Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer.
Participation in Colorectal cancer (CRC) screening programs is low in Saudi Arabia. Public awareness of CRC and knowledge of available screening tools are crucial for improving screening uptake. This study aimed to examine the level of awareness and knowledge of CRC among the Saudi population. A survey-based study was conducted on 1912 residents of Riyadh, Saudi Arabia. The survey comprised 20 questions; these concerned the definition of the colon and rectum; the function of the colon; the incidence, risk factors, symptoms, screening methods, prevention methods, and treatment methods for CRC; and the value of early detection of CRC. Of the 1912 participants who completed the survey, only 51.7% knew that the colon was the large intestine, while 57% knew that the rectum was the end of the large intestine. Colonoscopy was the preferred screening tool (72.8%). Most respondents believed early detection of CRC through colonoscopy is associated with high survival rates. However, 65.7% of the participants reported that they would not like to undergo a CRC screening. Higher education level was also associated with knowledge that CRC can develop asymptomatically, with postgraduates most likely to know this (P = 0.032). There is a lack of knowledge regarding CRC among certain demographic groups in Saudi Arabia, and education and screening programs should target populations with the most limited knowledge.
3 June 2020 in Dr. Sulaiman Al Habib Medical Journal
Objective: Intestinal anastomosis is among the most commonly performed major abdominal procedures; however, leaks are an ongoing problem. The aim of this study was to investigate the effect of Insulin-like Growth Factor (IGF-1) on colonic healing under hypoxia. Methods: Thirty-two Sprague–Dawley male rats underwent laparotomy with colonic transection and anastomosis. Rats were divided into four groups—Group A: normoxic (FiO2 21%) with saline [2 mg/kg, Intraperitoneally (IP)] at days 0, 2, 4, and 6; Group B: hypoxic (FiO2 11%) with saline injection; Group C: normoxic with IGF-1 injection at a dose of 2 mg/kg at days 0, 2, 4, and 6; Group D: hypoxic with IGF-1 treatment. On day 7, all animals were sacrificed, and intestine weight and bursting pressure were measured; anastomotic tissues were analyzed for mRNA level of collagen I and Matrix Metalloproteinase-13 (MMP-13) and cytokines analysis by enzyme-linked immunosorbent assay. Results: There was significant increase in intestinal length in normoxic group treated with IGF-1 as compared to control (129.9 cm vs. 99.38 cm, p < 0.05); the length increased significantly in hypoxic group treated with IGF as compared to hypoxic control (123.1 cm vs. 82.25, p < 0.01). In the normoxic groups, a 6.7% decrease in mean body weight was found; however, the normoxic IGF-1 group sustained a weight gain of 0.5% (p < 0.01). The average weight decreased in the hypoxic control group (28.3%) and in the hypoxic IGF-1 treated group (16.6%, p < 0.05). Anastomotic bursting pressure increased significantly (p < 0.05) after IGF-1 treatment. Collagen I and MMP-13 mRNA expressions increased significantly (p < 0.001) in the IGF-1 treated group. Interleukin-10 and tumor necrosis factor alpha levels decreased under hypoxia with IGF-1 (p < 0.05). Vascular endothelial growth factor (p < 0.001), transforming growth factor beta (p < 0.05), and IGF-1 (p < 0.001) were significantly elevated in response to IGF-1. Conclusion: IGF-1 stimulates the healing of colonic anastomosis under hypoxia. Factors promoting neoangiogenesis, collagen deposition, and paracrine expression were increased after IGF-1 treatment resulting in wound healing.
And suture the defect primarily or by patching large defects with a synthetic mesh. Recently, authors advocate the use of laparoscopic surgical techniques to repair such hernias especially the elective ones. This case discusses Morgagni's hernia repair using robotic surgery....