Effect of Bauhinia racemosa stem bark on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats

The aim of this study is to investigate the antioxidant defense system induced by the methanol extract of Bauhinia racemosa L.(MEBR) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in Wister albino rats. The effects of MEBR on surface visible macroscopic (Morphometry) liver lesions (neoplastic nodules) and the levels of serum enzymes, lipid peroxidation and antioxidants were evaluated in NDEA-induced hepatocarcinogenesis in rats. In rats treated, with NDEA, significantly elevated levels of serum enzymes (SGOT, SGPT and ALP), bilirubin and decreased levels of protein and uric acid were observed. Significantly elevated amount of malondialdehyde (MDA), the end product of lipidperoxidation, indicated higher levels of lipid peroxidation, which was accompanied by significantly decreased levels of antioxidants like vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Administration of MEBR was able to suppress nodule development/hepatocellular lesion formation in rats. The extract treatment increases in antioxidant levels and dramatic decreases in lipid peroxidation levels. MEBR also produced a protective effect by decreasing the level of serum enzymes, bilirubin and increased the protein and uric acid levels. The results suggest that MEBR exert chemopreventive effects by suppressing nodule development and decreasing lipid peroxidation and enhancing the levels of antioxidants in NDEA carcinogenesis by reducing the formation of free radicals.     

Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma.

PURPOSE: Few published studies have addressed individual patient risk after R0 resection for gastric cancer. We developed and internally validated a nomogram that combines these factors to predict the probability of 5-year gastric cancer-specific survival on the basis of 1,039 patients treated at a single institution. METHODS: Nomogram predictor variables included age, sex, primary site (distal one-third, middle one-third, gastroesophageal junction, and proximal one-third), Lauren histotype (diffuse, intestinal, mixed), number of positive lymph nodes resected, number of negative lymph nodes resected, and depth of invasion. Death as a result of gastric cancer was the predicted end point. The concordance index was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed. RESULTS: Gastric cancer-specific survival at 5 years was 50%. A nomogram was constructed on the basis of a Cox regression model. The bootstrap-corrected concordance index was 0.80. When compared with the predictive ability of American Joint Committee on Cancer stage, the nomogram discrimination was superior (P <.001). Nomogram calibration appeared to be excellent. CONCLUSION: A nomogram was developed to predict 5-year disease-specific survival after R0 resection for gastric cancer. This tool should be useful for patient counseling, follow-up scheduling, and clinical trial eligibility determination.     

Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer

OBJECTIVE: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. SUMMARY BACKGROUND DATA: Locally advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. METHODS: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6 cm from the anal verge (range 0-15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. RESULTS: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). CONCLUSIONS: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.     

Encoded Exposure and Social Norms in Entertainment-Education

Entertainment-education is an effective health communication strategy that combines or embeds educational messages into entertainment programs to bring about social and behavior change. For years, scholars have considered how entertainment-education works. Some contemporary theories posit that entertainment-education does not engender behavior change directly but does so through mediating variables. This study adds to the literature on this topic by exploring the direct relationship between exposure and social norms instead of their relationship through behavior as a mediator. Novel to this study is the use of encoded exposure, a continuous and recognition-based measure of exposure that includes ever watching, recall, involvement, and dose in its operationalization. Using cross-sectional data from Kyunki … Jeena Issi Ka Naam Hai, an entertainment-education program in India, this exploratory analysis indicates a positive and significant relationship between encoded exposure and social norms. How can this finding be applied to future programs? Questions remain, and replication is needed, but if it is not essential to go through behavior in order to change social norms, then implications emerge for the theory and practice of entertainment-education.     

Death-associated protein kinase 1 promotes growth of p53-mutant cancers

Estrogen receptor–negative (ER-negative) breast cancers are extremely aggressive and associated with poor prognosis. In particular, effective treatment strategies are limited for patients diagnosed with triple receptor–negative breast cancer (TNBC), which also carries the worst prognosis of all forms of breast cancer; therefore, extensive studies have focused on the identification of molecularly targeted therapies for this tumor subtype. Here, we sought to identify molecular targets that are capable of suppressing tumorigenesis in TNBCs. Specifically, we found that death-associated protein kinase 1 (DAPK1) is essential for growth of p53-mutant cancers, which account for over 80% of TNBCs. Depletion or inhibition of DAPK1 suppressed growth of p53-mutant but not p53-WT breast cancer cells. Moreover, DAPK1 inhibition limited growth of other p53-mutant cancers, including pancreatic and ovarian cancers. DAPK1 mediated the disruption of the TSC1/TSC2 complex, resulting in activation of the mTOR pathway. Our studies demonstrated that high DAPK1 expression causes increased cancer cell growth and enhanced signaling through the mTOR/S6K pathway; evaluation of multiple breast cancer patient data sets revealed that high DAPK1 expression associates with worse outcomes in individuals with p53-mutant cancers. Together, our data support targeting DAPK1 as a potential therapeutic strategy for p53-mutant cancers.