Apoptosis ; Inhibitor of Apoptosis Proteins ; Myocytes, Cardiac ; cytology

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.
Apoptosis ; Colorectal Neoplasms ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Intracellular Signaling Peptides and Proteins ; Mitochondrial Proteins ; Prognosis ; Proteins ; Statistics as Topic ; X-Linked Inhibitor of Apoptosis Protein

OBJECTIVE: Survivin is one of the inhibitor of apoptosis protein family proteins, which inhibits apoptosis through pathway different from that involving the Bcl-2 family. Overexpression of survivin has been reported in the most common human cancers. The purpose of this study is to investigate survivin expression and its relevance to histological malignancy and apoptosis of brain tumors. METHODS: Seventy-eight consecutive patients with brain tumor, who underwent operation, were included in this study. Pathological types of brain tumor were classified by World Health Organizaton classification. Survivin expression was detected by Western blot analysis and apoptosis was examined by DNA fragmentation. RESULTS: Survivin was expressed in 32(41.0%) of 78 patients with brain tumor and apoptosis was detected in 14(21.9%) patients. Histological malignancy of brain tumors was not correlated with survivin expression or apoptosis(p>0.05). However, survivin-positive tumors were strongly associated with anti-apoptosis(p=0.000) and apoptosis was significantly relevant to survivin-negative tumors(p=0.006). CONCLUSION: These results suggest that survivin expression is strongly related to the apoptosis of brain tumors, but not associated with biological malignancy. Therefore, survivin may be a potential target for brain tumor therapy based on apoptosis.
Apoptosis* ; Blotting, Western ; Brain Neoplasms* ; Brain* ; Classification ; DNA Fragmentation ; Humans ; Inhibitor of Apoptosis Proteins ; World Health

PURPOSE: Survivin is an inhibitor of apoptosis protein and it is overexpressed in most human cancers. Recent data demonstrated that survivin-HSP90 complex regulate apoptosis. We assessed expression of survivin and HSP90 by using immunohistochemistry with colorectal cancer tissue and correlate it with clinicopathologic prognostic parameters. METHODS: Using immunohistochemistry, survivin and HSP90 expression were evaluated on paraffin sections of fifty-six colorectal carcinomas. Various clinicopathologic parameters including histologic differentiation grade, T-stage, nodal metastasis, stage were obtained from pathologic records. RESULTS: Survivin expression were observed in 30 cases (53.6%). The expression of survivin showed no statistically significant correlation with histologic differentiation grade, T-stage, nodal metastasis, stage. HSP90 expression were observed in 31 cases (55.4%). The expression of HSP90 showed a statistically significant correlation with histologic differentiation grade (P=0.035) and stage (P=0.017). There were a significant correlation between survivin expression and HSP90 expression (P=0.018). CONCLUSION: Survivin and HSP90 was expressed in colorectal cancer. The expression of HSP90 correlates with histologic differentiation grade, stage. The above results suggest that HSP90 could be a prognostic marker of poor outcome in colorectal carcinoma.
Apoptosis ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Neoplasm Metastasis ; Paraffin

OBJECTIVETo investigate the proliferation effects of arsenic trioxide (As2O3) on salivary adenoid cystic carcinoma-2 (ACC-2) cells in vitro and to study the role of Survivin on the apoptosis of ACC-2 induced by As2O3.

METHODSACC-2 cells were treated with different concentration of As2O3 for different time. The inhibitory effects on cell's viability were assayed with methyl thiazolyl tetrazolium (MTT) test. Apoptosis was determined by flow cytometry. The expression of Survivin mRNA and protein were investigated by reverse transcription-polymerase chain raction (RT-PCR) and Western blot analysis respectively.

RESULTSCell viability after As2O3 treatment was markedly suppressed and exhibited as a dose- and time-dependent pattern. The apoptotic index showed the similar trend. The results of RT-PCR revealed gene expression of Survivin was suppressed significantly. Through Western blot analysis, a negative correlation between concentration and amount of protein product of Survivin was determined.

CONCLUSIONAs2O3 might markedly suppressed ACC-2 cell's viability in vitro. The inhibition of Survivin gene expression may play a critical role on ACC-2 cell apoptosis induced by As2O3.

Antineoplastic Agents ; Apoptosis ; Arsenicals ; Carcinoma, Adenoid Cystic ; Humans ; Inhibitor of Apoptosis Proteins ; Oxides

OBJECTIVETo investigate the expression of survivin protein in the tissues of prostatic carcinoma and its correlation with apoptosis of cancer cells.

METHODSExpression of survivin protein and apoptosis index(AI) were detected by immunohistochemical and terminal deoxynucleotidyl transterase-mediated dUTP biotin nich end labeling(TUNEL) technique in the tissues of 42 cases of prostatic carcinima (PCa) and 10 cases of normal prostate (NP).

RESULTSSurvivin prosteins were expressed in 34 of the 42 (80.59%) cases of PCa. The positive rate of survivin was strongly associated with pathological grades, clinical stages and lymphmetastasis in PCa(P < 0.05). In contrast, NP did not express survivin. Survivin protein expression was negatively correlated with AI in PCa(r = -0.679, P < 0.001).

CONCLUSIONSApoptosis inhibition by survivin may participate in the onset and progression of PCa, and the detection of survivin protein and AI in PCa may help to evaluate the degree of cell differentiation, decide therapeutic strategies and estimate prognosis.

Aged ; Apoptosis ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; analysis ; Middle Aged ; Neoplasm Proteins ; Prostatic Neoplasms ; chemistry ; pathology

Humans ; Hypertension, Pulmonary ; metabolism ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; metabolism

OBJECTIVETo observe the induction of apoptosis of cisplatin (DDP) to oral squamous cell carcinoma cell line (Tca8113) in vitro and study the role of Survivin on the apoptosis of Tca8113 cells induced by cisplatin.

METHODSThe inhibitory effects of different doses of DDP on Tca8113 cells were assayed with MTT test. Apoptosis was determined by flow cytometry. The expression of Survivin was detected by RT-PCR and immunocytochemistry.

RESULTSCisplatin obviously inhibited Tca8113 cells growth in a dose and time dependent manner. The apoptotic index showed the similar trend. Survivin gene expression was decreased with increasing of time and reached the lowest level at 24 hours after DDP treatment, then increased after that time.

CONCLUSIONCisplatin gene can effectively induce apoptosis in Tca8113 cells and the inhibition of Survivin gene expression may play a critical role on Tca8113 cell apoptosis induced by cisplatin.

Apoptosis ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins

OBJECTIVETo investigate the effect of siRNA targeting Livin and Survivin gene simultaneously on the proliferation and apoptosis of human colon cancer cells.

METHODSSiRNA recombinant expression vectors targeting Livin and Survivin gene simultaneously were constructed and transfected into human colon cancer cell line Lovo. The effects of siRNA recombinant expression vector on Lovo cells were detected by RT-PCR, Western blot, MTT reduction assay and flow cytometry.

RESULTSIt was confirmed by restriction endonuclease and sequence analysis that siRNA recombinant expression vector targeting Livin and Survivin gene simultaneously was constructed successfully. The suppressive rates of siRNA targeting Livin and Survivin gene simultaneously on Livin mRNA and protein expression were 27.9% and 22.3% respectively, and those on Survivin mRNA and protein expression were 32.2% and 40.9% respectively. The survival rate of cancer cells was decreased whereas the apoptotic rate was increased, but the coordinate repression was weaker than Livin and Survivin RNA interference alone.

CONCLUSIONSsiRNA targeting Livin and Survivin gene simultaneously can decrease the expression of Livin and Survivin gene, suppress cell proliferation and induce cell apoptosis in human colon cancer. The coordinate repression was weaker than Livin and Survivin RNA interference alone.

Adaptor Proteins, Signal Transducing ; genetics ; Apoptosis ; Cell Line, Tumor ; Colonic Neoplasms ; genetics ; pathology ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; RNA, Small Interfering

PURPOSE: The prognostic significance of survivin expression (SE), which has been reported to be an inhibitor of apoptosis protein, was examined in order to identify a more accurate prognostic grouping of neuroblastomas. METHODS: Thirty-seven tumor specimens were obtained between 1992 and 2002. The SE level was examined by immunohistochemical techniques using paraffin-embedded tissues, and was scored as being positive when more than 5% of the cells reacted with the anti-survivin antibody. The outcome of the stratified potential prognostic groups was evaluated according to age, location, stage, Shimada class and SE. The correlation between the SE level and the prognostic factors were analyzed using a univariate assessment. The predictive value of SE in the prognosis was determined using a multivariate assessment. RESULTS: The median follow up period was 23 months. The 5-year overall survival rate was significantly reduced with an advanced stage, adrenal primary, unfavorable Shimada class and positive SE (P=.01, .01, .02 and .00). A positive SE was correlated with old age, advanced stage and an unfavorable Shimada class (P=.03, .00 and .03). The relative risk of the SE positive group was 5.20 (P=.01). Survivin was expressed in 73% of recurred cases, but in only 31% of non-recurred cases (P=.04). CONCLUSIONS: Survivin expression is a valid independent prognostic factor for a neuroblastoma, which correlates withthe disease progression and a poor prognosis.
Disease Progression ; Follow-Up Studies ; Inhibitor of Apoptosis Proteins ; Neuroblastoma ; Prognosis* ; Survival Rate