Survivin expression in ovarian cancer

Aim: To examine the expression of survivin in benign ovarian tumors, ovarian carcinomas of different stages. Methods: We screened the expression of survivin mRNA by reverse transcription polymerase chain reaction in 114 ovarian tissue samples. Quantitative real-time PCR was used to estimate survivin mRNA levels in the samples with positive survivin expression. Results: No survivin mRNA was expressed in all normal ovarian specimens, while it appeared in 73% of ovarian carcinomas, 47% of borderline ovarian carcinomas and 19% of benign ovarian tumors. The survivin mRNA expression rate was positively associated with clinical stage (P = 0.026) and differentiation grade (P = 0.049). There was notably statistically significant difference in the survivin mRNA expression rate dependent on different histological types (serous, mucinous, endometrioid, P = 0.008), but not – dependent on lymph node metastasis (P = 0.921) and ascites (P = 0.87). In tissues with positive expression of survivin, we also found that mean survivin mRNA expression levels were higher in ovarian carcinomas than that in benign ovarian tumors and borderline ovarian carcinoma tissues (P < 0.001). Among ovarian carcinomas, the high survivin mRNA expression levels correlated with the clinical stages, differentiation grade, lymph node metastasis, but not — with ascites and histological type. Conclusion: Our study suggest that survivin is associated with progression of ovarian carcinoma.Цель: исследовать экспрессию сурвивина в доброкачественных и злокачественных новообразованиях яичника. Методы: экспрессия мРНК сурвивина исследована методом RT-PCR в 114 образах ткани яичника человека. Для установления уровня экспресии мРНК сурвивина применяли количественный PCR в режиме реального времени. Результаты: экспрессия мРНК сурвивина не выявлена в образцах нормальной ткани яичника, но зарегистрирована в 73% случаев рака яичника, 47% случаев серозных опухолей яичника серозного типа и 19% образцов доброкачественных опухолей. Установлена положительная зависимость между уровнем экспрессии мРНК сурвивина и клинической стадией заболевания (P = 0,026), и степенью дифференцировки опухоли (P = 0,049). Выявлена статистически значимая зависимость уровня экспрессии мРНК сурвивина от гистологического типа опухоли (серозного, мукозного, эндометриоидного, P = 0,008) и отсутствие таковой от наличия метастазов в лимфатических узлах (P = 0.921) или асцита (P = 0.87). Также установлено, что средние уровни экспрессии мРНК сурвивина выше при раке яичника, чем в ткани доброкачественных новобразований или серозных опухолей яичника пограничного типа (P < 0,001). При раке яичника высокий уровень экспрессии мРНК сурвивина коррелировал с клинической стадией заболевания, степенью дифференцировки опухолевых клеток, но не коррелировал с гистологическим типом новообразования. Выводы: результаты свидетельствуют о том, что экспрессия сурвивина ассоциирована с прогрессией рака яичника. Ключевые слова: сурвивин, рак яичника, опухолевая прогрессия

Equilibrium conditions for semi-clathrate hydrates formed with CO2, N2 or CH4 in the presence of tri-n-butylphosphine oxide

We measured the thermodynamic stability conditions for the N, CO, or CH semiclathrate hydrate formed from the aqueous solution of tri-n-butylphosphine oxide (TBPO) at 26 wt %, corresponding to the stoichiometric composition for TBPO·34.5HO. The measurements were performed in the temperature range 283.71-300.34 K and pressure range 0.35-19.43 MPa with the use of an isochoric equilibrium step-heating pressure-search method. The results showed that the presence of TBPO made these semiclathrate hydrates much more stable than the corresponding pure N , CO, and CH hydrates. At a given temperature, the semiclathrate hydrate of 26 wt % TBPO solution + CH was more stable than that of 26 wt % TBPO solution + CO, which in turn was more stable than that of 26 wt % TBPO solution + N. We analyzed the phase equilibrium data using the Clausius-Clapeyron equation and found that, in the pressure range 0-20 MPa, the mean dissociation enthalpies for the semiclathrate hydrate systems of 26 wt % TBPO solution + N, 26 wt % TBPO solution + CO, and 26 wt % TBPO solution + CH were 177.75, 206.23, and 159.00 kJ·mol, respectively

Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity

BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory / fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates acute radiation induced injury by inhibiting activation of TGFβ1 and downregulating the Smad 3 arm of its signal transduction pathway. METHODS: Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFβ1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine lung injury. RESULTS: Irradiated wild-type (XRT-WT) animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14 weeks. Expression of activated TGFβ1 and components of its signal transduction pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs. XRT-WT. CONCLUSION: This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFβ1 activation with a subsequent downregulation of the profibrotic TGFβ pathway

NOA1 Functions in a Temperature-Dependent Manner to Regulate Chlorophyll Biosynthesis and Rubisco Formation in Rice

NITRIC OXIDE-ASSOCIATED1 (NOA1) encodes a circularly permuted GTPase (cGTPase) known to be essential for ribosome assembly in plants. While the reduced chlorophyll and Rubisco phenotypes were formerly noticed in both NOA1-supressed rice and Arabidopsis, a detailed insight is still necessary. In this study, by using RNAi transgenic rice, we further demonstrate that NOA1 functions in a temperature-dependent manner to regulate chlorophyll and Rubisco levels. When plants were grown at 30°C, the chlorophyll and Rubisco levels in OsNOA1-silenced plants were only slightly lower than those in WT. However, at 22°C, the silenced plants accumulated far less chlorophyll and Rubisco than WT. It was further revealed that the regulation of chlorophyll and Rubisco occurs at the anabolic level. Etiolated WT seedlings restored chlorophyll and Rubisco accumulations readily once returned to light, at either 30°C or 15°C. Etiolated OsNOA1-silenced plants accumulated chlorophyll and Rubisco to normal levels only at 30°C, and lost this ability at low temperature. On the other hand, de-etiolated OsNOA1-silenced seedlings maintained similar levels of chlorophyll and Rubisco as WT, even after being shifted to 15°C for various times. Further expression analyses identified several candidate genes, including OsPorA (NADPH: protochlorophyllide oxidoreductase A), OsrbcL (Rubisco large subunit), OsRALyase (Ribosomal RNA apurinic site specific lyase) and OsPuf4 (RNA-binding protein of the Puf family), which may be involved in OsNOA1-regulated chlorophyll biosynthesis and Rubisco formation. Overall, our results suggest OsNOA1 functions in a temperature-dependent manner to regulate chlorophyll biosynthesis, Rubisco formation and plastid development in rice

Cirmtuzumab inhibits ibrutinib-resistant, Wnt5a-induced Rac1 activation and proliferation in mantle cell lymphoma.

Cirmtuzumab may enhance the therapeutic activity of ibrutinib by inhibiting ROR1-dependent signaling pathway in patients with chronic lymphocytic leukemia (CLL). Mantle cell lymphoma (MCL) is B-cell malignancy that also expresses ROR1. In this study, we found that the plasma of patients with MCL had high levels of Wnt5a, a ROR1 ligand, that were comparable to those found in patients with CLL; in contrast Wnt5a was virtually undetectable in the plasma of age-matched healthy adults. We also found that Wnt5a induced Rac1 activation in the primary MCL cells. Cirmtuzumab, but not ibrutinib, could inhibit the capacity of Wnt5a to induce primary MCL cells to activate Rac1. Addition of exogenous Wnt5a in vitro significantly enhanced the numbers of MCL cell divisions and the proportion of dividing MCL cells entering S/G2 in MCL cells over time in the presence of CD154 and IL-4/10. Treatment of the MCL cells with cirmtuzumab, but not ibrutinib, blocked Wnt5a-enhanced proliferation of MCL cells. This study indicates that cirmtuzumab and ibrutinib may have complementary activity in the treatment of patients with MCL