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Current Medicinal Chemistry Jun 2024This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD).
PURPOSE
This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD).
METHODS
Using the inverse-variance weighted method, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between 22 dietary habits and GERD. The stability and reliability of the results were assessed using leave-one-out analysis, heterogeneity tests, and tests for horizontal pleiotropy based on the effect measure odds ratio (OR) and 95% confidence interval (CI).
RESULTS
The results of the MR analysis indicated a positive association between alcohol drinking (OR=1.472; 95% CI, 1.331 to 1.629; p<1.0×10-3) and salt added to food (OR=1.270; 95% CI, 1.117 to 1.443; p<1.0×10-3) with the risk of GERD. Conversely, bread intake (OR=0.613; 95% CI, 0.477 to 0.790; p<1.0×10-3), cereal intake (OR=0.613; 95% CI, 0.391 to 0.677; p<1.0×10-3), cheese intake (OR=0.709; 95% CI, 0.593 to 0.846; p<1.0×10-3), dried fruit intake (OR=0.535; 95% CI, 0.404 to 0.709; p<1.0×10-3), fresh fruit intake (OR=0.415; 95% CI, 0.278 to 0.619; p<1.0×10-3), and oily fish intake (OR=0.746; 95% CI, 0.633 to 0.879; p<1.0×10-3) were negatively associated with the risk of GERD. Sensitivity analysis showed no evidence of reverse causation, pleiotropy, or heterogeneity.
CONCLUSION
Alcohol and salt added to food raised GERD risk, while bread intake, cereal intake, cheese intake, intake of certain dried fruits and certain fresh fruits, and oily fish lowered it. Our study affirms the potential causal link between these diets and GERD, offering insights into targeted prevention strategies.
PubMed: 38939994
DOI: 10.2174/0109298673314174240614091415 -
Annals of Surgery Jun 2024To determine the clinical utility of serum CA 19-9 surveillance for detecting recurrences in resected ampullary carcinomas (ACs).
OBJECTIVE
To determine the clinical utility of serum CA 19-9 surveillance for detecting recurrences in resected ampullary carcinomas (ACs).
INTRODUCTION
Although an established prognostic marker for pancreatic ductal adenocarcinoma, the value of CA 19-9 in resected ACs during follow-up is unknown.
METHODS
Retrospective analysis of ACs undergoing pancreaticoduodenectomy at Tata Memorial Centre-Mumbai, from January 2012 to January 2020 was performed. Survival, recurrence patterns, factors associated with recurrences and the utility of CA 19-9 surveillance were assessed.
RESULTS
The 5-year OS of 572 included patients with ACs, was 56.4%. There were 251(43.88%) recurrences, majority being distant (n=223). Higher 'T' & 'N' stage, margin involvement, perineural invasion, poor tumour differentiation and pancreatobiliary subtype were associated with poor outcomes. Optimal CA 19-9 level to predict recurrence was 77.85 U/mL (sensitivity-61.22%, specificity-76.67%, AUC-0.711); however, a serial rise was a more accurate predictor (sensitivity-71.05%, specificity-91.67%). The median duration between the first rise in CA 19-9 (>37 U/mL) and radiological evidence of recurrence was 4.04 months. The optimal level of relative rise in CA 19-9 in diagnosing a recurrence was established at 2.79x (sensitivity-46.26%, specificity-83.33%, AUC-0.614). A serial rise and absolute value of >200 U/mL was associated with recurrence in 87% & 92.9% of cases. Recurrence detection & treatment after serum CA 19-9 elevation was associated with superior median survival as compared to recurrence detection without elevation (12.8 mo vs. 7.6 mo, P=0.005).
CONCLUSION
Serum CA 19-9 testing during follow-up evaluation detects recurrences early and improves survival in resected ACs, and therefore should be recommended as a routine surveillance test.
PubMed: 38939924
DOI: 10.1097/SLA.0000000000006419 -
Acta Medica Philippina 2024Retinoblastoma is one of the most common intraocular cancers among children usually caused by the loss of retinoblastoma protein function. Despite being a highly...
BACKGROUND AND OBJECTIVE
Retinoblastoma is one of the most common intraocular cancers among children usually caused by the loss of retinoblastoma protein function. Despite being a highly heritable disease, conventional diagnostic and prognostic methods depend on clinical examination, with limited consideration of cancer genetics in the standard of care. , and are commonly explored genes for their utility in liquid biopsies of cancer including lung adenocarcinoma. To date, there are few extensive molecular studies on retinoblastoma in Filipino patients. To this end, the study aimed to describe the copy number of , and in retinoblastoma samples from a Filipino patient and quantitate the respective expression level of these genes.
METHODS
Hematoxylin & Eosin (H&E) staining was utilized to characterize the retinoblastoma tissue while fluorescence in situ hybridization (FISH) using probes specific to , and was performed to determine the copy number of genes in retinoblastoma samples from a Filipino patient (n = 1). The gene expression of , and was quantitated using RT-qPCR.
RESULTS
The H&E staining in the retinoblastoma tissue shows poorly differentiated cells with prominent basophilic nuclei. was approximately 1.5-fold overexpressed in the retinoblastoma tissue with respect to the normal tissue, while MUC1 and KRT19 are only slightly expressed. Multiple intense signals of each probe were localized in the same nuclear areas throughout the retinoblastoma tissue, with high background noise.
CONCLUSION
These findings suggest that is a potential biomarker for the staging and diagnosis of retinoblastoma in Filipino cancer patients. However, further optimization of the hybridization procedures is recommended.
PubMed: 38939426
DOI: 10.47895/amp.vi0.7666 -
Journal of Extracellular Biology Mar 2024Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis due to its highly metastatic profile. Intercellular communication between cancer...
Dysregulation of intercellular communication in vitro and in vivo via extracellular vesicles secreted by pancreatic duct adenocarcinoma cells and generated under the influence of the AG9 elastin peptide-conditioned microenvironment.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis due to its highly metastatic profile. Intercellular communication between cancer and stromal cells via extracellular vesicles (EVs) is crucial for the premetastatic microenvironment preparation leading to tumour metastasis. This study shows that under the influence of bioactive peptides derived from the extracellular matrix microenvironment, illustrated here by the AG-9 elastin-derived peptide (EDP), PDAC cells secrete more tumour-derived EVs. Compared to PDAC-derived EVs, tumour-derived EVs resulting from AG-9 treatment (PDAC AG-9-derived EVs) significantly stimulated cell proliferation. At constant amount, tumour-derived EVs were similarly taken up by PDAC and HMEC-1 cells. Tumour-derived EVs stimulated cell proliferation, migration, proteinase secretion, and angiogenesis. Bioluminescence imaging allowed tumour-derived EV/FLuc+ tracking in vivo in a PDAC mouse model. The biodistribution of PDAC AG-9-derived EVs was different to PDAC-derived EVs. Our results demonstrate that the microenvironment, through EDP release, may not only influence the genesis of EVs but may also affect tumour progression (tumour growth and angiogenesis), and metastatic homing by modifying the in vivo biodistribution of tumour-derived EVs. They are potential candidates for targeted drug delivery and modulation of tumour progression, and they constitute a new generation of therapeutic tools, merging oncology and genic therapy.
PubMed: 38939412
DOI: 10.1002/jex2.145 -
Cureus May 2024Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint...
Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.
PubMed: 38939277
DOI: 10.7759/cureus.61248 -
Przeglad Gastroenterologiczny 2024Colon adenocarcinoma (COAD) is one of the most frequently identified cancers of the digestive system. It is worth noting that the 5-year survival rates for patients...
INTRODUCTION
Colon adenocarcinoma (COAD) is one of the most frequently identified cancers of the digestive system. It is worth noting that the 5-year survival rates for patients diagnosed early are approximately 90%, whereas for patients with advanced diagnosis it is only 10%. It may indicate that metastasis is a critical cause of death for cancer patients.
AIM
The current study investigated the immunohistochemical expression of MnSOD in individuals living in Poland, who were diagnosed as colon adenocarcinoma patients, to assess its prognostic significance by correlating its expression with the clinicopathological factors and overall survival (OS).
MATERIAL AND METHODS
Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for MnSOD protein. The relationship between MnSOD immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated.
RESULTS
Immunohistochemical expression of MnSOD protein was detected in colon adenocarcinoma samples and non-pathological samples of colon tissues. As demonstrated, the level of the MnSOD immunohistochemical reactivity was not correlated with clinicopathological factors. A multivariate analysis demonstrated that the grade of tumour differentiation and MnSOD immunoexpression in healthy tissues were independent risk factors for worse survival of patients.
CONCLUSIONS
The high level of MnSOD immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.
PubMed: 38939067
DOI: 10.5114/pg.2024.139238 -
PeerJ 2024While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we...
While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we delved into the role of ICD in colorectal carcinoma, a topic not yet comprehensively explored. A novel ICD quantification system was developed to forecast patient outcomes and the effectiveness of immunotherapy. Utilizing single-cell sequencing, we constructed an ICD score within the tumor immune microenvironment (TIME) and examined immunogenic cell death related genes (ICDRGs). Using data from TCGA and GEO, we discovered two separate molecular subcategories within 1,184 patients diagnosed with colon adenocarcinoma/rectum adenocarcinoma (COADREAD). The ICD score was established by principal component analysis (PCA), which classified patients into groups with low and high ICD scores. Further validation in three independent cohorts confirmed the model's accuracy in predicting immunotherapy success. Patients with higher ICD scores exhibited a "hot" immune phenotype and showed increased responsiveness to immunotherapy. Key genes in the model, such as , , , and , were found to enhance COADREAD cell proliferation, invasion, and expression. These insights offered a new avenue for anti-tumor strategies by targeting ICD, marking advances in colorectal carcinoma treatment.
Topics: Humans; Colorectal Neoplasms; Immunogenic Cell Death; Prognosis; Tumor Microenvironment; Immunotherapy; Gene Expression Profiling; Male; Female; Adenocarcinoma; Middle Aged; Biomarkers, Tumor; Principal Component Analysis; Gene Expression Regulation, Neoplastic
PubMed: 38938617
DOI: 10.7717/peerj.17629 -
PeerJ 2024Patients with lung adenocarcinoma (LUAD) often develop a poor prognosis. Currently, researches on prognostic and immunotherapeutic capacity of aneuploidy-related genes...
Integrated bulk and single-cell RNA sequencing identifies an aneuploidy-based gene signature to predict sensitivity of lung adenocarcinoma to traditional chemotherapy drugs and patients' prognosis.
BACKGROUND
Patients with lung adenocarcinoma (LUAD) often develop a poor prognosis. Currently, researches on prognostic and immunotherapeutic capacity of aneuploidy-related genes in LUAD are limited.
METHODS
Genes related to aneuploidy were screened based on bulk RNA sequencing data from public databases using Spearman method. Next, univariate Cox and Lasso regression analyses were performed to establish an aneuploidy-related riskscore (ARS) model. Results derived from bioinformatics analysis were further validated using cellular experiments. In addition, typical LUAD cells were identified by subtype clustering, followed by SCENIC and intercellular communication analyses. Finally, ESTIMATE, ssGSEA and CIBERSORT algorithms were employed to analyze the potential relationship between ARS and tumor immune environment.
RESULTS
A five-gene ARS signature was developed. These genes were abnormally high-expressed in LUAD cell lines, and in particular the high expression of CKS1B promoted the proliferative, migratory and invasive phenotypes of LUAD cell lines. Low ARS group had longer overall survival time, higher degrees of inflammatory infiltration, and could benefit more from receiving immunotherapy. Patients in low ASR group responded more actively to traditional chemotherapy drugs (Erlotinib and Roscovitine). The scRNA-seq analysis annotated 17 cell subpopulations into seven cell clusters. Core transcription factors (TFs) such as CREB3L1 and CEBPD were enriched in high ARS cell group, while TFs such as BCLAF1 and UQCRB were enriched in low ARS cell group. CellChat analysis revealed that high ARS cell groups communicated with immune cells SPP1 (ITGA4-ITGB1) and MK (MDK-NCl) signaling pathways.
CONCLUSION
In this research, integrative analysis based on the ARS model provided a potential direction for improving the diagnosis and treatment of LUAD.
Topics: Humans; Adenocarcinoma of Lung; Lung Neoplasms; Aneuploidy; Prognosis; Single-Cell Analysis; CDC2-CDC28 Kinases; Cell Line, Tumor; Sequence Analysis, RNA; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Computational Biology; Male
PubMed: 38938612
DOI: 10.7717/peerj.17545 -
Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
Turk Patoloji Dergisi Jun 2024Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation,...
OBJECTIVE
Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation, express α-smooth muscle actin (α-SMA), and play a crucial role in injury and inflammation sites. This study aims to evaluate the relationship between α-SMA expression and histopathological parameters of pancreatic ductal adenocarcinoma (PDAC), and investigate their association with prognosis.
MATERIAL AND METHODS
Eighty-one consecutive pancreatectomies diagnosed as usual pancreatic ductal adenocarcinoma were included. The stromal density was scored as loose, moderate, or dense, and α-SMA expression was evaluated immunohistochemically.
RESULTS AND CONCLUSION
Mean survival was 19.6 months. Male gender, larger tumor diameter ( > 3.7 cm), and older age ( > 64 years) were identified as independent poor prognostic factors. Perineural invasion significantly effected survival. A statistically significant correlation was found between high α-SMA expression and the presence of angioinvasion (p=0.01). Stromal α-SMA expression in PDAC may help determine the risk of angioinvasion.
PubMed: 38938104
DOI: 10.5146/tjpath.2024.13521