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Zhongguo Fei Ai Za Zhi = Chinese... May 2024Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Molecular Targeted Therapy; Pleural Neoplasms; Animals; Endoplasmic Reticulum Chaperone BiP
PubMed: 38880927
DOI: 10.3779/j.issn.1009-3419.2024.102.18 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
Ear, Nose, & Throat Journal Jun 2024Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an...
Pleomorphic adenoma (PA) represents the most frequently occurring benign tumor within both major and minor salivary glands. However, in rare instances, nasal PA is an epithelial-derived borderline tumor, often originating from the nasal septum. Diagnosis usually relies on histopathological analysis. Under general anesthesia, these rare nasal tumors can be completely resected via endoscopic surgery. This article reports a case of PA originating from the nasal septum in a 49-year-old patient presenting with nasal congestion, along with a brief review of the current literature. The diagnostic nasal endoscopic examination showed a pink neoplastic mass in the left nasal cavity. Subsequent radiologic examination demonstrated a soft tissue mass in the anterior part of the nasal septum. After complete resection under nasal endoscopy, histopathological examination confirmed it as PA. Fortunately, no related complications occurred perioperatively and postoperatively. After surgery, performing a thorough examination with nasal endoscopy and scheduling regular follow-ups are crucial steps to prevent local recurrence.
PubMed: 38877652
DOI: 10.1177/01455613241261457 -
Ear, Nose, & Throat Journal Jun 2024
PubMed: 38877638
DOI: 10.1177/01455613241261557 -
Asian Journal of Surgery Jun 2024
Risk factors for postoperative pathological upgrading of low-grade intraepithelial neoplasia of colorectal adenoma after endoscopic treatment: A single-center, retrospective study.
PubMed: 38876866
DOI: 10.1016/j.asjsur.2024.05.286 -
Molecular Biology Reports Jun 2024Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic...
BACKGROUND AND AIM
Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic characteristics. CpG island methylator phenotype (CIMP) is found in about 15-20% of sporadic CRCs and is associated with hypermethylation of certain gene promoters. This study aims to find prognostic genes and compare their expression and methylation status as potential biomarkers in patients with serrated sessile adenomas/polyps (SSAP) and CRC, in order to evaluate which, one is a better predictor of disease.
METHOD
This study employed a multi-phase approach to investigate genes associated with CRC and SSAP. Initially, two gene expression datasets were analyzed using R and Limma package to identify differentially expressed genes (DEGs). Venn diagram analysis further refined the selection, revealing four genes from the Weissenberg panel with significant changes. These genes, underwent thorough in silico evaluations. Once confirmed, they proceeded to wet lab experimentation, focusing on expression and methylation status. This comprehensive methodology ensured a robust examination of the genes involved in CRC and SSAP.
RESULT
This study identified cancer-specific genes, with 8,351 and 1,769 genes specifically down-regulated in SSAP and CRC tissues, respectively. The down-regulated genes were associated with cell adhesion, negative regulation of cell proliferation, and drug response. Four highly downregulated genes in the Weissenberg panel, including CACNA1G, IGF2, MLH1, and SOCS1. In vitro analysis showed that they are hypermethylated in both SSAP and CRC samples while their expressions decreased only in CRC samples.
CONCLUSION
This suggests that the decrease in gene expression could help determine whether a polyp will become cancerous. Using both methylation status and gene expression status of genes in the Weissenberg panel in prognostic tests may lead to better prognoses for patients.
Topics: Humans; Colorectal Neoplasms; Suppressor of Cytokine Signaling 1 Protein; DNA Methylation; Insulin-Like Growth Factor II; Gene Expression Regulation, Neoplastic; MutL Protein Homolog 1; CpG Islands; Female; Colonic Polyps; Biomarkers, Tumor; Male; Down-Regulation; Computer Simulation; Middle Aged; Adenoma; Promoter Regions, Genetic; Calcium Channels, T-Type; Gene Expression Profiling; Aged; Prognosis
PubMed: 38874740
DOI: 10.1007/s11033-024-09683-3 -
Frontiers in Medicine 2024Tissue-invasive cytomegalovirus (CMV) disease represents a well-recognized complication after kidney transplantation. However, direct involvement of the urogenital tract...
Tissue-invasive cytomegalovirus (CMV) disease represents a well-recognized complication after kidney transplantation. However, direct involvement of the urogenital tract and CMV-ureteritis occur less frequently. Nephrogenic adenomas are benign lesions of the urinary tract preferentially reported in kidney transplant recipients. We herein report a second case of a 33-year-old male kidney transplant recipient with acute post-renal allograft dysfunction due to CMV-positive ureteral nephrogenic adenoma. A causal connection might be suspected but remains to be proven.
PubMed: 38873192
DOI: 10.3389/fmed.2024.1394028 -
Pathology Oncology Research : POR 2024Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric...
BACKGROUND
Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the cause, classification, and clinicopathological features of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms.
METHODS
37 cases diagnosed with GEN-FGMLs were included in this study. H&E-stained slides were reviewed and clinicopathological parameters were recorded. Immunohistochemical staining was conducted for MUC2, MUC5AC, MUC6, CD10, CD56, synaptophysin, chromograninA, p53, Ki67, pepsinogen-I, H/K-ATPase and Desmin.
RESULTS
The patients' ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between OGA, GA-FG, and GA-FGM. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. These cells resembled fundic gland cells. None of the OGA invaded the submucosal layer. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Non-atrophic gastritis was observed in more than half of the background mucosa. All cases were diffusely positive for MUC6 and pepsinogen-I on immunohistochemistry. H/K-ATPase staining was negative or showed a scattered pattern in most cases. MUC5AC was expressed on the surface of GA-FGMs. p53 was focally expressed and the Ki67 index was low (1%-20%). Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view ( < 0.05) and had larger sizes ( < 0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA ( < 0.0001). Specimens with Ki-67 proliferation indices >2.5% and size >4.5 mm are more likely to be diagnosed with GA-FG and GA-FGM than OGA.
CONCLUSION
GEN-FGMLs are group of well-differentiated gastric tumors with favourable biological behaviours, low cellular atypia, and low proliferation. Immunohistochemistry is critical for confirming diagnosis. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. Pathologists and endoscopists should be cautious to prevent misdiagnosis and overtreatment, especially in biopsy specimens.
Topics: Humans; Stomach Neoplasms; Male; Female; Middle Aged; Aged; Adult; Ki-67 Antigen; Gastric Mucosa; Biomarkers, Tumor; Adenocarcinoma; Gastric Fundus; Adenoma; Prognosis
PubMed: 38873175
DOI: 10.3389/pore.2024.1611734 -
Genome Medicine Jun 2024Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk...
BACKGROUND
Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population.
METHODS
To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRS). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants.
RESULTS
Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose-response effect of PRS on incident colorectal neoplasms. Incorporating PRS with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32).
CONCLUSIONS
Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.
Topics: Humans; Colorectal Neoplasms; Female; Early Detection of Cancer; Male; Middle Aged; Aged; Risk Assessment; Polymorphism, Single Nucleotide; Bayes Theorem; Risk Factors
PubMed: 38872215
DOI: 10.1186/s13073-024-01355-y -
Academic Radiology Jun 2024to develop a deep learning radiomics graph network (DLRN) that integrates deep learning features extracted from gray scale ultrasonography, radiomics features and...
RATIONALE AND OBJECTIVES
to develop a deep learning radiomics graph network (DLRN) that integrates deep learning features extracted from gray scale ultrasonography, radiomics features and clinical features, for distinguishing parotid pleomorphic adenoma (PA) from adenolymphoma (AL) MATERIALS AND METHODS: A total of 287 patients (162 in training cohort, 70 in internal validation cohort and 55 in external validation cohort) from two centers with histologically confirmed PA or AL were enrolled. Deep transfer learning features and radiomics features extracted from gray scale ultrasound images were input to machine learning classifiers including logistic regression (LR), support vector machines (SVM), KNN, RandomForest (RF), ExtraTrees, XGBoost, LightGBM, and MLP to construct deep transfer learning radiomics (DTL) models and Rad models respectively. Deep learning radiomics (DLR) models were constructed by integrating the two features and DLR signatures were generated. Clinical features were further combined with the signatures to develop a DLRN model. The performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis, calibration, decision curve analysis (DCA), and the Hosmer-Lemeshow test.
RESULTS
In the internal validation cohort and external validation cohort, comparing to Clinic (AUC=0.767 and 0.777), Rad (AUC=0.841 and 0.748), DTL (AUC=0.740 and 0.825) and DLR (AUC=0.863 and 0.859), the DLRN model showed greatest discriminatory ability (AUC=0.908 and 0.908) showed optimal discriminatory ability.
CONCLUSION
The DLRN model built based on gray scale ultrasonography significantly improved the diagnostic performance for benign salivary gland tumors. It can provide clinicians with a non-invasive and accurate diagnostic approach, which holds important clinical significance and value. Ensemble of multiple models helped alleviate overfitting on the small dataset compared to using Resnet50 alone.
PubMed: 38871552
DOI: 10.1016/j.acra.2024.05.023