MicroRNAs( miRNAs)are a family of endogenous noncoding small RNA molecules that are approximately 20 nucleotides in length. Aberrant expression or dysfunction of miRNAs and subsequent dysregulation of their target genes might be involved in the occurrence and development of various cancers. Gastric cancer is a leading malignant disease worldwide. Recent studies have shown that some miRNAs are closely associated with the proliferation,migration,invasion, apoptosis and chemosensitivity of gastric cancer cells by regulating their target genes. Advances in study on gastric cancer-related miRNAs,their target genes,and the use of miRNAs-targeted therapy in gastric cancer were reviewed in this article.

Objective To investigate the expression of Bmi-1,Mdm2 and Ki-67 in extrahepatic biliary duct carcinoma and to evaluate their clinical significance. Methods The expression of Bmi-1.Mdm2 and Ki-67 was detected in 10 normal extrahepatic biliary duct tissue and 30 cases of extrahepatic billary duct carcinoma with immunohistochemic0al staining and the their clinical significance were analyzed. Results No POsitlVe Bmi-1 expression was found in 10 normal extrahepatie biliary duct cages, while 18 of 30 extrahepatic biliary duct carcinoma cases showed positive Bim-1 expression.The expression of Bmi-I in extrahepatic biliary duct carcinoma(60.0%)was statistically higher than that in normal extrahepatie biliary duct(P<0.05).The positive expression rate of Mdm2 in extrahepatic biliary duct carcinoma was significantly higher than that in normal extrahepatic biliary duct (56.7%vs 20.0%,P<0.05).The cases of extrahepatic biliary duct carcinoma with Ki-67 proliferation index higher than 5%reached 60.0%,while the Ki-67 index was all lower than 1%in 10 normal extrahepatic biliary duct tissue, suggesting the higher proliferating activity of extrahepatic biliary duct carcinoma.No differences were found in the expressions of Bmi-1,Mdm2 and Ki-67 among extrahepatic biliary duct carcinoma cases with different clinical pathological features. Conclusion The results indicate that the expression of Bmi-1 and Mdm2 up-regulation may play an important role in carcinogenesis of extrahepatic biliary duct caroinoma. No clinical significances of the expressions of Bmi-1,Mdm2 and Ki-67 are found in extrahepatic biliary duct carcinomas.

Objective To investigate the expression and relationship of TIP30(HIV-1 Tat interactive protein 2), vascular endothelial growth factor (VEGF) and MVD (detected by CD34) in the angiogenesis of human brain astrocytomas. Methods Expression of TIP30, VEGF and CD34 in 19 cases of normal brain tissue and 71 cases of astrocytoma were immunohistochemically examined with Elivision plus two-step method. Results The positive expression of TIP30 could be seen in cytoplasm of neuroglial cells and neurons of 19 normal brain tissues. The positive expression rate of TIP30 in 71 cases of astrocytoma was 33.80 % (24/ 71). The positive expression rate of TIP30 in astrocytoma of different grades was 52 % for grade Ⅱ, 34.78 % for grade Ⅲ and 13.04 % for grade Ⅳ. The positive expression rate of TIP30 in high grade (Ⅲ+Ⅳ) of astrocytoma was found significantly lower than that in low grade(Ⅱ) (χ2=5.71, P <0.05); The expression of VEGF and MVD detected by CD34 in astrocytomas were higher than that in normal brain tissue and increased as the tumor grade increased; In astrocytoma, the negtive correlation was found between the expression of TIP30 and VEGF (r=-0.428, P<0.05); no correlation was found between TIP30 and MVD(r=-0.065, P 0.05); the positive correlation was found between VEGF and MVD(r=0.684, P<0.01). Conclusion The positive expression rate of TIP30 in normal brain tissue is significantly higher than that in astrocytoma. The positive expression rate of TIP30 significantly decreases as the pathological grade of the astrocytoma increases; The expression of TIP30 and VEGF is negatively correlated in astrocytoma.

BACKGROUND:Study confirmed that the de-epidermized dermis(DED)can be used as dermal substitute and may form epidermal structure after incubating keratinocytes.However,the cell biological activity,tissue structure characteristics and the basement membrane component analysis of dermal substitute have been reported less.OBJECTIVE:To investigate the cell activity and the tissue structure characteristics of DED.METHODS:Skin flap was treated with 56℃ phosphate buffered solution to remove the epidermis,and the dermal cell components were deleted by freezing and thawing with liquid nitrogen to obtain DED.The DED cell activity was detected with tissue culture method,hematoxylin nuclear staining was used to determine the DED cell nuclei,and vimentin immunohistochemistry was applied for fibroblast determinations.The basement membrane and its components were detected using Periodic Acid-Schiff staining and collagen type Ⅳ immunohistochemistry.Van Gieson stain,Weigart stain and those double staining were respectively used to determine DED collagen fibers and elastic fibers.The DED ultrastructure was observed under transmission and scanning electron microscope.RESULTS AND CONCLUSlON:Using tissue culture method,the cultured DED did not exhibit cell growth at 2 weeks.Hematoxylin-eosin staining showed no nuclear in DED,vimentin immunohistochemistry showed no vimentin expressed in DED.Van Gieson staining showed DED collagen fibers were stained as rose red,Weigert staining showed DED elastic fibers were stained as pu rplish black double staining further demonstrated uniform arrangement of collagen fibers and elastic fibers.DED surface and the remaining appendages were strongly positive for Periodic Acid-Schiff staining,and type Ⅳ collagen expression was significant.Transmission and scanning electron microscope results showed that,the DED elastic fibers and collagen overlap arranged with pore intervals,they intercrossed into a network.There is no living cell component in DED,dermal matrix surface and appending organ luminal wall still retain glycogen,type Ⅳ collagen and other basement membrane components,dermal matrix is rich in collagen and elastic fibers.it is a three-dimensional collagen matrix similar to in vivo dermis.

Background and purpose: Cetuximab-containing regimen has been increasingly applied in the treatment of patients with metastatic colorectal cancer. Simultaneously, the predictive factors of outcome for cetuximab have been thoroughly researched. The aim of this study was to evaluate the relationship between K-ras status and efficacy of cetuximab containing regimen in the treatment of patients with metastatic eolorectal cancer. Methods: Between March 2006 and June 2008, twenty-seven patients with metastatic colorectal cancer were treated with cetuximab in combination with chemotherapy. The K-ras mutation status [wild-type (wt) or mutation (nat)] was examined by polymerase chain reaction (PCR) and direct sequencing. The influence of K-ras mutation status on efficacy of cetuximab-containing regimen was analyzed. Results: For 27 patiants in this cohort, K-ras wt was detected in 55.6% (15/27) cases and K-ras mt in 44.4% (12/27) cases. Statistically significant differences were found between the patients with K-ras wt and K-ras mt in terms of overall response rate (ORR) (66.7% vs 25.0%,P=0.035) and progression-free survival (PFS) (8 months vs 4 months, P=0.0028). However, there was no significant difference in overall survival (OS) (19 months vs 12 months, P>0.05). The most common treatment-related adverse effect was skin reaction, with incidence rate of 80.0% and 66.7% (P>0.05), respectively. No treatment related death was observed. Conclusion: K-ras mutation status is a predictive factor of good efficacy of cetuximab-containing regimen in the treatment of patients with metastatic colorectal cancer. Patients with K-ras wt could benefit from cetuximab in combination with chemotherapy.

Objective:Recent studies have shown that in contrast to decrease in distal gastric adenocarcinoma (DGA), incidence of adenocarcinoma of the esophagogastric junction (AEG) has increased noticeably in numerous counties. However, the reasons remain unclear. This study evaluated the possible differences in the expression of KLF4, SP1, and Cyclin D1 in AEG and DGA, and explored the potential carcinogenesis of AEG. Methods:Immunohistochemistry was performed on paraffin-embedded tissues to evaluate the pu-tative differences in the expressions of KLF4, SP1, and Cyclin D1 at protein level between AEG (n=58) and DGA (n=47). The patholog-ical significance of these markers between the two groups was also compared and analyzed. Results:The percentage of positive KLF4 expression was significantly lower in DGA than in AEG (P<0.05). Lower KLF4 expression was found both in well-or moderately dif-ferentiated cases and in poorly differentiated cases with DGA compared with their AEG counterparts (P<0.05). However, positive stain-ing for SP1 was significantly higher in DGA (P<0.05). No significant difference was found in the expression of Cyclin D1 between the two groups. Further analysis showed that in DGA, the positive expression of KLF4, SP1, and Cyclin D1 were significantly correlated with lymph node metastasis. In AEG, only Cyclin D1 expression was correlated with lymph node metastasis (P<0.05). No correlation was found among the expression of KLF4, SP1, and Cyclin D1 in AEG. In DGA, KLF4 was inversely correlated with SP1 and Cyclin D1 (r=-0.334 and r=-0.341, respectively, P<0.05), and SP1 was positively correlated with Cyclin D1 expression (r=0.340, P<0.05).Conclusion:Different expression patterns and clinicopathological significance of KLF4, SP1, and Cyclin D1 were observed between AEG and DGA, suggesting the putative difference in the carcinogenesis and progression of AEG and DGA.

Objective To explore the effects of down regulation of osteopontin(OPN)on the bio- logical behavior of MKN28 and SGC7901 cell lines.Methods OPN siRNA was designed according to the relevant literature and was transfected into the two cell lines.Fluorescent labeling was used to test the transfected efficiency.The down-regulation of OPN protein was measured by Western blot.Real- time PCR was used to test the ratio and time difference of down-regulation of OPN mRNA after siRNA transfection.The biological changes before and after OPN siRNA transfected into these two cell lines were tested by flow cytometry(to test cell cycle and apoptosis)and MTT method(to test the prolifera- tion for the consecutive seven days)and the difference between OPN siRNA transfected or non-transfect- ed cells was compared using mixed model.The capability of moving and invasion of cancer cells were tested by Transwell method and analyzed by t-test.Results The transfected efficiency of OPN siRNA were more than 90% in the two cell lines.OPN mRNA down-regulated to 47% at the 72th hour in SGC7901,while 40% at the 48th hour in MKN28.The expression of OPN protein was both down- regulated after siRNA transfection in the two cell lines.The proliferation decreased after transfected with OPN siRNA both in MKN28 andSGC7901(P

The reported incidence of synchronous multiple primary cancer (SMPC) is rare, and it is even less common to observe synchronous solid tumor with a hematological malignancy. We report five cases of solid tumor presented synchronously with hematological malignancy, all observed within a 2 year period at the oncology department of a university hospital in Shanghai, China. These individual cases included lung adenocarcinoma with chronic myelogenous leukemia, colon cancer with solitary plasmocytoma, gastric adenocarcinoma with diffuse large B cell non-Hodgkin's lymphoma, lung adenocarcinoma with multiple myeloma, and colon cancer with diffuse large B cell non-Hodgkin's lymphoma. It is challenging to therapeutically control the biological behavior of concurrent multiple primary tumors, and there is no standard treatment for such rare conditions. In this paper we discuss these five cases of SMPC and their treatments.
Adenocarcinoma ; China ; Colonic Neoplasms ; Hematologic Neoplasms ; Incidence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Lung ; Lung Neoplasms ; Lymphoma, Non-Hodgkin ; Multiple Myeloma ; Neoplasms, Multiple Primary ; Plasmacytoma

OBJECTIVETo investigate the effect of 17-allylamino-demethoxygeldanamycin (17AAG) on the proliferative and invasive ability of gastric cancer cells and associated mechanism.

METHODSThe proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry(FCM) when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot.

RESULTSThe growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group (P<0.01). The cellular invasive ability decreased significantly (P<0.01). The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed.

CONCLUSION17AAG can inhibit the proliferative and invasive ability of SGC7901 cells, and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.

Apoptosis ; Benzoquinones ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; HSP70 Heat-Shock Proteins ; HSP90 Heat-Shock Proteins ; Humans ; Lactams, Macrocyclic ; pharmacology ; Neoplasm Invasiveness ; Stomach Neoplasms ; pathology

Objective:To explore the putative role of CD40 and COX-2 expression in human esophageal squamous cell carcinoma(ESCC)and to analyze their possible relationship with angiogenesis in ESCC.Methods:The expression of CD40 and COX-2 was detected in 79 ESCC and 28 normal esophageal epithelial tissue samples with immunohistochemical staining.The microvessel density by CD34 was determined and the clinicopathological significance of CD40 and COX-2 expression in ESCC was analyzed.In addition,the expression of CD40 and COX-2 in esophageal squamous cell carcinoma cell line Eca109 and primary cultured normal esophageal epithelial cells in vivo was comparatively studied with immunocytochemical staining andWestern blot.Results:Compared with that in normal epithelial tissues,the expression of CD40 and COX-2 in ESCC was significantly higher(54.43%vs 10.71%:69.62%vs 17.86%:respectively,P<0.05).The positive expression rate of CD40 in ESCC cases with lymph node metastasis was significantly higher than that in those without lymph node metastasis(70.37%vs 46.1 5%.P<0.05).No correlation was found between CD40 expression and patient age,sex,tumor location,size and differentiation of tumors.No clinicopathological significanca of COX-2 expression in ESCC was found.There was a positive correlation between CD40 expression and COX-2 expression in esophageal squamous cell carcinoma(P<0.05,φ=0.446).The mean MVD value in ESCC was significantly higher than that in normal esophageal tissue(25.02±5.52 vs 12.09±4.55,P<0.05).MVD value in ESCC was closely correlated with lymph node metastasis.The mean MVD value in ESCC cases with positive CD40 and COX-2 expression was higher than that in those with negative CD40 and COX-2expression(26.37±6.02 vs 22.58±5.25.P<0.05).Western blot results showed that CD40 and COX-2 expression in Eca109 was higher than that in cultured normal esophageal epithelial cells (P<0.05).Conclusion:The expression of CD40 is involved in the carcinogenesis and progression of esophageal squamous cell carcinoma.CD40 may play an important role in the angiogenesis of ESCC through promoting COX-2 expression.