Increased expression of MAP2 inhibits melanoma cell proliferation,invasion and tumor growth in vitro and in vivo

Please cite this paper as: Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo. Experimental Dermatology 2010; 19 : 958–964. Abstract: Malignant melanoma (MM) is characterized by aggressive metastasis and high mortality rate. Microtubule‐associated proteins 2 (MAP2) is expressed abundantly in majority of melanocytic nevi and primary melanomas, but absent in metastatic melanomas. To determine whether MAP2 correlates with tumor progression of MM, we investigated the effects of MAP2 inhibition on the biological behaviour of metastatic melanoma in vitro and in vivo. Our results demonstrated that adenovirus‐mediated MAP2 induced apoptotic cell death and cell cycle arrest in metastatic human and mouse melanoma cell lines in vitro, and substantially inhibited the growth of melanomas in nude mice in vivo. In addition, intracellular expression of MAP2 was found to induce the morphologic alteration, suppress the migration and invasion and affect the assembly, stabilization and bundling of microtubules in melanoma cells. This is the first study that MAP2 expression significantly inhibits the growth of MM in vivo. Our results suggest that MAP2 may serve as a promising molecular target for therapy and chemoprevention of MM in humans.     

Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma

Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti‐tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage‐independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia?

Immunosuppressive therapy (IST) has provided an alternative treatment option for cure of aplastic anemia patients who cannot receive bone marrow transplantation. Although there have been many recent studies on the efficacy of antithymoglobulin (ATG) combined with cyclosporine A (CsA), there is no data on the correlation between the variability of CsA levels and the response to IST. Therefore, we retrospectively assessed the factors associated with IST efficacy in patients with acquired severe aplastic anemia (SAA). Sixty‐six patients were treated with ATG combined with CsA for 6 months. In the response group, the CsA levels were increased rapidly to more than 200 ng/mL within the first 2 wk after starting the IST. However, the non‐response group had a pattern of slower increase of the CsA levels. The CsA levels, during the first and second week of treatment with IST, were significantly different in the responders and non‐responders. The factors predictive of response to IST and survival were analyzed. The univariate analysis showed that a younger age at the initiation of IST, a high absolute neutrophil count prior to starting IST, a short interval between the diagnosis and initiation of IST, and high CsA levels during the first and second week of IST treatment were positively associated with the response rate and overall survival. The multivariate analysis showed that these four factors were independent factors associated with a longer patient survival. A high response rate was associated with a short interval between diagnosis and initiation of IST as well as high CsA levels during the first and second week of IST. Therefore, early intensification of CsA levels might improve patient outcome.     

Active immunization against de novo hepatitis B virus infection in pediatric patients after liver transplantation

The shortage of donor organs occasionally mandates the use of hepatic allografts from anti-HBc (+) donors. HBIG and/or lamivudine are recommended for the prevention of de novo HBV infection in naive patients, but there are attendant problems, such as mutant strain emergence and high cost. Active immunization presents a better alternative than the use of HBIG or lamivudine, if it can be proven to be effective. Accordingly, we investigated the outcome of HBV vaccination in pediatric hepatic transplant recipients. Between July 1999 and October 2001, 19 pediatric recipients were administered HBV vaccinations after liver transplantation at Seoul National University Hospital. Nine patients received a graft from anti-HBc (+) donors and 10 from anti-HBc (-) donors. When steroid was withdrawn, recombinant HBV vaccine was administered. The median follow-up period after vaccination was 10.0 +/- 5.2 months. Seventeen of the 19 patients showed a positive response to vaccination. In 9 patients who received grafts from anti-HBc (+) donors, 2 patients showed no response, 4 patients low response (peak HBsAb titer <1,000 IU/L), and 3 patients high response (peak HBsAb titer >/=1,000 IU/L). De novo HBV infection developed in 1 of 2 patients who showed no response to vaccination. In 10 patients who received grafts from anti-HBc (-) donors, 5 showed a low response and 5 a high response. In conclusion, HBV vaccination in pediatric patients after liver transplantation appeared to exhibit some effectiveness at protecting young children that received a graft from anti-HBc (+) donors from de novo HBV infection.     

NIDDM患者单个核细胞胰岛素受体放射分析及其临床意义

采用乳过氧化物酶法制备A_(14)-~(125)I胰岛素,泛影葡胺-聚蔗糖分层液密度梯度离心法分离外周血单个核细胞,优选受体结合试验条件,建立了单个核细胞胰岛素受体放射分析法。测定了54例NIDDM患者、29例单纯肥胖症患者和27例正常人的单个核细胞胰岛素受体结合率(MIB)。结果表明NIDDM组的MIB显著低于正常组,空腹血浆胰岛素(FPI)高于正常组;NIDDM肥胖型组中MIB与FPI呈负相关。证实胰岛素受体缺陷是NIDDM产生胰岛素抵抗性的重要原因之一。     

保元汤加减对实验大鼠肺孢子虫作用的电镜观察

目的　探索中医药治疗卡氏肺孢子虫肺炎的途径。　方法　应用中药保元汤加减煎剂给实验大鼠灌胃 ,通过透射电镜观察其对实验大鼠肺内肺孢子虫的作用。　结果　实验组较对照组大鼠肺内肺孢子虫有明显改变。其中肺孢子虫胞浆内大量空泡形成 ;包囊壁明显破坏 ;虫体有溶解现象。　结论　保元汤加减煎剂 ,对实验大鼠体内的卡氏肺孢子虫具有抑制和杀灭作用。     

Prediction of therapeutic failure after adrenaline injection plus heater probe treatment in patients with bleeding peptic ulcer

BACKGROUND: Continued or recurrent bleeding after endoscopic treatment for bleeding ulcer is a major adverse prognostic factor. Identification of such ulcers may allow for alternate treatments. AIM: To determine factors predicting treatment failure with combined adrenaline injection and heater probe thermocoagulation. Methods: Consecutive patients with bleeding peptic ulcers who received endoscopic therapy between January 1995 and March 1998 were studied. Data on clinical presentation, endoscopic findings, and treatment outcomes were collected prospectively. Multiple logistic regression analysis was used to identify independent risk factors for treatment failure. RESULTS: During the study period, 3386 patients were admitted with bleeding peptic ulcers: 1144 (796 men, 348 women) with a mean age of 62.5 (SD 17.6) years required endoscopic treatment. There were 666 duodenal ulcers (58.2%), 425 gastric ulcers (37.2%), and 53 anastomotic ulcers (4.6%). Initial haemostasis was successful in 1128 patients (98.6%). Among them, 94 (8.2%) rebled in a median time of 48 hours (range 3-480). Overall failure rate was 9.6%. Mortality rate was 5% (57/1144). Multiple logistic regression analysis revealed that hypotension (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.40-3.48), haemoglobin level less that 10 g/dl (OR 1.87, 95% CI 1.18-2.96), fresh blood in the stomach (OR 2.15, 95% CI 1.40-3.31), ulcer with active bleeding (OR 1.65, 95% CI 1.07-2.56), and large ulcers (OR 1.80, 95% CI 1.15-2.83) were independent factors predicting rebleeding. CONCLUSIONS: Larger ulcers with severe bleeding at presentation predict failure of endoscopic therapy.