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INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common and fatal tumors in the world, ranking third in cancer-related mortality. Chronic HBV infection is one of the major risk factors for hepatocellular carcinoma in China, Korea, and Sub-Saharan Africa. The HBx protein encoded by the X gene of HBV is a broadly regulated protein involved in transcriptional activation, epigenetics, apoptosis, DNA repair, and other regulatory processes. This study aimed to investigate the mechanism of HBx regulation of miR-155 and PTEN (Phosphatase and tensin homolog deleted on chromosome ten) in HBV-HCC. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatocellular carcinoma and normal subjects. The analysis was divided into different subgroups according to HBV positivity or negativity. At the cellular level, the biological roles of HBX, microRNA-155 and PTEN on hepatocellular carcinoma cells and their regulatory relationships with each other were verified. RESULTS: MicroRNA-155 and PTEN expression in HBV-positive HCC liver cancer tissues were negatively correlated, and HBX and miR-155 expression were positively correlated; microRNA-155 could target and inhibit PTEN expression, thereby promoting hepatocellular carcinoma cell activity, inhibiting apoptosis, and promoting invasion and migration; HBX could upregulate microRNA-155 thereby inhibit PTEN to promote malignant transformation of hepatocellular carcinoma. CONCLUSIONS: HBX could promote malignant transformation of hepatocellular carcinoma cells by upregulating microRNA-155 expression and thereby inhibiting the PTEN/PI3K-AKT pathway. Blocking miR-155 expression could attenuate the proliferation-promoting and invasive effects of HBX.

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BACKGROUND: Pathological examination of liver biopsies remains the gold standard for evaluating the stage of hepatic fibrosis, which are a number of disadvantages associated with biopsy. The aim of the present study was to investigate the potential of exosomal microRNA (miR)-155 as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatic fibrosis and a hepatic fibrosis rat model. A total of 94 patients were divided into three groups based on Child-Pugh rating. Additionally, 30 patients with primary liver fibrosis who underwent liver transplantation were divided into the low miR-155 expression group and the high expression group; 56 rats were divided into 7 groups (n=8, 0, 2, 4, 6, 8, 10, and 12 weeks). Rats in every group were intravenously injected with CCl4 (3% vol/vol in olive oil; 0.3 mL/100 g body weight) twice weekly to produce different degrees of liver necrosis and liver fibrosis. RESULTS: Exosomal miR-155 was found to be closely associated with the progression of cirrhosis and clinical prognostic indicators of cirrhosis. Exosomal miR-155 gradually increased with the severity of hepatic necrosis and fibrosis. CONCLUSIONS: The findings of the present study indicate that exosomal miR-155 can act as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis.

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BACKGROUND: Ipsilateral supraclavicular lymph node metastasis (ISLM) with breast cancer patients has always been a hard problem for breast surgery. It is generally believed that radiotherapy can benefit the survival of patients, but whether local surgical resection is needed or not is controversial. The study aims to compare the efficacy between supraclavicular lymph node (SLN) dissection combined with radiotherapy and radiotherapy alone in the treatment of breast cancer with ISLM. METHODS: A retrospective analysis was performed using 122 cases of breast cancer with ISLM but without distant metastasis. Among them, 14 cases were eliminated due to insufficient data. The 108 remaining cases were divided into 2 groups based on different treatment proposals for metastatic SLNs. The groups were dissection plus radiotherapy (surgery group), and simple radiotherapy (radiotherapy group). RESULTS: For the 108 patients, the overall 5-year disease-free survival (DFS) and overall survival (OS) rates were 30.6% and 67.8%, respectively. In the surgery group, distant metastases occurred in 41 patients, and the 5-year DFS was 34.3%; in the radiotherapy group, 18 patients had distant metastases, and the 5-year DFS was 26.1%; the difference was not statistically significant (P>0.05). In the surgery group, 11 patients died, and the 5-year OS rate was 67.9%; in the radiotherapy group, 6 patients died, and the 5-year OS rate was 67.5%; the difference was not statistically significant (P>0.05). CONCLUSIONS: The dissection of SLN combined with radiotherapy and radiotherapy alone had similar effects on the survival rates in breast cancer patients with ISLM. The local control in the surgery group was better than that in the radiotherapy group. The status of estrogen receptors (ER) and the number of axillary lymph node metastases were independent influencing factors of DFS. The ER status is an independent factor affecting the OS rate of patients.

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Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

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BACKGROUND: Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis. Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy. Although acquired resistance to endocrine treatment has been extensively studied, the underlying mechanisms are unclear. We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy. Therefore, we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells. METHODS: Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively. Stem-cell markers (SOX-2, OCT-4, and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR. Morphological observation was performed to characterize EMT. RESULTS: After induction of TAM resistance, TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P < 0.05), indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells. TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P < 0.01), demonstrating the elevated CSC properties of TAM-R MCF7 cells. Consistently, qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2, OCT-4, and CD133, compared to those of WT MCF7 cells (P < 0.05). Morphologically, TAM-R MCF7 cells showed a fibroblastic phenotype, but WT MCF7 cells were epithelial-like. After induction of TAM resistance, qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail, vimentin, and N-cadherin and decreased levels of E-cadherin, which are considered as EMT characteristics (P < 0.05). CONCLUSION: TAM-R MCF7 cells possess CSC characteristics and may be responsible for TAM resistance during breast cancer therapy.

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OBJECTIVE: To analyze breast cancer bone metastasis related gene-CXCR4. METHODS: This research screened breast cancer bone metastasis related genes by high-flux gene chip. RESULTS: It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. CONCLUSIONS: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.

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OBJECTIVE: To explore the effects and underlying mechanisms of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435. METHODS: The invasiveness of MDA-MB-435 was determined by Matrigel-coated transwell chambers. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to analyze the cellular expression of matrix metalloproteinase-9/matrix metalloproteinase-2/E-cadherin (MMP-9/MMP-2/E-cadherin) gene/protein. RESULTS: The invasive breast cancer cell numbers of each group (Glu 5.5, 11 and 25 mmol/L) were 50 ± 5, 65 ± 6 and 77 ± 3 respectively. Cellular invasion was dramatically enhanced in the Glu 11 and 25 mmol/L group compared with the 5.5 mmol/L group. The MMP-9/MMP-2 protein expression increased significantly in the Glu 11 and 25 mmol/L groups compared with 5.5 mmol/L group while high glucose (Glu 11 and 25 mmol/L group) down-regulated significantly the E-cadherin mRNA/protein expression. CONCLUSION: High glucose can promote the in vitro invasiveness of human breast cancer cells through the altered expression of MMP-9/MMP-2/E-cadherin.

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OBJECTIVE: To investigate the approaches to improve therapeutic effect of stomach cancer by analysis of the long-term results of surgical treatment of this disease. METHODS: Prognostic factors of stomach cancer were analyzed by Cox multivariate regression model based on clinical data of 2561 stomach cancer cases who underwent surgical treatment from 1964 to 2004 at Sun Yat-sen University Cancer Center. Survival rates were calculated by life table method. RESULTS: Gastrectomy was performed for 1950 cases with resectability of 76.1%, among which there were 1192 cases of curative resection (46.5%) and 758 cases of non-curative resection (29.6%). The other 611 cases of palliative operation included bypass procedures and laparotomy. Operative mortality of all cases was 0.8% and morbidity was 5.1%. For all cases the 1-, 3- and 5-year survival rate was 52.4%, 38.6% and 35.5%, respectively. The stage-specific 5-year survival rate was 86.8% (Stage I), 58.7% (Stage II), 28.4% (Stage III) and 7.6% (Stage IV), respectively. The 5-year survival after curative resection in the period of 40 years was 45.5%, and increased to 52.7% in the last two decades and 61.8% in recent decade. Stage-specific case proportion during the earlier two decades was 1.4% (Stage I), 10.6% (Stage II), 23.1% (Stage III) and 64.9% (Stage IV), respectively, and that during the recent two decades was 9.3%, 18.5%, 35.3% and 36.8%, respectively. The 5-year survival rate of cases during the earlier two decades was 18.0% and increased to 37.5% during the recent two decades. Multivariate analysis indicated that main prognostic factors of stomach cancer included TNM staging, curative resection and multidisciplinary treatment. CONCLUSIONS: Early detection and curative resection were the most important measures to improve therapeutic effect of stomach cancer. A surgery-predominant multidisciplinary treatment individualizing biological characteristics of tumor, staging of disease and tumor site will contribute to improvement of therapeutic effect of stomach cancer.

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