K-ras gene mutation is a common event in our 118 Chinese CRC patients, with an obvious relationship with gender. However, it seems not to be an independent prognostic factor in CRC patients. The BRAF gene is rarely mutated in Chinese CRC patients.
It has been shown by epidemiological and animal studies that microcystin is an important exogenous factor involved in the carcinogenesis of colorectal cancer (CRC). However, details of the mechanism remain unclear. Transformation of colorectal cells is an important initial step in carcinogenesis. Whether microcystin is capable of transforming immortalized colorectal crypt cells, and what the mechanism might be, was investigated. In the present study, we demonstrated that immortalized colorectal crypt cells could be transformed by microcystin. Transformed colorectal crypt cells showed an anchorage-independent growth phenotype, and the proliferation activities of microcystin-transformed cells were also greater than that of immortalized colorectal crypt cells. The Akt and the p38, JNK of mitogen-activated protein kinase (MAPK) pathways in microcystin-transformed cells were found to be constitutively activated. In microcystin-transformed cells, PI3K, MAPKAPK2, Akt, cyclin D1 and cyclin D3 in the Akt pathway; IQGAP-2, RabGTPase, Rap1GAP, RasGAP, R-Ras, Krev-1 and TC21 of the Ras GTP/GDP protein family; and A-Raf, B-Raf and PAK in the Ras/MAPK pathway were all markedly upregulated. However, in positive control cells, dimethylhydrazine-transformed cells, only the Akt pathway was activated by PI3K, and no evidence of alteration of any molecules of the Ras superfamily was observed. Inhibition of Akt, p38 and JNK activation led to a reduced proliferation of microcystin-transformed cells. This implies that the constitutive activation of Akt and the p38, JNK of MAPK pathways in microcystin-transformed cells may be the mechanism by which this important external factor acts in the carcinogenesis of CRC.
Our results suggest that PCDH10 is an important tumor suppression gene with key roles of suppressing cell proliferation, clonogenicity, and inhibiting cell invasion in the development of colorectal cancer. Thus, PCDH10 methylation may constitute a useful biomarker of colorectal cancer patients.
SummaryThe Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosaassociated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagAtransfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.
Hepatocellular carcinomas represent the third leading cause of cancer-related deaths worldwide. Survivin, a structurally unique member of the inhibitor of apoptosis protein (IAP) family, is overexpressed in a wide range of malignancies, including hepatocellular carcinoma. Due to its involvement in cancer progression and treatment resistance, survivin is currently undergoing extensive investigation as a novel intervention target to induce apoptosis in cancer cells by phytochemicals or synthetic agents. Brazilein, a compound obtained in a large amount from the dried heartwood of Caesalpinia sappan Linn., which has long been used in traditional medicine in China, has some pharmacological activities. Human hepatocellular carcinoma HepG2 cells were treated with brazilein and analyzed for survivin protein and mRNA levels by Western blotting and real-time RT-PCR, respectively. Brazilein treatment of cells for 48 h at 5 and 10 microg/ml doses resulted in significantly decrease in survivin protein expression. We also observed that brazilein caused a strong decrease in survivin mRNA expression. In other studies, down-regulation of survivin by brazilein was associated with a strong and prominent caspases-9 and -3 activation as well as PARP cleavage. It was also shown that brazilein induced a strong apoptotic cell death, as shown by DNA ladder assay, and growth inhibition of HepG2 cells. Further studies are needed to investigate in vivo effect of brazilein on survivin expression and associated biological effects in hepatocellular carcinoma that could provide useful information for brazilein efficacy in the prevention/intervention of human hepatocellular carcinoma.
INTRODUCTION:
Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM.
METHODS:
Archived endoscopic white light images with corresponding gastric biopsies were collected from 14 hospitals located in different regions of China. Corresponding images by anatomic sites containing AG, GIM, and chronic non-AG were categorized using pathology reports. The participants were randomly assigned (8:1:1) to the training cohort for developing the CNN model (TResNet), the validation cohort for fine-tuning, and the test cohort for evaluating the diagnostic accuracy. The area under the curve (AUC), sensitivity, specificity, and accuracy with 95% confidence interval (CI) were calculated.
RESULTS:
A total of 7,037 endoscopic images from 2,741 participants were used to develop the CNN for recognition of AG and/or GIM. The AUC for recognizing AG was 0.98 (95% CI 0.97–0.99) with sensitivity, specificity, and accuracy of 96.2% (95% CI 94.2%–97.6%), 96.4% (95% CI 94.8%–97.9%), and 96.4% (95% CI 94.4%–97.8%), respectively. The AUC for recognizing GIM was 0.99 (95% CI 0.98–1.00) with sensitivity, specificity, and accuracy of 97.9% (95% CI 96.2%–98.9%), 97.5% (95% CI 95.8%–98.6%), and 97.6% (95% CI 95.8%–98.6%), respectively.
DISCUSSION:
CNN using endoscopic white light images achieved high diagnostic accuracy in recognizing AG and GIM.
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