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Background: Gastric cancer (GC) is a malignant tumor originating from the gastric mucosa epithelium, and there is a low survival rate of GC patients after treatment, with a poor prognostic outcome. The inflammatory response within the tumor microenvironment plays an important role in GC progression. Methods: We downloaded GC-related datasets and inflammation-related genes from GEO, TCGA and MSigDB databases, performed differential analysis, protein-protein interaction analysis, immunoinfiltration analysis and Lasso analysis to screen inflammation-related hub genes affecting GC progression, and carried out qRT-PCR for validation. In order to explore the role of ADH1A, we constructed overexpressed plasmids, treated GC cells with cGMP/PKG pathway agonist 8-Br-cGMP, and tested cell functions with CCK8, EdU, Transwell, scratch assay and other experiments. On this basis, GC cells were co-cultured with monocyte THP-1 to explore the effect of ADH1A on the polarization of macrophages. Results: ADH1A was significantly decreased in GC cells, and its expression trend was consistent with the results of bioinformatics analysis. Therefore, we chose ADH1A for subsequent functional validation. Overexpression of ADH1A in GC cells revealed ADH1A's role in inhibiting the activity, proliferation, migration and invasion of GC cells, promoting apoptosis and secretion of IL-6, IFN-γ, CCL5 and CSF2, and facilitating the transformation of macrophages to a pro-inflammatory M1 phenotype. ssGSEA results demonstrated the potential involvement of ADH1A in the cGMP/PKG signaling pathway, and significant changes in the expression of proteins related to the cGMP/PKG signaling pathway. The use of the cGMP/PKG signaling pathway agonist 8-Br-cGMP in ADH1A-overexpressing GC cells substantiated ADH1A's capacity to inhibit the cGMP/PKG signaling pathway, thereby suppressing the malignant progression of GC and promoting the transformation of macrophages to a pro-inflammatory M1 phenotype. Conclusion: ADH1A is able to influence the malignant progression of GC and the transformation of macrophages to the pro-inflammatory M1 phenotype through the cGMP/PKG signaling pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Age-adjusted thyroid cancer incidence is lower in the Hispanic population than in the non-Hispanic White and Asian Pacific Islander populations. However, prior studies have shown an increased prevalence of advanced disease features such as larger tumor sizes and nodal involvement among Hispanics. We sought to characterize the demographic features and tumor characteristics of Hispanic thyroid cancer risk in California. We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry. Overall, 56,638 diagnosed thyroid cancer cases were identified, including 16,852 (29.75%) Hispanics. Hispanics had the greatest female-to-male ratio disparity, average annual percentage change in incidence, and advanced disease features at diagnosis, as well as an increased mortality risk. After adjusting for demographic and tumor covariates, Hispanic ethnicity remained a significant independent variable for mortality risk. Consequently, further investigation into other possible factors associated with Hispanic ethnicity in thyroid cancer is needed. Background: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. Methods: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. Results: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18–1.25, p < 0.0001), remained a significant independent contributor to mortality risk. Conclusions: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed. [ABSTRACT FROM AUTHOR]

Purpose: Neurofibromatosis type 1 (NF1) is a complex, multisystem disorder that is characterized, among other features, by a higher risk of developing benign and malignant tumors. Despite NF1 being one of the most common autosomal dominant genetic disorders, data from adult individuals in several world regions remain elusive, including Hispanics. Methods: The present is a retrospective cohort study conducted among adult patients with a confirmed diagnosis of NF1 who attended a single cancer-reference center, the Instituto Nacional de Cancerologia in Mexico City from 2001 to 2021. Data were extracted from electronic health records and collected in an anonymous database by an NF1-expert physician in order to obtain demographic characteristics and detailed information regarding the development of tumors among this patient subgroup. All patients with malignant tumors or with benign tumors, which severely affected their quality of life, were included in this study. Results: Patient records were reviewed from 2001 to 2021. A total of N = 29 patients met the criteria, with a higher proportion of female compared with male subjects [N = 22 (75.9%) vs. N = 7 (24.1%)]. Patients had a mean age at diagnosis of tumors of 32.2 years (SD = 11.2 years). In terms of malignant neoplasms, the most frequent malignant tumor presented by patients in this cohort was malignant peripheral nerve sheath tumors (N = 7, 24.1%), this was followed by breast cancer (n = 4, 13.8% among all patients, 18.2% among female patients). Other tumors also identified in this cohort included melanoma, gastrointestinal stromal tumors, and rectal cancer. Conclusion: In Mexico, patients diagnosed with NF1 develop diverse tumors as adults. As described in other studies, the most frequent malignant tumor in this patient population is the malignant peripheral nerve sheath tumor. Further studies are required to increase the scarce information available for adult Hispanics with NF1. [ABSTRACT FROM AUTHOR]

Background: Research studies have demonstrated that Midkine (MDK) can influence the expression and activity of Renin-angiotensin system (RAS) components. Angiotensin II is involved in tumor growth and angiogenesis in different cancers. We previously observed Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with oral cancers. These findings have prompted us to investigate whether MDK can influence the RAS pathway, mainly through its association with angiotensin II type 1 receptor (AT1R), which contributes to the observed poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients. Methods: MDK and AT1R expressions were examined in 150 HNSCC patients post-operation by immunohistochemical staining between 1 January 2010 and 31 December 2016. We tested the over-expression and silencing of MDK to evaluate the AT1R expression and functional biological assays in HNSCC cell lines HSC-3 and SAS. Results: Positive expression of MDK is correlated with positive AT1R expression. MDK predicted poor NSCC patients' survival. Silencing MDK could suppress AT1R and pAKT expression and reduce the growth, migration, and invasion of HNSCC cells. ARB also inhibits MDK stimulating HNSCC cell proliferation. Overexpression of MDK could upregulate AT1R and pAKT. Conclusions: MDK is an independent prognostic factor of HNSCC post-operation, and AT1R regulates HNSCC cell growth, invasion, and migration. Positive MDK and AT1R expressions are highly correlated. Mechanistically, the interaction between MDK and AT1R is crucial for MDK-mediated cell viability, and inhibiting AT1R can effectively counteract or abolish these effects. Furthermore, MDK exerts a regulatory role in the expression of AT1R, as well as in the growth and motility of HNSCC cells. These findings highlight the involvement of the interaction between MDK, AT1R, and the pAkt signaling pathways in HNSCC cell viability growth. [ABSTRACT FROM AUTHOR]

Background Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. Methods This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. Results A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94–1.60), compared with an eGFR of 60–89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00–1.22). Conclusions In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies. Methods: We sequenced BRCA1/2 and twelve other DDR genes from a Mexicanmestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Results: Overall, we found 22 variants -9 of them reported for the first time- and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort. Discussion: Our results reflected the unique characteristics of the Mexicanmestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population. [ABSTRACT FROM AUTHOR]

Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant. We identified founder mutations in BRCA1 and a novel variant in APC that led to the creation of an in-house detection process for the whole family. The most frequent syndrome was hereditary breast and ovarian cancer syndrome (HBOC) (41 cases with BRCA1 germline variants in most of the cases), followed by eight cases of hereditary non-polyposic cancer syndrome (HNPCC or Lynch syndrome) (with MLH1 as the primarily responsible gene), and other high cancer risk syndromes. Genetic counseling in HCS is still a global challenge. Multigene panels are an essential tool to detect the variants frequency. Our program has a high detection rate of probands with HCS and pathogenic variants (40%), compared with other reports that detect 10% in other populations. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a timelimited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating nonfermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is gynecologic cancer with the highest mortality rate. It is estimated that 13–17% of ovarian cancers are due to heritable mutations in BRCA1 and BRCA2. The BRCA1 (BRCA1 -Del ex9-12) Mexican founder mutation is responsible for 28–35% of the cases with ovarian cancer. The aim was to describe the PFS of OC patients treated with olaparib, emphasizing patients carrying the Mexican founder mutation (BRCA1 -Del ex9-12). Methods: In this observational study, of 107 patients with BRCA m, 35 patients were treated with olaparib from November 2016 to May 2021 at the Ovarian Cancer Program (COE) of Mexico; patient information was extracted from electronic medical records. Results: Of 311 patients, 107 (34.4%) were with BRCA m; 71.9% (77/107) were with BRCA1 , of which 27.3% (21/77) were with BRCA1 -Del ex9-12, and 28.1% (30/107) were with BRCA2 mutations. Only 35 patients received olaparib treatment, and the median follow-up was 12.87 months. The PFS of BRCA1 -Del ex9-12 was NR (non-reach); however, 73% of the patients received the treatment at 36 vs. 11.59 months (95% CI; 10.43–12.75) in patients with other BRCA m (p = 0.008). Almost 50% of patients required dose reduction due to toxicity; the most frequent adverse events were hematological in 76.5% and gastrointestinal in 4%. Conclusion: Mexican OC BRCA1 -Del ex9-12 patients treated with olaparib had a significant increase in PFS regardless of the line of treatment compared to other mutations in BRCA. [ABSTRACT FROM AUTHOR]

Summary: The relative mRNA abundance of 10 genes associated with folliculogenesis was compared between late preantral (secondary) and early antral (tertiary) ovarian follicles in goats. In total, 100 follicles in each category were mechanically isolated. The relative transcript abundance of the mRNAs were determined by qPCR. Data were analyzed using unpaired Student's t-test. Of the 10 tested genes, ABLIM mRNA was not detected in either follicle category, six genes (SLIT3, TYMS, GTPBP1, AKR1C4, PIK3R6, and MAOB) were upregulated in secondary follicles compared with tertiary follicles, and three genes (ARHGEF12, CLEC6A, and CYTL1) showed similar mRNA abundances in both secondary and tertiary follicles. In conclusion, SLIT3, GTPBP1, AKR1C4, and PIK3R6 mRNA abundance was upregulated in secondary follicles (preantral phase) compared with in tertiary follicles (antral phase) in goats. [ABSTRACT FROM AUTHOR]