The inherent resistance of tumors to DNA damage often limits the efficacy of chemotherapy. The aim of this work is to explore the potential mechanism for development of chemoresistance in gastric cancer. Our data revealed that AKT1 mRNA and protein expression were induced by doxorubicin (a chemotherapeutic agent); the doxorubicin-induced AKT1 expression and activation increased the binding of NF-kappaB on Notch1 DNA promoter and then promoted the Notch1 transcription and expression; enhanced expression of Notch1 further upregulated PTEN expression through CBF-1 binding to PTEN DNA promoter; and inhibition of AKT1 expression and activity sensitized the gastric cancer cell to doxorubicin treatment in cultured gastric cancer cell lines and xenograft nude mice gastric cancer model. Furthermore, our data demonstrated that both Notch1 and PTEN were absent or minimally expressed in gastric cancer tissue but abundant in paired normal gastric mucosa, and the expression of Notch1 correlated with that of PTEN. Together, these novel results suggested that a novel AKT1/NF-kappaB/Notch1/PTEN axis has an important role in the development of chemoresistance in gastric cancer. Notch1 has an anti-cancer role in gastric cancer.
Some tumours respond favourably to tumour necrosis factor-alpha (TNF-alpha). Despite this preferential sensitivity, resistance to TNF-alpha remains a clinical problem and more interest is now being focused on finding compounds that induce apoptosis through other pathways. Sodium butyrate (NaBt) has anti-tumour effects on colon cancer cells, inhibiting cell growth and promoting differentiation and apoptosis. In this study we investigated whether NaBt induced apoptosis in the human colon cancer cell line HT-29 and examined the intracellular mechanisms involved. Pre-incubation of cells with NaBt significantly increased apoptosis as measured by fluorescence activated cell sorter analysis and mitochondrial membrane potential determination. This effect could be blocked with the caspase inhibitors, z-VAD-fmk (pan-caspase inhibitor), z-DEVD-fmk (caspase-3 inhibitor) and z-LEHD-fmk (caspase-9 inhibitor), but not with z-IETD-fmk (caspase-8 inhibitor). Enhancement of caspase-3 and caspase-9 activities suggests that NaBt induces apoptosis via mitochondrial pathways not involving TNF-alpha.
The aim of this study was to investigate the prevalence of coexistent duodenal ulcer and gastric cancer in China, then to explore the features of clinical manifestations, endoscopy, pathology and possible pathogenesis. A retrospective analysis has been made on medical records in Remin Hospital, Wuhan University, Hubei Province, China from January 1991 to December 2002. 37 cases of coexistent duodenal ulcer and gastric cancer were found. 24.3% (9/37) had previous history of duodenal ulcer. 81.0% (30/37) of them lack alarm symptoms or signs and 87.1% (27/31) had alleviation in abdominal pain by acid inhibitor. Duodenal ulcer was single in all cases with seven in A1 stage, three in A2 stage, one in H1 stage, one in H2 stage, seven in S1 stage and 18 in S2 stage. 89.2% (33/37) of concurrent gastric cancer were in the corpus and antrum, with 78.1% (29/37) of them belonging to Bormann type II and 87.1% (27/37) being moderately differentiated adenocarcinoma. 83.7% of patients (31/37) had positive rapid urease test. The coexisting gastric cancer in patients with duodenal ulcer is infrequent but not rare. Gastroscopy screening and routine follow-up are necessary for patients with duodenal ulcer. Helicobacter pylori may be important pathogen for it. Helicobacter pylori eradication is recommended in patients with duodenal ulcer to reduce the risk of contaminant gastric cancer.
The objective of this study was to evaluate the diagnostic value of colonoscopy plus biopsy in patients with ulcerative colitis (UC). Retrospective analysis was performed on clinical data in 186 cases. Erosions, or ulcers, together with mucosal hyperemia and oedema were the most common manifestations of colonoscopy in 87% of patients. In about 56.4% of 186 cases, such manifestations occurred in the rectum and the sigmoid colon. Nearly 65.6% of the patients had a chronic intermittent clinical course. One case developed colon cancer, and another case had toxic megacolon; each case represents 0.05% of the total 186 patients. Therefore, prevalence of both malignancy and complication is low. Colonoscopy plus biopsy is considered to be the major means of the diagnosis of UC, demonstrating its value in differential diagnosis.
SUMMARYIn order to study the clinical characteristics of patients with acute acalculous cholecystitis (AAC) in China, we retrospectively analysed the epidemiology, clinical manifestations and treatment of hospitalised cases with AAC in our hospital between January 1991 and October 1998, and compared the results with western reports. Most AAC cases in our series were younger than 60 years, and there was no significant difference between males and females. Their clinical manifestations were usually not serious. Only one patient suffered complications. The rate of complications and mortality was lower than those in western countries. All patients were treated and recovered; none needed an emergency operation and there were no deaths.
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