Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study

xlomafota13 shared this article with you from Inoreader Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5016-5026. eCollection 2021. ABSTRACT Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulat ive obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer. PMID:34765308 | PMC:PMC8569344 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sensitization of breast cancer to Herceptin by redox active nanoparticles

xlomafota13 shared this article with you from Inoreader Sensitization of breast cancer to Herceptin by redox active nanoparticles Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4884-4899. eCollection 2021. ABSTRACT Herceptin-resistant tumor relapse remains a major clinical issue responsible for the poor prognosis of HER2+ breast cancer. Understanding the underlying mechanisms and finding a therapeutic solution are of paramount urgency to improve the patient management. Here we report that anticancer redox active cerium oxide nanoparticles (CONPs) can potently sensitize the cancer cells to the cytotoxicity of Herceptin. By comparing between Herceptin-sensitive and Herceptin-resistant human breast cancer cell lines under normoxic as well as hypoxic culture conditions, we found that in the presence of CONPs, Herceptin can kill the Herceptin-resistant cells equally effectively as it kills the Herceptin-sensitive cells under the hypoxic, but not normoxic, culture conditions by inhibiting the cell viability, survival and proliferation. Signaling analysis reveals that u nder the normoxic conditions, the levels of hypoxia induced factor 1α as well as vascular endothelial growth factor are higher in the Herceptin-resistant cells than that in the Herceptin-sensitive cells and are strongly induced once the culture is switched to the hypoxic conditions, which can be potently suppressed by CONPs. Treatment with CONPs plus Herceptin significantly slows down the primary tumor growth and lung metastasis of the Herceptin-resistant cells in a xenograft mouse model of orthotopic breast cancer through inhibiting the cell proliferation and survival as well as tumor angiogenesis. These results shed new lights on the mechanisms underlying the Herceptin resistance of the HER2+ breast cancer and provide insights into introducing CONPs-like agents to Herceptin-based therapy to improve treatment outcomes. PMID:34765298 | PMC:PMC8569362 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Postoperative complications and open gastrectomy affect non-cancer-related death and shorten life expectancy in elderly patients with gastric cancer

xlomafota13 shared this article with you from Inoreader Postoperative complications and open gastrectomy affect non-cancer-related death and shorten life expectancy in elderly patients with gastric cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5038-5044. eCollection 2021. ABSTRACT Postoperative complications contribute to recurrences and poor long-term outcomes for gastric cancer patients, especially among the elderly. However, the prognostic effect of postoperative complications on non-cancer-related death in elderly patients with gastric cancer has not been reported. Two hundred and twenty elderly (> 75 years of age) patients with stage I gastric cancer were retrospectively identified from consecutive admissions between 1995 and 2020. Non-cancer-related death following gastrectomy occurred in 13.6% (30/220) of patients. Non-cancer-related death was associated with respiratory disease in 46.7% (14/30) of cases. Although there was no association with any preoperative comorbidities, postoperative complications [P < 0.001, HR 4.16 (95% CI: 1.91-9.02)] and open gastrectomy [P=0.002, HR 3.87 (95% CI: 1.54-9.66)] were indepe ndently associated with a poorer prognosis for non-cancer-related death. Poor nutritional status [P=0.028, OR 4.25 (95% CI: 1.17-15.4)] was an independent risk factor for postoperative complications. Postoperative complications shortened life expectancy from 8.8 years to 6.1 years. Specifically, postoperative complications shortened life expectancy from 6.7 years to 3.9 years in elderly patients over 80 years of age. Postoperative complications and open gastrectomy affected the incidence of non-cancer-related death among elderly patients with gastric cancer, primarily attributed to respiratory disease. Efforts should be made to perform minimally invasive surgery, improve preoperative nutrition, and avoid postoperative complications. PMID:34765310 | PMC:PMC8569366 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical impact of postoperative prognostic nutritional index in colorectal cancer patients undergoing adjuvant chemotherapy

xlomafota13 shared this article with you from Inoreader Clinical impact of postoperative prognostic nutritional index in colorectal cancer patients undergoing adjuvant chemotherapy Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4947-4955. eCollection 2021. ABSTRACT Preoperative Prognostic Nutritional Index (PNI) could be a crucial factor for the prognosis of colorectal cancer (CRC). However, the clinical impact of postoperative PNI is still unclear, and there have been no reports on the significance of postoperative PNI in patients undergoing adjuvant chemotherapy (AC). We retrospectively analysed 227 consecutive patients who underwent AC after radical surgery for high-risk stage II or stage III CRC. PNI value was calculated before radical surgery and before the introduction of AC. In our study, patients with a low PNI value before surgery showed significantly poorer long-term outcomes than those with a high PNI value. Next, we divided the patients into four groups: patients with a high PNI value before surgery and remained after surgery (Group High-High), a high PNI value before surgery but decreased after surgery (Group H igh-Low), a low PNI value before surgery but recovered after surgery (Group Low-High), and a low PNI value but did not recover after surgery (Group Low-Low). Although the patients in Group Low-Low showed significantly poorer long-term outcomes than those in Group High-High, the prognosis of patients in Group Low-High was the same as that of patients in Group High-High. In addition, in patients with recurrence after AC, those with a high PNI value at the time of recurrence showed a significantly better survival after recurrence than patients with a low PNI value. Postoperative PNI value could be a prognostic biomarker for CRC patients undergoing AC. Even though the PNI value was low before the surgery, recovery of PNI value by the introduction of AC could improve the prognosis of CRC patients. PMID:34765302 | PMC:PMC8569341 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of exercise on peritoneal microenvironment and progression of ovarian cancer

xlomafota13 shared this article with you from Inoreader Effect of exercise on peritoneal microenvironment and progression of ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5045-5062. eCollection 2021. ABSTRACT Ovarian cancer is one of the deadliest gynecological malignancies and lacks treatments that do not significantly impact patient health-related quality of life. Exercise has been associated with reduced cancer risk and improved clinical outcomes; however the underlying molecular mechanisms are unknown. In this study, we utilized a treadmill-running exercise model to investigate the effects of exercise on high-grade serous ovarian carcinoma (HGSOC) progression and chemotherapy outcomes. We found that treadmill-running suppressed peritoneal colonization of tumors in a syngeneic mouse ovarian cancer model. Acute exercise stimulated the production of CCL2 and IL-15 in the peritoneal microenvironment while downregulating CCL22, VEGF, and CCL12. Using a co-culture model, we demonstrated the role of CCL2 in mediating the activity of peritoneal cells to inhibit cancer cel l viability. We showed that the activation of M1 macrophages may contribute to the exercise-induced changes in the peritoneal microenvironment. We identified that chronic exercise modulates gene expression of intraperitoneal fat tissues related to lipid formation, thermogenesis, browning, and inflammation, which can contribute to inhibiting the colonization of metastatic ovarian cancer. Treadmill running also lowered blood urea nitrogen levels and reduced incidence of neutropenia and thrombocytopenia during chemotherapy in a mouse model, suggesting the potential beneficial effects of exercise in improving chemotherapy outcomes. Our data provided new insights into the acute and chronic effects of physical activity on ovarian cancer at the molecular and in vivo levels. PMID:34765311 | PMC:PMC8569339 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hypoxia-related prognostic model in bladder urothelial reflects immune cell infiltration

xlomafota13 shared this article with you from Inoreader Hypoxia-related prognostic model in bladder urothelial reflects immune cell infiltration Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):5076-5093. eCollection 2021. ABSTRACT Hypoxia is a common feature of tumor microenvironment (TME). This study aims to establish the genetic features related to hypoxia in Bladder urothelial carcinoma (BLCA) and investigate the potential correlation with hypoxia in the TME and immune cells. We established a BLCA outcome model using the hypoxia-related genes from The Cancer Genome Atlas using regression analysis and verified the model using the Gene Expression Omnibus GSE32894 cohort. We measured the effect of each gene in the hypoxia-related risk model using the Human Protein Atlas website. The predictive abilities were compared using the area under the receiver operating characteristic curves. Gene Set Enrichment Analysis was utilized for indicating enrichment pathways. We analyzed immune cell infiltration between risk groups using the CIBERSORT method. The indicators related to immune status between the two groups were also analyzed. The findings indicated that the high-risk group had better outcomes than the low-risk group in the training and validation sets. Each gene in the model affected the survival of BLCA patients. Our hypoxia-related risk model had better performance compared to other hypoxia-related markers (HIF-1α and GLUT-1). The high-risk group was enriched in immune-related pathways. The expression of chemokines and immune cell markers differed significantly between risk groups. Immune checkpoints were more highly expressed in the high-risk group. These findings suggest that the hypoxia-related risk model predicts patients' outcomes and immune status in BLCA risk groups. Our findings may contribute to the treatment of BLCA. PMID:34765313 | PMC:PMC8569353 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of potential immune-related circRNA-miRNA-mRNA regulatory network in cutaneous squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Identification of potential immune-related circRNA-miRNA-mRNA regulatory network in cutaneous squamous cell carcinoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Oct 15;11(10):4826-4843. eCollection 2021. ABSTRACT Circulating RNAs (circRNAs) are involved in tumor development and progression by participating in immune regulation. Nevertheless, the circRNAs expression profiles and their roles on the immunomodulatory effects in cutaneous squamous cell carcinoma (cSCC) have rarely been studied. In our study, we identified the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), mRNAs (DEmRNAs) in cSCC and established the circRNA competing endogenous RNAs (ceRNAs) network. Subsequently, the hub differentially expressed immune-related genes were identified and validated by immunochemistry as well as the GO and KEGG pathway analysis were performed. 54 differentially expressed circRNAs were identified and hub differentially expressed immune-related genes were identified and they were mostly associated with immune response in the progression of cSCC. Our results indic ated that the potential immune-related circRNA-miRNA-mRNA network may assist in understanding the molecular mechanisms underlying the carcinogenesis and progression in cSCC. Moreover, the immune-related genes may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets for cSCC patients. PMID:34765295 | PMC:PMC8569358 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.