Mechanism of polycomb Bmi1-targeted therapy for colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the Bmi1 protein level in human colorectal cancer specimen and associated clinicopathological parameters, and to determine the influence of Bmi1 on the proliferation and apoptosis of colorectal cancer cells.</p><p><b>METHODS</b>Bmi1 protein level was assessed in 85 patients with colorectal cancer and adjacent normal tissue by immunohistochemistry. SW480 cells were transfected with Bmi siRNA plasmid. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of Bmi1 and Bcl-2 were measured by Western blot.</p><p><b>RESULTS</b>The positive rate of Bmi1 expression in colorectal cancer tissues was 56.5%(48/85), significantly higher than that in the adjacent noncancerous tissues[17.6%(15/85), P<0.05)]. It was found that the overexpression of Bmi1 was associated with degree of differentiation, status of lymph nodes metastasis, and TNM staging in colorectal cancer(P<0.05). After transfection of SW480 with Bmi1 siRNA, the cell proliferation was inhibited and the apoptosis was significant. The cell proliferation inhibitory rates were 13.1%, 16.5%, and 18.3% at 24 h, 48 h and 72 h after transfection. The apoptotic rates were 15.7%, 45.6%, 40.2%, respectively. Expression of Bmi1 was downregulated after 48 h, as was that of Bcl-2.</p><p><b>CONCLUSIONS</b>Bmi1 expression is associated with the clinicopathological characteristics of colorectal cancer. Blockade of Bmi1 can inhibit the proliferation and accelerate the apoptosis of colorectal cancer cells.</p>

Clinical value of screening hereditary nonpolyposis colorectal cancer in China with protocol recommended by NCCN guidelines / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of the protocol recommended by NCCN-2007 on the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in China.</p><p><b>METHODS</b>NCCN protocol consists of identifying HNPCC characteristics according to the revised Bethesda Guidelines,genetic counseling with immunohistochemistry and finally genetic testing. Four hundred and nineteen patients diagnosed as colorectal cancer from January 2002 to February 2006 were selected. The hMLH1 and hMSH2 immunostaining were implemented for 90 patients who fulfilled the revised Bethesda Guidelines, in whom 8 patients fulfilling the Amsterdam II (Criteria were classified as group A and the other 82 patients as group B. The frozen tissues were collected from patients who showed loss of hMLH1 or hMSH2 protein expression, then RNA was extracted, and RT-PCR and cDNA sequencing were adopted to detect the germline mutations of hMLH1 and hMSH2.</p><p><b>RESULTS</b>Tumor tissues from 18 patients showed loss of hMLH1 or hMSH2 protein expression (5 patients in group A and 13 in group B). Finally, 21 patients(8 in group A and 13 in group B showed loss expression of MMR protein) were diagnosed as HNPCC, including 2 cases of hMLH1 and 1 case of hMSH2 mutations. These 3 cases with cDNA mutations did not fulfill the Amsterdam II( Criteria, and were finally diagnosed as HNPCC.</p><p><b>CONCLUSION</b>The protocol recommended by NCCN-2007 offers a useful approach to identify HNPCC patients,and reduces the possibility of missed diagnosis of HNPCC.</p>

The role of cyclooxygenase-2/prostanoid pathway in visceral pain induced liver stress response in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prostanoids from arachidonic acid. COX-2 is the inducible enzyme in the COX family, together with the prostanoids forms the COX-2/prostanoid pathway. Research showed that the COX-2/prostanoid pathway is activated in hepatic diseases and liver stress reaction, such as fibrogenesis, portal hypertension, carcinogenesis, and ischemic/reperfusion injury. But there was no report on visceral pain induced liver stress. This study was to investigate the role of the COX-2/prostanoid pathway in liver stress response in rat acute colitis visceral pain liver stress model.</p><p><b>METHODS</b>Fifty-three male SD rats were randomly divided into Naive, Model, NS398 treatment, and Morphine treatment groups. The rat acute colitis visceral pain liver stress model was established under anesthesia by the colonic administration of 0.5 ml of 6% acetic acid using a urethral catheter. NS398 and morphine were administrated 30 minutes prior to model establishment in NS398 and Morphine treatment groups respectively. Spontaneous activities and pain behavior were counted and the extent of colonic inflammation was assessed histologically. Liver tissue levels of Glutathione-S-Transferase (GST) activity, COX-2 mRNA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-Ketone-prostaglandin F1alpha (6-K-PGF1alpha) contents were assessed.</p><p><b>RESULTS</b>Thirty minutes after the colonic administration of acetic acid, a significant decrease in spontaneous activities and an increase in pain behaviors were observed in Model group (P < 0.01 and P < 0.05 respectively), accompanied by colonic inflammation. Liver GST activity levels significantly dropped (P < 0.05). Liver COX-2 mRNA expression significantly increased, accompanied by an increase in liver concentrations of PGE2 and TXB2, but no obvious change in 6-K-PGF1alpha concentrations. NS398 and morphine both ameliorated post-stress liver GST activity (P < 0.05 and P < 0.01 respectively), decreased stress-induced COX-2 expression, decreased PGE2 and TXB2 production, but increased liver 6-K-PGF1alpha levels. Morphine attenuation in colonic tissue inflammation was apparent at 24 hours (P < 0.05).</p><p><b>CONCLUSIONS</b>Acute colitis visceral pain liver stress can induce liver injury. Liver injury might have occurred through the activation of the COX-2/prostanoid pathway and increased production of PGE2 and TXB2. Effective analgesia might offer protective effect during visceral pain stress.</p>

MEK inhibitor improves the epirubicin sensitivity of breast carcinoma cell line MCF-7 / 中国癌症杂志

Background and purpose:Chemotherapy plays an important role in the treatment of breast carcinoma by inhibiting the tumor growth and inducing the apoptosis.MAPK transduction pathway is closely related to proliferation and apoptosis of varieties of tumor cells,inhibition of MAPK pathway may increase the efficiency and decrease the toxicity of chemotherapy.Our study was to investigate the effect of MEK inhibitor PD98059 in response of breast cancer cell lines to Epirubicin.Methods:Human breast cancer cell lines MCF-7 and MCF-7/ADR were used as cell models.Epirubicin(EADM),PD98059(inhibitor of MAPK Kinase-MEK),or EADM+PD98059 was added into the culture medium,the expression of MEK2 and p-ERK were measured by Western blot,the growth of the two cell lines were measured by MTT.Results:ERK activity was elevated in MCF-7 after the treatment of EADM,the cells were more sensitive to EADM if combined with PD98059,while in MCF-7/ADR,ERK activity kept unchanged after EADM treatment,and PD98059 has no effect on the sensitivity of cells to EADM.Conclusion:MAPK signal transduction may be activated in some cells treated by EADM,adding inhibitor of MAPK signal transduction could improve the sensitivity of the cells to EADM.

Expression and significance of estrogen receptor isoforms in the development of human breast carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the estrogen receptors (ER)alpha and ERbeta expression and their relationship with clinicopathological parameters in human breast carcinoma.</p><p><b>METHODS</b>Samples were obtained from 30 breast carcinoma, reverse transcriptase polymerase chain reaction was used to measure the expression of ERalpha and ERbeta mRNA.</p><p><b>RESULTS</b>ERalpha mRNA level was up-regulated in breast carcinoma tissue compared with adjacent normal tissue (t = 7.399, P < 0.01) while down-regulated in ERbeta. The relative ratio of ERalpha and ERbeta was decreased in normal tissue vs. carcinoma (t = 6.385, P < 0.01), in patients with lymph node metastasis vs. those without lymph node metastasis (t = 2.602, P < 0.05), in late stage carcinoma vs. early stage (t = 3.754, P < 0.05).</p><p><b>CONCLUSION</b>ERalpha and ERbeta play divergent role in the development of human breast carcinoma.</p>