Effects of Weight Loss on Key Obesity-Related Biomarkers Linked to the Risk of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Endometrial cancer (EC) includes various histologic types, with estrogen-dependent endometrioid carcinoma being the most common. Obesity significantly increases the risk of developing this type, especially in postmenopausal women, due to elevated estrogen production by adipocytes. This review examines the impact of weight loss from different interventions on reducing obesity-related risk factors for endometrioid EC. A systematic review and meta-analysis were conducted on three weight loss interventions: bariatric surgery, pharmacotherapy, and lifestyle changes. The effects of these interventions on inflammatory biomarkers (CRP, TNF-α, IL-6) and hormones (leptin, estrogen) were analyzed. Data from controlled studies were pooled to assess the significance of weight loss in reducing these biomarkers. Despite heterogeneity, bariatric surgery resulted in an overall 25.8% weight reduction, outperforming lifestyle and pharmacotherapy interventions. Weight loss reduced CRP levels by 33.5% and IL-6 levels by 41.9%. TNF-α levels decreased by 13% with percent weight loss over 7%. Leptin levels also decreased significantly, although the exact weight loss percentage was not statistically significant. Weight loss effectively reduces proinflammatory markers and hormones associated with increased risk of endometrioid EC. The strengths of this review include a comprehensive examination of different weight-loss interventions and a large pool of participants. However, limitations include high heterogeneity among studies and only 43% of the participants being postmenopausal. Limited data on sex hormones and racial disparities underscore the need for further research.

The interplay of obesity, microbiome dynamics, and innovative anti-obesity strategies in the context of endometrial cancer progression and therapeutic approaches.

Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, and its incidence and mortality are rising. Obesity is more tightly associated with EC than any other cancer. Thus, the rising prevalence of obesity and associated risk factors, including diabetes and insulin resistance, cause alarm. The metabolic derangements of obesity increase the bioavailability of estrogen, hyperinsulinemia, and inflammation in a complex system with direct and indirect effects on the endometrium, resulting in proliferation and, ultimately, carcinogenesis. In addition, the gut dysbiosis associated with obesity helps contribute to these metabolic derangements, priming an individual for developing EC and perhaps affecting treatment efficacy. More recent studies are beginning to explore obesity's effect on the local tumor microbiome of EC and its role in carcinogenesis. Significant and sustained weight loss in individuals can considerably decrease the risk of EC, likely through reversal of the altered metabolism and dysbiosis resulting obesity. Bariatric surgery is the gold standard for successful weight loss and highlights how reversing of the systemic effects of obesity can reduce EC risk. However, the current limited availability, knowledge, and imposed stigma of bariatric surgery prohibits population-level reductions in EC. Therefore, effective and maintainable non-surgical dietary and pharmacologic interventions are needed.

Clinical trial-identified inflammatory biomarkers in breast and pancreatic cancers.

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancer-specific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immune-associated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes.

Ketogenic therapies for glioblastoma: Understanding the limitations in transitioning from mice to patients.

Glioblastoma Multiforme is an aggressive brain cancer affecting children and adults frequently resulting in a short life expectancy. Current cancer therapies include surgery and radiation followed by chemotherapy, which due to their ineffectiveness, requires repeated exposure to the same therapies. Since the 1990s, researchers and doctors have explored other therapies, such as diet therapies, to aid in combating gliomas. The ketogenic diet has gained popularity due to Otto Warburg's theory that tumor cells prefer "aerobic glycolysis" and cannot metabolize ketones. The inability of gliomas to use ketones provides an excellent opportunity to weaken the tumor while protecting healthy cells during cancer treatments. This review will examine some of the current research using the ketogenic diet as a form of cancer therapy to determine if this intervention is manageable and effective in patients with glioblastoma. Peer-reviewed articles from 2009 to 2019 were used. The primary objective is to distinguish differences between pre-clinical and clinical research to determine if the ketogenic diet is reproducible from mouse models into humans to determine its effectiveness. The analysis revealed several limitations of the ketogenic diet as an intervention. The effectiveness is more robust in mice than in human studies. Furthermore, tolerability is marginally supported in human studies requiring more reproducible research to validate that the intervention is manageable and effective in patients with glioblastoma.