Metformin: A Dual-Role Player in Cancer Treatment and Prevention.

Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.

Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.

This comprehensive review thoroughly explores the intricate involvement of insulin receptor (IR) isoforms and insulin-like growth factor receptors (IGFRs) in the context of the insulin and insulin-like growth factor (IGF) signaling (IIS) pathway. This elaborate system encompasses ligands, receptors, and binding proteins, giving rise to a wide array of functions, including aspects such as carcinogenesis and chemoresistance. Detailed genetic analysis of IR and IGFR structures highlights their distinct isoforms, which arise from alternative splicing and exhibit diverse affinities for ligands. Notably, the overexpression of the IR-A isoform is linked to cancer stemness, tumor development, and resistance to targeted therapies. Similarly, elevated IGFR expression accelerates tumor progression and fosters chemoresistance. The review underscores the intricate interplay between IRs and IGFRs, contributing to resistance against anti-IGFR drugs. Consequently, the dual targeting of both receptors could present a more effective strategy for surmounting chemoresistance. To conclude, this review brings to light the pivotal roles played by IRs and IGFRs in cellular signaling, carcinogenesis, and therapy resistance. By precisely modulating these receptors and their complex signaling pathways, the potential emerges for developing enhanced anti-cancer interventions, ultimately leading to improved patient outcomes.

Absolute quantification of senescence mediators in cells using multiple reaction monitoring liquid chromatography-Tandem mass spectrometry.

BACKGROUND: The identification of unique senescence markers remains challenging. Current hallmarks of senescent cells, including increased senescence-associated ß-galactosidase activity, increased levels of cell cycle regulators such as p16INK4a, p27, and p53, and altered levels of sirtuins and lamins, are detected commonly by Western blot and immunohistochemistry methods. Mass spectrometry outperforms these conventional quantification methods in terms of high throughput, specificity, and reproducibility. OBJECTIVES: To develop multiple reaction monitoring-based tandem mass spectrometric senescence assay for simultaneous measuring of p16INK4a, p27, p53, p53-ß, the seven proteins of the sirtuins family and the four transcript variants of lamins proteins in aging cell model and cancerous cell lines. METHODOLOGY: Multiple reaction monitoring-tandem mass transitions per protein were developed for each signature peptide(s) and stable isotope-labeled internal standard. The developed assay was validated in a matrix using breast cancer MCF7 cell lines according to the US-FDA guidelines for bioanalytical assays. RESULTS: The analytes chromatographic peaks were baseline separated and showed linear behavior in a wide dynamic range with r2 ≥ 0.98. The method for all proteins has passed the inter/intra-day precision and accuracy validation using three levels of quality control samples. The accuracy and the precision for most analytes were 80-120% and ≤20%, respectively. The method's sensitivity for the panels' signature peptides ranged from 1 ng µL-1 to 1 µg mL-1. Extraction recovery assessed in two quality control levels was >60% for most analytes. This LC-MS-MS validated senescence assay showed reduced lamin A, lamin A△10, lamin A△50, SIRT1, SIRT3, SIRT5, p53, and p16INK4a, as well as p53-ß induction, are implicated in replicative senescence. Meanwhile, increased lamin C: lamin A ratio was evident and can diagnose breast carcinogenesis. Moreover, in breast cancer metastasis, reduced SIRT2 and p27 and elevated levels of lamin A△50, SIRT5, SIRT7, and p53-ß are evident. CONCLUSION: LC-MS/MS is a potent alternative tool to the currently available assays. The high throughput method established can study senescence's role in different pathophysiological processes.

Ogilvie's Syndrome after Cesarean Section: Case Report in Saudi Arabia and Management Approach.

BACKGROUND: Acute colonic pseudoobstruction or Ogilvie's syndrome is a rare entity that is characterized by acute dilatation of the colon without any mechanical obstruction. It is usually associated with medical disease or surgery and rarely occurs spontaneously. If not diagnosed early, Ogilvie's syndrome may cause bowel ischemia and perforation. CASE: A G7P4+2, 40-year-old woman, who is a known case of gestational diabetes mellitus during her current pregnancy, four previous cesarean sections, two early pregnancy losses at six-week gestation, and hypothyroidism, underwent uncomplicated elective cesarean section, after which she complained of abdominal distention. CONCLUSION: Ogilvie's syndrome is a rare condition yet of interest to obstetricians, midwifery staff, and general surgeons because its early diagnosis and prompt treatment are the keystones to avoid any subsequent fatal complications. This case report reviews the clinical characteristics, diagnostic methods, and management of Ogilvie's syndrome. Moreover, we suggest a management approach to help in early diagnosis and prompt management to improve the outcome of this potentially serious condition.