Differential expression, diagnostic and prognostic significance of stathmin-1 and CD147 in various uterine smooth muscle tumors / Expresión diferencial, diagnóstico y significado de pronóstico de stathmin-1 y CD147 en diferentes tumores del músculo liso uterino

SUMMARY: Uterine smooth muscle tumors (USMT) are common, behavior-distinct gynecological tumors; including: leiomyoma (ULM), leiomyosarcoma (ULMS), and smooth muscle tumors of undetermined malignant potential (STUMP). Pre-operative distinction is difficult, thus diagnosis relies on histopathology. Immunohistochemistry (IHC) had been used to help in distinction. We studied two markers (stathmin-1 and CD147) to demonstrate whether they have diagnostic/ prognostic assist. Sixty seven USMT are studied. Age, follow up, and recurrence/metastasis data were collected. Representative slides were stained and Histologic score (HS) calculated as stain intensity (SI) X percentage of positive tumor cells (PP). Results were grouped as low expression (LE) and high expression (HE); then correlated to tumor types, and risk of recurrence/ metastasis. Statistical analysis (P < 0.05); Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were calculated. Stathmin-1 HS (p= 0.000) and HE (p=0.002) were different among groups. Same as for CD147 HS and HE (both p=0.000), with a gradient increase from LM to STUMP to ULMS. Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were as following: For stathmin-1 HS: 92 %; 20 %; 42 %; and 80 % (CI= 44-96 %). For Stathmin-1 HE: 80 %; 66 %; 60 %; and 84 % (CI=66-94 %). For CD147 HS: 85 %; 22 %; 41 %; and 69 %. For CD147 HE: 58 %; 49 %; 42 %; and 65 % (CI= 45-80 %), respectively. Recurrence / metastasis were documented in 6 cases (4 ULMS; 2 STUMP) with follow up ranging from 6 months to 102 months. 5 tumors had stathmin-1 HE (p=0.099); 2 had CD147 HE (p=0.393) in the primary tumors. STMN1 and CD147 are helpful diagnostic tests for USMT sub-typing, especially for ULMS. Gradient increase of expression from LM, to STUMP, to ULMS may indicate a role in malignant transformation in USMT, and in increased risk of recurrences/metastasis.

RESUMEN: Los tumores del músculo liso uterino (USMT, por sus siglas en inglés) son tumores ginecológicos comunes y de comportamiento distinto; incluyendo: leiomioma (ULM), leiomiosarcoma (ULMS) y tumores de músculo liso de potencial maligno indeterminado (STUMP). La distinción preoperatoria es difícil, por lo que el diagnóstico se basa en la histopatología. La inmunohistoquímica (IHQ) se había utilizado para ayudar en la distinción. Estudiamos dos marcadores (stathmin-1 y CD147) para demostrar si había efecto diagnóstico / pronóstico. Se estudiaron 67 USMT. Se recopilaron los datos de edad, seguimiento y recurrencia / metástasis. Las muestras representativas se tiñeron y la puntuación histológica (HS) se calculó como la intensidad de la tinción (IS) x porcentaje de células tumorales positivas (PP). Los resultados se agruparon como expresión baja (EB) y expresión alta (EA); luego se correlacionaeon con los tipos de tumores y el riesgo de recurrencia / metástasis. Análisis estadístico (P <0,05); se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS. Stathmin-1 HS (p = 0,000) y HE (p = 0,002) fueron diferentes entre los grupos. Igual que para CD147 HS y HE (ambos p = 0,000), con un aumento de gradiente de LM a STUMP a ULMS. La sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS fueron los siguientes: Para stathmin-1 HS: 92 %; 20 %; 42 %; y 80 % (IC = 44-96 %). Para Stathmin-1 HE: 80 %; 66 %; 60 %; y 84 % (IC = 66-94 %). Para CD147 HS: 85 %; 22 %; 41 %; y el 69 %. Para CD147 HE: 58 %; 49 %; 42 %; y 65 % (IC = 45-80 %), respectivamente. La recurrencia / metástasis se documentaron en 6 casos (4 ULMS; 2 STUMP) con un seguimiento que osciló entre 6 meses y 102 meses. Cinco tumores tenían stathmin-1 HE (p = 0,099); dos tenían CD147 HE (p = 0,393) en los tumores primarios. STMN1 y CD147 son pruebas de diagnóstico útiles para la subclasificación de USMT, especialmente para ULMS. El aumento en el gradiente de la expresión de LM, a STUMP, a ULMS puede indicar un papel en la transformación maligna en USMT y en un mayor riesgo de recurrencias / metástasis.

Stathmin Expression in Breast Carcinoma as A Severity Marker Related to Staging, Grading and Receptor Evaluation

Background: Breast cancer is now the most common malignant tumor in women. Pathway specific therapy is the future of cancer management. Stathmin, a microtubule destabilizing cytosolic phosphoprotein which has profound influence on cell proliferation, differentiation and cellular motility is an accurate signature IHC marker of PI3K pathway. From overexpression of Stathmin in breast carcinoma one get information about disease progression, prognosis, drug resistance and change in treatment modality. Objective:1. To study and compare the result of Stathmin with level of Estrogen Receptor, Progesterone Receptor and Her-2-neu expression in breast carcinoma. 2. To study Stathmin expression in relation to staging, grading and type of breast cancer. 3. To study the possibility of role of Stathmin as a therapeutic target in breast carcinoma. Methods: A cross- sectional study was done. All cases were grossly and microscopically examined and were subjected to immunohistochemical stains of Estrogen, Progesterone, Her-2-neu, Stathmin and were correlated to staging and grading. Statistical Analysis: There were altogether 41 cases. In primary breast carcinoma specimens the Stathmin levels were measured by immunohistochemistry and graded from 0 – 3. Scores more than 3 were high expressors with more than 50% tumor cells showing positivity. Conclusion: Stathmin over expression in breast carcinoma seems to co relate with loss of Estrogen receptors and Progesterone receptors

Clinical significance of STMN1 expression in cervical cancer and effect of inhibition of its expression on viability and apoptosis of cervical cancer Si-Ha cells / 中国病理生理杂志

AIM:To investigate the clinical significance of stathmin 1 (STMN1) expression in cervical cancer and the influence of its expression on the viability and apoptosis of cervical cancer cells. METHODS:Western blot was used to detect the protein expression of STMN1 in cervical cancer tissues, and the relationship between the expression and clinical characteristics of cervical cancer was analyzed. STMN1-siRNA was transfected into cervical squamous-cell carcino-ma SiHa cells. The protein levels of STMN1, STAT3, p-STAT3 and survivin were determined by Western blot after trans-fection for 48 h. The cell viability was measured by MTT assay. The apoptosis was analyzed by flow cytometry. DCFH-DA probe was used to detect the level of reactive oxygen species (ROS). RESULTS:The protein expression of STMN1 in cer-vical cancer tissues was significantly higher than that in paracancerous tissues (P<0.01). The STMN1 protein expression level was not correlated with age and histological types of cervical cancer patients, but was related to clinical stage, histo-logical differentiation and lymph node metastasis ( P<0.01). Transfection with STMN1-siRNA significantly reduced the expression of STMN1 in SiHa cells. Compared with control group, the cell viability in STMN1-siRNA group was significant-ly decreased, the apoptotic rate and ROS content were increased, and the protein levels of p-STAT3 and survivin were down-regulated (P<0.01). However, no significant difference of the STAT3 protein level was observed between STMN1- siRNA group and control group. CONCLUSION:STMN1 is highly expressed in cervical cancer, and its expression is re-lated to clinical stage, histological differentiation and lymph node metastasis. Inhibition of STMN1 expression reduces the viability and promotes apoptosis of cancer cells by down-regulating STAT3 signaling pathway.

The effect of downregulation of Stathmin gene on biological behaviors of U373 and U87-MG glioblastoma cells

BACKGROUND: Stathmin as a critical protein involved in microtubule polymerization, is necessary for survival of cancer cells. However, extremely little is known about Stathmin in glioblastoma. So, this study was designed to elucidate the function of Stathmin gene in the tumorigenesis and progression of glioblastoma cells. METHOD: The lentiviral interference vector pLV3-si-Stathmin targeting Stathmin gene and the control vector pLV3-NC were established for the co-transfection of 293T cells together with the helper plasmids. Viral titer was determined via limiting dilution assay. Then pLV3-si-Stathmin and pLV3-NC were stably co-transfected into U373 and U87-MG glioblastoma cells. Expression levels of Stathmin protein in each group were determined by using Western Blot, and the proliferation and migration ability of the cells with downregulated Stathmin were evaluated through CCK8 assay and transwell invasion assay, respectively. Cell cycles and cell apoptosis were detected with flow cytometry. Finally, the effect of Stathmin in tumor formation was determined in nude mice. RESULT: DNA sequencing and viral titer assay indicated that the lentiviral interference vector was successfully established with a viral titer of 4 × 108 TU/ml. According to the results from Western Blotting, Stathmin protein expression level decreased significantly in the U373 and U87-MG cells after transfected with pLV3-si-Stathmin, respectively, compared with those transfected with pLV3-NC. In glioblastoma cells, the cell proliferation and migration were greatly inhibited after the downregulation of Stathmin protein. Flow cytometry showed that much more cells were arrested in G2/M phasein Stathmin downregulated group, compared with the non-transfection group and NC group. But Stathmin downregulation did not induce significant cell apoptosis. Tumor formation assay in nude mice showed that tumor formation was delayed after Stathmin downregulation, with a reduction in both tumor formation rate and tumor growth velocity. CONCLUSION: Stathmin downregulation affected the biological behaviors of U373 and U87-MG glioblastoma cells, inhibiting the proliferation and migration of tumor cells. Stathmin gene may serve as a potential target in gene therapy for glioblastoma.

Relevant coexpression of STMN1, MELK and FOXM1 in glioblastoma and review of the impact of STMN1 in cancer biology / Coexpressão relevante de STMN1, MELK e FOXM1 em glioblastoma e revisão do impacto de stmn1 na biologia do câncer

OBJECTIVE: To analyze the associated expression of STMN1, MELK and FOXM1 in search of alternative drugable target in glioblastoma (GBM) and to review relevant functional roles of STMN1 in cancer biology. METHOD: STMN1, MELK and FOXM1 expressions were studied by quantitative PCR and their coexpressions were analyzed in two independent glioblastoma cohorts. A review of articles in indexed journals that addressed the multiple functional aspects of STMN1 was conducted, focusing on the most recent reports discussing its role in cancer, in chemoresistance and in upstream pathways involving MELK and FOXM1. RESULTS: Significant associated expressions of MELK and FOXM1 were observed with STMN1 in GBM. Additionally, the literature review highlighted the relevance of STMN1 in cancer progression. CONCLUSION: STMN1 is very important to induce events in cancer development and progression, as cellular proliferation, migration, and drug resistance. Therefore, STMN1 can be an important therapeutic target for a large number of human cancers. In glioblastoma, the most aggressive brain tumor, the MELK/FOXM1/STMN1 presented significant associated expressions, thus pointing MELK and FOXM1 as alternative targets for therapy instead of STMN1, which is highly expressed in normal brain tissue. Continuous functional research to understand the STMN1 signaling pathway is worthwhile to improve the therapeutic approaches in cancer.

OBJETIVO: Analisar as expressões associadas de STMN1, MELK e FOXM1 na procura de alvos alternativos de tratamento em glioblastoma (GBM) e revisar os papeis funcionais relevantes de STMN1 na biologia do câncer. MÉTODO: As expressões de STMN1, MELK e FOXM1 foram estudadas por PCR quantitativo e suas coexpressões foram analisadas em dois coortes independentes de GBM. A revisão dos artigos publicados em revistas indexadas na procura dos aspectos funcionais múltiplos de STMN1 foi conduzida focando-se nos estudos mais recentes discutindo o seu papel em câncer, quimiorresistência e vias de sinalização envolvendo MELK e FOXM1. RESULTADOS: Observou-se expressões associadas significantes de MELK e FOXM1 com STMN1. Adicionalmente, a revisão da literatura salientou a relevância do STMN1 na progressão do câncer. CONCLUSÃO: STMN1 é muito importante nos eventos relacionados ao desenvolvimento e progressão do câncer, como proliferação celular, migração e resistência ao tratamento. Desta forma, STMN1 pode ser um forte alvo terapêutico em um grande número de cânceres humanos. Em GBM, o tumor cerebral mais agressivo, MELK/FOXM1/STMN1 apresentaram significativa associação em suas expressões gênicas, indicando, portanto, MELK e FOXM1 como alvos alternativos para terapia em substituição ao STMN1, que apresenta alta expressão no tecido cerebral normal. Perseverar nos estudos funcionais para o entendimento da via de sinalização do STMN1 é relevante para melhorar os esquemas terapêuticos para câncer.

Expression of Stathmin gene in ovarian cancer tissue and its valuation value on effect of Paclitaxel combined with cisplatin chemotherapy / 中国生化药物杂志

Objective To study the expression of Stathmin gene in ovarian cancer tissue and its valuation value on effect of Paclitaxel combined with cisplatin chemotherapy.Methods 92 cases of ovarian cancerpatients underwent surgical and postoperative chemotherapy treatment in our hospital during July 2012 to February 2016 were selected with research subject.The expression of Stathmin gene in ovarian cancer tissues and adjacent tissues was measured by fluorescence quantitative PCR.All ovarian cancer patients were divided into high Stathmin group and low Stathmin group with 46 cases according to the expression of Stathmin gene in ovarian cancer tissues.Comparison the chemotherapy effectin ovarian cancerpatients with different Stathmin gene expression.Results The expression of Stathmin mRNA in ovarian cancer tissues was significantly higher than that in adjacent tissues(P<0.05).After chemotherapy, serum tumor markers such as HE4, CA199, CA153, β-HCG in high Stathmin group were higher than those in low Stathmin group, angiogenesis indexes such as CXCR4, SDF-1, VEGF, Ang2 were lower than those in low Stathmin group, apoptotic indexes such as Fas/Apo-1 and Bcl-2 were higher than those in low Stathmin group(P<0.05).Conclusion Stathmin gene is highly expressed in ovarian cancer tissues, and the expression of Stathmin is negatively correlated with chemotherapy.

The associations between human papilloma viruse persistent infection and Stathmin-1 expression and the clinical significance in cervical intraepithelial neoplasia / 中国医师进修杂志

Objective To explore the relationship between Stathmin-1 and human papilloma viruse (HPV) persistent infection after conization of uterine cervix, and to show the clinical significance to recurrent of cervical intraepithelial neoplasia (CIN). Methods One hundred and six patients who were treated with conization of uterine cervix for CIN 2-3 grades were enrolled. Thirty-six recurrent patients were enrolled in recurrence group, and the others were enrolled in control group. The expression of Stathmin-1 in primary CIN tissues in two groups was detected by immunohistochemistry. The HPV infection was detected by HPV-DNA test. The relationship of HPV persistent infection and recurrence was analyzed. Results The positive expression rate of HPV persistent infection and HPV persistent infection rate in recurrence group were 88.89%(32/36), 83.33%(30/36), in control group were 34.29%(24/70) and 22.86%(16/70), and there were significant difference (P 0.05). Conclusions Stathmin-1 positive expression is related to HPV persistent infection. The two factors can affect the prognosis of high-grade CIN, and can provide new cues and theory basis for the prevention of recurrence.

Application value of detection on stathmin, p16 and Ki-67 in the cervical intractable cases / 肿瘤研究与临床

Objective To investigate the clinical application value of stathmin, p16 and Ki-67 in the cervical intractable cases. Methods Immunohistochemical method was used to detect the expressions of stathmin, p16 and Ki-67 in surgical specimens of 288 cervical intractable cases, including 30 cases of cervical benign changes, 70 cases of cervical intraepithelial neoplasia (CIN)Ⅰ, 78 cases of CINⅡ, 85 cases of CINⅢand 25 cases of squamous cell carcinoma (SCC, as control group). The application value of stathmin, p16 and Ki-67 in the cervical cases were analyzed. Results The positive expression rates of Ki-67 of cervical benign changes and CINⅠwere 20.0 % (6/30) and 54.3 % (38/70) (χ2 = 3.29, P> 0.05). The expression rates of Ki-67 in CINⅡ, CINⅢ and SCC were all 100.0 %, and compared with the cervix benign changes, the differences were statistically significant (χ2= 112, P0.05), but the expression rates in CINⅢ and SCC were higher than those in cervical benign change, CINⅠand CIN Ⅱ(P< 0.01). The positive expressions of stathmin, p16 and Ki-67 in each group of CIN were positively correlated (r= 0.412, P< 0.05). Conclusions Combined detection of p16 and Ki-67 can assist in the differential diagnosis of cervical intractable cases, and provide objective indicators for the classification and accurate diagnosis of CIN. Combined detection of p16 and stathmin may help to identify high-grade, low-grade CIN and cervix benign changes for the reduction of over-treatment.

Expression of stathmin and its influence on taxol sensitivity in esophageal squamous cell carcinoma / 医学研究生学报

Objective Stathmin, a microtubule-destabilizing protein , has high expression in esophageal squamous cell carci-noma(ESCC), while taxol is a common chemotherapy microtubule-targeted drug for esophageal cancer .This study aimed to investigate the impact of stathmin expression and its influence on taxol sensitivity in ESCC . Methods We established 2 cell models with ST-MN1 gene overexpression in KYSE 510 and KYSE 170 cell lines, including KYSE 510-Stathmin, KYSE 170-Stathmin, KYSE 510-Control and KYSE 170-Control.MTT assay and colony formation were applied to compare the taxol sensitivity between experimental group and control group .Flow cytometry was used to measure the apoptosis of KYSE 510-Stathmin and KYSE 510-Control after taxol treatment.Western blot was used to test the changes of related factors to apoptosis and autophagy . Results ①Stathmin protein ex-pressions in KYSE 510-Stathmin and KYSE 170-Stathmin cells were higher than those of control cells (P<0.01).② The percentages of inhibition were significantly decreased in KYSE 510-Stathmin and KYSE 170-Stathmin cells 24 h after 50, 100,250 nmol/L taxol treat-ment compared with KYSE 510-Stathmin cells(P <0.01).③The percentages of inhibition were significantly reduced in KYSE 510-Stathmin and KYSE 170-Stathmin cells after 250 nM taxol treatment for 24, 48, 60 h (P<0.01).④After taxol treatment,the number of colony formation in KYSE 510-Stathmin cells was higher com-pared with KYSE 510-Control cells (P<0.01).⑤The percentage of cell apoptosis in KYSE 510-Stathmin was significantly lower than that of KYSE 510-Control cells by flow cytometry (11.90%±0.78%vs 29.63%±3.26%, P<0.05).Western blot showed the ap-optosis of associated proteins such as the activation of Caspase 8 and Caspas9. Conclusion The result indicates that overexpression of stathmin inhibits taxol sensitivity in ESCC cell lines .

Correlation of Breast Cancer Cells Invasive and Stathmin Gene Expression / 现代检验医学杂志

Objective To explore the relationship between the Stathmin gene expression in breast cancer cells MDA-MB-231, MCF-7 and the biological behaviours such as cell growth,adhesion and invasion,and provide experimental basis of breast cancer metastasis for further study.Methods Used RT-PCR and Western Blot methods to detect the Stathmin gene expres-sion levels in MDA-MB-231 and MCF-7 cells,and in the mean while to test the MDA-MB-231 and MCF-7 cell growth,adhe-sion,invasion ability by CCK-8 cell proliferation experiments,cell adhesion experiments,cell invasion experiments,then, analyed the relationship of Stathmin gene expression and cell growth,adhesion,invasion ability.Results Over-expression levels of Stathmin gene were observed both in the MDA-MB-231 and MCF-7 cells (F=10.173,P<0.05),and furthermore, the expression levels of Stathmin gene in MDA-MB-231 cells was higher than in MCF-7 cells (t=4.562,P<0.05).While, the growth,adhesion and invasion ability of the MDA-MB-231 cells was higher than that of MCF-7 cells(P<0.05).Conclu-sion The higher level of Stathmin gene expression,the stronger breast cancer cells had ability of growth,invasion,and ad-hesive.The Stathmin gene expression levels was closely correlated with breast cancer cell invasive.

Stathmin for promoting cell proliferation and invasion ability in human SMMC-7721 hepatocellular carcinoma cells / 重庆医学

Objective To construct the stable stathmin-overexpression SMMC-7721 hepatocellular carcinoma cells and to explore the effect of stathmin-overexpression on the cell proliferation and metastasis in SMMC-7721 cells .Methods By using liposome , Flag-pcDNA3 .1 and Flag-pcDNA3 .1-stathmin plasmid were transfected into SMMC-7721 cells respectively ,the stable Flag-pcD-NA3 .1 expression cells(control group) and the stable stathmin-overexpression cells(experimental group) were established after an-tibiotic resistant gene screening ,and the cell lines were identified by Western Blot .Subsequently ,the cell proliferation was detected by cell count kit(CCK-8) and the soft agar assay ,the apoptosis and cell cycle were determined by the flow cytometry (FCM ) ,and the cell motility and invasion were analyzed by the Transwell assay in vitro .Results The stathmin protein expression of the experi-mental group was significantly increased compared with the control group (0 .76 ± 0 .12 vs .0 .16 ± 0 .05 ,P<0 .05) ,which indicated that the stathmin-overexpression human SMMC-7721 hepatocellular carcinoma cell line was successfully constructed .CCK-8 and the soft agar assay showed that the cell proliferation of the experimental group was higher than that of the control group (0 .29 ± 0 .03 vs .0 .60 ± 0 .05 ,P< 0 .01);additionally ,the apoptotic ratio of the experimental group was decreased compared with the control group[(11 .57 ± 1 .09)% vs .(5 .80 ± 0 .33)% ,P<0 .05] ,the cell cycle was arrested in the stage G2/M ;the Transwell experiment results verified that the cell motility and the invasive ability of the experimental group were obviously reinforced compared with the control group[transmenbrane cell numbers in migrant assay :(54 .03 ± 7 .21) vs .(130 .45 ± 14 .13);transmenbrane cell numbers in invasive assay :(17 .75 ± 2 .52) vs .(57 .76 ± 8 .50) respectively] ,the differences had statistical significance(P<0 .01) .Conclusion The overexpression of stathmin promotes the cell proliferation and the invasive ability in SMMC-7721 hepatocellular carcinoma cells .

A preliminary exploration for the proteome of children neuroblastoma / 国际儿科学杂志

Objective To screen the differential expression proteins in the children with neuroblastoma (NB) by proteomics tools.Methods Three specimens were collected from the patients diagnosed Ⅳstage NB by biopsy at Department of Pediatric Surgery of Chinese PLA General Hospital in Beijing from July to December,2011.Another three specimens were acquired from the same patients underwent tumor excision.Average age was 3.17 years.Proteins in neuroblastoma before and after chemotherapy were separated by two dimensional gel electrophoresis,analyzed by high performance liquid chromatography-eleetrospray tandem MS (Nano-UPLC-ESIMS/MS).Results After two dimensional gel electrophoresis,we obtained the maps about tissues before and after chemotherapy.There were 7 differential protein spots identified by using the Image Master two dimensional gel electrophoresis software,in which 2 were up-regulated,including Nm23 protein and neuropolypeptide h3,5were down-regulated after chemotherapy,including stathminl,heat shock protein 27,mitochondrial short-chain enoyl-coenzyme A,peroxiredoxin 1 and peroxiredoxin 3.Conclusion The differential expression proteins of children neuroblastoma before and after chemotherapy were successfully identified by two dimensional gel electrophoresis and Nano-UPLC-ESI-MS/MS.

Expression of stathmin and its influence to anti-microtube chemotheropy in non-small-cell lung cancer / 中华胸心血管外科杂志

Objective To investigate the expression of stathmin and evaluate its influence to anti-microtubule adjuvant chemotherapy in non-small-cell lung cancer(NSCLC).Methods The clinical data and survival status of 78 NSCLC patients were collected,and their paraffin-embedded tissue were detected immunohistochemically with a rabbit anti-human stathmin polyclonal antibody.The clinical significance of stathmin expression and its influence to overall survival rate were analyzed statistically between patients who received paclitaxel or vinblastine adjuvant chemotherapy.Results The positive expression of stathmin could only be observed in the cytoplasm of cancer cells.Among 78 patients,40 (51.3 ％ ) patients were stained stathmin-positive.The positive rate of stathmin was significantly higher in male than female,in central type than peripheral type,in pleura-involved than non-involved,and in dead patients than survival patients ( P ＜ 0.05 ),but showed no significant differences in patients with different age,differentiated grade,pathological type,clinical stage,or lymph-node metastasis status.The expression of stathmin had a significant influence to overall survival rate(x2 =4.348,P ＜0.05 ),and those stathmin-negative patients showed a longer survival time.In stathmin-negative patients,those who received adjuvant chemotherapy with vinblastine exhibited a shorter survival time than those with paclitaxel,but the P =0.06.In stathmin-positive patients,the survival rate or time showed no difference between groups with paclitaxel and vinblastine.The differentiated grade,metastasis to lymph node and expression of stathmin were independent risk factors influencing survival rate.The positive expression of stathmin could only be observed in the cytoplasm of cancer cells.Among 78 patients,40 (51.3 ％ )patients were stained stathminpositive.The positive rate of stathmin was significantly higher in male than female,in central type than peripheral type,in pleura-involved than non-involved,and in dead patients than survival patients ( P ＜ 0.05 ),but showed no significant differences in patients with different age,differentiated grade,pathological type,clinical stage,or lymph-node metastasis status.The expression of stathmin had a significant influence to overall survival rate(x2 =4.348,P ＜ 0.05 ),and those stathmin-negative patients showed a longer survival time.In stathmin-negative patients,those who received adjuvant chemotherapy with vinblastine exhibited a shorter survival time than those with paclitaxel,but the P =0.06.In stathmin-positive patients,the survival rate or time showed no difference between groups with paclitaxel and vinblastine.The differentiated grade,metastasis to lymph node and expression of stathmin were independent risk factors influencing survival rate.Conclusion Our study suggested that the detection of stathmin in resected NSCLC tumor tissues may be helpful for prediction of prognosis,but helpless for making a choice between paclitaxel and vinblastine.NSCLC patients with stathmin-negative,no metastasis to lymph node or good-differentiated grade may have a better prognosis.

Monoclonal antibody against human stathmin 1 in combination with vinblastine inhibits proliferation of K562 cell lines / 基础医学与临床

Objective To investigate the effects of monoclonal antibody against stathmin 1 in combination with vinblastine on the proliferation of K562 cells. Methods K562 cells were treated with monoclonal antibody against stathmin 1, vinblastine alone or with their combination, 24, 48, 72, 96 hours later, inhabitation rate was studied by MTT assay;The apoptosis was analyzed by invert microscope and flow cytometry with Annexin V/PI. Results The quantity decreased and shape, size changed after treatment with different concentration of experimental groups. Monoclonal antibodies against stathmin 1 and vinblastine used alone or in combination both inhibited the proliferation of K562 cells,the inhibition ratio of their combination is higher (P <0. 05) ,and a synergistic effect of the two agents was noted in their combined action ( P < 0. 05 ). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P <0. 05). Conclusion Monoclonal antibody against stathmin 1 and vinblastine used alone or in combination both can inhibite proliferation of K562 cells and induce apoptsis. A synergistic effect is observed between the monoclonal antibodies against stathmin 1 and vinblastine in their inhibition of K562 cell proliferation.

Stathmin: a potential tumor biomarker / 肿瘤

Stathmin, a ubiquitously expressed cytosolic protein(Mr=19×10~3), is also called oncogene protein 18 (Op18). Stathmin is involved in the assembly of microtubule (MT) and spindle by binding the tubulin protein. It plays a key role in cell proliferation, differentiation, regeneration, and migration and has regulatory effects on the signal transduction. Recently, it is reported that stathmin is overexpressed in a variety of human malignancies. It induces tumor cell migration and invasion by regulating MT depolymeri-zation. Its post-translational modification influences the interaction with p53 protein and is involved in the initiation and progression of malignant tumor. Stathmin alone or in combination with chemotherapeutics has been used for tumor therapy. The internal association of stathmin with cancer etiology is still unknown. So, further studies are needed to determine the role of stathmin as potential tumor biomarker and a drug target in tumor therapy.

Analysis of the differential expression of Stathmin in HEK293 cells infected with human-tropic porcine endogenous retrovirus / 中华微生物学和免疫学杂志

Objective To analyze the differential expression of Stathmin in human cells infected with human-tropic porcine endogenous retrovirus(PERV)and to explore the potential molecular effect of human-tropic PERV on human cells.Methods HEK293 cells were infected with the human-tropic PERV infectious molecular clone.PCR,real-time RT-PCR and immunofluorescence analysis were applied to confirm that HEK293 cells were infected.Then real-time RT-PCR and Western blot were carried out to analyze the differential expression of Stathmin at the mRNA level and protein level,respectively.Results HEK293 cells were infected by human-tropic PERV.Real-time RT-PCR and Western blot analysis showed that Stathmin was up-regulated in HEK293 cells infected with PERV compared with the control cells.Conclusion Stathmin was up-regulated in HEK293 cells infected with human-tropic PERV.These studies will be helpful for revealing the interaction of PERV and human cells,and for understanding the molecular effect of humantropic PERV on human cells.In addition,it suggested that PERV infection may infect cell growth and physiological functions,even be pathogenic.These will help to clarify the biologic characteristics of PERV and evaluate the safety of PERV in pig to human xenotransplantation.

Molecular cloning and expression analysis of evolutionarily conserved stathmin from Gekko japonicus spinal cord.

The cDNA encoding stathmin is identified from the brain and spinal cord cDNA library of Gekko japonicus. It contains a 450 bp open-reading-frame, corresponding to a deduced protein of 149 amino acids. At amino acid level, gecko stathmin shares more than 76.4% identities with vertebrate stathmins, and especially, it shares 100% identity with human stathmin, suggesting that the selective pressure must have been extremely high for the conservation of stathmin during the vertebrates including reptile evolution. Reverse transcriptase polymerase chain reaction (RT-PCR) shows that gecko stathmin is ubiquitously expressed in all tissues examined. In situ hybridization reveals that stathmin transcript mainly appear in the gray matter of spinal cord. The change of stathmin expression in spinal cord after tail amputation is examined by semi-quantitative RT-PCR. Stathmin expression increases at 1 day and 3 day after amputation and decreases to the control level at 1 week. However, the expression level increases again at 2 weeks. These suggest that stathmin may be associated with the immune protection of the injury, as well as in the regeneration of spinal cord.

The expression stathmin gene in laryngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To observe expression of stathmin gene in laryngeal squamous cell carcinoma(LSCC) and relation between expression of stathmin gene and occurance and development of LSCC.Method:The expression of the stathmin gene was determined in 35 LSCC of specimens and 18 normal laryngeal tissues(NLT) of specimens by in situ hybridizaion with Digoxigenin labled probe of stathmin mRNA.Result:Expression of stathmin gene was observed in 35 cases of laryneal squamous cell carcinoma tissue (positive rate, 69%) and positive signal was observed in both cytoplasm and nuclear. Among 18 cases of normal tissue, only 6 showed weak positive signal. There was significant difference in expression of stathmin gene between laryneal squamous cell carcinoma tissue and nomal tissue.Conclusion:Expreesion of stathmin gene may play a key role in the pathogenisis and development of laryneal squamous cell carcinoma. It may be a very important biotherapy target in the treatment of laryneal squamous cell carcinoma.

Progression of stathmin / 国际肿瘤学杂志

Many transcription factors, kinases and phosphorylase regulate the expression and activity of stuthmin. The abnormality of stathmin expression or its activity is closely involved in lots of pathological or phys-iological events such as cell proliferation, development of tumor. Many kinds of malignant tumors have high ex-pression of stathmin, and inhibiting the expression of stathmin protein is a new biotherapy target in tumor geneth-erapy. Moreover, stathmin protein can influence curative effect of some chemotherapeutics ,which target microtu-bular. This has some significance with regard to the guidance of clinical medication.

Effect of Stathmin Decoy-oligodeoxynucleotides on the Proliferation and Differentiation of Precartilainous Stem Cells / 华中科技大学学报（医学）（英德文版）

By using decoy-oligodeoxynucleotides (decoy-ODNS) technique, the effects of Stathmin gene on the proliferation and differentiation of in vitro cultured precartilainous stem cells (PSCs) were investigated. The Stathmin decoy-ODNs were transfected into PSCs in rats by using gene trans- fection technique. Under the induction of cortisol (1 μmol/L), electrophoretic mobility shift assay was used the inhibitory effects of decoy-ODNS on Stathmin gene. MTT and cytometry were used to test the cell proliferation. The expression of collagen Ⅱ and Ⅴ and Stathmin protein was detected by using Western blot. The results showed that Stathmin decoy-ODNs inhibited the Stathmin activity in a dose-dependent manner. When the concentration of decoy-ODNs was 10 times of standard con- centration, the proliferation of PSCs was obviously suppressed and the differentiation happened. Compared to the control group, the difference was significant (P<0.05). It was concluded that de-coy-ODNs could inhibit the proliferation and promote the differentiation of PSCs by antagonizing Stathmin activity.