Common Tumor Research Articles

The incidence of incidental neoplasia in pathology samples of patient who underwent appendectomy due to acute appendicitis. A single center experience: 6446 cases.

Appendectomy is the standard treatment of acute appendicitis. However, recent advancements have introduced medical treatment as a potential alternative. Within this context, it's important to recognize the rare occurrence of appendiceal tumors, often incidentally discovered during histopathological examination following appendectomy. Consequently, there's a concern about the possibility of overlooking appendiceal neoplasms, particularly in cases where conservative treatment for acute appendicitis is considered. The files of patients who underwent surgery for acute appendicitis between January 2015 and December 2023 and were diagnosed with neoplasia in their pathology reports were retrospectively registered. Demographic characteristics of the patients, laboratory and imaging features, details of the surgery performed, preoperative and intraoperative suspicion of neoplasm and data from pathology reports were collected and analyzed. A total of 6446 patients were operated for acute appendicitis. Neoplasia was detected in the histopathological examination of 93 patients (1.44%). Acute appendicitis was diagnosed in 51.6% of the patients by computed tomography. Neoplasm suspicion was present in 9.7% of patients in preoperative imaging methods and in 6.5% of patients intraoperatively. Only appendectomy was performed in 94.5% of patients. The most common appendiceal neoplasm is neuroendocrine tumors (40.9%), followed by appendiceal mucinous neoplasm (29%), sessile serrated adenoma (15%), and adenocarcinoma (6.5%). Although appendiceal neoplasms are relatively rare in proportion, they represent a significant numerical value due to the density of cases. Therefore, this information should be taken into consideration when evaluating treatment options for acute appendicitis.

Investigation of the Relationship Between Prostate-Specific Antigen Levels and Prostate Cancer in Patients Attending a Urology Clinic from 2014 to 2023

Background: Prostate cancer is the second most common neoplasm and the fifth most aggressive cancer among men worldwide, with approximately 1.4 million new cases diagnosed annually. The incidence and mortality of prostate cancer increase with age, with a mean age at diagnosis of 66 years. Prostate cancer may be asymptomatic in its early stages and often has a latent period. The use of the Prostate-Specific Antigen (PSA) Index in the definitive diagnosis of prostate cancer remains a challenge for many urologists, and further research in this area can help to better understand the precise relationship between PSA levels and prostate cancer. Objectives: The present study aimed to investigate the relationship between PSA levels and prostate cancer in patients attending a urology clinic from 2014 to 2023, with the goal of improving diagnosis, developing effective treatments, and enhancing clinical outcomes. Methods: In this cross-sectional study, 242 patients with prostate cancer who attended a urology surgical clinic over a nine-year period from 2014 to 2023 were included. The patients were divided into two groups—youngest and oldest—based on the duration of their disease diagnosis. Demographic and clinical laboratory data were collected and entered into a checklist. Subsequently, the patients underwent a biopsy, and the results were recorded. Upon completion of the study, the collected data were entered into SPSS software for statistical analysis. Multiple regression analysis was used for correlation tests, while nonparametric tests, such as the Kruskal-Wallis test and the Mann-Whitney U test, were applied for nonparametric data analysis. Results: This study included 242 out of 276 samples for analysis. The ages of the participants ranged from 41 to 90 years, with a mean age of 67 ± 9.42 years. The data indicated that at PSA concentrations of 4 - 10 ng/mL, 5% of the samples were healthy, 15.2% had cancer, 46% had benign prostatic hyperplasia (BPH), and 33% had prostate intraepithelial neoplasia (PIN). At PSA concentrations of 10 - 50 ng/mL, 6% of the samples were healthy, 37% had cancer, 26% had BPH, and 29% had PIN. At PSA concentrations greater than 50 ng/mL, 3% of the samples were healthy, 76% had cancer, 14% had BPH, and 7% had PIN. A chi-square test revealed a significant association between PSA levels and pathological response (P < 0.001). Additionally, an analysis of variance (ANOVA) test showed a significant difference between different age and severity groups (P < 0.001). The free PSA-to-total PSA ratio in this study was 0.18, and the PSA-to-prostate volume ratio was 0.15, both of which were significantly associated with biopsy results (P < 0.01). Conclusions: Overall, the data obtained from this study indicated that plasma PSA levels were directly associated with the likelihood of prostate cancer. Additionally, the results showed that plasma PSA levels were not only directly associated with age but also correlated with the severity of trophic disorders, such as cancer, as indicated by biopsy results.

Clinical and Morphological Aspects of Aggressive Salivary Gland Mixed Tumors: A Narrative Review

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors.

Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.

Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice.

Progressive Acute Lower Extremity Ischemia Resulting From Cardiac Myxoma Embolization: A Case Report.

Cardiac myxomas are the most common primary benign tumors of the heart. The occlusion of peripheral arteries and complete obstruction of the abdominal aorta by a tumor embolus presents with distinct clinical manifestations. Herein, we present the case of a 38-year-old male with acute paresthesia, muscle weakness, erythematous, and violaceous changes in skin color localized to the dorsum of the left forefoot initially treated as cutaneous vasculitis. Further studies revealed the total occlusion of the terminal abdominal aorta by a saddle embolus from a cardiac myxoma. A multidisciplinary team consisting of cardiothoracic and vascular surgeons were involved in treating the patient, which resulted in full resolution of the case. This paper details the progression of acute bilateral limb ischemia to chronic limb threatening ischemia resulting from the total occlusion of the terminal abdominal aorta by a saddle embolus.

Construction of circRNA-mediated ceRNA network and immunoassay for investigating pathogenesis of COPD

BackgroundThe chronic respiratory condition known as chronic obstructive pulmonary disease (COPD) was one of the main causes of death and disability worldwide. This study aimed to explore and elucidate new targets and molecular mechanisms of COPD by constructing competitive endogenous RNA (ceRNA) networks.MethodsGSE38974 and GSE106986 were used to select DEGs in COPD samples and normal samples. Cytoscape software was used to construct and present protein-protein interaction (PPI) network, mRNA-miRNA co-expression network and ceRNA network. The CIBERSORT algorithm and the Lasso model were used to screen the immune infiltrating cells and hub genes associated with COPD, and the correlation between them was analyzed. COPD cell models were constructed in vitro and the expression level of ceRNA network factors mediated by hub gene was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsIn this study, 852 differentially expressed genes were screened in the GSE38974 dataset, including 439 upregulated genes and 413 downregulated genes. Gene clustering analysis of PPI network results was performed using the Minimum Common Tumor Data Element (MCODE) in Cytoscape, and seven hub genes were screened using five algorithms in cytoHubba. CCL20 was verified as an important hub gene based on mRNA-miRNA co-expression network, GSE106986 database validation and the analysis of ROC curve results. Finally, we successfully constructed the circDTL-hsa-miR-330-3p-CCL20 network by Cytoscape. Immune infiltration analysis suggested that CCL20 can co-regulate immune cell migration and infiltration through chemokines CCL7 and CXCL3. In vitro experiments, the expression of circDTL and CCL20 was increased, while the expression of hsa-miR-330-3p was decreased in the COPD cell model.ConclusionBy constructing the circDTL-hsa-miR-330-3p-CCL20 network, this study contributes to a better understanding of the molecular mechanism of COPD development, which also provides important clues for the development of new therapeutic strategies and drug targets.

Deubiquitinating enzyme USP28 inhibitor AZ1 alone and in combination with cisplatin for the treatment of non-small cell lung cancer.

Lung cancer is one of the most common malignant tumors. Despite decades of research, the treatment of lung cancer remains challenging. Non-small cell lung cancer (NSCLC) is the primary type of lung cancer and is a significant focus of research in lung cancer treatment. The deubiquitinase ubiquitin-specific protease 28 (USP28) plays a role in the progression of various tumors and serves as a potential therapeutic target. This study aims to determine the role of USP28 in the progression of NSCLC. We examined the impact of the USP28 inhibitor AZ1 on the cell cycle, apoptosis, DNA damage response, and cellular immunogenicity in non-small cell lung cancer. We observed that AZ1 and siUSP28 induce DNA damage, leading to the activation of Noxa-mediated mitochondrial apoptosis. The dsDNA and mtDNA released from DNA damage and mitochondrial apoptosis activate tumor cell immunogenicity through the cGAS-STING signaling pathway. Simultaneously, targeting USP28 promotes the degradation of c-MYC, resulting in cell cycle arrest and inhibition of DNA repair. This further promotes DNA damage-induced cell apoptosis mediated by the Noxa protein, thereby enhancing tumor cell immunogenicity mediated by dsDNA and mtDNA. Moreover, we found that the combination of AZ1 and cisplatin (DDP) can enhance therapeutic efficacy, thereby providing a new strategy to overcome cisplatin resistance in NSCLC. These findings suggest that targeting USP28 and combining it with cisplatin are feasible strategies for treating NSCLC.

Auranofin Suppresses the Growth of Canine MammaryTumour Cells and Induces Apoptosis via thePI3K/AKT Pathway.

Canine mammary gland tumour (CMT) is the most common spontaneous tumour in intact female dogs and often exhibits metastases. Auranofin (AF) is a gold complex used for treating rheumatism. The excellent anti-tumour ability of AF has been demonstrated in various types of human and canine tumours. In this study, five CMT cell lines (CIPp, CMT-7364, CHMp, CIPm and CTBp) and three CMT primary cells (G7894, L1883 and L6783) were used to explore the anti-tumour effect of AF on CMT. Two CMT cell lines (CIPp and CMT-7364) were used to search the underlying mechanism of the effect of AF on CMT. The results showed that AF inhibited the growth, migration, invasion, and colony formation abilities of CMT cells. Additionally, the growth of CMT in a 3D cell culture model was effectively suppressed by AF. Furthermore, AF induced cell apoptosis of CMT cells via the PI3K/AKT pathway. In conclusion, AF effectively induces CMT apoptosis by regulating the PI3K/AKT pathway, indicating that AF should be explored as a potential CMT treatment in future studies.

Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.

Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa. Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines. The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

Imaging of thymic epithelial tumors-a clinical practice review.

This review article comprehensively examines the diagnostic approach to thymic epithelial tumors (TETs) and other mediastinal masses, focusing on imaging modalities and differential diagnosis. Beginning with a discussion on traditional and contemporary classification systems for mediastinal tumors, including the Japanese Association for Research on the Thymus (JART) and International Thymic Interest Group (ITMIG) classifications, it highlights the shift towards computed tomography (CT)-based categorizations. Emphasis is placed on the importance of distinguishing between solid and cystic lesions in the anterior mediastinum, with detailed insights into imaging characteristics and histological features of various TET subtypes such as thymomas, thymic carcinomas, and thymic neuroendocrine tumors (NETs). The review also elucidates common differential diagnoses, including lymphomas and germ cell tumors, providing guidance on key imaging findings and considerations for accurate diagnosis. Furthermore, it underscores the significance of patient background and blood tests in differential diagnosis, discussing age-related prevalence patterns and tumor marker assessment. After addressing the diagnostic challenges posed by thymic cysts offering insights into their radiological features, management considerations, and potential complications, this review extends to other rare mediastinal lesions highlighting the need for a comprehensive evaluation for accurate identification and management of these tumors. Finally, as illustrative examples, we present six cases highlighting various aspects of anterior mediastinal tumors, including TET. These cases provide valuable insights into the diagnostic challenges, imaging characteristics, and management considerations encountered in clinical practice. The cases presented herein do not all illustrate typical images, courses, and diagnoses. However, they each contain significant implications. Thus, we present them with the belief that they will aid in understanding the intricate nuances of image diagnosis in actual clinical practice.

Overexpression of H2AFX gene in neuroblastoma is associated with worse prognosis.

Neuroblastoma (NB) is the most common solid tumour in childhood, and rises in the sympathetic nervous system. Here, we addressed the in silico analysis of the association between the expression of H2AFX gene involved in DNA damage response, and the survival of a cohort of 786 NB patients. In silico gene expression was retrieved from the publicly available dataset summarised by Cangelosi etal., including 13,696 gene expression profiles of 786 NB tumours at onset of disease. The prognostic value of H2AFX (H2A histone family member X) gene expression for event-free survival (EFS) and overall survival (OS) was evaluated by Kaplan-Meier and Cox regression analysis. The main results were validated on another openly accessible in silico database (NRC-283) containing 13,489 gene expressions in 283 NB patients. The expression of H2AFX protein was then tested by immunofluorescence on 48 primary NB samples of different tumour stages. H2AFX activity as an oncogene has been further validated in vitro by silencing the molecule in two NB cell lines, characterised by MYCN amplified or not, and performing cell growth and migration assays. A strong inverse association between H2AFX expression and patients' survival was observed and confirmed by immunofluorescence results on primary NB tissue sections. Cox regression analysis also disclosed H2AFX as an independent predictor of EFS and OS. The gene-silencing experiments strongly suggested an oncogenic role for H2AFX on NB cells, regardless of MYCN amplification. H2AFX is a prognostic marker for unfavourable NB and could be considered a target for therapeutic interventions.

Predicting peritumoral glioblastoma infiltration and subsequent recurrence using deep-learning-based analysis of multi-parametric magnetic resonance imaging.

Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor. The standard treatment approach is surgical resection to target the enhancing tumor mass, followed by adjuvant chemoradiotherapy. However, malignant cells often extend beyond the enhancing tumor boundaries and infiltrate the peritumoral edema. Traditional supervised machine learning techniques hold potential in predicting tumor infiltration extent but are hindered by the extensive resources needed to generate expertly delineated regions of interest (ROIs) for training models on tissue most and least likely to be infiltrated. We developed a method combining expert knowledge and training-based data augmentation to automatically generate numerous training examples, enhancing the accuracy of our model for predicting tumor infiltration through predictive maps. Such maps can be used for targeted supra-total surgical resection and other therapies that might benefit from intensive yet well-targeted treatment of infiltrated tissue. We apply our method to preoperative multi-parametric magnetic resonance imaging (mpMRI) scans from a subset of 229 patients of a multi-institutional consortium (Radiomics Signatures for Precision Diagnostics) and test the model on subsequent scans with pathology-proven recurrence. Leave-one-site-out cross-validation was used to train and evaluate the tumor infiltration prediction model using initial pre-surgical scans, comparing the generated prediction maps with follow-up mpMRI scans confirming recurrence through post-resection tissue analysis. Performance was measured by voxel-wised odds ratios (ORs) across six institutions: University of Pennsylvania (OR: 9.97), Ohio State University (OR: 14.03), Case Western Reserve University (OR: 8.13), New York University (OR: 16.43), Thomas Jefferson University (OR: 8.22), and Rio Hortega (OR: 19.48). The proposed model demonstrates that mpMRI analysis using deep learning can predict infiltration in the peri-tumoral brain region for GBM patients without needing to train a model using expert ROI drawings. Results for each institution demonstrate the model's generalizability and reproducibility.

Identification and validation of a novel robust glioblastoma prognosis model based on bioinformatics

BackgroundGlioblastoma (GBM) is a very common primary malignant tumor of the central nervous system (CNS). Aging, macrophage, autophagy, and methylation related genes are hypothesized to be crucial to its pathogenesis. In this study, we aimed to explore the role of these genes in the prognosis of GBM. MethodsThe RNA sequence (RNA-seq) and clinical information were downloaded from The Cancer Genome Atlas database (TCGA) and the Chinese Glioma Genome Atlas database (CGGA). We performed univariate and least absolute shrinkage and selection operator (LASSO) multivariate Cox regression analysis to identify risk signatures related to overall survival (OS). We further developed a nomogram to predict individual outcomes. In addition, the immune microenvironment was analyzed by CIBERSORT. Results256 differentially expressed genes (DEGs) were obtained based on aging, macrophage, autophagy, and methylation related genes between GBM samples and normal tissues in TCGA-GBM cohort. We identified five optimal risk signatures with prognostic values in TCGA-GBM cohort and established a prognostic risk score model. The validity of the model was verified in the CGGA cohort and Huanhu cohort. Finally, we constructed a nomogram for clinical application by combining age, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and risk score. Activated NK cells and resting mast cells were highly expressed and memory B cells, plasma cells, resting NK cells, M1 macrophages, and neutrophils exhibited low expression in the high-risk score group. GBM patients with a low-risk score had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. The risk score of hot tumors was higher than that of the cold tumors. Additionally, 29 genes involved in glucose and lipid metabolism were highly expressed with a high-risk score. 31 metabolism-related pathways were significantly different between high-risk and low-risk groups. ConclusionsWe constructed and validated a novel prognostic model for GBM. Aging, macrophage, autophagy, and methylation related genes may serve as prognostic and therapeutic biomarkers. The model developed may assist in guiding treatment for GBM patients. Our research had great significance in accurately predicting the prognosis of GBM and may offer reference for immunotherapy decision for GBM patients.

Investigating the Effect of EX-527 as SIRT1 Inhibitor in Breast Cancer Cell Line

Background: Breast cancer is one of the most common malignant and metastatic tumors worldwide that cause death in women. Therefore, preventing the growth and metastasis of cancerous cells is essential for enhancing the prognosis and efficacy of treatment for breast cancer. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase that has been linked to a number of biological processes, including genomic stability, cell cycle, cell survival and cancer metastasis. EX-527 is a selective and potent SIRT1 inhibitor. Recent studies have revealed that SIRT1 has an oncogenic role in breast cancer. Objective: To evaluate the effect of EX-527 on the MCF-7 breast cancer cell line. Methods: MCF-7 was cultured in complete DMEM and treated with and without EX-527. Cell viability of the breast cancer cell line was evaluated by MTT assay and apoptosis by Annexin V/PI staining. Migration and invasion of breast cancer cells were determined by wound healing and transwell invasion assays, respectively. Results: Results revealed that EX-527 at a concentration of 25.30 µM was associated with a significant anti-proliferative effect and induction of apoptosis (98.3%) in breast cancer cells. Treatment with EX-527 was also associated with significant suppression of migration and invasion of MCF-7. Conclusions: The current investigation showed that inhibition of SIRT1 by EX-527 inhibits proliferation, migration, invasion and apoptosis of human breast cancer cells.

458. THORACOSCOPY VERSUS ENDOSCOPY IN THE TREATMENT OF ESOPHAGEAL LEIOMYOMA: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract Background Esophageal leiomyoma, also called Esophageal Smooth Muscle Tumor (SMT), is one of the most common benign tumors of the esophagus. Surgical treatment is the most widely used method, including thoracic surgery such as thoracotomy, and VATS, and endoscopic surgery such as ESD and STER. We aimed to conduct a retrospective analysis of all esophageal leiomyoma surgeries in our center to assist decision-making in minimally invasive surgery for leiomyomas. Methods From January 2015 to September 2023 patients with pathologically diagnosed esophageal leiomyoma at our hospital were retrospectively enrolled. Those who had any pathological malignant component or lack of detailed clinical information were excluded. At the same time, a 1:1 propensity matching analysis was conducted for thoracoscopy and endoscopic surgery. The matching factors included age, gender, tumor location, and size and the caliper was set as 0.2. Results Finally, 1376 patients were included, of whom 153 underwent thoracic surgery and 1223 underwent endoscopic treatment. Endoscopic surgeries were mainly composed of ESD (54.5%) and STER (45.5%), with respective proportions, of which 2 cases used thoracoscopic-assisted endoscopic resection. In the surgical group, 131 patients, accounting for 85.6%, underwent thoracoscopic surgery, of which 65 patients (42.5%) used endoscopic-assisted examination during the operation. In terms of operation time, endoscopic resection was shorter than surgical surgery (44.9 ±39.7 versus 109.4 ± 67.9 min, p<0.001). Similarly, for the postoperative hospitalization days, endoscopic resection was shorter than surgical surgery (2.0 [1.0, 3.0] versus 5.0 [3.0, 6.0] days, p<0.001), we also found that the maximum diameter of surgical resection specimens was significantly larger than that of endoscopic surgery (1.3 [0.8, 2.5] versus 5.0 [3.5, 7.0] cm, p <0.001). After PSM, the operation duration (p=0.031) and hospital stay (p<0.001) were still statistically different between the surgical treatment group and the endoscopic group. Conclusion Most esophageal leiomyomas can be resected endoscopically, which can shorten the operation duration and hospital stay compared with thoracic surgery. When the maximum diameter of the tumor is too large or near important organs, thoracic surgery should be the first choice. In order to prevent possible esophageal mucosal damage, thoracoscopic surgery combined with intraoperative endoscopy examination is a safe and effective surgical treatment method.

CSF1R Ligands Expressed by Murine Gliomas Promote M-MDSCs to Suppress CD8+ T Cells in a NOS-Dependent Manner

Glioblastoma (GBM) is the most common malignant primary brain tumor, resulting in poor survival despite aggressive therapies. GBM is characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME) made up predominantly of infiltrating peripheral immune cells. One significant immune cell type that contributes to glioma immune evasion is a population of immunosuppressive cells, termed myeloid-derived suppressor cells (MDSCs). Previous studies suggest that a subset of myeloid cells, expressing monocytic (M)-MDSC markers and dual expression of chemokine receptors CCR2 and CX3CR1, utilize CCR2 to infiltrate the TME. This study evaluated the mechanism of CCR2+/CX3CR1+ M-MDSC differentiation and T cell suppressive function in murine glioma models. We determined that bone marrow-derived CCR2+/CX3CR1+ cells adopt an immune suppressive cell phenotype when cultured with glioma-derived factors. Glioma-secreted CSF1R ligands M-CSF and IL-34 were identified as key drivers of M-MDSC differentiation while adenosine and iNOS pathways were implicated in the M-MDSC suppression of T cells. Mining a human GBM spatial RNAseq database revealed a variety of different pathways that M-MDSCs utilize to exert their suppressive function that is driven by complex niches within the microenvironment. These data provide a more comprehensive understanding of the mechanism of M-MDSCs in glioblastoma.

Optimizing ctDNA: An Updated Review of a Promising Clinical Tool for the Management of Uveal Melanoma

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Distant metastasis is common, affecting around 50% of patients. Prognostic accuracy relies on molecular characterization of tumor tissue. In these patients, however, conventional biopsy can be challenging due to the difficulty of obtaining sufficient tissue for the analysis due to the small tumor size and/or post-brachytherapy shrinkage. An alternative approach is liquid biopsy, a non-invasive technique that allows for real-time monitoring of tumor dynamics. Liquid biopsy plays an increasingly prominent role in precision medicine, providing valuable information on the molecular profile of the tumor and treatment response. Liquid biopsy can facilitate early detection and can be used to monitor progression and recurrence. ctDNA-based tests are particularly promising due to their ease of integration into clinical practice. In this review, we discuss the application of ctDNA in liquid biopsies for UM. More specifically, we explore the emerging technologies in this field and the advantages and disadvantages of using different bodily fluids for liquid biopsy. Finally, we discuss the current barriers to routine clinical use of this technique.

Metabotropic Glutamate Receptors Type 3 and 5 Feature the "NeuroTransmitter-type" of Glioblastoma: A Bioinformatic Approach.

Glioblastoma (GBM) represents an aggressive and common tumor of the central nervous system. The prognosis of GBM is poor, and despite a refined genetic and molecular characterization, pharmacological treatment is largely suboptimal. Contribute to defining a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine. Here, we performed a computational analysis focused on the expression of type 3 and 5 metabotropic glutamate receptor subtypes (mGlu3 and mGlu5, respectively) in high- and low-grade gliomas. The analysis allowed the identification of a particular high-grade glioma type, characterized by a high expression level of both receptor subtypes and by other markers of excitatory and inhibitory neurotransmission. This so-called neurotransmitter-GBM (NT-GBM) also shows a distinct immunological, metabolic, and vascularization gene signature. Our findings might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer

ObjectiveTo report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. MethodsEligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control. ResultsIn the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2–4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). ConclusionSLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.Study registration:NCT02494063 (ClinicalTrials.gov).

Weakly supervised deep learning image analysis can differentiate melanoma from naevi on haematoxylin and eosin-stained histopathology slides.

The broad histomorphological spectrum of melanocytic pathologies requires large data sets to develop accurate and generalisable deep learning (DL)-based diagnostic pathology classifiers. Weakly supervised DL promotes utilisation of larger training data sets compared to fully supervised (patch annotation) approaches. To evaluate weakly supervised DL image classifiers for discriminating melanomas from naevi on haematoxylin and eosin (H&E)-stained pathology slides. A representative H&E slide for 260 naevi and 260 melanomas from mucocutaneous sites at one tertiary institution was digitized. Clinicopathological features were recorded for each case including thickness and histological subtype. Whole-slide or whole-tissue section labels were applied. The ground truth was established by consensus diagnosis from two pathologists. Multiple-instance learning models, Trans-MIL, CLAM and DTFD-MIL were evaluated at 10×, 20× and 40× magnifications using stratified fivefold Monte Carlo cross-validation, with 80/10/10 splits for training/validation/test groups, to predict melanoma from naevus. Heatmaps were generated to understand model performance. Naevi cases were younger (median age: 51 years; melanoma median age: 71.5 years), with more balanced sex distribution (males: 48.8%, melanoma male subgroup: 64.2%). The most frequent histological subtypes of naevi and melanomas were dysplastic compound (n = 99, 38.1%) and superficial spreading (n = 124, 47.7%), respectively. Average AUC (±1 SD) for Trans-MIL, CLAM and DTFD-MIL across test groups were 0.9952 ± 0.006, 0.9925 ± 0.0052 and 0.9708 ± 0.0328, at 20× magnification, respectively. Performance of the models varied according to the magnification used. Heatmaps from the two best performing models, Trans-MIL and CLAM, generally indicated attention on appropriate tissue regions for interpretation. Weakly supervised DL on pathological slides of common mucocutaneous melanocytic tumours provides highly accurate diagnostic value for discrimination of melanomas and naevi. External validation and further assessment on less frequently occurring histologic subtypes and borderline cases using this method is required.