786, P = 0.007). Among WB-TLSRE parameters, WB-TLSRE35%, WB-TLSRE40%, and WB-TLSRE50% had the highest prognostic value (C-index = 0.689, CI = 0.604-0.774, P = 0.008).
CONCLUSION: The fixed relative threshold method was found to be the most effective and easily applicable method to measure SRETV on pretreatment 68Ga-DOTATATE PET/CT to predict prognosis in GEPNET patients. WB-SRETV45% (cutoff value of 11.8 cm3) and WB-SRETV60% (cutoff value of 6.3 cm3) were found to be the strongest predictors of prognosis in GEPNET patients.
PMID:38745508 | DOI:10.1097/MNM.0000000000001861
Am J Case Rep. 2024 May 15;25:e942881. doi: 10.12659/AJCR.942881.
ABSTRACT
BACKGROUND Schwannomas are tumors that arise from Schwann cells that surround and support nerve cells. Most common sites for presentations are head, neck, and extremities. Schwannomas of gastrointestinal tract are rare, slow-growing tumors, usually benign, arising from gastrointestinal tract's neural plexus. They are histologically distinguishable from conventional schwannomas that arise in soft tissue or the central nervous system. Preoperative diagnosis of gastrointestinal schwannoma is challenging, requiring immunohistological confirmation of the nature of the tumor. Here, we report a case of 57-year-old woman with an incidental finding of an asymptomatic submucosal jejunal schwannoma. CASE REPORT A 57-year-old woman with a medical history of hematological disorder underwent a contrast abdominal computed tomography as part of medical follow-up. The imaging revealed the presence of a jejunal mass. The patient underwent laparoscopic surgical resection of the lesion, followed by side-to-side jejuno-jejunal anastomosis with 4-cm clear surgical margins. The final pathologic study revealed the presence of jejunal schwannoma, as tested positive for S-100 protein. The patient was discharged home on the fourth postoperative day, having an uneventful recovery. CONCLUSIONS Jejunal schwannoma are usually benign and asymptomatic, and they are often discovered incidentally during diagnostic tests for other conditions; therefore, it should be included in the differential diagnosis of gastrointestinal tumors. Surgical treatment appears to be necessary to achieve a definitive diagnosis through a biopsy of the tumor tissue. Benign jejunal schwannomas have a good prognosis.
PMID:38745406 | DOI:10.12659/AJCR.942881
J Exp Clin Cancer Res. 2024 May 15;43(1):144. doi: 10.1186/s13046-024-03064-1.
ABSTRACT
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a lethal subset of prostate cancer which is characterized by neuroendocrine differentiation and loss of androgen receptor (AR) signaling. Growing evidence reveals that cell lineage plasticity is crucial in the failure of NEPC therapies. Although studies suggest the involvement of the neural transcription factor PAX6 in drug resistance, its specific role in NEPC remains unclear.
METHODS: The expression of PAX6 in NEPC was identified via bioinformatics and immunohistochemistry. CCK8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay were used to illustrate the key role of PAX6 in the progression of in vitro. ChIP and Dual-luciferase reporter assays were conducted to confirm the binding sequences of AR in the promoter region of PAX6, as well as the binding sequences of PAX6 in the promoter regions of STAT5A and MET. For in vivo validation, the xenograft model representing NEPC subtype underwent pathological analysis to verify the significant role of PAX6 in disease progression. Complementary diagnoses were established through public clinical datasets and transcriptome sequencing of specific cell lines. ATAC-seq was used to detect the chromatin accessibility of specific cell lines.
RESULTS: PAX6 expression was significantly elevated in NEPC and negatively regulated by AR signaling. Activation of PAX6 in non-NEPC cells led to NE trans-differentiation, while knock-down of PAX6 in NEPC cells inhibited the development and progression of NEPC. Importantly, loss of AR resulted in an enhanced expression of PAX6, which reprogramed the lineage plasticity of prostate cancer cells to develop NE phenotypes through the MET/STAT5A signaling pathway. Through ATAC-seq, we found that a high expression level of PAX6 elicited enhanced chromatin accessibility, mainly through attenuation of H4K20me3, which typically causes chromatin silence in cancer cells.
CONCLUSION: This study reveals a novel neural transcription factor PAX6 could drive NEPC progression and suggest that it might serve as a potential therapeutic target for the management of NEPC.
PMID:38745318 | PMC:PMC11094950 | DOI:10.1186/s13046-024-03064-1
J Natl Compr Canc Netw. 2024 May 14:1-8. doi: 10.6004/jnccn.2024.7005. Online ahead of print.
ABSTRACT
BACKGROUND: High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs.
PATIENTS AND METHODS: We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX.
RESULTS: A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities.
CONCLUSIONS: mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.
PMID:38744314 | DOI:10.6004/jnccn.2024.7005
ESMO Open. 2024 May 13;9(5):103461. doi: 10.1016/j.esmoop.2024.103461. Online ahead of print.
ABSTRACT
BACKGROUND: Results from the JAVELIN Merkel 200 study led to the approval of avelumab [an anti-programmed death-ligand 1 (PD-L1) antibody] for the treatment of metastatic Merkel cell carcinoma (mMCC) in multiple countries and its inclusion in the treatment guidelines as a preferred or recommended therapy in this setting. Here, we report 4-year follow-up results from the cohort of patients with mMCC who received avelumab as first-line treatment.
PATIENTS AND METHODS: In part B of JAVELIN Merkel 200, a single-arm, open-label, phase II study, patients with mMCC who had not received prior systemic therapy for metastatic disease received avelumab 10 mg/kg via intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term overall survival (OS), patient disposition, and subsequent treatment were analyzed.
RESULTS: In total, 116 patients received first-line avelumab. At the data cutoff (2 February 2022), the median follow-up was 54.3 months (range 48.0-69.7 months). Seven patients (6.0%) remained on treatment and an additional 21 patients remained in follow-up (18.1%); 72 patients (62.1%) had died. The median OS was 20.3 months [95% confidence interval (CI) 12.4-42.0 months], with a 4-year OS rate of 38% (95% CI 29% to 47%). In patients with PD-L1+ or PD-L1- tumors, the 4-year OS rate was 48% (95% CI 26% to 67%) and 35% (95% CI 25% to 45%), respectively. In total, 48 patients (41.4%) received poststudy anticancer drug therapy, most commonly etoposide (20.7%), carboplatin (19.0%), and avelumab (12.1%).
CONCLUSIONS: Avelumab first-line monotherapy in patients with mMCC resulted in meaningful long-term OS, which compared favorably with historical studies of first-line chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.
PMID:38744102 | DOI:10.1016/j.esmoop.2024.103461
Wounds. 2024 Apr;36(4):119-123.
ABSTRACT
BACKGROUND: Leg ulcers have various etiologies, including malignancy, although vascular issues are the most frequent cause. Malignant wounds present diagnostic challenges, with a reported prevalence rate ranging from 0.4% to 23%. This significant variability in reported prevalence appears to be due to the different settings in which data are collected, which suggests potential influence by medical specialty. Consequently, the misdiagnosis of neoplastic ulcers (eg, ulcerated melanoma) as vascular wounds is relatively common, leading to delayed diagnosis, inadequate treatment, and a dramatic worsening of the patient's prognosis. Identifying malignancy in nonresponsive wounds involves recognizing signs such as hypertrophic granulation tissue, bleeding, unusual pigmentation, and raised edges. The appearance of the perilesional skin, together with dermoscopic observation, is also crucial to differentiation. Ultimately, a biopsy may provide valuable diagnostic clarification.
CASE REPORT: A case is presented of lower limb melanoma that for years was misdiagnosed as a vascular wound by multiple specialists, with delayed referral to a dermatologist and resulting recognition and diagnosis, at which time nodular satellite metastases were found. Dermoscopy and biopsy confirmed the diagnosis. The disease was already advanced, with in-transit and distant site metastases, and the prognosis was regrettably poor.
CONCLUSION: This case underscores the importance of early detection and accurate diagnosis of malignant wounds, emphasizing the need to refer patients with suspicious nonresponsive ulcers to a dermatologist.
PMID:38743857
Sci Signal. 2024 May 14;17(836):eadd5073. doi: 10.1126/scisignal.add5073. Epub 2024 May 14.
ABSTRACT
The Ras-mitogen-activated protein kinase (MAPK) pathway is a major target for cancer treatment. To better understand the genetic pathways that modulate cancer cell sensitivity to MAPK pathway inhibitors, we performed a CRISPR knockout screen with MAPK pathway inhibitors on a colorectal cancer (CRC) cell line carrying mutant KRAS. Genetic deletion of the catalytic subunit of protein phosphatase 6 (PP6), encoded by PPP6C, rendered KRAS- and BRAF-mutant CRC and BRAF-mutant melanoma cells more resistant to these inhibitors. In the absence of MAPK pathway inhibition, PPP6C deletion in CRC cells decreased cell proliferation in two-dimensional (2D) adherent cultures but accelerated the growth of tumor spheroids in 3D culture and tumor xenografts in vivo. PPP6C deletion enhanced the activation of nuclear factor κB (NF-κB) signaling in CRC and melanoma cells and circumvented the cell cycle arrest and decreased cyclin D1 abundance induced by MAPK pathway blockade in CRC cells. Inhibiting NF-κB activity by genetic and pharmacological means restored the sensitivity of PPP6C-deficient cells to MAPK pathway inhibition in CRC and melanoma cells in vitro and in CRC cells in vivo. Furthermore, a R264 point mutation in PPP6C conferred loss of function in CRC cells, phenocopying the enhanced NF-κB activation and resistance to MAPK pathway inhibition observed for PPP6C deletion. These findings demonstrate that PP6 constrains the growth of KRAS- and BRAF-mutant cancer cells, implicates the PP6-NF-κB axis as a modulator of MAPK pathway output, and presents a rationale for cotargeting the NF-κB pathway in PPP6C-mutant cancer cells.
PMID:38743809 | DOI:10.1126/scisignal.add5073
Ann Surg Oncol. 2024 May 14. doi: 10.1245/s10434-024-15439-x. Online ahead of print.
NO ABSTRACT
PMID:38743279 | DOI:10.1245/s10434-024-15439-x
J Cancer Res Clin Oncol. 2024 May 14;150(5):252. doi: 10.1007/s00432-024-05713-6.
ABSTRACT
INTRODUCTION: Adjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.
METHODS: In the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients' ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.
RESULTS: The preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60-65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18-22% for ICI and + 15% for TT.
CONCLUSION: Our study highlights the importance of understanding the patient's perspective and a potential difference to the doctor's view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.
PMID:38743104 | DOI:10.1007/s00432-024-05713-6
Exp Dermatol. 2024 May;33(5):e15094. doi: 10.1111/exd.15094.
ABSTRACT
Melasma is a common condition of hyperpigmented facial skin. Picosecond lasers are reported to be effective for the treatment of melasma. We aimed to identify the most effective therapeutic mode and elucidate the potential molecular mechanisms of picosecond lasers for the treatment of melasma. Female Kunming mice with melasma-like conditions were treated using four different picosecond laser modes. Concurrently, in vitro experiments were conducted to assess changes in melanin and autophagy in mouse melanoma B16-F10 cells treated with these laser modes. Changes in melanin in mouse skin were detected via Fontana-Masson staining, and melanin particles were evaluated in B16-F10 cells. Real-time polymerase chain reaction and western blotting were used to analyse the expression levels of melanosome and autophagy-related messenger ribonucleic acid (mRNA) and proteins. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers resulted insignificant decreases in melanin as well as in mRNA and protein expression of melanin-synthesizing enzymes (TYR, TRP-1 and MITF). This combination also led to increased expression of the autophagy-related proteins, Beclin1 and ATG5, with a marked decrease in p62 expression. Intervention with the PI3K activator, 740 Y-P, increased TYR, TRP-1, MITF, p-PI3K, p-AKT, p-mTOR and p62 expression but decreased the expression of LC3, ATG5 and Beclin1. A combination of large-spot low-fluence 1064-nm and fractional 1064-nm picosecond lasers proved more effective and safer. It inhibits melanin production, downregulates the PI3K/AKT/mTOR pathway, enhances melanocyte autophagy and accelerates melanin metabolism, thereby reducing melanin content.
PMID:38742793 | DOI:10.1111/exd.15094
J Laryngol Otol. 2024 Jun;138(6):591. doi: 10.1017/S0022215124000793. Epub 2024 May 14.
NO ABSTRACT
PMID:38742775 | DOI:10.1017/S0022215124000793
Vestn Oftalmol. 2024;140(2):5-13. doi: 10.17116/oftalma20241400215.
ABSTRACT
Circumscribed choroidal hemangioma (CCH) and early non-pigmented choroidal melanoma (CM) have similar clinical, ultrasound and morphometric features, which in some cases makes their differential diagnosis difficult. There are few studies in the literature devoted to a comparative analysis of the molecular genetic features of CCH and non-pigmented CM, and the results of those studies are contradictory.
PURPOSE: This study attempts to develop a method of non-invasive molecular genetic differential diagnostics of CCH and non-pigmented CM.
MATERIAL AND METHODS: Based on the results of clinical and instrumental examination methods, 60 patients (60 eyes) with CCH (n=30) and non-pigmented CM (n=30) were included in this prospective study. The control group consisted of 30 individuals without intraocular tumors. Mutations in the GNAQ/GNA11 genes were determined by real-time PCR using the analysis of genomic circulating tumor DNA isolated from peripheral blood plasma. The average follow-up period was 12.1±1.8 months.
RESULTS: The study revealed a significant association of mutations in exons 4 and 5 of the GNAQ/GNA11 genes with the presence of non-pigmented CM (27/30; 90%). These mutations were not detected in the group of patients with CCH. Mutations in exons 4 and 5 of the GNAQ/GNA11 genes were also not detected in the control group of healthy individuals.
CONCLUSION: This study proposes a method of non-invasive and low-cost differential diagnostics based on molecular genetic analysis and detection of mutations in exons 4 and 5 of the GNAQ and GNA11 genes, which are specific for CM (90%).
PMID:38742493 | DOI:10.17116/oftalma20241400215
Skin Res Technol. 2024 May;30(5):e13607. doi: 10.1111/srt.13607.
ABSTRACT
BACKGROUND: Timely diagnosis plays a critical role in determining melanoma prognosis, prompting the development of deep learning models to aid clinicians. Questions persist regarding the efficacy of clinical images alone or in conjunction with dermoscopy images for model training. This study aims to compare the classification performance for melanoma of three types of CNN models: those trained on clinical images, dermoscopy images, and a combination of paired clinical and dermoscopy images from the same lesion.
MATERIALS AND METHODS: We divided 914 image pairs into training, validation, and test sets. Models were built using pre-trained Inception-ResNetV2 convolutional layers for feature extraction, followed by binary classification. Training comprised 20 models per CNN type using sets of random hyperparameters. Best models were chosen based on validation AUC-ROC.
RESULTS: Significant AUC-ROC differences were found between clinical versus dermoscopy models (0.661 vs. 0.869, p < 0.001) and clinical versus clinical + dermoscopy models (0.661 vs. 0.822, p = 0.001). Significant sensitivity differences were found between clinical and dermoscopy models (0.513 vs. 0.799, p = 0.01), dermoscopy versus clinical + dermoscopy models (0.799 vs. 1.000, p = 0.02), and clinical versus clinical + dermoscopy models (0.513 vs. 1.000, p < 0.001). Significant specificity differences were found between dermoscopy versus clinical + dermoscopy models (0.800 vs. 0.288, p < 0.001) and clinical versus clinical + dermoscopy models (0.650 vs. 0.288, p < 0.001).
CONCLUSION: CNN models trained on dermoscopy images outperformed those relying solely on clinical images under our study conditions. The potential advantages of incorporating paired clinical and dermoscopy images for CNN-based melanoma classification appear less clear based on our findings.
PMID:38742379 | PMC:PMC11091779 | DOI:10.1111/srt.13607
Zhonghua Zhong Liu Za Zhi. 2024 May 23;46(5):449-456. doi: 10.3760/cma.j.cn112152-20230903-00114.
ABSTRACT
Objectives: To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Methods: Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. Results: The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Conclusion: Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.
PMID:38742358 | DOI:10.3760/cma.j.cn112152-20230903-00114
Radiol Case Rep. 2024 May 4;19(8):3023-3027. doi: 10.1016/j.radcr.2024.03.079. eCollection 2024 Aug.
ABSTRACT
Pheochromocytoma, a neuroendocrine tumor, represents a rare medical condition characterized by the excessive secretion of catecholamines. These tumors often exhibit distinctive features on imaging studies, notably appearing hypervascular. Furthermore, they may present as cystic masses with thin walls, a characteristic that becomes more evident following the administration of contrast medium. The cystic form of adrenal pheochromocytoma, as exemplified in our case, is particularly uncommon, thus underscoring the importance of recognizing its atypical presentation. Accurate diagnosis hinges on a thorough understanding of both the clinical manifestations and radiological findings suggestive of pheochromocytoma. However, definitive confirmation typically necessitates histological examination of the surgical specimen post-adrenalectomy. By shedding light on this rare variant, our case emphasizes the critical role of comprehensive diagnostic approaches in managing such complex medical conditions. Additionally, it underscores the significance of multidisciplinary collaboration among clinicians, radiologists, and pathologists to ensure timely and accurate diagnosis, ultimately guiding appropriate treatment strategies and optimizing patient outcomes.
PMID:38741687 | PMC:PMC11089287 | DOI:10.1016/j.radcr.2024.03.079
World Neurosurg. 2024 May;185:476. doi: 10.1016/j.wneu.2024.02.076.
NO ABSTRACT
PMID:38741313 | DOI:10.1016/j.wneu.2024.02.076
World Neurosurg. 2024 May;185:474-475. doi: 10.1016/j.wneu.2024.01.022.
NO ABSTRACT
PMID:38741312 | DOI:10.1016/j.wneu.2024.01.022
CMAJ. 2024 May 12;196(18):E625. doi: 10.1503/cmaj.240037.
NO ABSTRACT
PMID:38740415 | PMC:PMC11090637 | DOI:10.1503/cmaj.240037
PLoS One. 2024 May 13;19(5):e0300413. doi: 10.1371/journal.pone.0300413. eCollection 2024.
ABSTRACT
Castration-resistant prostate cancer (CRPC) is associated with resistance to androgen deprivation therapy, and an increase in the population of neuroendocrine (NE) differentiated cells. It is hypothesized that NE differentiated cells secrete neuropeptides that support androgen-independent tumor growth and induce aggressiveness of adjacent proliferating tumor cells through a paracrine mechanism. The cytochrome b561 (CYB561) gene, which codes for a secretory vesicle transmembrane protein, is constitutively expressed in NE cells and highly expressed in CRPC. CYB561 is involved in the α-amidation-dependent activation of neuropeptides, and contributes to regulating iron metabolism which is often dysregulated in cancer. These findings led us to hypothesize that CYB561 may be a key player in the NE differentiation process that drives the progression and maintenance of the highly aggressive NE phenotype in CRPC. In our study, we found that CYB561 expression is upregulated in metastatic and NE prostate cancer (NEPC) tumors and cell lines compared to normal prostate epithelia, and that its expression is independent of androgen regulation. Knockdown of CYB561 in androgen-deprived LNCaP cells dampened NE differentiation potential and transdifferentiation-induced increase in iron levels. In NEPC PC-3 cells, depletion of CYB561 reduced the secretion of growth-promoting factors, lowered intracellular ferrous iron concentration, and mitigated the highly aggressive nature of these cells in complementary assays for cancer hallmarks. These findings demonstrate the role of CYB561 in facilitating transdifferentiation and maintenance of NE phenotype in CRPC through its involvement in neuropeptide biosynthesis and iron metabolism pathways.
PMID:38739593 | PMC:PMC11090301 | DOI:10.1371/journal.pone.0300413
Vestn Oftalmol. 2024;140(2. Vyp. 2):16-20. doi: 10.17116/oftalma202414002216.
ABSTRACT
Optical coherence tomography (OCT) is currently widely used for the diagnosis of choroidal melanoma (CM), but the problem of predicting the outcomes of planned CM treatment remains unsolved.
PURPOSE: This study was conducted to identify OCT signs that adversely affect the outcome of organ-preserving CM treatment.
MATERIAL AND METHODS: OCT scan images of 30 patients who underwent organ-preserving treatment and were under observation were selected for this study. Brachytherapy (BT) as monotherapy was performed in 27 patients (in 2 cases - twice, and in 1 case - three times), in one patient - in combination with the previous transpupillary thermotherapy (TTT). Multiple TTT (4 sessions within 4 months) as monotherapy were performed in 2 patients. In 9 cases, a single organ-preserving treatment (BT - 6 patients, TTT - 3 patients) was ineffective. In these cases, the effectiveness of the first stage of organ-preserving treatment was taken into account.
RESULTS: Seven signs of an unfavorable prognosis of the performed treatment were identified by analyzis of tomograms and statistical processing of the obtained data. These signs include: the presence of intraretinal edema, detachment of the neuroepithelium (NED) over the tumor, including with a break in the photoreceptors, accumulation of transudate over the tumor, the presence of large cysts, intraretinal cavities and NED near the tumor (secondary retinal detachment). A combination of three or more signs were observed in all cases of inefficiency of the first stage of treatment. Most often, intraretinal edema and NED over the tumor were combined with the accumulation of subretinal transudate and NED near the tumor. The presence of 6 or all 7 signs took place in cases of a negative therapeutic effect after local destruction.
CONCLUSION: When planning organ-preserving CM treatment, in addition to biometric parameters, it is necessary to pay special attention to the identification of such morphological signs as NED over and near the tumor, accumulation of transudate under the NED, the presence of intraretinal edema, large intraretinal cysts and cavities.
PMID:38739126 | DOI:10.17116/oftalma202414002216
Vet Med Sci. 2024 May;10(3):e1471. doi: 10.1002/vms3.1471.
ABSTRACT
A 15-month-old, grey, Thoroughbred filly presented for investigation of a 6-week history of corneal oedema and blepharospasm on the right eye (OD). The filly was otherwise healthy. Following ophthalmic examination, glaucoma on the OD was diagnosed. A space occupying mass within the anterior chamber was documented on transpalpebral ultrasonographic examination. This mass obliterated most of the anterior intraocular structures on the peripheral nasal side (corneal endothelium and drainage angle), leading to secondary glaucoma. After systemic and topical treatment addressing secondary glaucoma, the corneal oedema reduced. The mass was visualised as an irregularly rounded brown structure associated with the iris on the peripheral nasal side of the anterior chamber. Given the filly's signalment, location and appearance of the mass, a tentative diagnosis of intraocular melanoma was made and enucleation was performed. Histopathological evaluation of the globe revealed solid sheets of heavily pigmented melanocytic cells, disrupting the normal ciliary body architecture and extending into the iris and subretinal. The cells were pleomorphic, polyhedral to round with occasional spindle-shaped cells, and contained moderate to large amounts of granular black-brown pigment (melanin). The iridal component expanded into the anterior chamber, with cells directly opposed to Descemet's membrane, with loss of the endothelium and expanding and occluding the filtration angle in this area. The lesion infiltrated locally into the edge of the sclera, but did not extend through the sclera, though occasional perivascular clusters of melanophages were observed within the scleral stroma adjacent to the optic nerve. Diagnosis of a uveal melanocytic neoplasm was confirmed, with characteristics similar to only one reported case . This is a unique case of a rapidly growing, invasive, uveal melanoma in a young horse. Intraocular melanoma should be considered as a differential diagnoses for glaucoma in grey horses, regardless of the age and absence of melanocytic skin lesions.
PMID:38739097 | PMC:PMC11090147 | DOI:10.1002/vms3.1471
J Endocr Soc. 2024 May 8;8(6):bvae078. doi: 10.1210/jendso/bvae078. eCollection 2024 Apr 6.
ABSTRACT
Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.
PMID:38737592 | PMC:PMC11087876 | DOI:10.1210/jendso/bvae078
Pan Afr Med J. 2024 Feb 26;47:88. doi: 10.11604/pamj.2024.47.88.36616. eCollection 2024.
ABSTRACT
Ectopic ACTH-secreting pheochromocytoma is a very rare cause of Cushing´s syndrome, posing diagnostic and therapeutic challenges. We here report the case of a female patient with suspected severe Cushing´s syndrome associated with melanoderma, arterial hypertension resistant to triple therapy and unbalanced diabetes treated with insulin therapy. Biologically, urinary ethoxylated, 24-hour urinary free cortisol and ACTH were very high. Imaging showed a 3.5 cm left adrenal mass. The patient underwent left adrenalectomy after medical preparation, with good clinico-biological outcome. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. This case study highlights the importance of measuring methoxylated derivatives in any patient with ACTH-dependent Cushing´s syndrome associated with an adrenal mass. The aim is to ensure early treatment and avoid life-threatening complications.
PMID:38737225 | PMC:PMC11087280 | DOI:10.11604/pamj.2024.47.88.36616
Radiol Case Rep. 2024 May 3;19(8):2978-2983. doi: 10.1016/j.radcr.2024.04.015. eCollection 2024 Aug.
ABSTRACT
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high risk of recurrence and metastasis. Regular surveillance through physical exams and imaging studies is crucial for the timely detection of recurrences. MCC patients who produce antibodies to the Merkel cell polyomavirus oncoprotein may benefit from antibody testing in addition to routine imaging surveillance for the early detection of disease recurrence. The clinically available Anti MERKel cell panel (AMERK) is a sensitive tumor marker for Merkel cell polyomavirus positive MCC. Although AMERK is highly sensitive, imaging remains necessary to confirm the location of disease recurrence. MCC exhibits characteristic imaging features, making appropriate imaging modalities, and interpretation important for detection. We present 3 representative patient cases that highlight effective utilization of the AMERK test in addition to imaging for the early detection of MCC recurrence. The rise in the AMERK titer may occur before the disease reaches detectable size on computed tomography scans. Positron emission tomography (PET)-CT can serve as an alternative modality for the early detection of disease. Even subtle abnormalities in 18F-FDG uptake may be significant if accompanied by an increased AMERK titer. Alternative imaging modalities, such as 68Ga-DOTATATE PET-CT and magnetic resonance imaging, can be useful in revealing clinically occult disease in MCC patients. In summary, the AMERK antibody test, alongside imaging, enhances sensitivity in detecting recurrence. By combining these strategies of blood test and imaging, healthcare professionals can identify early signs of MCC recurrence, leading to prompt interventions and improved patient outcomes.
PMID:38737184 | PMC:PMC11087905 | DOI:10.1016/j.radcr.2024.04.015
J Nanobiotechnology. 2024 May 12;22(1):237. doi: 10.1186/s12951-024-02504-6.
ABSTRACT
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors.
RESULTS AND CONCLUSION: In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment.
PMID:38735920 | PMC:PMC11089713 | DOI:10.1186/s12951-024-02504-6
Nihon Shokakibyo Gakkai Zasshi. 2024;121(5):389-399. doi: 10.11405/nisshoshi.121.389.
ABSTRACT
A 53-year-old man with an abnormal routine physical examination was referred to our hospital. Colonoscopy showed a 5-mm submucosal tumor that was 7cm proximal to the ileocecal valve. It was identified as a neuroendocrine tumor (NET) on biopsy. Preoperatively, we conducted a double balloon endoscopy to examine the entire small intestine. Another 7-mm submucosal tumor was found on the ileocecal valve, which was missed during the first colonoscopy. A final diagnosis of multiple ileal NETs (<10mm in diameter) was made, and the patient underwent ileocecal resection with lymphadenectomy. Histopathological evaluation of the surgical specimen verified the diagnosis of NET Grade 1 with submucosal invasion. Metastasis to lymph node #202 was also detected. He remained relapse-free for 5 years and 5 months after the operation. In conclusion, this was a case of multiple ileal NETs (<10mm in diameter) with lymph node metastasis that could not be detected preoperatively on contrast-enhanced computed tomography. This case highlights the significance of detailed endoscopic observation of the terminal ileum.
PMID:38735747 | DOI:10.11405/nisshoshi.121.389
Endocrinol Diabetes Nutr (Engl Ed). 2024 Apr;71(4):187-188. doi: 10.1016/j.endien.2024.01.011.
NO ABSTRACT
PMID:38735680 | DOI:10.1016/j.endien.2024.01.011
Arch Dermatol Res. 2024 May 11;316(5):168. doi: 10.1007/s00403-024-02907-3.
NO ABSTRACT
PMID:38734853 | DOI:10.1007/s00403-024-02907-3
Arch Dermatol Res. 2024 May 11;316(5):165. doi: 10.1007/s00403-024-02922-4.
NO ABSTRACT
PMID:38734782 | DOI:10.1007/s00403-024-02922-4
Diagnostics (Basel). 2024 Apr 26;14(9):907. doi: 10.3390/diagnostics14090907.
ABSTRACT
The present report describes the history of a 58-year-old woman with a rapidly progressing neuroendocrine pancreatic tumor (initially G2) presenting with extensive liver, bone, and lymph node metastases. Previous treatments included chemotherapy, hemithyroidectomy for right lobe metastasis, Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE, Lanreotide, Everolimus, and liver embolization. Due to severe disease progression, after a liver biopsy revealing tumor grade G3, PRRT with the somatostatin receptor antagonist LM3 was initiated. [68Ga]GaDOTA-LM3 PET/CT showed intense tracer uptake in the liver, pancreatic tumor, lymph nodes, and bone metastases. Three TANDEM-PRRT cycles using [177Lu]LuDOTA-LM3 and [225Ac]AcDOTA-LM3, administered concurrently, resulted in significant improvement, notably in liver metastases, hepatomegaly reduction, the complete regression of bone and lymph node metastases, and primary tumor improvement. Partial remission was confirmed by positron emission tomography/computed tomography, chest-abdomen-pelvis contrast-enhanced computed tomography, and magnetic resonance of the abdomen, with marked clinical improvement in pain, energy levels, and quality of life, enabling full resumption of physical activity.
PMID:38732321 | PMC:PMC11083426 | DOI:10.3390/diagnostics14090907
Int J Mol Sci. 2024 May 4;25(9):5023. doi: 10.3390/ijms25095023.
ABSTRACT
Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations. Here, we review the current landscape and progress of standard therapies and explore what personalized oncology techniques may entail in the scope of melanoma. Our purpose is to provide an up-to-date summary of the tools at our disposal that work to circumvent the common barriers faced when battling melanoma.
PMID:38732242 | PMC:PMC11084485 | DOI:10.3390/ijms25095023
Int J Mol Sci. 2024 Apr 29;25(9):4858. doi: 10.3390/ijms25094858.
ABSTRACT
Melatonin and sericin exhibit antioxidant properties and may be useful in topical wound healing patches by maintaining redox balance, cell integrity, and regulating the inflammatory response. In human skin, melatonin suppresses damage caused by ultraviolet radiation (UVR) which involves numerous mechanisms associated with reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and enhancing apoptosis. Sericin is a protein mainly composed of glycine, serine, aspartic acid, and threonine amino acids removed from the silkworm cocoon (particularly Bombyx mori and other species). It is of interest because of its biodegradability, anti-oxidative, and anti-bacterial properties. Sericin inhibits tyrosinase activity and promotes cell proliferation that can be supportive and useful in melanoma treatment. In recent years, wound healing patches containing sericin and melatonin individually have attracted significant attention by the scientific community. In this review, we summarize the state of innovation of such patches during 2021-2023. To date, melatonin/sericin-polymer patches for application in post-operational wound healing treatment has been only sparingly investigated and it is an imperative to consider these materials as a promising approach targeting for skin tissue engineering or regenerative dermatology.
PMID:38732075 | PMC:PMC11084828 | DOI:10.3390/ijms25094858
Int J Mol Sci. 2024 Apr 28;25(9):4811. doi: 10.3390/ijms25094811.
ABSTRACT
Melanoma, the deadliest type of skin cancer, has a high propensity to metastasize to other organs, including the brain, lymph nodes, lungs, and bones. While progress has been made in managing melanoma with targeted and immune therapies, many patients do not benefit from these current treatment modalities. Tumor cell migration is the initial step for invasion and metastasis. A better understanding of the molecular mechanisms underlying metastasis is crucial for developing therapeutic strategies for metastatic diseases, including melanoma. The cell adhesion molecule L1CAM (CD171, in short L1) is upregulated in many human cancers, enhancing tumor cell migration. Earlier studies showed that the small-molecule antagonistic mimetics of L1 suppress glioblastoma cell migration in vitro. This study aims to evaluate if L1 mimetic antagonists can inhibit melanoma cell migration in vitro and in vivo. We showed that two antagonistic mimetics of L1, anagrelide and 2-hydroxy-5-fluoropyrimidine (2H5F), reduced melanoma cell migration in vitro. In in vivo allograft studies, only 2H5F-treated female mice showed a decrease in tumor volume.
PMID:38732030 | PMC:PMC11084881 | DOI:10.3390/ijms25094811
Int J Mol Sci. 2024 Apr 26;25(9):4742. doi: 10.3390/ijms25094742.
ABSTRACT
ADORA2A (adenosine A2a receptor) and ADORA2B propagate immunoregulatory signals, including restricting both innate and adaptive immunity, though recent data also suggest a tumor suppressor effect in certain settings. We evaluated the RNA expression from 514 tumors in a clinical-grade laboratory; 489 patients with advanced/metastatic disease had clinical outcome correlates. Transcript expression was standardized to internal housekeeping genes and ranked (0-100 scale) relative to 735 specimens from 35 different cancer types. Transcript abundance rank values were defined as "low/moderate" (0-74) or "high" (75-100) percentile RNA expression ranks. Overall, 20.8% of tumors had high ADORA2A (≥75 percentile RNA rank). The greatest proportion of high ADORA2A expressors was found in neuroendocrine and breast cancers and sarcomas, whereas the lowest was found in colorectal and ovarian cancers, albeit with patient-to-patient variability. In multivariable logistic regression analysis, there was a significant positive correlation between high ADORA2A RNA expression and a high expression of the immune checkpoint-related molecules PD-1 (p = 0.015), VISTA (p ≤ 0.001), CD38 (p = 0.031), and CD39 (p ≤ 0.001). In 217 immunotherapy-treated patients, high ADORA2A did not correlate significantly with progression-free (p = 0.51) or overall survival (OS) (p = 0.09) from the initiation of the checkpoint blockade. However, high versus not-high ADORA2A transcript expression correlated with longer OS from the time of advanced/metastatic disease (N = 489 patients; (HR 0.69 (95% CI 0.51-0.95) (p = 0.02)). Therefore, high ADORA2A transcript levels may be a favorable prognostic factor, unrelated to immunotherapy. Importantly, ascertaining co-expression patterns of ADORA2A with PD-1 and VISTA in individual tumors as a basis for the precision co-targeting of ADORA2A and these other checkpoint-related molecules warrants investigation in clinical trials.
PMID:38731962 | PMC:PMC11083822 | DOI:10.3390/ijms25094742
J Clin Med. 2024 Apr 25;13(9):2535. doi: 10.3390/jcm13092535.
ABSTRACT
Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study's main endpoints. Statistical analysis was performed using MedCalc® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22-116.99], HR: 12.54 [95% CI: 1.28-122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients' clinical outcomes.
PMID:38731064 | PMC:PMC11084244 | DOI:10.3390/jcm13092535
J Clin Med. 2024 Apr 24;13(9):2508. doi: 10.3390/jcm13092508.
ABSTRACT
Pituitary apoplexy (PA) is an acute, life-threatening clinical syndrome caused by hemorrhage and/or infarction of the pituitary gland. It is clinically characterized by the sudden onset of headache. Depending on the severity, it may also be accompanied by nausea, vomiting, visual disturbances, varying degrees of adenohypophyseal hormone deficiency, and decreased level of consciousness. Corticotropic axis involvement may result in severe hypotension and contribute to impaired level of consciousness. Precipitating factors are present in up to 30% of cases. PA may occur at any age and sometimes develops during pregnancy or the immediate postpartum period. PA occurs more frequently in men aged 50-60, being rare in children and adolescents. It can develop in healthy pituitary glands or those affected by inflammation, infection, or tumor. The main cause of PA is usually spontaneous hemorrhage or infarction of a pituitary adenoma (pituitary neuroendocrine tumor, PitNET). It is a medical emergency requiring immediate attention and, in many cases, urgent surgical intervention and long-term follow-up. Although the majority of patients (70%) require surgery, about one-third can be treated conservatively, mainly by monitoring fluid and electrolyte levels and using intravenous glucocorticoids. There are scoring systems for PA with implications for management and therapeutic outcomes that can help guide therapeutic decisions. Management of PA requires proper evaluation and long-term follow-up by a multidisciplinary team with expertise in pituitary pathology. The aim of the review is to summarize and update the most relevant aspects of the epidemiology, etiopathogenesis, pathophysiology, clinical presentation and clinical forms, diagnosis, therapeutic strategies, and prognosis of PA.
PMID:38731037 | PMC:PMC11084238 | DOI:10.3390/jcm13092508
Cancers (Basel). 2024 May 1;16(9):1765. doi: 10.3390/cancers16091765.
ABSTRACT
BACKGROUND: Colorectal cancer remains the second leading cause of cancer-related death in the US. As early-onset colorectal cancer (EO-CRC) becomes more prevalent in the US, research attention has shifted towards identifying at-risk populations. Previous studies have highlighted the rising rate of early-onset adenocarcinoma (ADC) and neuroendocrine tumors (NET) in the US. However, data on geographical variations of EO-CRC are scarce. Hence, our study aims to analyze time trends in EO-CRC incidence rates across various US regions and to assess these trends by sex and histopathological subtypes (ADC and NET).
METHODS: We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20-54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria "BIC" method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET.
RESULTS: Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.
PMID:38730717 | PMC:PMC11083665 | DOI:10.3390/cancers16091765
Cancers (Basel). 2024 Apr 29;16(9):1731. doi: 10.3390/cancers16091731.
ABSTRACT
Phenotype transformation in pituitary neuroendocrine tumors is a little-known and unpredictable clinical phenomenon. Previous studies have not clearly defined and systematically concluded on the causes of this rare phenomenon. Additionally, the mechanisms of phenotype transformation are not well known. We reviewed cases reported in the literature with the aim of defining phenotype transformation in pituitary neuroendocrine tumors. We present an overview of the wide spectrum of phenotype transformation and its clinical features. We also discuss findings on the potential mechanism of this rare transformation, which may be related to PC1/3, the bioactivity of secretory hormones, gene mutations and the plasticity of pituitary neuroendocrine tumors. Clinicians should be aware of this rare phenomenon and more studies on the underlying mechanisms are required.
PMID:38730682 | PMC:PMC11083144 | DOI:10.3390/cancers16091731
Br J Cancer. 2024 May 10. doi: 10.1038/s41416-024-02705-8. Online ahead of print.
ABSTRACT
BACKGROUND: High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55).
METHODS: We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1.
RESULTS: Frequent genomic alterations affected TP53 (26%), APC (20%), KRAS and MEN1 (both 11%) genes. NET G3 were enriched in MEN1 (p = 0.02) mutations, while both NECs groups were enriched in TP53 (p = 0.001), APC (p = 0.002) and KRAS (p = 0.02) mutations and tumors with TMB ≥ 10 muts/Mb (p = 0.01). No differentially expressed (DE) gene was found between NECs <55% and NECs ≥55%, while 1129 DE genes were identified between NET G3 and NECs. A slight enrichment of CD4+ and CD8+ T cells in NECs and of cancer-associated fibroblasts and macrophages (M2-like) in NET G3. Multivariate analysis identified histologic type and Rb1 loss as independent prognostic factors for overall survival.
CONCLUSIONS: This study showed that GEP-NET G3 and GEP-NECs exhibit clear genomic and transcriptomic differences, differently from GEP-NECs <55% and GEP-NECs ≥55%, and provided molecular findings with prognostic and potentially predictive value.
PMID:38729995 | DOI:10.1038/s41416-024-02705-8
J Gastrointest Surg. 2024 May 8:S1091-255X(24)00448-7. doi: 10.1016/j.gassur.2024.05.006. Online ahead of print.
NO ABSTRACT
PMID:38729419 | DOI:10.1016/j.gassur.2024.05.006
Otol Neurotol. 2024 Jun 1;45(5):587-593. doi: 10.1097/MAO.0000000000004189.
ABSTRACT
OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure.
STUDY DESIGN: Multi-institutional historical cohort study.
SETTING: Five tertiary care referral centers.
PATIENTS: Adults ≥18 years old with sporadic VS.
INTERVENTION: Primary and repeat treatment with SRS.
MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS.
RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery.
CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.
PMID:38728563 | DOI:10.1097/MAO.0000000000004189
Sci Immunol. 2024 May 10;9(95):eadi4191. doi: 10.1126/sciimmunol.adi4191. Epub 2024 May 10.
ABSTRACT
Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation. Transcriptional and metabolic studies showed that mregDC functionality is dependent on the mevalonate biosynthetic pathway and its master transcription factor, SREBP2. We found that melanoma-derived lactate activates SREBP2 in tumor DCs and drives conventional DC transformation into mregDCs via homeostatic or tolerogenic maturation. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promoted antitumor CD8+ T cell activation and suppressed melanoma progression. CD63+ mregDCs were found to reside within the lymph nodes of several preclinical tumor models and in the sentinel lymph nodes of patients with melanoma. Collectively, this work suggests that a tumor lactate-stimulated SREBP2-dependent program promotes CD63+ mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.
PMID:38728412 | DOI:10.1126/sciimmunol.adi4191
Pancreas. 2024 May 1;53(5):e467-e469. doi: 10.1097/MPA.0000000000002348.
NO ABSTRACT
PMID:38728214 | DOI:10.1097/MPA.0000000000002348
Histopathology. 2024 May 10. doi: 10.1111/his.15206. Online ahead of print.
ABSTRACT
The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm2, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low- to intermediate-grade neuroendocrine tumours (NETs), while large-cell neuroendocrine carcinoma (NEC) and small-cell lung carcinoma are high-grade NECs. In small-sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively. Ki-67 antigen, a well-known marker of cell proliferation, has been included in the WHO classification as a non-essential but desirable criterion, especially to distinguish NETs from high-grade NECs and to delineate the provisional category of carcinoid tumours/NETs with elevated mitotic counts (> 10 mitoses per mm2) and/or Ki-67 proliferation index (≥ 30%). However, a wider use of this marker in the spectrum of lung NENs continues to be highly reported and debated, thus witnessing a never-subsided attention. Therefore, the arguments for and against incorporating Ki-67 in the classification and clinical practice of these neoplasms are discussed herein in detail.
PMID:38728050 | DOI:10.1111/his.15206
Cells. 2024 May 2;13(9):777. doi: 10.3390/cells13090777.
ABSTRACT
CD133, a cancer stem cell (CSC) marker in tumors, including melanoma, is associated with tumor recurrence, chemoresistance, and metastasis. Patient-derived melanoma cell lines were transduced with a Tet-on vector expressing CD133, generating doxycycline (Dox)-inducible cell lines. Cells were exposed to Dox for 24 h to induce CD133 expression, followed by RNA-seq and bioinformatic analyses, revealing genes and pathways that are significantly up- or downregulated by CD133. The most significantly upregulated gene after CD133 was amphiregulin (AREG), validated by qRT-PCR and immunoblot analyses. Induced CD133 expression significantly increased cell growth, percentage of cells in S-phase, BrdU incorporation into nascent DNA, and PCNA levels, indicating that CD133 stimulates cell proliferation. CD133 induction also activated EGFR and the MAPK pathway. Potential mechanisms highlighting the role(s) of CD133 and AREG in melanoma CSC were further delineated using AREG/EGFR inhibitors or siRNA knockdown of AREG mRNA. Treatment with the EGFR inhibitor gefitinib blocked CD133-induced cell growth increase and MAPK pathway activation. Importantly, siRNA knockdown of AREG reversed the stimulatory effects of CD133 on cell growth, indicating that AREG mediates the effects of CD133 on cell proliferation, thus serving as an attractive target for novel combinatorial therapeutics in melanoma and cancers with overexpression of both CD133 and AREG.
PMID:38727313 | PMC:PMC11083289 | DOI:10.3390/cells13090777
Front Immunol. 2024 Apr 25;15:1354710. doi: 10.3389/fimmu.2024.1354710. eCollection 2024.
ABSTRACT
Cancer vaccines are gaining ground as immunotherapy options. We have previously demonstrated in cutaneous melanoma (CM) patients that adjuvant treatment with VACCIMEL, a mixture of four irradiated CM cell lines co-adjuvanted with BCG and GM-CSF, increases the cellular immune response to melanocyte differentiation antigens, cancer-testis antigens and neoantigens, with respect to basal levels. On the other hand, it is also known that treatment with anti-PD-1 monoclonal antibodies (MAbs), acting on pre-existing tumor-reactive lymphocytes, induces clinical responses in CM patients, albeit in a fraction of treated patients. A combination of both treatments would appear therefore desirable. In this paper, we describe CM patients who, having progressed even years after vaccination, were treated with anti-PD-1 MAbs. In 5/5 of such progressor patients, complete responses were obtained which lasted between 3 and 65+ months. Three of the patients remain disease-free and two recurred. One of the patients passed away after a recurrence of brain metastases. We suggest that clonally expanded reactive lymphocytes induced by VACCIMEL partially remain as memory cells, which may be recalled after tumor recurrence and may foster ulterior activity of anti-PD-1 MAbs.
PMID:38726010 | PMC:PMC11079628 | DOI:10.3389/fimmu.2024.1354710
Front Oncol. 2024 Apr 23;14:1332387. doi: 10.3389/fonc.2024.1332387. eCollection 2024.
ABSTRACT
BACKGROUND: Accurate detection of the histological grade of pancreatic neuroendocrine tumors (PNETs) is important for patients' prognoses and treatment. Here, we investigated the performance of radiological image-based artificial intelligence (AI) models in predicting histological grades using meta-analysis.
METHOD: A systematic literature search was performed for studies published before September 2023. Study characteristics and diagnostic measures were extracted. Estimates were pooled using random-effects meta-analysis. Evaluation of risk of bias was performed by the QUADAS-2 tool.
RESULTS: A total of 26 studies were included, 20 of which met the meta-analysis criteria. We found that the AI-based models had high area under the curve (AUC) values and showed moderate predictive value. The pooled distinguishing abilities between different grades of PNETs were 0.89 [0.84-0.90]. By performing subgroup analysis, we found that the radiomics feature-only models had a predictive value of 0.90 [0.87-0.92] with I2 = 89.91%, while the pooled AUC value of the combined group was 0.81 [0.77-0.84] with I2 = 41.54%. The validation group had a pooled AUC of 0.84 [0.81-0.87] without heterogenicity, whereas the validation-free group had high heterogenicity (I2 = 91.65%, P=0.000). The machine learning group had a pooled AUC of 0.83 [0.80-0.86] with I2 = 82.28%.
CONCLUSION: AI can be considered as a potential tool to detect histological PNETs grades. Sample diversity, lack of external validation, imaging modalities, inconsistent radiomics feature extraction across platforms, different modeling algorithms and software choices were sources of heterogeneity. Standardized imaging, transparent statistical methodologies for feature selection and model development are still needed in the future to achieve the transformation of radiomics results into clinical applications.
SYSTEMATIC REVIEW REGISTRATION: [https:] identifier CRD42022341852.
PMID:38725633 | PMC:PMC11080013 | DOI:10.3389/fonc.2024.1332387
J Zhejiang Univ Sci B. 2024 Mar 12;25(5):410-421. doi: 10.1631/jzus.B2300579.
ABSTRACT
Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently, the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study, we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis, we identified 111 differential metabolites between the healthy group and the patient group, among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes, we inferred that the cysteine-methionine, pyrimidine, and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.
PMID:38725340 | PMC:PMC11087189 | DOI:10.1631/jzus.B2300579
Chem Biol Drug Des. 2024 May;103(5):e14536. doi: 10.1111/cbdd.14536.
ABSTRACT
This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 μm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.
PMID:38725079 | DOI:10.1111/cbdd.14536
Am J Surg Pathol. 2024 May 9. doi: 10.1097/PAS.0000000000002244. Online ahead of print.
ABSTRACT
The presence of epithelial cells within lymph node parenchyma is typically indicative of a metastatic malignancy. However, there are rare instances in which non-neoplastic epithelial or epithelioid cells may be found within lymph nodes, either due to aberrant embryologic migration, mechanical displacement, or physiological trafficking. These can potentially lead to serious potential diagnostic pitfalls, as when such situations are encountered by surgical pathologists, there is substantial risk of overdiagnosing these as metastatic malignancy. Herein, we describe 2 cases of benign pancreatic islet cells within peripancreatic lymph nodes, and underscore the potential for misdiagnosis of this phenomenon as foci of metastatic well-differentiated neuroendocrine tumor. The benign nature of these intranodal islet cells was supported by: (1) the absence of a well-differentiated neuroendocrine tumor in the entirely submitted concomitant pancreatic resection specimen and (2) the presence of an admixture of insulin and glucagon expressing cells by immunohistochemistry in a distribution characteristic of non-neoplastic pancreatic islets. Both cases were incidental microscopic findings in pancreatic resections for intraductal papillary mucinous neoplasms that were previously biopsied and showed associated microscopic areas of fibrosis and chronic pancreatitis and thus this phenomenon may be related to mechanical displacement from prior injury and/or biopsy.
PMID:38722694 | DOI:10.1097/PAS.0000000000002244
Mol Biomed. 2024 May 10;5(1):17. doi: 10.1186/s43556-024-00182-2.
ABSTRACT
Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations. One of the promising approaches is using liquid biopsies, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), for detecting and monitoring the disease at the early stages. These non-invasive methods can help us identify the most effective treatment strategies for each patient. Single-cellular is a brand-new analysis platform that gives treasured insights into diagnosis, prognosis, and remedy. The incorporation of this data with known clinical and genomics information will give a better understanding of the complicated molecular mechanisms that UM diseases exploit. In this review, we focused on the heterogeneity and molecular panorama of UM, and to achieve this goal, the authors conducted an exhaustive literature evaluation spanning 1998 to 2023, using keywords like "uveal melanoma, "heterogeneity". "Targeted therapies"," "CTCs," and "single-cellular analysis".
PMID:38724687 | PMC:PMC11082128 | DOI:10.1186/s43556-024-00182-2
Asian J Surg. 2024 May 8:S1015-9584(24)00872-8. doi: 10.1016/j.asjsur.2024.04.190. Online ahead of print.
NO ABSTRACT
PMID:38724378 | DOI:10.1016/j.asjsur.2024.04.190
Asian J Surg. 2024 May 8:S1015-9584(24)00876-5. doi: 10.1016/j.asjsur.2024.04.194. Online ahead of print.
NO ABSTRACT
PMID:38724359 | DOI:10.1016/j.asjsur.2024.04.194
J Nucl Med. 2024 May 9:jnumed.123.266991. doi: 10.2967/jnumed.123.266991. Online ahead of print.
ABSTRACT
Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [177Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [177Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [177Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.
PMID:38724277 | DOI:10.2967/jnumed.123.266991
Australas J Dermatol. 2024 May;65 Suppl 1:89-105. doi: 10.1111/ajd.14284.
NO ABSTRACT
PMID:38724103 | DOI:10.1111/ajd.14284
Ann Surg Oncol. 2024 May 9. doi: 10.1245/s10434-024-15390-x. Online ahead of print.
NO ABSTRACT
PMID:38722424 | DOI:10.1245/s10434-024-15390-x
Endocr Connect. 2024 May 1:EC-24-0097. doi: 10.1530/EC-24-0097. Online ahead of print.
ABSTRACT
Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Due to its aggressive growth and difficulty in complete resection, resulting in a high recurrence rate. The cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpression in various cancers, which contributes tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three GEO cohorts. This study aimed to investigate the role of SLC7A11 in invasive PitNETs. Cell proliferation was assessed using CCK-8 and colony formation assays, while cell apoptosis was estimated with flow cytometry. The wound healing assay and transwell assay was utilized to evaluate migration and invasion ability. Our findings demonstrated that SLC7A11 was markedly upregulated in invasive PitNETs, and was associated with the invasiveness of PitNETs. Knockdown of SLC7A11 could largely suppress tumor cell proliferation, migration, and invasion, while inducing apoptosis. Furthermore, SLC7A11 depletion was implicated in regulating EMT and inactivating the PI3K/AKT signaling pathway. These insights suggest SLC7A11 as a potential therapeutic target for invasive PitNETs.
PMID:38722255 | DOI:10.1530/EC-24-0097
J Pathol. 2024 May 9. doi: 10.1002/path.6290. Online ahead of print.
ABSTRACT
Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/β (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PMID:38721894 | DOI:10.1002/path.6290
Cureus. 2024 Apr 7;16(4):e57793. doi: 10.7759/cureus.57793. eCollection 2024 Apr.
ABSTRACT
Insulinoma is a neuroendocrine tumor of the pancreas, and its identification with bedside ultrasonography (US) is extremely rare. With the aim of providing a comprehensive description of the main US characteristics of this rare form of neuroendocrine neoplasm, we are here describing an interesting case of a young woman with insulinoma, identified by using both bedside and endoscopic ultrasounds.
PMID:38721178 | PMC:PMC11077476 | DOI:10.7759/cureus.57793
Cureus. 2024 Apr 8;16(4):e57852. doi: 10.7759/cureus.57852. eCollection 2024 Apr.
ABSTRACT
A 63-year-old woman presented with hypokalemia, hypertension, weight gain, limb edema, and tremors. She was diagnosed with Cushing syndrome, with a 24-hour urine cortisol level of 41,013 nmol/day. Investigations revealed a grade 2 pancreatic neuroendocrine tumor with extensive hepatic metastases. Owing to excessive adrenocorticotropic hormone production from her disease, her hypercortisolemia and Cushing symptoms worsened despite ketoconazole, somatostatin analogs, and right liver lobe chemoembolization. Stereotactic body radiotherapy (SBRT) at a dose of 39 Gy in three fractions was administered to her bilateral adrenal glands in the hope of reducing her cortisol levels and improving her symptoms. Her 24-hour urine cortisol levels decreased following SBRT, but not rapidly enough; her clinical condition continued to deteriorate, and she died 21 days after treatment. SBRT was not effective as an urgent intervention in this setting; a greater latency to realize a response is likely necessary.
PMID:38721167 | PMC:PMC11077502 | DOI:10.7759/cureus.57852
Front Endocrinol (Lausanne). 2024 Apr 24;15:1381093. doi: 10.3389/fendo.2024.1381093. eCollection 2024.
ABSTRACT
Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7, ZNF225, and MED23. The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH-mutated VPGL was characterized by a molecular phenotype different from SDHx-mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.
PMID:38721148 | PMC:PMC11076847 | DOI:10.3389/fendo.2024.1381093
Eur J Med Res. 2024 May 8;29(1):273. doi: 10.1186/s40001-024-01792-w.
ABSTRACT
BACKGROUND: Previous studies suggested that zinc finger protein 536 (ZNF536) was abundant in the central brain and regulated neuronal differentiation. However, the role of ZNF536 in cancer has remained unclear.
METHODS: ZNF536 mutation, copy number alteration, DNA methylation, and RNA expression were explored using public portals. Data from The Cancer Genome Atlas (TCGA) were utilized to analyze pathways and tumor microenvironment (TME), with a focus on prognosis in both TCGA and immunotherapy pan-cancer cohorts. Methylated ZNF536 from small cell lung cancer (SCLC) cell lines were utilized to train with probes for conducting enrichment analysis. Single-cell RNA profile demonstrated the sublocalization and co-expression of ZNF536, and validated its targets by qPCR.
RESULTS: Genetic alterations in ZNF536 were found to be high-frequency and a single sample could harbor different variations. ZNF536 at chromosome 19q12 exerted a bypass effect on CCNE1, supported by CRISPR data. For lung cancer, ZNF536 mutation was associated with longer survival in primary lung adenocarcinoma (LUAD), but its prognosis was poor in metastatic LUAD and SCLC. Importantly, ZNF536 mutation and amplification had opposite prognoses in Stand Up To Cancer-Mark Foundation (SU2C-MARK) LUAD cohort. ZNF536 mutation altered the patterns of genomic alterations in tumors, and had distinct impacts on the signaling pathways and TME compared to ZNF536 amplification. Additionally, ZNF536 expression was predominantly in endocrine tumors and brain tissues. High-dimensional analysis supported this finding and further revealed regulators of ZNF536. Considering that the methylation of ZNF536 was involved in the synaptic pathway associated with neuroendocrine neoplasms, demonstrating both diagnostic and prognostic value. Moreover, we experimentally verified ZNF536 upregulated neuroendocrine markers.
CONCLUSIONS: Our results showed that ZNF536 alterations in cancer, including variations in copy number, mutation, and methylation. We proved the involvement of ZNF536 in neuroendocrine regulation, and identified highly altered ZNF536 as a potential biomarker for immunotherapy.
PMID:38720348 | PMC:PMC11077744 | DOI:10.1186/s40001-024-01792-w
J Nanobiotechnology. 2024 May 8;22(1):230. doi: 10.1186/s12951-024-02498-1.
ABSTRACT
Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.
PMID:38720322 | PMC:PMC11077755 | DOI:10.1186/s12951-024-02498-1
Sci Rep. 2024 May 8;14(1):10578. doi: 10.1038/s41598-024-58531-8.
ABSTRACT
Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.
PMID:38719853 | PMC:PMC11079067 | DOI:10.1038/s41598-024-58531-8
Asian J Surg. 2024 May 7:S1015-9584(24)00819-4. doi: 10.1016/j.asjsur.2024.04.137. Online ahead of print.
NO ABSTRACT
PMID:38719635 | DOI:10.1016/j.asjsur.2024.04.137
J Nucl Med. 2024 May 6;65(Suppl 1):19S-28S. doi: 10.2967/jnumed.123.266945.
ABSTRACT
Melanin is one of the representative biomarkers of malignant melanoma and a potential target for diagnosis and therapy. With advancements in chemistry and radiolabeling technologies, promising strides have been made to synthesize radiolabeled melanin-binding molecules for various applications. We present an overview of melanin-targeted radiolabeled molecules and compare their features reported in preclinical studies. Clinical practice and trials are also discussed to elaborate on the safety and validity of the probes, and expanded applications beyond melanoma are reviewed. Melanin-targeted imaging holds potential value in the diagnosis, staging, and prognostic assessment of melanoma and other applications. Melanin-targeted radionuclide therapy possesses immense potential but requires more clinical validation. Furthermore, an intriguing avenue for future research involves expanding the application scope of melanin-targeted probes and exploring their value.
PMID:38719238 | DOI:10.2967/jnumed.123.266945
Ann Surg Oncol. 2024 May 8. doi: 10.1245/s10434-024-15374-x. Online ahead of print.
ABSTRACT
BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries.
METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions.
RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups.
CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.
PMID:38717544 | DOI:10.1245/s10434-024-15374-x
Ear Nose Throat J. 2024 May 8:1455613241249270. doi: 10.1177/01455613241249270. Online ahead of print.
ABSTRACT
Objective: Laryngeal neuroendocrine neoplasms (LNEN) are rare, and there have been previous uncertainties regarding their classification and treatment modalities. This article aims to share our treatment experience, elucidate changes in LNEN classification, and discuss the treatment implications of different types and stages. Methods: A retrospective analysis was conducted on 11 cases of LNEN treated through surgical intervention at the Department of Otolaryngology, Qilu Hospital of Shandong University, Qingdao, from January 2014 to November 2023. Among the 11 cases, there were 9 males and 2 females, with ages ranging from 61 to 77 years. Pathological classifications included neuroendocrine tumors (NET) G1 (1 case), G2 (2 cases), G3 (5 cases), small-cell neuroendocrine carcinoma (2 cases), and large-cell neuroendocrine carcinoma (1 case). The follow-up period ranged from 1 to 115 months. Results: Treatment modalities varied among the cases: 5 patients underwent transoral laser microsurgery (TLM) without neck dissection, 1 patient underwent TLM with unilateral neck lymph node dissection, 1 patient underwent open partial supraglottic laryngectomy (OPSL) with ipsilateral neck lymph node dissection, and 4 patients underwent OPSL with bilateral neck lymph node dissection. Among the 11 patients, 4 died, with 2 succumbing to distant metastasis, 1 to local recurrence, and 1 to other diseases. Conclusion: The prognosis of LNEN is closely associated with the latest pathological classification and TNM staging. For a more detailed and specific clinical staging, further research involving multicenter large-scale data is needed.
PMID:38717053 | DOI:10.1177/01455613241249270
Front Neurosci. 2024 Apr 22;18:1294417. doi: 10.3389/fnins.2024.1294417. eCollection 2024.
ABSTRACT
Patients with pituitary neuroendocrine tumors (PitNETs) often experience neuropsychiatric disorders due to factors such as hormonal imbalances, and inadequate management of medications, surgeries, and radiation therapies. Commonly observed disorders include depression, anxiety, and cognitive dysfunction, which significantly impact patients' quality of life and prognosis. PitNETs have a significant presence of immune cells within the tumor microenvironment (TME), predominantly macrophages and T lymphocytes. These immune cells secrete a variety of cytokines, growth factors, and chemokines, which regulate the biological behaviors of PitNETs, including tumor initiation, proliferation, migration, invasion, and angiogenesis. In addition, this review provides a pioneering summary of the close relationships between the aberrant secretion of proinflammatory cytokines within the TME of PitNETs and the occurrence of neuropsychiatric disorders, along with their potential underlying mechanisms. The cytokines produced as a result of TME dysregulation may affect various aspects of the central nervous system, including neurotransmitter metabolism, neuroendocrine function, and neurovascular plasticity, thereby leading to a higher susceptibility to neurobehavioral disorders in PitNET patients.
PMID:38716256 | PMC:PMC11075501 | DOI:10.3389/fnins.2024.1294417
Transl Gastroenterol Hepatol. 2024 Mar 22;9:24. doi: 10.21037/tgh-23-84. eCollection 2024.
ABSTRACT
BACKGROUND AND OBJECTIVE: Esophageal carcinoma with switch/sucrose nonfermenting (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutation is a rare variant of malignant esophageal epithelial neoplasm, which is characterized by the loss of SMARCA4/BRG1 protein on immunohistochemistry or alterations in the SMARCA4 gene on sequencing. Only a few case series and case reports of esophageal carcinoma with SMARCA4 mutations have been published in the English literature; the rarity of the disease poses significant diagnostic challenges for surgical pathologists and could potentially lead to delayed or suboptimal patient care. Herein, we reviewed the available literature on esophageal carcinoma with SMARCA4 mutations to discuss its epidemiology, clinical presentation, pathological and molecular features, diagnostic challenges, treatment, and prognosis.
METHODS: The PubMed, Scopus, Ovid, and Google Scholar databases were extensively reviewed. The references included in the articles were cross-examined to identify any missing articles. We searched for all published literature on esophageal carcinoma with SMARCA4 mutations from inception of the databases to date.
KEY CONTENT AND FINDINGS: Esophageal carcinoma with SMARCA4 mutations is most common in middle-aged and older men. Barrett esophagus and gastroesophageal reflux disease (GERD) are the most associated risk factors. Dysphagia was the most common initial clinical presentation. Esophagogastroduodenoscopy (EGD) is the preferred diagnostic modality. Microscopically, the tumor cells exhibited epithelioid features mixed with variable components of rhabdoid and glandular differentiation. The tumor cells showed variable immunoreactivity for cytokeratin and sometimes weakly expressed neuroendocrine or B-lymphocyte markers (Pax5), which are potential diagnostic pitfalls. Melanoma marker tests showed negative results. The SMARCB1/INI1 protein remains intact, and a definitive diagnosis necessitates the presence of either SMARCA4/BRG1 protein loss or SMARCA4 gene mutations. Esophageal carcinoma with SMARCA4 mutations shows overly aggressive behavior and presents with advanced stages of disease; most patients succumb to the disease within 1 year of initial diagnosis.
CONCLUSIONS: Esophageal carcinoma with SMARCA4 mutation is an overly aggressive disease, and further research on the affected molecular pathway may help improve its prognosis.
PMID:38716209 | PMC:PMC11074479 | DOI:10.21037/tgh-23-84
Ups J Med Sci. 2024 Apr 10;129. doi: 10.48101/ujms.v129.10660. eCollection 2024.
ABSTRACT
BACKGROUND: Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with BRAF V600E-mutated NEC. However, since only eight such patients have been reported in the literature, our object was to confirm the validity of this recommendation.
METHODS: This was a single-center retrospective cohort study conducted at Uppsala University Hospital. The included patients 1) had a histopathologically confirmed diagnosis of NEC, 2) were diagnosed between January 1st, 2018 and December 31st, 2023, 3) had tumor tissue genetically screened by a broad next-generation sequencing (NGS) panel, and 4) showed a tumor mutation for which there is a currently available targeted therapy.
RESULTS: We screened 48 patients diagnosed with NEC between January 1st, 2018 and December 31st, 2023. Twelve had been analyzed with a broad NGS-panel, and two had a targetable mutation. Both these patients harbored a BRAF V600E-mutated colon-NEC and were treated with BRAF- and MEK-inhibitors dabrafenib and trametinib in second-line. At first radiological evaluation (RECIST 1.1), both patients had a reduction of tumor size, which decreased by 31 and 40%. Both had short response periods, and their overall survival was 12 and 9 months.
CONCLUSIONS: BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.
PMID:38716076 | PMC:PMC11075439 | DOI:10.48101/ujms.v129.10660
Case Rep Otolaryngol. 2024 Apr 29;2024:9963521. doi: 10.1155/2024/9963521. eCollection 2024.
ABSTRACT
The carotid body paraganglioma is a rare benign neoplasm arising from the chemoreceptor cells of the carotid bulb. The carotid body has the largest collection of paraganglia in the head and neck with 60-70% of head and neck paraganglioma. Paraganglia are clusters of cells originating from the neural crest with histological and cytochemical characteristics of neuroendocrine cells. It is mostly asymptomatic in early presentation but become symptomatic and difficult to manage when the tumor is large. We present a case of a 26-year-old male who presented with a painless, pulsatile, progressively increasing left lateral neck swelling of 5 years duration with Shamblin IIIa. The diagnosis of the tumor was confirmed based on clinical features, histology, and radiological findings. We had difficult surgical dissection of the tumor with neurovascular damage.
PMID:38715736 | PMC:PMC11074773 | DOI:10.1155/2024/9963521
Int J Nanomedicine. 2024 May 3;19:4007-4019. doi: 10.2147/IJN.S455158. eCollection 2024.
ABSTRACT
INTRODUCTION: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated.
METHODS: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2-MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor.
RESULTS: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2-MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10-3 μg. Antares2-MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2-MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo.
CONCLUSION: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.
PMID:38715701 | PMC:PMC11075688 | DOI:10.2147/IJN.S455158
Obes Surg. 2024 May 7. doi: 10.1007/s11695-024-07257-7. Online ahead of print.
ABSTRACT
BACKGROUND: Obesity is a well-established risk factor for cancer. Laparoscopic sleeve gastrectomy (LSG) is established as a safe procedure providing accelerated weight loss and comorbidity improvement or remission. Additionally, it is approved as a bridging procedure for various non-oncologic surgeries, with very limited data for oncologic procedures. The aim of this study is to present a series of patients with severe obesity and concomitant cancer who underwent LSG prior to definitive oncological procedure.
METHODS: A retrospective review (2008-2023) was conducted in three institutions, identifying 5 patients with cancer and severe obesity who underwent LSG as bridging procedure. Variables analyzed were initial weight, initial body mass index (BMI), type of malignancy, comorbidities, interval between LSG and oncological surgery, weight and BMI before the second intervention, percentage of excess weight loss (%EWL), and postoperative morbidity and mortality.
RESULTS: Malignancies identified were 2 prostate cancers, 1 periampullary neuroendocrine tumor, 1 rectal cancer, and 1 renal clear cell carcinoma. Mean age of patients was 50.2 years, mean initial BMI 47.4 kg/ m 2 , and mean BMI before oncological surgery 37 kg/ m 2 . Mean time interval between LSG and oncological surgery was 8.3 months. Mean %EWL achieved was 45.2%. Two thromboembolic events were encountered after LSG, while none of the patients developed complications after definitive oncological treatment. The mean follow-up after oncological surgery was 61.6 months.
CONCLUSION: LSG can be proposed as bridging procedure before oncological surgery in meticulously selected patients. Achieved weight loss can render subsequent oncological procedures easier and safer.
PMID:38714594 | DOI:10.1007/s11695-024-07257-7
PET Clin. 2024 May 6:S1556-8598(24)00023-3. doi: 10.1016/j.cpet.2024.03.008. Online ahead of print.
ABSTRACT
Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells. NEN are ideally suited for a theragnostic approach due to their specific expression of somatostatin receptors (SSTR). SSTR imaging of NEN dates back to the 1980s, but has evolved recently due to the introduction of more sensitive SSTR PET radiotracers. SSTR PET is a primary imaging modality for identifying NEN and characterizing SSTR expression. SSTR PET is complementary to anatomic imaging for assessing tumor response to treatment. SSTR PET is mandated to determine eligibility for peptide receptor radionuclide therapy. Here, the role of imaging to aid management of NEN is reviewed.
PMID:38714399 | DOI:10.1016/j.cpet.2024.03.008
Cancer Immunol Immunother. 2024 May 7;73(7):116. doi: 10.1007/s00262-024-03697-3.
ABSTRACT
OBJECTIVES: Nivolumab is approved as adjuvant therapy for resected stage III/IV melanoma based on the phase 3 CheckMate 238 trial. This analysis compared outcomes from CheckMate 238 with those from the real-world Flatiron Health electronic health record-derived de-identified database in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab.
MATERIALS: Outcomes included baseline characteristics, overall survival (OS) in the CheckMate 238 cohort (randomization until death or last known alive), and real-world overall survival (rwOS) in the Flatiron Health cohort (nivolumab initiation until death or data cutoff). rwOS was compared with OS using unadjusted and adjusted Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was combined with the adjusted model to reduce baseline discrepancies.
RESULTS: The CheckMate 238 and real-world cohorts included 369 and 452 patients, respectively (median age, 56.0 and 63.0 years; median follow-up, 61.4 vs. 25.5 months). rwOS was not different from OS in the unadjusted (hazard ratio [HR] 1.27; 95% CI 0.92-1.74), adjusted (HR 1.01; 95% CI 0.67-1.54), and adjusted IPTW (HR 1.07; 95% CI 0.70-1.63) analyses. In the adjusted analysis, 2-year OS and rwOS rates were 84%. Median OS and rwOS were not reached. After IPTW, OS and rwOS were not different (HR 1.07; 95% CI 0.70-1.64).
CONCLUSIONS: In this comparative analysis, OS in the CheckMate 238 trial was similar to rwOS in the Flatiron Health database after adjustments in patients with resected stage III melanoma (per AJCC-8) treated with adjuvant nivolumab, validating the trial results.
PMID:38713408 | PMC:PMC11076438 | DOI:10.1007/s00262-024-03697-3
Radiologie (Heidelb). 2024 May 7. doi: 10.1007/s00117-024-01296-y. Online ahead of print.
ABSTRACT
CLINICAL/METHODICAL ISSUE: Neuroendocrine tumors (NET) represent a heterogeneous group of rare tumors that predominantly arise in the gastrointestinal tract. At the time of initial diagnosis, the NET has already spread locoregionally in about half of the patients, and 27% of patients have already developed distant metastases. Since this plays a crucial role in therapy planning, accurate diagnostic imaging is important.
STANDARD RADIOLOGICAL METHODS: Due to its high temporal and spatial resolution (multiphasic including arterial phase), computed tomography (CT) plays a decisive role in primary staging and follow-up care, while magnetic resonance imaging (MRI) with its excellent soft tissue contrast offers advantages in the assessment of parenchymal organs in the upper abdomen.
METHODICAL INNOVATIONS: Somatostatin receptor (SSR) positron emission tomography (PET) provides additional functional information that not only helps to detect the primary tumor and distant metastases, but also has a significant influence on therapeutic management in a theranostic approach.
PERFORMANCE: Hybrid imaging using SSR-PET/CT has proven to be particularly effective in the detection of NET. Compared to conventional imaging, it provides additional information in 68% of patients, which has a significant impact on clinical management.
ACHIEVEMENTS: Imaging of NET requires the combined use of various methods such as ultrasound, CT, MRI, and PET/CT to enable accurate diagnosis and effective treatment planning.
PRACTICAL RECOMMENDATIONS: SSR-PET/CT is a valuable tool for the accurate staging of neuroendocrine tumors of the gastrointestinal tract, especially with small metastases, while MRI with hepatocyte-specific contrast agent and diffusion-weighted imaging is useful for the specific assessment of liver metastases.
PMID:38713221 | DOI:10.1007/s00117-024-01296-y