Oxaliplatin plus intravenous bolus fluorouracil and leucovorin has been shown to be superior for disease-free survival when compared to intravenous bolus fluorouracil and leucovorin. In addition, oxaliplatin regimens were more likely to result in successful surgical resections. First line treatment with cetuximab plus fluorouracil, leucovorin and irinotecan has been found to reduce the risk of metastatic progression in patients with epidermal growth factor receptor-positive colorectal cancer with unresectable metastases. The addition of bevacizumab has been shown to significantly increase overall and progression-free survival when given in combination with standard therapy.
Celecoxib, a selective cyclo-oxygenase-2 (Cox-2) inhibitor, prevents the formation of prostaglandins, responsible for maintenance of renal function. Celecoxib administration may lead to renal damage. Since free radicals and antioxidant mechanisms play a significant role in renal injury; this study was designed to evaluate the role of oxidative stress in celecoxib-induced renal damage. The administration of celecoxib resulted in moderate and mild tubulointerstitial nephritis in chronic and acute group. The renal function tests were significantly altered only in the chronic group. The results in both the acute and the chronic group showed (1) a significant increase in the lipid peroxidation and in the activities of superoxide dismutase, catalase and glutathione-S-transferase and (2) a decrease in nitrite, reactive thiols and glutathione. In conclusion, our study suggests that chronic administration of celecoxib may have a damaging effect on kidney, as evident through altered histopathology and renal functions. This damage may be mediated by oxidative stress.
Cancer is one of the most dreaded diseases in humans and most common cause of death in twenty-first century. New cancer therapies are urgently required because of the existing pharmacological side effects of the conventional chemotherapy, radiation, or surgery. Newer modalities such as cancer vaccines and biological therapies are proving very helpful in the treatment of cancer along with the conventional therapies. The success of these novel cancer therapies is attributed to their lesser toxicity and the specific killing of the cancer cells. Bacterial therapy for cancer has been recognized a century ago. Live, attenuated, or genetically modified obligate or facultative anaerobic bacterial species exhibit the inherent property of colonizing the tumors and are capable of multiplying selectively inside the tumors, thereby inhibiting cancerous growths. The bacteria and their spores are used in the target specific therapies, delivering the prodrugs and the various proteins to the tumors. Albeit bacterial treatment of cancer is providing new perspective in the treatment of disease, the use of microorganisms to target tumors has certain confinements. The biosafety, genetic instability and the confounded interaction of the bacteria with treatment drugs, requires the more noteworthy consideration regarding the use of this novel treatment in the cancer treatment.
n-3 Polyunsaturated fatty acids (PUFA) have a chemopreventive effect while n-6 PUFA promote carcinogenesis. The effect of these essential fatty acids may be related to oxidative stress. Therefore, the study was designed to evaluate the effect of different ratios of fish oil (FO) and corn oil (CO) in the prevention of colon cancer. Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO + CO (1:1) and FO + CO (2.5:1). All the groups, except the control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 h later (initiation phase) or kept for 16 weeks (post initiation phase). DMH treatment in the initiation phase animals showed mild to moderate inflammation, decreased ROS and TrxR activity, increased antioxidants, apoptosis and ACF multiplicity. The post initiation study showed severe inflammation with hyperplasia, increased ACF multiplicity and ROS levels, a decrease in antioxidants and apoptosis. The FO + CO (1:1) treated animals showed severe inflammation, a decrease in ROS, an increase in antioxidants and apoptosis in the initiation phase. FO + CO (1:1) in the post initiation phase and FO + CO (2.5:1) in the initiation showed mild inflammation, increased ROS, apoptosis and decreased antioxidants. There was a decrease in ACF multiplicity and ROS levels, increased antioxidants and apoptosis in the post initiation phase study. The present study suggests that FO has a dose- and time-dependent chemopreventive effect in colon cancer mediated through oxidative stress and apoptosis.
Background and Aim Acute kidney injury (AKI) in severe acute pancreatitis (SAP) has a high mortality rate. Traditionally used serum creatinine is an insensitive biomarker for the early detection of AKI. We aimed to study the role of plasma and urinary neutrophil gelatinase‐associated lipocalin (NGAL) in predicting AKI and a severe course in patients with acute pancreatitis (AP). Methods Consecutive patients of AP who presented within 72 h of symptom onset and age‐ and gender‐matched healthy controls were included. Urinary and serum NGAL levels [enzyme‐linked immunosorbent assay (ELISA)] were evaluated within 24 h of and 72 h after admission and once in controls. Urine and serum NGAL levels were correlated with development of AKI, severity, and outcomes of AP. Results Fifty patients with AP and 30 controls were enrolled. The mean serum and urine NGAL levels in patients on day 1 were significantly higher than the serum and urine NGAL levels in controls (P < 0.001). After excluding patients with AKI on day 1 (n = 10), both serum and urinary NGAL levels on days 1 and 3 were significantly higher in patients who subsequently developed AKI (n = 11) compared to those who did not (n = 29) (P = 0.02, 0.01 and P < 0.001, 0.03). A urinary NGAL level of 221.03 ng/mL on day 1 predicted AKI with a sensitivity and specificity of 82 and 80%, respectively (AUC = 0.9). Mean serum and urinary NGAL levels on day 1 were significantly elevated in patients with SAP compared to those without SAP (P = 0.04 and <0.001). Conclusion NGAL levels in urine and serum can predict severity of AP and development of AKI.
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