Rats ; Animals ; Urinary Bladder Neck Obstruction/pathology* ; Survivin/genetics* ; Urinary Bladder/pathology* ; Fibrosis

OBJECTIVE: To investigate the expression and significance of Survivin mRNA in xenotransplanted nasopharyngeal carcinoma treated by paclitaxel combined with radiotherapy. METHOD: Xenotransplanted nasopharyngeal carcinoma was established by CNE-2 cell line, then grouped and treated with paclitaxel, radiotherapy, paclitaxel combined with radiotherapy respectively. Xenotransplanted tumor volume was measured; tumor specimens were confirmed by routine hemotoxylin-eosin staining; apoptosis index was assayed by flow cytometry and Survivin mRNA was detected by one step RT-PCR. RESULT: Xenotransplanted tumor growth was significantly inhibited by paclitaxel combined with radiotherapy and its inhibition rate was 99.3%. Compared to control group, apoptosis index was apparently increased in the other three groups (P<0.05), especially in the combined therapy group (P<0.05). Survivin mRNA expression was obviously decreased in the combined therapy group (P<0.05); whereas there was no difference in its expression among the groups of paclitaxel, radiotherapy, and control group (P>0.05). CONCLUSION Paclitaxel combined with radiotherapy can induce significant killing effect in xenotransplanted nasopharyngeal carcinoma; paclitaxel can enhance the radiosensitivity of xenotransplanted nasopharyngeal carcinoma and its mechanism may rely on the down-regulation of Survivin expression.
Animals ; Brachytherapy ; Cell Line, Tumor ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; metabolism ; therapy ; Paclitaxel ; therapeutic use ; RNA, Messenger ; genetics ; Repressor Proteins ; genetics ; metabolism ; Survivin ; Xenograft Model Antitumor Assays

OBJECTIVE: This study aimed to explore the relationship among expression of Survivin and MRP and drug resistance in NPC. METHOD: Expression of Survivin were detected by immunohistochemistry method in 45 cases of NPC and 24 cases of normal mucous membrane of nasopharynx (NMMN). The relationship between expression of Survivin and pathological factors in NPC were analysized. Expression of Survivin and MRP were detected in 31 patients of NPC with paclitaxel resistance and 20 patients of NPC without paclitaxel resistance. The relation- ship among the expression of Survivin or MRP and paclitaxel resistance in NPC were analysized. The paclitaxel resistance cell line, 5-8F-PTX(+); was established by a step-increased method. The expression of Survivin and MRP were detected by western blot in 5-8F-PTX(+) and 5-8F. RESULT: The positive were 71. 1% (32/45) in NPC and 8.33% (2/24) in NMMN. And there were significantly differences between them (P < .05). There were relationship among expression of Survivin and differentiation degree, lymph node metastasis, distant metastasis, and clinic stages of NPC. The positive were 75.9% (31/39) in moderately differentiated NPC and 16.7% (1/6) in lowly differentiated NPC, respectively. There were significantly differences between them (P < 0.05). The positive of Survivin were 83.9% (26/31) in NPC patients with paclitaxel resistance and 45.0% (9/20) in NPC patients without Paclitaxel resistance, respectively. There were significantly differences between them (P < 0.05). The positive of MRP were 87.1% (27/31) in NPC patients with paclitaxel resistance and 40.0% (8/20) in NPC patients without paclitaxel resistance, respectively. There were significantly differences between them (P < 0.05). There were positive correlation between the expression of Survivin and MRP in NPC patients with Paclitaxel resistance. The expression of Survivin and MRP were higher in 5-8F-PTX(+) than in 5-8F. The IC50 of paclitaxel, cDDP, 5-FU and Vincristine were significantly higher in 5-8F-PTX(+) than in 5-8F. CONCLUSION There were relationship among the expression of Survivin and difference, metastasis and TNM stages of NPC. Survivin may serves as a molecular marker for development and progress in NPC. There were relationship among the high expression of Survivin and MRP and increasing of drug resistance in NPC.
Antineoplastic Agents ; pharmacology ; Carcinoma ; Cisplatin ; Drug Resistance, Neoplasm ; Fluorouracil ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Lymphatic Metastasis ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; Nasopharynx ; metabolism ; Paclitaxel ; pharmacology ; Survivin ; Vincristine

OBJECTIVE: To study the combined transfection of the siRNA target for Hif-lα and Survivin gene to human NPC CNE-2 cell and its effects on the proliferation and cycle of this cell. METHOD: Combined transfection of the siRNA target for Hif-lα and Survivin gene to human NPC CNE-2 cell, these plasmids were respectively transfected into the same cells. Cell proliferation was detected with MTT assay. The inhibitory effects on target genes were evaluated with RT-PCR and Western Blot at the levels of mRNA and protein, respectively. RESULT: MTT showed that CNE-2 cell proliferation in multi-gene plasmid group was more significantly inhibited than a single gene. The expression of mRNA and protein of two different genes were both decreased in HS group, and the interference effect of multiple genes was better than the single-gene(P<0.01). CONCLUSION HS group could restrain cell proliferation and interference the mRNA and protein expression in nasopharyngeal carcinoma CNE-2 cell, which was better than the other groups.
Apoptosis ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; Inhibitor of Apoptosis Proteins ; genetics ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; genetics ; Plasmids ; RNA, Messenger ; RNA, Small Interfering ; Survivin ; Transfection

OBJECTIVE: To determine the expressions of survivin and proliferating cell nuclear antigen (PCNA)in non-small cell lung cancer (NSCLC) and to explore its clinical pathological significance. METHODS: Immunohistochemical SP method was used to detect the expressions of survivin and PCNA in 43 patients with NSCLC and 15 normal epithelial tissues of the lung. PCNA labeling proliferative index was assessed. Forty-three patients with NSCLC were followed up for more than 5 years. RESULTS: The positive expression of survivin in NSCLC (79.1%) was significantly higher than that in normal epithelial tissues of the lung (P < 0.01). The survivin expression in Stage I + II was lower than in Stage III (P < 0.05). The overall survival time was significantly shorter in patients with high survivin expression than that in patients with absent or low survivin expression. The survivin expression was not related to sex, age, tumor size and site, histological type, grade, and lymphoid node metastasis (P > 0.05). The mean proliferative index of PCNA in NSCLC was much higher than that in normal epithelial tissues of the lung (P < 0.01). A positive correlation was present between the proliferative index and the tumor size, lymph node metastase, and clinical stage (P <0.01), while a negative correlation between the proliferative index and survival time (P <0.01). There was no correlation between proliferative index and age, sex, site, histological type and grade. The proliferative index was larger in patients with moderate or strong positive survivin expression than that in patients with negative or weak survivin expression (P < 0.05). CONCLUSION Over expression of survivin and PCNA is closely correlated to the progression and prognosis of patients with NSCLC, which is helpful to evaluate the progression of cancer and to predict the prognosis of NSCLC. The up-regulation of survivin expression and its close relationship with the cell proliferation in NSCLC suggest that survivin may play an important role in the carcinogenesis and development of lung cancer.
Adult ; Aged ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Lung Neoplasms ; metabolism ; Male ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Middle Aged ; Neoplasm Proteins ; biosynthesis ; genetics ; Neoplasm Staging ; Prognosis ; Proliferating Cell Nuclear Antigen ; biosynthesis ; genetics ; Survivin

OBJECTIVE: To observe wether pSIREN-survivin/shRNA can induce the apoptosis and inhibit it's growth of nude mice xenograft tumor of nasopharyngeal carcinoma cell. METHOD: Subcutaneous tumors in athymic mice were induced by inoculation of NPC and divided into the blank group A, the negative group B,the experimental group C randomly. PBS,the negative and positive pSIREN-survivin/shRNA were injected into the subcutaneous tumors poly site. The inhibition ratio was measured by the tumor size calculation after inoculation. The expression of survivin in the xenograft tumor was observed by RT-PCR and immunohistochemistry. The cell apoptosis in tumor tissues was detected by TEM. The liver and kidney function was tested by blood routine test. RESULT: The inhibition ratio of group C and group B was (52. 11 +/- 1. 03)%, (2. 15 0. 11)% respectively, the inhibition rate in expression level of survivin mRNA was (77. 5+/-2. 03) %, (1. 39+/-0. 14) % respectively. The dyeing of survivin was more shallow in group C, the intensity is also less than group B. Nuclear chromatin was deepened, split into pieces, flake, and nuclear membrane was surrounded to edge. Cytoplasmic color and density were deepened, and organelles such as mitochondria was disappeared, the microscopic changes of cellular apoptosis at the earlier stage were watched, the difference of the function in liver and kidney was not statistically in statistical. CONCLUSION The expression of survivin in xenograft tumor was significantly inhibited by pshRNA-survivin/shRNA,the apoptosis of tumor cells was accelerated and the growth speed of NPC cells in xenograft tumor was retarded. The high expression of nasopharyngeal carcinoma's gene could significantly be silenced by using technology of RNAi, the growth of tumors could be inhibited also. Its a novel treatment that have a good prospect.
Animals ; Apoptosis ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Silencing ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; RNA, Small Interfering ; genetics ; Survivin ; Xenograft Model Antitumor Assays

OBJECTIVE: (1)To obtain the perfusion parameters of hepatocellular carcinomas(HCCs), peritumour livers and normal livers by multi-slice CT(MSCT)and to investigate their characteristics and clinical significances;(2)To investigate the correlation among perfusion parameters, survivin expression, microvessel density(MVD)and pathologic grade of HCCs. METHODS: A total of 31 patients with HCC (5 well-differentiated HCCs, 17 moderately differentiated HCCs, and 9 poorly differentiated HCCs) and 10 normal liver were studied. All underwent CT plain scan, perfusion scan, and conventional enhancement scan of the whole liver using 16-slice spiral CT (Philips Brilliance 16). Perfusion parameters were obtained by time-density curves (TDC) of region of interest (ROI) through the perfusion scans. Tissue sections of HCCs and their corresponding peritumour liver tissues of the 31 patients were detected by immunohistochemistry (SABC methods) for protein expression of survivin and MVD, and 10 normal liver tissue sections were as used as negative controls. The correlation among the perfusion parameters, survivin expression, MVD and pathology grade were analysed. RESULTS: (1)The mean values of HAP, HPP, TLP, and HAI of HCCs were 27.50 mL/(min.100 mL), 19.37 mL/(min.100 mL), 46.87 mL/(min.100 mL), and 60.38%, respectively. The mean values of those of the peritumour livers were 14.93 mL/(min.100 mL), 55.70 mL/(min.100 mL), 69.63 mL/(min.100 mL), and 21.51%, respectively. The mean value of those of the normal livers were 12.22 mL/(min.100mL), 74.56 mL/(min.100 mL), 86.78 mL/(min.100 mL), and 14.00%, respectively. The values of HAP and HAI of HCCs were significantly higher than those of the peritumor livers and the normal livers(P<0.01), and the HPP and TLP of HCCs were significant lower than those of the normal livers(P<0.01).The increase of HAP and decrease of HPP of peritumor livers were both significant compared with that of the normal livers(P<0.05). The HAP, HPP, and HAI of HCCs were significantly different from those of peritumor livers (P<0.01)except TLP. (2) Survivin expression in HCCs was detected in 23/31(74.1%), which was significantly higher than that in corresponding non-cancerous adjacent liver tissues and normal liver tissues (P<0.01). Survivin expression was positively correlated with MVD in HCCs. (3) HAP values were significantly and positively correlated with survivin expression (r=0.932,P<0.01)in HCCs.(4)The values of HAP and HAI were correlated with the pathologic grade in HCCs, and those values were increased gradually(P<0.05) among well differentiated HCCs, moderately differentiated, and poorly differentiated HCCs. CONCLUSION CTPI can quantitatively reflect abnormal blood supply of HCCs, which will be helpful for the detection and differentiation of lesions. CT perfusion parameters well correlate with survivin expression, MVD, and the pathologic grade in HCCs, which illustrate that CTPI could hopefully be used to evaluate the angiogenesis and biological behaviors of HCCs prospectively, noninvasively, and dynamically.
Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; biosynthesis ; genetics ; Liver Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Male ; Microvessels ; diagnostic imaging ; Middle Aged ; Perfusion Imaging ; methods ; Survivin ; Tomography, Spiral Computed

OBJECTIVE: To determine the diagnostic value of the expression of survivin mRNA in sputum samples and pleural effusions in lung cancer. METHODS: The sputum samples of 104 patients with lung cancer and 30 patients with chronic obstructive pulmonary disease (COPD), and the pleural effusion of 56 patients with lung cancer and 30 patients with tuberculosis pleural effusions were detected.Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the survivin mRNA expression in the specimens. The results were compared with their cytological examinations. RESULTS: The sensitivity of the cytological examinations combined with the detection of survivin mRNA in sputum samples was higher than that of either cytological examination or survivin mRNA detection of sputum samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer increased from 37.5% (sputum cytology alone) to 78.8% (sputum survivin mRNA detection combined with sputum cytology) (P<0.01), and the negative predictive value increased from 31.6% (sputum cytology alone) to 43.5% (sputum survivin mRNA detection combined with sputum cytology) (P<0.01). The sensitivity of the cytological examinations combined with the detection of survivin mRNA in pleural effusion samples was higher than that of cytological examination of pleural effusion samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer increased from 42.9% (pleural effusion cytology alone) to 80.4% (pleural effusion survivin mRNA detection combined with cytology) (P<0.01), and the negative predictive value increased from 48.4% (pleural effusion cytology alone) to 77.8% (pleural effusion survivin mRNA detection combined with cytology) (P<0.01). CONCLUSION The detection of survivin mRNA from sputum samples and pleural effusions samples is a new diagnostic method for lung cancer.
Adolescent ; Adult ; Aged ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; analysis ; Lung Neoplasms ; diagnosis ; genetics ; Male ; Middle Aged ; Pleural Effusion ; metabolism ; Predictive Value of Tests ; RNA, Messenger ; analysis ; Sensitivity and Specificity ; Sputum ; metabolism ; Survivin ; Young Adult

OBJECTIVE: To determine the molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin. METHODS: Effects of ADR and puerarin on NF-kappaB activity of K562,K562/AO2 were tested by immunofluorescence. The expression of survivin of K562,K562/AO2 was examined by immunocytochemistry. The p-gp expression was detected by flow cytometry. RESULTS: The NF-kappaB activity of K562 was significantly higher than that of K562/AO2. The NF-kappaB activity of K562 treated by ADR was significantly higher than untreated. The NF-kappaB activity of K562 which was pretreated by puerarin and then treated by ADR was much lower than that treated by ADR alone. The NF-kappaB activity of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin.The p-gp and survivin expression of K562/AO2 was significantly higher than K562. The p-gp and survivin expression of K562 treated by ADR was higher than that untreated by ADR. But the p-gp and survivin expression of K562 which was pretreated by puerarin and then treated by ADR was much lower than that not pretreated by puerarin.The p-gp and survivin expression of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin. The expression was negatively correlated to the duration of intervention. The inhibition effect demonstrated time dependence. CONCLUSION The activation of NF-kappaB can increase the expression of p-gp and survivin, which may be part of the molecular mechanism of multi-drug resistance of K562. Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-kappaB and the expression of p-gp and survivin.
ATP Binding Cassette Transporter, Subfamily B ; biosynthesis ; genetics ; Antineoplastic Agents, Phytogenic ; pharmacology ; Drug Resistance, Multiple ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; Isoflavones ; pharmacology ; K562 Cells ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; NF-kappa B ; metabolism ; Survivin

OBJECTIVE: To investigate the simultaneous inhibition of X-linked inhibitor of apoptosis protein (XIAP) and survivin expression on epithelial-mesenchymal transition (EMT) and invasiion of pancreatic cancer cells Panc-1, and its mechanism. METHODS: On the established human pancreatic cancer cells Panc-1-XS, the expression of XIAP and survivin was inhibited simultaneously. Cell invasion and migration were detected by Transwell chamber experiments and scratch test, and the expression of epithelial marker E-cadherin, mesenchymal markers Slug, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and P-Akt protein was determined by Western blot. RESULTS: Cell invasion and migration of Panc-1-XS cells decreased significantly, accompanied by significantly upregulated protein expression of E-cadherin, and significantly declined protein expression of the Slug, indicating increased mesenchymal-epithelial conversion (MET); and increased protein expression of PTEN, and declined protein expression of P-Akt. CONCLUSION Simultaneously inhibiting the expression of XIAP and survivin can partially reverse EMT phenotype of pancreatic cancer Panc-1 cells, which then significantly reduces the cell invasion and migration of Panc-1 cell lines. This process may be regulated by PTEN/PI3K/Akt signaling pathway.
Antigens, CD ; Cadherins ; metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; PTEN Phosphohydrolase ; metabolism ; Pancreatic Neoplasms ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; Snail Family Transcription Factors ; Survivin ; Transcription Factors ; metabolism ; X-Linked Inhibitor of Apoptosis Protein ; genetics ; metabolism