The mechanism by which Ginkgo biloba extract induces the apoptosis of human laryngeal cancer Hep-2 cells by reducing reactive oxygen species level and activating JNK signaling pathway / 中国基层医药

Objective:To investigate the apoptosis-inducing effect of Ginkgo biloba extract (Ginaton) on human laryngeal cancer Hep-2 cells and the underlying molecular mechanism.Methods:Human laryngeal cancer Hep-2 cells were cultured in vitro and human laryngeal cancer Hep-2 cells in the log phase were treated with Ginaton in time and concentration gradients. The cell counting kit-8 (CCK-8) assay was performed to investigate the inhibitory effects of Ginaton on Hep-2 cells. Flow cytometry was performed to detect apoptosis and determine the level of reactive oxygen species (ROS). Western blot assay was performed to detect apoptosis and signaling pathway-related protein expression. Results:Ginaton inhibited the proliferation of Hep-2 cells in a time-dependent and concentration-dependent manner. Malondialdehyde level decreased gradually in a time-dependent manner, and decreased to 2.98 μmol/g after 24 hours of Ginaton treatment. Superoxide dismutase level increased gradually in a time-dependent manner and increased to 90.35 U/g after 24 hours of Ginaton treatment. ROS level decreased gradually in a time-dependent manner and deceased to 18.7% of the level before treatment after 24 hours of Ginaton treatment. There was no significant difference in ROS level between before and after 24 hours of Ginaton treatment ( F = 14.98, 19.65, 11.47, all P < 0.001). After 3, 6, 12 and 24 hours of Ginaton treatment, the expression of phosphorylated N-terminal protein kinase increased to 1.98, 2.57, 2.91 and 3.28 in a time-dependent manner. There was significant difference in the expression of phosphorylated N-terminal protein kinase between before treatment and after 3, 6, 12 and 24 hours of Ginaton treatment ( F = 16.37, P < 0.001). Conclusion:Ginaton can effectively inhibit the proliferation and induce apoptosis of human laryngeal cancer Hep-2 cells in vitro, which may be related to regulating ROS level and activating JNK signaling pathway.

A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

The role of Survivin as a biomarker and potential prognostic factor for breast cancer

SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

RESUMO O câncer de mama (CM) é um dos principais problemas de saúde em todo o mundo. Como o câncer mais comum em mulheres no mundo e no Brasil, precedido apenas pelo câncer de pele não melanoma, essa neoplasia corresponde a aproximadamente 28% dos novos casos por ano no país. O CM também afeta homens, embora a incidência corresponda a apenas 1% do total de casos. Atualmente, a maioria dos agentes quimioterápicos utilizados no tratamento do CM são extremamente tóxicos e causam efeitos colaterais a longo prazo. Há também a necessidade de se obterem diagnósticos mais precoces, prognósticos mais precisos e disponibilizar novas terapias seletivas e efetivas, a fim de melhorar o cenário atual. Portanto, este trabalho buscou avaliar a importância do biomarcador Survivina (Sur) em relação ao CM, por meio do detalhamento do papel do Sur como biomarcador, da correlação entre essa proteína com o prognóstico de pacientes com CM e de um resumo do tratamento terapêutico e das estratégias que visam utilizar a Sur para o desenvolvimento de novas terapias anticâncer.

Effect of electroacupuncture on c-IAP1 mRNA and c-lAP2 mRNA in synovial tissues of rats with adjuvant arthritis / 针灸推拿医学（英文版）

Objective:To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points on adjuvant arthritis rats,and explore the mechanism of EA treatment of rheumatoid arthritis (RA).Methods:Sixty male rats were randomly divided into a normal group,a model group,a methotrexate group and an EA group,with 15 rats in each group.Rats in the normal group and the model group were routinely raised and did not receive treatment;rats in the methotrexate group received methotrexate at a dose of 0.35 mg/(kg·bw),twice a week for 3 weeks;rats in the EA group received acupuncture at Zusanli (ST 36),Guanyuan (CV 4) and Ashi points,and the bilateral Zusanli (ST 36) and Ashi points were connected to EA apparatus,once a day for 3 weeks.The general status,the swelling degree of the toe,the arthritis index (AI) score,the pathological morphology of the ankle joint,and the mRNA expressions of cellular inhibitor of apoptosis protein (c-IAP) 1 and c-IAP2 in joint synovial tissue cells of the rats in each group were observed.Results:The swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the model group were significantly higher than those in the normal group (all P＜0.05).Compared with the model group,the swelling degree of the toe,AI score and mRNA expressions of c-IAP1 and c-IAP2 in the methotrexate group and the EA group improved (P＜0.01 or P＜0.05);the expressions of c-IAP1 mRNA and c-IAP2 mRNA in rat synovial tissues in the EA group were significantly higher than those in the methotrexate group (P＜0.01).Conclusion:EA alleviates joint swelling in rats with adjuvant arthritis.The mechanism may be related to suppressing mRNA expressions of c-IAP1 and c-IAP2,thus to induce apoptosis of synoviocytes.

New strategy for antagonizing drug resistance: targeting survivin / 中国药理学通报

Multidrug resistance ( MDR) often leads to failure of cancer chemotherapy. survivin, a member of the inhibitor of apoptosis proteins (IAP) family, is overexpressed in almost all kinds of tumor cells. Importantly, survivin has been identified as one of the most important molecules involved in the regulation of MDR. Therefore, inhibiting the activity of survivin or down-reg-ulating the expression of survivin might be an effective strategy to overcome tumor MDR. In this article, the roles of survivin in-volved in the development of drug resistance and the strategies to overcome drug resistance by targeting survivin are thus re-viewed.

Evaluation of survivin immunoexpression in the differentiation of high- and low-grade breast ductal carcinoma in situ / Expressão da proteína survivina em carcinoma ductal in situ de mama de alto e de baixo grau

ABSTRACT Objective To evaluate the expression of survivin protein in low- and high-grade ductal carcinoma in situ. Methods Breast tissue fragments obtained by incisional biopsy and surgical procedures of 37 women with ductal carcinoma in situ of the breast were subdivided into two groups: Group A, composed of women with low-grade ductal carcinoma in situ, and Group B, women with high-grade ductal carcinoma in situ. Survivin protein expression test was performed by immunohistochemistry, using a monoclonal antibody clone I2C4. The criterion to evaluate survivin immunoexpression was based on the percentage of neoplastic cells that presented brown-gold staining. This criterion was positive when the percentage of stained cells was ≥10%. Results The survivin protein was expressed in 22 out of 24 cases of high-grade ductal carcinoma in situ (78%), whereas, in Group A, of low-grade ductal carcinoma in situ (n=13), it was positive in only 6 cases (21.40%; p=0.004). Conclusion The frequency of expression of survivin was significantly higher in the group of patients with high-grade ductal carcinoma in situ compared to those in the low-grade ductal carcinoma in situ group.

RESUMO Objetivo Avaliar a imunoexpressão da proteína survivina nos carcinomas ductais in situ de mama de baixo e de alto graus. Métodos Fragmentos de tecido mamários obtidos por biópsia incisional e procedimentos cirúrgicos de 37 mulheres acometidas por carcinoma ductal in situ de mama foram subdivididos em dois grupos: Grupo A, formado por mulheres com carcinoma ductal in situ de baixo grau; e Grupo B, por mulheres com carcinoma ductal in situ de alto grau. A pesquisa de expressão da proteína survivina foi realizada pela técnica de imuno-histoquímica, utilizando-se anticorpo monoclonal clone I2C4. O critério de avaliação da imunoexpressão da survivina baseou-se na percentagem de células neoplásicas que apresentava coloração castanho-dourada. Considerouse tal critério positivo quando a percentagem de células apresentasse marcação ≥10%. Resultados A proteína survivina apresentou-se expressa em 22 dos 24 casos de carcinoma ductal in situ de alto grau (78%), enquanto no Grupo A, de carcinoma ductal in situ de baixo grau (n=13), apresentou-se positiva em apenas 6 casos (21,40%; p=0,004). Conclusão O índice de frequência de expressão da survivina foi significativamente mais elevado no grupo de pacientes com carcinoma ductal in situ de alto grau, quando comparado às do grupo com carcinoma ductal in situ de baixo grau.

Expression significance of cellular inhibitor of apoptosis proteins 2 in patients with hepatitis B related HCC / 重庆医学

Objective To investigate the significance of cellular inhibitor of apoptosis proteins 2 (cIAP2) expression in the patients with hepatitis B and non-hepatitis B related hepatocellular carcinoma (HCC).Methods The medical record data and tissue samples in the patients with HCC resection operation were collected.Expression of cIAP2 in HCC cancer lesion,adjacent tissues and cancer-distant tissues was detected by immunohistochemical staining and Western blotting.Results In the cancer lesion,paracancerous tissues and cancer-distant tissues of the two groups,the cIAP2 expression amount was decreased in turn.But in the non-hepatitis B related HCC group,the cIAP2 expression in the cancer-distant tissues was significantly lower than that in the HCC cancer lesion and paracancerous tissues,while in the hepatitis B related HCC group,the cIAP2 expression amounts had no significant difference between the caner-distant tissues and paracancerous tissues,while lower than that in the cancer lesion.Conclusion cIAP2 is one of important mechanisms causing hepatic B related HCC and can serve as a therapeutic target point for inhibiting HCC development and eliminating hepatitis B virus.

Evaluation of the Expression of the Inhibitor of Apoptosis Protein Family and Human Telomerase Reverse Transcriptase in Patients With Advanced Colorectal Adenoma

BACKGROUND: It has been reported that the expression of the inhibitor of apoptosis protein (IAP) family increases in patients with colon cancer. We evaluated the expression of the IAP family and human telomerase reverse transcriptase (hTERT) in normal colon mucosa from patients with advanced colorectal adenoma and investigated their features according to characteristics of advanced colorectal adenoma. METHODS: While resections of polyps were performed in patients (n = 80) diagnosed with advanced colorectal adenoma or carcinoma in situ, additional normal tissues were obtained from the sigmoid colon. In healthy patients (n = 16), blind biopsies were performed on the sigmoid colon. The expression of the IAP family, including survivin, XIAP, cIAP1, and cIAP2, and hTERT, were analyzed by real-time PCR in both groups. RESULTS: A total of 80 advanced colorectal adenoma patients (71.3% male, mean age of 60.4 years) and 16 control patients were enrolled in this study. The mean ranking of cIAP2 was higher in the control group (68.88 vs. 44.43, P = 0.001). The expression levels of hTERT, survivin, XIAP, and cIAP from both groups showed no differences. The expression of survivin, XIAP, cIAP1, cIAP2, and hTERT depending on certain factors of advanced adenoma, including the number (two or fewer vs. three or more), size (smaller than 1 cm vs. larger than 1 cm), grade of dysplasia (low grade adenoma vs. high grade adenoma), pathology (tubular adenoma vs. villous adenoma), and presence of endometrial intraepithelial neoplasms, showed no significant correlations in the Mann-Whitney U-test. CONCLUSIONS: The expression of the IAP family and hTERT, except cIAP2, in the normal mucosa of patients with advanced colorectal adenoma were not different from those of the control group. There were no differences in the IAP family and hTERT according to the characteristics of advanced adenoma.

The expression of cIAP and Caspase-7 in endometrial adenocarcinoma and its relationship with the prognosis / 重庆医学

Objective To study the expression of cIAP and Caspase‐7 in endometrial adenocarcinoma tissue and its relation with prognosis .Methods Fifty‐five cases tissues of endometrial adenocarcinoma patients were detected by immunohistochemistry assay from the First Affiliated Hospital of Henan University of Science and Technology from 2009 to 2010 .Histological classifica‐tion ,pathological stage ,lymph node metastasis ,age and other parameters were collected ,the survival and overall survival of the tumor were followed up ,immunohistochemistry was used to observe the expression of cIAP and Caspase‐7 in paraffin sections of pathological specimens ,and the relationship between them and the parameters were analyzed .Results The expression level of cIAP and Caspase‐7 was related to the histological classification ,pathological stage and lymph node metastasis of endometrial carcinoma (P0 .05) .There was significant difference between the positive expression and the negative expression of cIAP and Caspase‐7(P<0 .05) .Conclusion The expression level of cIAP and Caspase‐7 in patients with endometrial carcinoma is correlated with tumor grade and overall survival ,or can be used as a prognostic indicator for endometrial cancer .

Effect of Vav3 gene inhibition on inhibitor of apoptosis proteins and multidrug resistance in gastric cancer cells / 第二军医大学学报

Objective To explore the role of Vav3 gene in multidrug resistance (MDR) of gastric cancer and the related mechanism. Methods QRT-PCR was used to examine the expressions of Vav3 gene in gastric cancer tissues, tumor-adjacent tissues, human gastric cancer cell line SGC7901, and gastric epithelial cell line GES-1. Then Vav3-siRNA was synthesized and tansfected into SGC7901 cells. MTT assay was then used to determine the inhibition rates of tumor cells exposed to chemotherapeutic agents (5-FU, L-OHP) before and after Vav 3-siRNA transfection. Realtime RT-PCR and Western blotting analysis were used to observe the expressions of inhibitor of apoptosis proteins (IAPs) : xIAP, Survivin, and Livin; meanwhile, the expression and activity of Caspase-3 and Caspase-8 were also determined. Results Vav3 was over-expressed in gastric cancer tissues and gastric cell line compared with those in tumo-adjacent tissues and gastric epithelial cell line GES-1 (P<0.05). Expression of Vav3 was significantly inhibited by Vav3-siRNA (P<0.01). Inhibition rates of tumor cells exposed to 5-FU and L-OHP were significantly increased 48 h after Vav3-siRNA tansfection (P<0.05). The expressions of xIAP and Survivin were significantly decreased in cancer cells after Vav3-siRNA tansfection (both P<0.05), and no notable change was found for Livin expression; also the expression and activity of Caspase-3 and Caspase-8 protein were significantly increased after Vav3-siRNA tansfection in SGC7901 cells (all P<0.05). Conclusion Vav3 can participate in MDR of gastric cancer by regulating apoptotic pathways, and inhibition of Vav3 can help reverse MDR of gastric cancer cells by regulating some IAPs.

Study on Proliferation of Pancreatic Cancer SW1990 Cell Lines by Small Interfering RNA Targeted Apollon / 现代检验医学杂志

Objective To study the effect of small interfering RNA targeted on Apollon for proliferation on pancreatic cancer cells and its possible acting mechanism.Methods The small interfering RNA targeted on apollon in our previous study was transfected to the cells using LipofectamineTM 2000,after 48 hours transtection.The inhibitory effects of small interfering RNA targeted on Apollon (Apollon siRNA)on cell proliferation were detected by WST-8.Their inhibition rate and IC50 were calculated.The percentage of apoptosis cells were determined by flow cytometry.The expression of Apollon mRNA was analyzed by real time fluorescent quantitative reverse transcription polymerase chain reaction.The Apollon protein ex-pression levels were detected by western blotting.Results Apollon siRNA could effectively inhibit the proliferation of pan-creatic cancer cell.The amount of apoptotic cells increased significantly.The early apoptotic rate was 37.1%,and the RT-PCR results showed that the relative expression levels of Apollon mRNA were down-regulate,and shows a dose-effective-ness relations.The protein expression levels were decreased by Apollon siRNA.Conclusion Apollon siRNA can effectively inhibit the proliferation of pancreatic cancer cell.The mechanism may be work together to promote pancreative cancer cell early apoptosis and decreased the expression levels of gene and protein,which provides a novel potential approach for treat-ment of target therapy of pancreatic cancer.

Livin and Urological Malignancy, related research and progress / 医学研究生学报

Oncogenesis is a sophisticated process which is polygenic , multi-stage,and multi-step.Livin as an apoptosis inhibi-ting factor , is one of the members of apoptosis inhibiting factor family , it expresses highly in many tumor tissues , and is closely related to the occurrence and development of urological tumor .Tumor growth can be inhibited by interfering the expression of Livin in tumor tis-sue,which will reduce the resistance to apoptosis and increase the rate of cell apoptosis .In recent years , more and more attention was paid to the studies of Livin on gene targeting therapy .Further research of Livin might provide new ideas for the early diagnosis , clinical treatment and evaluation of prognosis of tumor .

Inhibition of silent information regulator 1 induces glucose metabolism disorders of hepatocytes and enhances hepatitis C virus replication / 中华传染病杂志

Objective The aim of this study was to investigate the effect of hepatitis C virus (HCV) replication on expression of silent information regulator 1 (SIRT1) and glucose metabolism of hepatocytes using Huh 7.5 cells harboring HCV replicon.Methods The level of reactive oxygen species (ROS),value of nicotinamide adenine dinucleotide (NAD+)/reduced form of nicotinamide adenine dinucleotide (NADH) was detected by flow cytometry and chromatometry.The activity,mRNA expression,and protein level of SIRT1 were detected by a scintillation counter,real-time fluorescence quantitative polymerase chain reaction (RT-PCR),and Western blot,respectively.Glucose uptake by hepatocytes and gluconeogenesis were detected using radioactive isotope method and glucose oxidase method.The mRNA levels of SIRT1 downstream glucose-metabolism genes were measured by RT-PCR.Measurement date were compared by t test.Results In replicon cells,the level of ROS (3.8±0.5 vs 1.0±0.2; t=12.736,P＜0.01) was increased and the value of NAD+/NADH (0.03±0.01 vs 0.12±0.03; t=6.971,P＜0.01) decreased compared with Huh 7.5 cells.The activity (0.3±0.1 vs 1.0±0.2; t=7.668,P＜0.01),mRNA expression(0.4±0.1 vs 1.0± 0.3; t=4.648,P＜0.01) and protein level(0.3±0.1 vs 0.8±0.2; t=5.941,P＜0.01) of SIRT1 were reduced.Inhibition of SIRT1 not only increased insulin receptor substrate-1 (IRS-1) phosphorylation (0.7±0.2 vs 0.4±0.1; t=3.286,P＜0.01),decreased protein kinase B (Akt) phosphorylation (0.3 ± 0.1 vs 0.6 ± 0.2; t=3.286,P＜0.01),down regulated cell surface expression of glucose transporler 2 (GLUT2,0.4±0.1 vs 1.0 ± 0.2; t =6.573,P＜0.01) and suppressed cellular glucose uptake (count per minute:4600±500 vs 21 000±4600; t=8.682,P＜0.01); but also decreased phosphorylation of forkhead box O1 (FoxO1,0.2＝0.1 vs 0.5±0.1; t=5.196,P＜ 0.01),up-regulated phosphoenolpyruvate carboxykinase (PEPCK,2.8±0.6 vs 1.0±0.3; t=6.573,P＜0.01) and glucose 6-phosphatase (2.6±0.5 vs 1.0±0.2; t=7.278,P＜0.01) genes,and promoted glucose production (2.5±0.5 vs 1.0±0.2; t=5.543,P＜0.01).Conclusions HCV replication decreases NAD+/NADH ratio,which might down-regulate the activity and the expression of SIRT1,leading to changes in the expression profile of glucose metabolism related genes and causing glucose metabolism disorders of hepatocytes by a decrease in glucose uptake and an increase in glucose production,and promotes HCV replication.

Expression and significance of Livin and Smac protein in basal cell carcinoma lesions / 中华皮肤科杂志

Objective To detect the expression of Livin,an apoptosis-inhibiting protein,and Smac,an apoptosis-promoting protein,in basal cell carcinoma (BCC) lesions.Methods Skin specimens were obtained from the lesions of 80 patients with BCC and normal skin of 30 human controls.Immunohistochemical SP method was used to detect the pmtein expression of Livin and Smac in these specimens.Chi-square test was conducted to compare the expression rate of Livin and Smac protein between the lesional and control specimens.The relationship between the protein expression of Livin and Smac in BCC was analyzed by Spearman correlation coefficients.Results The expression rate of Livin protein was significandy higher (77.50％ vs.3.33％,x2 =49.04,P ＜ 0.001),while that of Smac protein was statistically lower (46.25％ vs.100％,x2 =26.47,P ＜ 0.001),in BCC than in the control specimens.No significant difference was observed in the expression rate of Livin or Smac protein between nodular ulcerative and pigmented BCC specimens (75.41％ vs.80.00％,x2 =0.001,P ＞ 0.05; 47.54％ vs.40.00％,x2 =0.28,P＞ 0.05) or between nodulocystic and pigmented BCC specimens (73.58％ vs.80.00％,x2 =0.03,P ＞ 0.05; 45.28％ vs.40.00％,x2 =0.13,P ＞ 0.05).There was a negative relationship between the protein expression of Livin and Smac in BCC lesions (r =-0.432,P ＜ 0.01).Conclusion The upregulated expression of Livin and downregulated expression of Smac may be invoved in the occurrence and development of BCC.

The expression of Apollon gene silenced by RNA interference combined with ligustrazine intervention may increase the sensitivity of leukemia cells to chemotherapeutic agents / 肿瘤

Objective: To investigate whether the expression of Apollon (an apoptosis inhibitory gene) silenced by using RNA interference (RNAi) technology in combination with tetramethylpyrazine (TMP) intervention can increase the sensitivity of human myeloid leukemia K562 cells to vincristine (VCR) and daunorubicin (DNR). Methods: Using the best small interference RNA (siRNA) targeting Apollon gene which was screened out in a previous experiment, the eukaryotic expression vector pGPHI-GFP-Neo-Apollon was constructed. Then, the K562 cells were transfected with pGPHI-GFP-Neo-Apollon by LipofectamineTM 2000 and screened out by G418. After Apollon siRNA was transfected stably into K562 cells, the expressions of Apollon mRNA and protein were detected by reverse transcription (RT)-PCR and immunofluorescence, respectively. The sensitivities to chemotherapeutic agents VCR and DNR after RNAi in combination with TMP intervention were detected by MTT method, and apoptosis rate was detected by flow cytometry. Results: pGPHI-GFP-Neo-Apollon vector was constructed successfully and it could express stably in K562 cells, which silenced the expressions of Apollon mRNA and protein effectively. The sensitivity to VCR or DNR increased significantly after RNAi in combination with TMP intervention. The half inhibitory concentration (IC50) values of VCR and DNR were significantly lower than those in the group of TMP intervention alone (P < 0.05). The apoptosis rate of K562 cells after transfection with Apollon siRNA in combination with TMP intervention was significantly increased comparing with that of the untreated control group and TMP intervention alone group (P < 0.05). Conclusion: RNAi targeting Apollon gene in combination with TMP intervention can obviously increase the sensitivity to VCR or DNR in K562 cells and significantly reduce the dosage of chemotherapeutic agents as well as improve apoptosis induced by chemotherapy. These results suggest that Apollon gene silenced by RNAi in combination with TMP intervention may reverse the drug resistance of leukemia cells. Copyright © 2013 by TUMOR.

Expression and clinical significance of Livin and Smac protein in pancreatic carcinoma / 中华胰腺病杂志

Objective To investigate the expression and clinical significance of apoptosis inhibitory protein, Livin and Smac,in pancreatic carcinoma. Methods The expressions of Livin and Smac protein in 46 cases of pancreatic carcinoma tissues and 15 cases of insulinoma tissues and 14 cases of normal pancreatic tissues were examined by using immunohistochemical SP staining, and its relationship with clinicopathological parameters was analyzed. Results The positive expression rates of Llivin protein were 73.9％ ( 34/46),73.3％ (11/15) and 14.3％ (2/14) in pancreatic carcinoma, insulinoma and normal pancreatic tissue. Livin was highly expressed in pancreatic carcinoma and insulinoma, but there was no significant difference between the two groups, however, both were significantly higher than that in normal pancreatic tissues group ( P ＜ 0.05 ). The expression of Livin was significantly correlated with lymph node metastasis, histopathological grading and clinical staging (P ＜ 0.05 or P ＜0.01 ). The positive expression rates of Smac protein were 39.1％ (18/46), 100％ ( 15/15 ) and 92.9％ (13/14) in pancreatic carcinoma, insulinoma and normal pancreatic tissue. Smac was highly expressed in normal pancreatic tissues and insulinoma, but there was no significant difference between the two groups, however, both were significantly higher than that in pancreatic cancer group (P ＜ 0.05 ). The expression rote of Smac protein was significantly correlated with lymph node metastasis, histopathological grading, chnical staging and patients' age (P ＜0.05 or P ＜0.01 ).Conclusions Livin protein may play an important role in genesis and development of pancreatic carcinoma,but Smac protein may play a role in preventing the development of pancreatic carcinoma.

Effect of sevoflurane on Survivin expression in human adenocarcinoma cell line A549 / 中华麻醉学杂志

Objective To investigate the effects of different concentrations of sevoflurane on Survivin expression in human adenocarcinoma cell line A549. Methods A549 cells were obtained from Shanghai Cell Biology Medical Research Institute, Chinese Academy of Sciences and inoculated in 96 well culture plate. After being cultured for 24 h, the cells were randomly divided into 4 groups: Ⅰ , Ⅱ , Ⅲ and Ⅳ groups exposed to 95 % O2 -5 %CO2,1.7%, 3.4% and 5.1% sevoflurane respectively. A549 cells were exposed to sevoflurane for 2, 4 and 6 h respectively and then cultured for another 48 h in Ⅱ , Ⅲ and Ⅳ groups. Proliferation of A549 cells were measured by methyl thiazolyl tetrazolium (MTT) assay, and apoptosis was detected with flow cytometer at 48 h after 2, 4 and 6 h sevoflurane exposure. The expression of Survivin in A549 cells was determined by Western blot analysis at 48h after 4 h sevoflurane exposure. Results The rate of proliferation inhibition and percentage of apoptotic cells were significantly higher while the expression of Survivin was significantly lower in a concentration-dependent manner in Ⅱ , Ⅲ and Ⅳ groups as compared with group Ⅰ . Conclusion Sevoflurane can inhibit proliferation and induce apoptosis of A549 cells by inhibition of Survivin expression.

Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma

BACKGROUND: The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance. METHODS: Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method. RESULTS: Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041). CONCLUSIONS: Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

Expression and clinical significance of Survivin in cervical cancer / 肿瘤研究与临床

Objective To investigate the expression of Survivin gene and the relationship between Survivin and genesis and development of cervical cancer. Methods The expression of Survivin gene in tissues of 40 patients with cervical cancer, 38 patients with cervical hyperplasia and 10 cases of normal cervical were detected by immunohistochemical SP method, and the relationships between Survivin and the clinical pathological factors were analyzed. Results The expression positive rate of Survivin in cervical cancer tissues (60 %) was significantly higher than that in cervical hyperplasia and normal cervical tissues (42.1 % and 0, respectively), and their differences were statistically significant (P < 0.05). The positive expression rate of Survivin was related with histological grade and the clinical stages of cervical cancer.Conclusion Survivin is related to the genesis and development of cervical cancer.

Effects of selective cyclooxygenase-2 inhibitor NS-398 on apoptosis and survivin, XIAP and c-IAP1 expressions of hepatocellular carcinoma BEL-7402 cells / 肿瘤

Objective:To investigate the effect and elucidate the mechanism of the selective cyclooxygenase-2(COX-2)inhibitor NS-398 on apoptosis and survivin, XIAP and c-IAP1 expressions of hepatocarcinoma cell lines. Methods:The proliferation of hepatocarcinoma BEL-7402 cells treated with NS-298 at different concentrations were evaluated by MTT assay. The apoptosis was detected by flow cytometry (FCM) and TUNEL assay. Expressions of COX-2, survivin, XIAP and c-IAP1 were analyzed by immunocytochemical staining. Results: NS-398 significantly inhibited cell proliferation of BEL-7402 cells and induced apoptosis. Immunocytochemisty indicated that the expressions of COX-2, survivin, XIAP and c-IAP1 were significantly down-regulated in BEL-7402 cells by NS-398 treatment compared with untreatment group (P<0.01). Conclusion:NS-398 inhibits the proliferation and induced apoptosis of BEL-7402 cells. The mechanism may be related with down-regulation of the survivin, XIAP and c-IAP1 expression.