[Mechanism of ß-carboline alkaloids inhibiting migration and invasion of SGC-7901 cells].

To explore the mechanism of ß-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of ß-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of ß-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofß-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the ß-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the ß-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of ß-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).ß-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by ß-carboline alkaloids.

[Role of tumor necrosis factor-alpha in spinal cord injury of rabbits with decompression sickness].

OBJECTIVE: To observe the pathological changes in rabbits with spinal cord injury induced by decompression sickness (DCS), and to investigate the role of tumor necrosis factor-alpha (TNF-α) in spinal cord injury induced by DCS. METHODS: Rabbits were randomly divided into normal control group, DCS group, and safe decompression group. The rabbit model of DCS was established. Light microscopy, real-time PCR, and immunohistochemical method were used to observe the pathomorphological changes in the thoracolumbar spinal cord and the mRNA and protein expression of TNF-α, respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to observe the apoptosis in the spinal cord. RESULTS: In the DCS group, cavities formed in the white matter of spinal cord and gliosis occurred around necrotic areas. Moreover, the mRNA and protein expression of TNF-α was significantly higher in the DCS group than in the normal control group and the safe decompression group (P<0.01). The results of TUNEL showed that the number of positive apoptotic cells was significantly larger in the DCS group than in the normal control group and the safe decompression group (P<0.05). CONCLUSION: Apoptosis plays an important role in spinal cord injury induced by DCS. In the early stage of DCS, the massive release of TNF-α initiates apoptosis and contributes to the pathological changes in spinal cord injury induced by DCS.

[Screening for Lynch syndrome in colorectal cancer].

OBJECTIVE: To evaluate the application of mismatch repair (MMR) genes proteins expression to screen for Lynch syndrome in colorectal cancer patients. METHODS: One hundred consecutive colorectal cancers cases collected from 2012 to 2013 were tested immunohistochemically for the protein expression of MLH1, MSH2, MSH6 and PMS2, and also by the ARMS method for the mutation status of BRAF genes in those cases lacking protein expression for MLH1. RESULTS: The result of MMR immunocytochemistry showed that nine of 100 cases lacked MMR protein expression, including three cases each that were MLH1-/PMS2- and MSH2-/MSH6- respectively, two cases were MLH6- and one case was PMS2-; overall, the majority of these cases lacked protein expression of MLH1 and MSH2. The BRAF genes mutation test showed one case of mutation, indicating that the patient might have MLH1 gene methylation as a result of the mutation of BRAF genes, and that was a sporadic case. The age of onset for patients lacking MMR protein expression was lower than patients with sporadic colorectal cancer (P = 0.011). Colorectal cancers associated with the lack of MMR protein expression mostly occurred in the right colon (P = 0.001), and histomorphologically were often accompanied by mucinous adenocarcinoma (P = 0.010) and tumor lymphocytic infiltration. CONCLUSION: Immunohistochemical staining for MMR proteins in patients with colorectal cancer, accompanied by testing for BRAF genes mutation, may be an effective approach to screen for Lynch syndrome.

[Changes in levels of TNF-α and GFAP in brain and spinal cord of rabbits with decompression disease].

OBJECTIVE: To investigate the changes in expression of tumor necrosis factor-alpha (TNF-α) and glial fibrillary acidic protein (GFAP) in rabbits with decompression disease (DCS), and to investigate the functioning mechanism. METHODS: A total of 21 healthy adult rabbits were randomly divided into 3 groups: normal control group, DCS group, and safe relief group, with 7 rabbits in each group. A rabbit DCS model was established by quick decompression. The changes in pathological morphology and mRNA and protein expression of TNF-α and GFAP in the brain and spinal cord of rabbits with DCS were determined by light microscopy, real-time PCR, and immunohistochemistry, respectively. RESULTS: Cavity formation was observed in the white matter of spinal cord in DCS group. The mRNA and protein expression of TNF-α and GFAP was significantly higher in the DCS group than in the normal control group and safe relief group (P < 0.01), while no significant differences were observed in the brain (P > 0.05). CONCLUSION: Spinal cord is the main part of central nervous system injury in DCS. Activation of TNF-α and GFAP genes accompanied by increase in their protein expression can be observed at the early stage of DCS. The astrocytes and TNF-α play important roles in the process of spinal cord injury in DCS.

[Expression of Wnt5a, APC, ß-catenin and their clinical significance in human colorectal adenocarcinoma].

OBJECTIVE: To study the expression of Wnt5a gene mRNA and Wnt5a, APC, ß-catenin proteins in human colorectal adenocarcinoma (CRC) and explore its clinical significance. METHODS: Wnt5a mRNA level was measured in 30 patients with CRC and paired non-tumor tissues by real-time PCR. Immunohistochemical staining of Wnt5a, APC, ß-catenin was performed in samples of 62 patients with CRC using SP system. RESULTS: The relative expression level of Wnt5a mRNA in fresh CRC is 0.1232 ± 0.0140, which is significantly higher than that in adjacent colorectal mucosa (0.0497 ± 0.0074, P = 0.02). A low expression of Wnt5a protein was observed in 38 of 62 CRC. Wnt5a protein expression was closely correlated with the tumor types and the degree of tumor differentiation (P < 0.05). There was no apparent relationship with lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). APC protein was decreased in 38 of 62 CRC. The expression of APC was closely correlated with the tumor types (P < 0.05). There was no apparent relationship with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P > 0.05). The expression of ß-catenin was observed in cytoplasm and/or cell nuclei in 50 of 62 CRC. The positive rate of ß-catenin expression was closely correlated with the degree of tumor differentiation, lymph node metastasis, depth of myometrial invasion and TNM stages (P < 0.05). There was no apparent relationship with the tumor types (P > 0.05). The expressions of Wnt5a (r = 0.271, P = 0.027) and APC (r = 0.343, P = 0.004) were correlated with that of ß-catenin in CRC, respectively, but there was no correlation between the expressions of Wnt5a and APC protein (r = 0.218, P = 0.078) in the tumors. CONCLUSIONS: Wnt5a, APC and ß-catenin genes might be involved in the carcinogenesis and development of CRC. It is hypothesized that down-regulation of APC and Wnt5a proteins may be one of causes of ectopic expression of ß-catenin in CRC.

Multi-Objective Optimization Design of Ladle Refractory Lining Based on Genetic Algorithm.

Genetic algorithm is widely used in multi-objective mechanical structure optimization. In this paper, a genetic algorithm-based optimization method for ladle refractory lining structure is proposed. First, the parametric finite element model of the new ladle refractory lining is established by using ANSYS Workbench software. The refractory lining is mainly composed of insulating layer, permanent layer and working layer. Secondly, a mathematical model for multi-objective optimization is established to reveal the functional relationship between the maximum equivalent force on the ladle lining, the maximum temperature on the ladle shell, the total mass of the ladle and the structural parameters of the ladle refractory lining. Genetic algorithm translates the optimization process of ladle refractory lining into natural evolution and selection. The optimization results show that, compared with the unoptimized ladle refractory lining structure (insulation layer thickness of 0 mm, permanent layer thickness of 81 mm, and working layer thickness of 152 mm), the refractory lining with insulation layer thickness of 8.02 mm, permanent layer thickness of 76.20 mm, and working layer thickness of 148.61 mm has the best thermal insulation performance and longer service life within the variation of ladle refractory lining structure parameters. Finally, the results of the optimization are verified and analyzed in this paper. The study found that by optimizing the design of the ladle refractory lining, the maximum equivalent force on the ladle lining, the maximum temperature on the ladle shell and the ladle mass were reduced. The thermal insulation performance and the lightweight performance of the ladle are improved, which is very important for improving the service life of the ladle.

[Large cell calcifying Sertoli cell tumor of the testis: a clinicopathological observation].

OBJECTIVE: To investigate the clinicopathological characteristics of large cell calcifying Sertoli cell tumor (LCCSCT) of the testis. METHODS: We studied a case of LCCSCT by light microscopy, Western blotting and immunohistochemistry, reviewed relevant literature, and analyzed the clinical, morphological and immunohistochemical features, treatment and prognosis of the tumor. RESULTS: The patient was a 25 years old man. Pathohistologically, the tumor was characterized by a mass of polygonal tumor cells in a tubular and trabecular growth pattern, with abundant acidophilic cytoplasm, enlarged vesicular nuclei, and extensive calcified debris in stroma. The tumor cells were positive for inhibin, S-100, vimentin and alcian blue, but negative for PLAP, SMA, CK, AFP and periodic acid-Schiff (PAS) reaction. CONCLUSION: LCCSCT is a rare testicular sex cord stromal tumor. Its diagnosis is based on immunohistochemical staining, and it is to be differentiated from other lesions of the testis, including seminoma, Leydig cell tumor, Sertoli cell node, and androgen insensitivity syndrome. For the treatment of LCCSCT, surgical resection often has a good prognosis.

[Anti-tumor effects of chemotherapeutic drugs on human gastric cancer cells in vitro and the relationship with expression of hTERT mRNA].

OBJECTIVE: To evaluate in vitro antitumor effects of chemotherapeutic drugs, and investgate the relationship with expression of hTERT mRNA in human gastric cancer tissues. METHODS: Fresh samples of gastric cancer obtained from operation room were prepared to single-cell suspension (3 x 10(5) to 5 x 10(5) cells ml(-1)) and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-Fu), adriamycin (ADM), mitomycin (MMC) for 48 hours. Metabolic activity and inhibitory rate of the cells were determined by trypan blue exclusion and MTT assay. Expression of hTERT mRNA was detected by in situ hybridization (ISH). RESULTS: The inhibition rate of cancer cells exposed to chemotherapeutic drugs was different, and that of TAX, CDDP, 5-Fu was significantly higher than that of ADM and MMC. The positive rate of hTERT mRNA expression was 90.0% (54/60) and positive cells showed resistance to 5-Fu and ADM. CONCLUSION: Overexpression of hTERT mRNA may contribute to primary drug-resistance of tumors. Chemosensitivity tests by MTT assay may contribute to prediction of effectness in applying chemotherapeutic drugs and identify drug-resistant cases.

Transplantation of Pro-Oligodendroblasts, Preconditioned by LPS-Stimulated Microglia, Promotes Recovery After Acute Contusive Spinal Cord Injury.

Spinal cord injury (SCI) is a significant clinical challenge, and to date no effective treatment is available. Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair. However, the poor posttransplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as donor cells. Here we report the generation of an OL lineage population [i.e., pro-oligodendroblasts (proOLs)] that is relatively more mature than OPCs for transplantation after SCI. We found that proOLs responded to lipopolysaccharide (LPS)-stimulated microglia conditioned medium (L+M) by preserving toll-like receptor 4 (TLR4) expression, improving cell viability, and enhancing the expression of a myelinating OL marker myelin basic protein (MBP), compared to other OL lineage cells exposed to either LPS-stimulated (L+M) or nonstimulated microglia conditioned medium (LM). When L+M-stimulated proOLs were intrathecally delivered through a lumbar puncture after a T10 thoracic contusive SCI, they promoted behavioral recovery, as assessed by the BassoBeattieBresnahan (BBB) locomotor rating scale, stride length, and slips on the grid tests. Histologically, transplantation of L+M proOLs caused a considerable increase in intralesional axon numbers and myelination, and less accumulation of invading macrophages when compared with the vehicle control or OPC transplantation. Thus, transplantation of proOLs, preconditioned by L+M, may offer a better therapeutic potential for SCI than OPCs since the former may have initiated the differentiation process toward OLs prior to transplantation.

Oncocytic carcinoma of the salivary gland with thymoma: A case report and review of the literature.

Oncocytic carcinoma (OC) arising in the salivary gland is a very rare tumor with only 32 previously reported cases. In this report, we describe a novel case of oncocytic carcinoma with associated thymoma, which arose in the left parotid gland of a 66-year-old male with a history of a painless left parotid mass for 1 year. Oncocytes are large, polygonal cells that are characterized by marked cellular atypia, frequent mitoses, wide eosinophilic granular cytoplasm, a central nucleus and a prominent nucleolus. The follow-up data showed no evidence of recurrence and the patient is in a good health 20 months after the surgery. In the current case, the patient had not only OC but also thymoma, which is exceedingly rare and may represent the first documented case in the literature.

Wnt5a involved in regulation of the biological behavior of hepatocellular carcinoma.

OBJECTIVE: Wnt5a has been shown to be involved in cancer progression in a variety of tumor types. Previous experimental studies have indicated that it has been shown to be down-regulated in hepatocellular carcinoma (HCC). The goal of this study was to explore the effect of Wnt5a overexpression in an HCC cell line. METHODS: We transfected the human HCC cell line Huh7 with a pcDNA3.1-Wnt5a overexpression vector or an empty vector control. The integration of the plasmid DNA and the expression of Wnt5a in Huh7 cells were confirmed by real-time RT-PCR and Western blot. A plate colony formation test was used to calculate the clone formation rate and the cell cycle was analyzed by flow cytometry. The effect of Wnt5a overexpression on cell migration was studied in vitro using a scratch assay and in vivo by xenograft studies in nude mice. RESULTS: Our results showed that in Huh7 cells with overexpression of Wnt5a, the fraction of cells in the G1 and S phases of the cell cycle was significantly increased compared with untransfected cells. In agreement with this finding, overexpression of Wnt5a was associated with a lower colony formation rate compared with control cells. In our xenograft studies, nude mice injected with Huh7 cells with overexpression of Wnt5a had decreased tumor volumes compared with controls. The vitro scratch assay revealed that Wnt5a overexpression cells had a diminished capacity for cell migration. Furthermore, we studied the expression of important proteins associated with Wnt5a signaling pathway, and it was found that Ror2 and E-cadherin were both increased in Huh7 cells with overexpression of Wnt5a, whereas p53 expression was unaffected. CONCLUSION: Overexpression of Wnt5a in Huh7 cells was associated with decrease of cell proliferation and migration. Wnt5a may act as a tumor-suppressor gene in HCC, which works through the non-canonical Wnt signaling pathway by binding to the Ror2 and E-cadherin receptor.

Expression of Wnt-5a and ß-catenin in primary hepatocellular carcinoma.

It has been reported that changes in Wnt5a expression are closely related to hepatocellular carcinoma (HCC) development, while decreased or abnormal ß-catenin expression may promote the invasion and metastasis of tumor cells. In this study, the roles and clinical significance of Wnt-5a and ß-catenin expression were analyzed in primary HCC. Real-time PCR (RT-PCR) analysis of Wnt-5a mRNA expression was performed in 26 fresh HCC samples and the corresponding para-carcinoma tissues. Wnt-5a and ß-catenin protein expression was detected by immunohistochemical staining of paraffin-embedded tissues of 85 cases of HCC and corresponding para-carcinoma tissues and 15 cases of hepatic cirrhosis. Results showed that Wnt-5a mRNA levels were significantly higher in HCC tissue than in the para-carcinoma tissue (0.102 ± 0.159 and 0.020 ± 0.022, respectively; P < 0.05), while Wnt-5a protein was absent or low in HCC. Wnt-5a expression was detected in significantly fewer HCC tissue samples than in the para-carcinoma and hepatic cirrhosis tissue samples (21.2% (18/85), 81.26% (69/85) and 86.7% (13/15), respectively; P < 0.01). Abnormal localization of ß-catenin protein shown by intracytoplasmic or intranuclear staining was observed in 72.94% (62/85) of HCC samples. These observations indicate that the role of Wnt-5a in HCC is mediated at the protein level rather than the transcriptional level. Furthermore, the abnormal localization of ß-catenin observed in HCC tissues may be associated with gene mutation leading to the generation of truncated ß-catenin proteins, which in turn, may represent an initiating or contributing factor in the development of HCC.

MicroRNA in hepatic fibrosis and cirrhosis.

Hepatic fibrosis is caused by an imbalance between production and dissolution of extracellular matrix after chronic and inflmmatory injury, when hepatic stellate cells are stimulated to proliferate and secret extracellular matrix. The most common causes of liver fibrosis are chronic viral hepatitis B and C. Cirrhosis is the most advanced stage of fibrosis, which usually develop into hepatocellular carcinoma (HCC). microRNAs participate the pathogenesis of hepatic fibrosis and cirrhosis or even the onset of HCC. In this review, we will summarize the role of miRNA in the pathogenesis of viral hepatitis fibrosis, non-alcoholic steatohepatitis fibrosis, primary biliary cirrhosis and HCC onset, especially in the regulation of stellate cells.

Ovarian mucinous cystic tumor with sarcoma-like mural nodules and multifocal anaplastic carcinoma: a case report.

A 48-year-old woman presented with left abdominal pain and fullness. Computed tomography scan revealed a multicystic mass with multifocal mural nodules. Histologic examination showed a mucinous cystic tumor with cystadenoma, borderline malignant cystadenoma and cystadenocarcinoma, which were associated with sarcoma-like mural nodules (SLMNs) and multifocal anaplastic carcinoma. Mural nodules showed a positive reaction for CD56 and vimentin, but were negative for cytokeratin 7 and SMA. She underwent postoperative chemotherapy and is currently under follow-up; no recurrence or metastases were found in the first year of follow-up. Ovarian mucinous cystic tumor with SLMNs and foci of anaplastic carcinoma is extremely rare. To our knowledge, this case reports the most complex neoplastic and reactive components. Our findings shed some light on the pathogenesis of this rather rare carcinoma. We think that the formation of SLMNs may be the result of the reactive proliferation of undifferentiated mesenchymal cells, while the anaplastic carcinoma may be derived from mucinous epithelium. Moreover, because of difficulties encountered in their differential diagnosis, we think that the existence of foci of anaplastic carcinoma along with SLMNs necessitates careful histologic and immunohistochemical analysis of mural nodules for the determination of treatment and prognosis.

Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer.

BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, cisplatin and 5-fluorouracil were in general more effective than adriamycin and mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-fluorouracil or adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483.

Differential Expression of Wnt Pathway Genes in Sporadic Hepatocellular Carcinomas Infected With Hepatitis B Virus Identified With OligoGE Arrays.

BACKGROUND: Epidemiological evidence has clearly indicated that chronic infection with the hepatitis B virus (HBV) is the major risk factor for developing hepatocellular carcinoma (HCC). Nonetheless, the mechanisms by which HBV contributes to the pathogenesis of HCC have not been fully elucidated. OBJECTIVES: Our aim was to characterize differential gene expression profiles related to the Wnt signaling pathway between primary tumor and adjacent normal tissues in HCC patients with concomitant HBVinfection . MATERIALS AND METHODS: An oligoGEArray® (an oligonucleotide-based gene expression array platform) containing 126 Wnt signaling pathway-related genes was used to compare gene expressions between primary HCC and adjacent non-tumorous liver tissues from 10 patients with HCC. Selected differential genes were identified with real-time RT-PCR and immunohistochemistry (IHC). In particular, the protein of the differential gene DVL3 (disheveled, dsh homolog 3 [Drosophila]) was chosen to investigate whether it is up regulated in primary tumor correlated with the clinic pathological characteristics of HCC patients. For this purpose we examined 56 HCC tissue samples via IHC for the presence of DVL3 protein. RESULTS: Sixteen genes were identified with significant differential expression between HCC and adjacent non-tumorous liver tissue. These genes have been previously associated with the Frizzled signaling pathway, cell cycle, transcription, or protein degradation. All (100%) of the tumor samples results from 56 HCC patients tested were positive for DVL3 via IHC. Based on the intensity of DVL3 immunoreactivity, 25 (44.6%) and 31 (55.4%) of the patients were classified aslow and high-DVL3, respectively, which correlated with tumor stage (P = 0.029). CONCLUSIONS: This study clarified a number of Wnt pathway-related genes which are dysregulated in HBV-associated HCC. These genes may be contributedto the frequent activation of the Wnt signaling pathway. Our results promote the role of the Wnt signaling pathway in HBV-associated HCC.

Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis.

AIM: To investigate the expression and clinical significance of Wnt member 5a (Wnt5a) and receptor tyrosine kinase-like orphan receptor 2 (Ror2) in hepatocellular carcinoma (HCC). METHODS: In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Ror2, ß-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3'-diaminobenzidine tetrahydrochloride (DAB) before brief counterstaining with Mayer's hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Ror2 was examined by real-time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models. RESULTS: Compared to nontumorous (hepatitis or cirrhotic) tissues, Ror2 mRNA expression was clearly decreased in HCC. Ror2 and Wnt5a protein expressions in the majority of HCC patients (63% and 77%, respectively) was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% (58/85) of the HCC cases, the expression of ß-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression (P = 0.016, P = 0.007, respectively). CONCLUSION: Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.

Association of clinicopathological features with UbcH10 expression in colorectal cancer.

PURPOSE: UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme, and its overexpression has been demonstrated in a variety of malignancies. The aim of this study is to investigate the association of UbcH10 gene expression with the carcinogenesis and tumor progression of colorectal cancer. METHODS: The expression levels of UbcH10 in human malignant colorectal carcinoma tissues and their adjacent normal tissues were examined using real-time quantitative RT-PCR and immunohistochemical analysis. The correlations of UbcH10 expression to the clinicalpathologic characteristics of the colorectal cancer were analyzed. Cell proliferation and Matrigel invasion assays were performed in HT-29 cells transfected with UbcH10 expression plasmid pcDNA3.1-UbcH10, UbcH10 RNA interference vector pUbcH10-RNAi as well as their control vectors. RESULTS: Our study demonstrated that the expression of UbcH10 in colorectal carcinoma tissues was significantly higher than that in non-cancerous tissues (P < 0.01), and the UbcH10 overexpression was related to the degree of tumor differentiation and lymph node metastasis of colorectal cancer patients (P < 0.05). In vitro, the overexpression of UbcH10 promoted cell proliferation and tumor invasiveness, but the downregulation of UbcH10 expression significantly reduced the growth rate and the invasiveness activity of tumor cell line. CONCLUSIONS: Our study suggests that the overexpression of UbcH10 gene plays a critical role in the carcinogenesis and tumor progression of colorectal cancer. It may be a new marker in diagnosis and prognosis of colorectal cancer, and the inhibition of UbcH10 may be a therapeutic potential for the treatment of colorectal cancer.

[Relationship of the expression of cyclin D1 and P21WAF1 with the sensitivity to chemotherapeutic drugs on gastric cancers].

OBJECTIVE: To investigate the relationship between the sensitivity to chemotherapeutic drugs and the expression of cyclin D1 and P21WAF1 in gastric carcinoma. METHODS: The sensitivity of 80 samples of gastric cancer cells to HCPT, CDDP, 5-FU, ADM and MMC was evaluated with MTT assay. The protein expression of cyclin D1 and P21WAF1 was detected by immunohistochemistry. RESULTS: The sensitivity of gastric carcinoma cells to chemotherapeutic drugs was different. Inhibitory rates of tumor cells exposed to 5-FU, MMC and DDP were significantly higher than those exposed to ADM and HCPT (P <0.05). Positive expression rates of cyclin D1 and P21WAF1 in gastric cancer were 70.0% and 47.5% respectively. Cyclin D1 positive cells showed more sensitive to 5-FU and HCPT than cyclin D1 negative cells. P21WAF1 negative cells showed more sensitive to MMC, 5-FU and DDP than P21WAF1 positive cells. CONCLUSION: Expression of cyclin D1 and P21WAF1 is related with drug-resistance of tumor. Examination of cyclinD1 and P21WAF1 would have reference value in selection of chemotherapeutic drugs.