Previous studies have demonstrated that the persistent exposure of human bronchial epithelial cells to nicotine (Nic) through nicotinic acetylcholine receptors increases cyclin D1 promoter activity and protein expression. The main purpose of this study is to elucidate the carcinogenic role of cyclin D3, which is involved in breast tumorigenesis when induced by Nic. Real-time PCR analysis revealed that cyclin D3 is highly expressed at the mRNA level in surgically dissected breast tumor tissue, compared to the surrounding normal tissue (tumor/normal fold ratio = 17.93, n = 74). To test whether Nic/nicotinic acetylcholine receptor (nAChR) binding could affect cyclin D3 expression in human breast cancer cells, the transformed cell line MCF-10A-Nic (DOX) was generated from normal breast epithelial cells (MCF-10A) with inducible α9-nAChR gene expression, using the adenovirus tetracycline-regulated Tet-off system. Tet-regulated overexpression of α9-nAChR in MCF-10A-Nic (DOX) xenografted BALB/c-nu/nu mice resulted in a significant induction of cyclin D3. In contrast, cyclin D3 expression was down-regulated in α9-nAChR knock-down (siRNA) MDA-MB-231-xenografted tumors in NOD.CB17-PRKDC(SCID)/J(NOD-SCID) mice. Furthermore, we found that Nic-induced human breast cancer (MDA-MB-231) cell proliferation was inhibited by 1 μM of garcinol (Gar), isolated from the edible fruit Garcinia indica, through down-regulation of α9-nAChR and cyclin D3 expression. These results suggest that α9-nAChR-mediated cyclin D3 overexpression is important for nicotine-induced transformation of normal human breast epithelial cells. The homeostatic regulation of cyclin D3 has the potential to be a molecular target for antitumor chemotherapeutic or chemopreventive purposes in clinical breast cancer patients.

Phloretin (Ph), which can be obtained from apples, apple juice, and cider, is a known inhibitor of the type II glucose transporter (GLUT2). In this study, real-time PCR analysis of laser-capture microdissected (LCM) human hepatoma cells showed elevated expression (>5-fold) of GLUT2 mRNA in comparison with nonmalignant hepatocytes. In vitro and in vivo studies were performed to assess Ph antitumor activity when combined with paclitaxel (PTX) for treatment of human liver cancer cells. Inhibition of GLUT2 by Ph potentiated the anticancer effects of PTX, resensitizing human liver cancer cells to drugs. These results demonstrate that 50-150 microM Ph significantly potentiates DNA laddering induced in Hep G2 cells by 10 nM PTX. Activity assays showed that caspases 3, 8, and 9 are involved in this apoptosis. The antitumor therapeutic efficacy of Ph (10 mg/kg body weight) was determined in cells of the SCID mouse model that were treated in parallel with PTX (1 mg/kg body weight). The Hep G2-xenografted tumor volume was reduced more than fivefold in the Ph + PTX-treated mice compared to the PTX-treated group. These results suggest that Ph may be useful for cancer chemotherapy and chemoprevention.

GRP78 is a positive modifier for sorafenib resistance acquisition in HCC and represents a prime target for overcoming sorafenib resistance.

Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.

The benefits of laparoscopic appendectomy appear to be controversial. Since 1994, several abdominal procedures have been completed by using the needlescopic technique, but there appear to be no prospective studies to demonstrate the perceived benefits of needlescopic appendectomy. The authors compared open, laparoscopic, and needlescopic appendectomy in a randomized fashion with regard to duration of surgery, length of hospitalization, analgesic dosage, and surgery-associated complications. From March to July 1998, 75 patients admitted at the emergency station of the authors' hospital with a final diagnosis of acute appendicitis without tumor formation were randomized to receive one of the three treatment categories: open (OA), laparoscopic (LA), and needlescopic (nLA) appendectomy. Laparoscopic and needlescopic appendectomy were performed by using a three-port technique, although the size of the trocar used varied. There were 26 patients in the OA group, 23 in the LA group, and 26 in the nLA group. The mean operation durations for the OA, LA, and nLA groups were 55.4 +/- 28.0 minutes, 69.1 +/- 48.8 minutes, and 62.3 +/- 26.3 minutes, respectively, and these were not significantly different from one another. The mean number of the analgesic doses (Pethidine 1 mg/kg) required was 1.3 +/- 1.2 mg/kg, 0.5 +/- 0.8 mg/kg, and 0.2 +/- 0.6 mg/kg, respectively. Significant differences were noted when comparing the OA with the LA or nLA groups (OA vs. LA, P = 0.02; OA vs. nLA, P = 0.0002; LA vs. nLA, P = 0.06). The mean oral intake durations were 32.2 +/- 16.9 hours, 21.0 +/- 14.6 hours, and 20.8 +/- 16.4 hours, respectively, after surgery for the OA, LA, and nLA groups, and the between-group differences were statistically significant for the OA versus LA group ( P = 0.004) and for the OA versus nLA group ( P = 0.003). The mean durations of hospitalization for the OA, LA, and nLA groups were 3.6 +/-1.8 days, 2.8 +/- 1.4 days, and 2.4 +/- 0.9 days, and difference was detected between the OA and the nLA groups ( P = 0.02). The OA group rendered a greater wound-complication rate and ileus than did the other two groups, but the differences were not detected between the three categories ( P = 0.065, 0.6935). The result of the current study confirmed that the nLA procedure is a feasible and safe one. The nLA procedure provided substantial advantages over the OA procedure in the contexts of diminished postoperative pain and shorter hospital stay without significant increases in postoperative complication rate or surgical time.

Divalent lead (Pb(2+) ) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb(2+) was found to promote tumorigenesis, which may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb(2+) exposure, we investigated the ability of Pb(2+) to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 μM, Pb(2+) induced IL-8 gene activation in gastric carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription factor activator protein 1 (AP-1) was identified as a necessary component of Pb(2+) -induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein expression was induced in cells treated with Pb(2+) , and overexpression of c-Jun enhanced Pb(2+) -induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb(2+) -induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb(2+) -related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 315-322, 2015.

Members of the miR-200 family (miR-200a and miR-200b) play important roles in HCC migration by regulating E-cadherin expression.

Metastasis is the most life-threatening complication in all cancers. The chemokine receptor 4 (CXCR4) is expressed at high levels in many breast-cancer tumors and may modulate metastasis. We compared the time-to-metastasis and the sites of metastasis between breast-cancer tumors expressing CXCR4 at high or low levels. We enrolled 191 early breast cancer patients in our study. The expression of CXCR4 was evaluated using immunohistochemical staining, and the patients were divided into low-level (CXCR4-) and high-level (CXCR4+) CXCR4 expression groups. Associations between the patients' level of CXCR4 expression and their basic clinical characteristics, time-to-metastasis, and metastatic sites were examined using a Cox proportional-hazards regression model. A total of 107 CXCR4+ patients (56 %) were identified. No statistical differences were evident in basic characteristics between the CXCR4+ and CXCR4- groups. The CXCR4+ group had a higher incidence of distant metastasis during the first year (10.3 % versus 1.1 %, P = 0.009) and shorter event-free survival (17.43 months versus 27.5 months, P = 0.026) than those of the CXCR4- group. The CXCR4+ group also had a higher incidence of bone metastasis (P = 0.008) than the CXCR4- group. No significant difference in metastasis sites in other organs was observed between the two groups. A high level of CXCR4 expression in breast cancer is associated with early distant and bone metastases. The CXCR4+ phenotype may be a useful predictor for the prevention of early treatment failure and bone metastasis in breast cancer patients. This retrospective study shows that a high expression of CXCR4 in breast cancer is associated with earlier distant metastasis and bone metastasis in breast cancer.