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1.
Cureus ; 16(7): e65627, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39205763

RESUMO

Medulloblastoma (MB) is a common malignant intracranial neoplasms in children. The treatment and prognosis of this tumor depends on histology and molecular subtypes. Survivin, implicated in various malignancies, may hold prognostic significance. We investigated survivin and p53 immunoreactivity in different histological subtypes in 20 MB cases from January 2018 to June 2021. Immunohistochemistry revealed survivin expression in 75% (15/20) of cases, with cytoplasmic (10 cases), nuclear (four cases), or combined expression (one case). p53 nuclear expression was present in 35% (7/20) of cases. Classical variant MB exhibited predominant p53 and cytoplasmic survivin expression. Given the association of survivin and p53 expression with poor prognosis, especially in the prevalent classical variant, targeted therapies may hold promise for MB treatment advancement.

2.
Mikrochim Acta ; 188(9): 301, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34409498

RESUMO

An ultrathin micro-patterned MXene/PEDOT:PSS-based organic electrochemical transistor biosensor was constructed, which can significantly amplify the amperometric signal and transistor's performance. A novel interdigitated OECTs biosensor has been developed for reliable determination of survivin for the following considerations: (1) The synergistic effect of intercalated MXene and ionic PEDOT:PSS enhanced the mobility and volumetric capacitance of OECTs biosensor. (2) Compared with the best previous literatures, our assay demonstrated enhanced detection limit of survivin down to 10 pg mL-1, as well as satisfactory selectivity, reproducibility, and reliability. (3) Comparison of OECTs against commercial ELISA kit yielded favorable linearity (Y = 1.0015*X + 0.0039) and correlation coefficient (R2 = 0.9717). Those advantages are expected to pave the way to design of an OECTs biosensor with robustness, non-invasiveness, and miniaturization for the point-of-care applications.


Assuntos
Eletroquímica/métodos , Osteossarcoma/terapia , Poliestirenos/uso terapêutico , Survivina/metabolismo , Criança , Humanos , Poliestirenos/farmacologia
3.
Biomolecules ; 10(2)2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973079

RESUMO

Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of -amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and -amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells' differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.


Assuntos
Adipócitos/citologia , Antineoplásicos Fitogênicos/farmacologia , Flores/química , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Mieloide Aguda/metabolismo , Oleaceae/química , Survivina/metabolismo , Células 3T3-L1 , Alcenos/química , Animais , Proliferação de Células , Avaliação Pré-Clínica de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração Inibidora 50 , Células Jurkat , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucócitos Mononucleares/citologia , Células MCF-7 , Camundongos , Simulação de Acoplamento Molecular , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia
4.
J Orthop Surg Res ; 14(1): 259, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412899

RESUMO

BACKGROUND: The aim of this study was to evaluate the effects of different doses of ginsenoside Rb1 (GRb1) pretreatment on spinal cord ischemia-reperfusion (SCII) in rats and explore the potential mechanisms about the expression of survivin protein after the intervention. METHODS: A total of 90 healthy adult Sprague-Dawley (SD) rats were randomly divided into six groups: sham-operated (n = 15), SCII model (n = 15), and GRb1-treated groups (n = 60). The GRb1-treated group was divided into four subgroups: 10 mg/kg, 20 mg/kg, 40 mg/kg, and 80 mg/kg (n = 15). The corresponding dose of GRb1 was injected intraperitoneally 30 min before operation and every day after operation. Forty-eight hours after model establishment, the neurological function of hind limbs was measured with Basso, Beattie, and Bresnahan (BBB) scale. The superoxide dismutase (SOD) and malondialdehyde (MDA) levels in serum and spinal cord tissue were detected respectively. The expression of survivin protein was observed by immunofluorescence staining. HE and TUNEL staining were used to observe neural cell injury and apoptosis, respectively, in the spinal cord of rats with SCII. RESULTS: The intervention of different doses of GRb1 could increase SOD activity and decrease MDA content in serum and spinal cord tissue, increase survivin protein expression, and decrease neuronal apoptosis. It was dose-dependent, but there was no significant change between 40 mg/kg and 80 mg/kg. CONCLUSIONS: GRb1 could reduce the cell apoptosis induced by SCII through inhibiting oxidative stress. It can also inhibit apoptosis by promoting the expression of Survivin protein. Ginsenoside Rb1 had a dose-dependent protective effect on SCII in the dose range of 10 mg/kg-40 mg/kg.


Assuntos
Ginsenosídeos/uso terapêutico , Panax , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/tratamento farmacológico , Isquemia do Cordão Espinal/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ginsenosídeos/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Isquemia do Cordão Espinal/patologia
5.
Biosens Bioelectron ; 137: 58-71, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31078841

RESUMO

The development of biosensors for cancer biomarkers has recently been expanding rapidly, offering promising biomedical applications of these sensors as highly sensitive, selective, and inexpensive bioanalytical tools that can provide alternative methodology to that afforded by the advanced hyphenated-instrumental techniques. In this review, we focus particularly on the detection of a member of the inhibitor of apoptosis proteins (IAP) family, protein survivin (Sur), a ubiquitous re-organizer of the cell life cycle with the ability to inhibit the apoptosis and induce an enhanced proliferation leading to the unimpeded cancer growth and metastasis. Herein, we critically evaluate the progress in the development of novel biosensing systems and biosensors for the detection of two survivin (Sur) biomarkers: the Sur protein and its messenger RNA (Sur mRNA), including immunosensors, electrochemical piezo- and impedance-sensors, electrochemi-luminescence biosensors, genosensors based on oligonucleotide molecular beacons (MBs) with fluorescent or electrochemical transduction, as well as the microfluidic and related analytical platforms based on solution chemistry. The in-situ applications of survivin biomarkers' detection technologies to equip nanocarriers of the controlled drug delivery systems with MB-based fluorescence imaging capability, apoptosis control, and mitigation of the acquired drug resistance are also presented and critically evaluated. Finally, we turn the attention to the application of biosensors for the analysis of Sur biomarkers in exosomes and circulating tumor cells for a non-invasive liquid biopsy. The prospect of a widespread screening for early cancers, based on inexpensive point-of-care testing using biosensors and multiplex biosensor arrays, as a means of reducing the high cancer fatality rate, is discussed.


Assuntos
Proteínas Reguladoras de Apoptose/isolamento & purificação , Técnicas Biossensoriais , Neoplasias/diagnóstico , Survivina/isolamento & purificação , Apoptose , Proteínas Reguladoras de Apoptose/genética , Detecção Precoce de Câncer , Humanos , Neoplasias/genética , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Survivina/genética
6.
Aging Clin Exp Res ; 30(5): 419-431, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28752477

RESUMO

BACKGROUND: Number of elderly patients subjected to extensive surgical procedures in the presence of cardiovascular morbidities is increasing every year. Therefore, there is a need to make preoperative diagnostics more accurate. AIMS: To evaluate the usefulness of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator as a predictive tool in preoperative assessment of cardiovascular risk in elderly patients. METHODS: This prospective pilot study included 78 patients who were being prepared for extensive non-cardiac surgeries under general anaesthesia. Their data have been processed on the interactive ACS NSQIP calculator. Blood sampling has been performed 7 days prior to surgery, and serum has been separated. Clinical, novel, and experimental biomarkers [hsCRP, H-FABP, and Survivin (BIRC5)] have been measured in specialized laboratories. RESULTS: Mean age of included patients was 71.35 ± 6.89 years. In the case of heart complications and mortality prediction, hsCRP and ACS NSQIP showed the highest specificity and sensitivity with AUC, respectively, 0.869 and 0.813 for heart complications and 0.883 and 0.813 for mortality. When combined with individual biomarkers AUC of ACS NSQIP raised, but if we combined all three biomarkers with ACS NSQIP, AUC reached as much as 0.920 for heart complications and 0.939 for mortality. DISCUSSION: ACS NSQIP proved to reduce inaccuracy in preoperative assessment, but it cannot be used independently, which has already been proved by other authors. CONCLUSIONS: Our results indicate that ACS NSQIP represents an accurate tool for preoperative assessment of elderly patients, especially if combined with cardiac biomarkers.


Assuntos
Doenças Cardiovasculares/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/cirurgia , Feminino , Humanos , Masculino , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Medição de Risco/métodos , Sensibilidade e Especificidade , Estados Unidos
7.
Bioengineered ; 8(5): 511-523, 2017 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-28051906

RESUMO

BACKGROUND: Survivin has been shown to play an important role in cancer pathogenesis. However, its role in cervical cancer development is still controversial. This study was performed to evaluate the clinical significance of survivin expression in cervical cancer. METHODS: Search of some online electronic databases was conducted to identify available studies. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Finally, 18 eligible studies with 791 cervical cancer patients, 1,013 cervical intraepithelial neoplasia (CIN) lesions, 199 normal cervical tissues, and 95 samples with chronic cervicitis were identified in this analysis. The pooled OR of survivin expression was found to be significantly higher in the samples from cervical cancer than in those from CIN lesions, normal cervical tissues, and chronic cervicitis. When cervical cancer was compared to CIN lesions, the subgroup analysis by ethnicity showed that survivin expression was associated with a risk of cervical cancer in Asians (P < 0.001), but not in Caucasians (P = 0.659). In addition, survivin was significantly more overexpressed in high-grade cervical cancer than in low-grade cervical cancer. Its expression was also more elevated in advanced-stage patients than in early-stage patients, in lymph node metastasis than in lymph node without metastasis, and in squamous cell carcinoma (SCC) than in adenocarcinoma (AC). CONCLUSIONS: The expression of survivin may play a key role in the carcinogenesis, progression, and metastasis of cervical cancer. However, survivin expression may be involved in the progression of CIN lesions only in the Asian population. Survivin expression is associated with an increased risk of SCC. Additional studies with larger sample sizes are needed in the future to confirm our findings.


Assuntos
Povo Asiático/estatística & dados numéricos , Biomarcadores Tumorais/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Displasia do Colo do Útero/etnologia , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Survivina , Neoplasias do Colo do Útero/patologia , População Branca/estatística & dados numéricos , Displasia do Colo do Útero/patologia
8.
Oncotarget ; 7(49): 81463-81473, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27806337

RESUMO

Human HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitin-like-modifier family of proteins, which have been implicated in cancer development. In addition, the Survivin protein promotes proliferation in bladder cancer (BC). In this study, we explored the link between FAT10 and Survivin. FAT10 expression was dramatically up-regulated in BC tissue samples, and Kaplan-Meier survival analysis revealed that BC patients with high FAT10 expression had shorter overall survival than those with low FAT10 expression. Moreover, RNAi-mediated FAT10 knockdown decreased Survivin protein levels and inhibited BC proliferation both in vitro and in vivo. FAT10 directly bound to and stabilized Survivin protein, thereby promoting cancer cell proliferation by inhibiting ubiquitin-mediated degradation. These results reveal a novel mechanism by which FAT10 promotes tumor proliferation by directly stabilizing Survivin protein in BC.


Assuntos
Proliferação de Células , Proteínas Inibidoras de Apoptose/metabolismo , Ubiquitinas/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Proteínas Inibidoras de Apoptose/genética , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Estabilidade Proteica , Proteólise , Interferência de RNA , Transdução de Sinais , Survivina , Fatores de Tempo , Transfecção , Carga Tumoral , Ubiquitinação , Ubiquitinas/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Adulto Jovem
9.
Korean J Radiol ; 17(4): 497-508, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27390541

RESUMO

OBJECTIVE: To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. MATERIALS AND METHODS: Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. RESULTS: Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). CONCLUSION: Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Microbolhas , Neoplasias da Próstata/tratamento farmacológico , RNA Interferente Pequeno/metabolismo , Animais , Antibióticos Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/toxicidade , Humanos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Lipossomos/química , Masculino , Camundongos , Microscopia Confocal , Neoplasias da Próstata/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Survivina , Transfecção , Transplante Heterólogo , Ultrassonografia
10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-29166

RESUMO

OBJECTIVE: To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo. MATERIALS AND METHODS: Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo. RESULTS: Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027). CONCLUSION: Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.


Assuntos
Animais , Humanos , Camundongos , Anticorpos , Apoptose , Western Blotting , Linhagem Celular , Sobrevivência Celular , Doxorrubicina , Xenoenxertos , Técnicas In Vitro , Microbolhas , Microscopia Confocal , Próstata , Neoplasias da Próstata , Receptores ErbB , RNA Interferente Pequeno , Ultrassonografia
11.
Cancer Med ; 4(5): 643-50, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25533314

RESUMO

Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m(2) ) in combination with YM155 (5 mg/m(2) per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m(2) and 56 patients received 75 mg/m(2) of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3-48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5-43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose , Biomarcadores , Docetaxel , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacocinética , Estimativa de Kaplan-Meier , Masculino , Melanoma/metabolismo , Melanoma/mortalidade , Pessoa de Meia-Idade , Naftoquinonas/administração & dosagem , Naftoquinonas/farmacocinética , Metástase Neoplásica , Estadiamento de Neoplasias , Taxoides/administração & dosagem , Taxoides/farmacocinética , Resultado do Tratamento
12.
International Journal of Surgery ; (12): 164-167,封3, 2015.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-601277

RESUMO

Objective To investigate the effect on ER expression in MCF-7 cell by siRNA against survivin mediated by adenovirus vector.Methods An adenovirus vector of siRNA against survivin was constructed and used to infect MCF-7 cell.The change of expression of survivin and ER was detected by Western Blot.Results The expression strength of survivin are 0.09 ± 0.04、0.86 ± 0.08、0.82 ± 0.17;expression strength of ER are 1.57 ± 0.09、1.16 ± 0.10、1.23 ± 0.01 respectively in the experimental group,negative control group and blank control group.Statistics analysis shows that the adenovirus vector of siRNA against survivin constructed in the study can suppress the expression of survivin significantly,and suppress the expression of survivin can up-regulate the estrogen receptor (ER) expression.Conclusions The results suggest that there may be a certain regulatory mechanism between survivin and ER signal pathway in MCF-7 cell and siRNA against survivin is of important potential value in the endocrine therapy of hormone receptor positive breast cancer.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-419047

RESUMO

Objective To investigate the radiosensitization effect and underlying mechanism of Paeonol on human lung adenocarcinoma cell line A549 in vitro. Methods Cells were assigned to following groups:control,Paeonol alone,irradiation alone,Paeonol combined with irradiation.The effect of Paeonol on cell proliferation was evaluated by the MTT assay. Clonogenic assay was performed to measure the radiosensitization effect of Paeonol under three concentrations around 20% IC50.Cell apoptosis was determined by TUNEL assay and flow cytometry (FCM).The expression of Survivin protein was analyzed by Western blot.Results Cell growth was inhibited by Paeonol in a dose-dependent manner and the IC50 of Paeonol was (25.2 ± 2.1 ) mg/L. Clonogenic assay showed that Paeonol could markedly enhance cell radiosensitivity and the sensitizing enhancement ratio (SER) was 1.29.After the pretreatment of Paeonol with different concentrations,radiation-induced apoptosis increased with the doses at 24,48,and 72 h post-irradiation ( t =4.95,3.03,3.78,4.59,2.88,3.70,5.54,P < 0.05 ). Moreover,the protein expression of Survivin was obviously down-regulated by 22.6% - 56.7% ( t =4.15,7.30,13.47,P <0.05 ) due to the treatment of Paeonol.When the Paeonol-treated cells were further irradiated with 6 Gy X-rays,the expression of Survivin was reduced to 22.2% - 69.4% ( t =4.30,8.36,16.34,P < 0.05 ).Conclusions Paeonol had radiosensitization effect on the human lung adenocarcinoma cell line A549 in vitro,where the down-regulated Survivin protein might be involved.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1032657

RESUMO

Objective To explore the expression of survivin in gliomas and its clinical significance. Methods The immunohistochemistry was used to measure protein expression of survivin in 90 cases ofglioma with grade Ⅰ 30cases, gradeⅡ30 cases and gradeⅢ-Ⅳ30 cases. We also used ten normal immunohistochemistry slices resulted from decompression after traumatic brain injury as control group. Results There are survin protein expressions in glioma cytoplasm and the higher the malignancy is, the expression becomes higher. The positive rate of survivin was 16.67% with glioma grade Ⅰ(6/30), 46.67% with gradeⅡ (14/30), and 86.67 % with grade Ⅲ- Ⅳ(26/30) which had statistical significance. However, in normal cerebral tissue, the expression of survivin was negative. Conclusion Survivin expression in gliomas is related to themalignancy of the tumor and it's targeted therapy may become a new management for gliomas.

15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-96568

RESUMO

Suvivin is a novel member of the inhibitor of apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (MTC) and a MTC cell line TT, correlate suvivin expression with clinicopathologic features of MTC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffin-embedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin-targeted gene therapy for MTC.


Assuntos
Masculino , Humanos , Feminino , Adulto , Fatores de Tempo , Neoplasias da Glândula Tireoide/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Oligonucleotídeos Antissenso/genética , Proteínas de Neoplasias/genética , Proteínas Associadas aos Microtúbulos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Carcinoma Medular/metabolismo , Apoptose/efeitos dos fármacos
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-562858

RESUMO

Objective To investigate the expression and significance of Survivin and Fhit protein in colorectal benign and malignant disease.Methods Test the expression of Survivin and Fhit proteins in 20 cases normal colorectal mucosa,30 cases low grade colorectal intraepithelial lesion,30 cases high grade colorectal intraepithelial lesion and 68 cases colorectal adenocarcinoma by immunohistochemical staining S-P method.Results The unexpression of Survivin in normal colorectal mucosa,postive expression rates of Survivin in low grade colorectal intraepithelial lesion,high grade colorectal intraepithelial lision and colorectal adenocarcinoma were 43.3%,76.7% and 91.2%(P

17.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wpr-150295

RESUMO

BACKGROUND: Survivin, a novel member of inhibitor-of-apoptosis, is undetectable in most terminally differentiated nonproliferative adult tissue, but is overexpressed in some human malignancies. The survivin gene expression is repressed by binding of wild-type p53 with the survivin promotor. In this study, we investigated the prevalence of survivin expression, its association with p53 overexpression and proliferative index, and clinicopathological significance in non-small cell lung carcinomas (NSCLC). METHODS: Immunohistochemical stainings were performed in 59 cases of primary NSCLC for survivin, p53 and Ki-67. Correlations between the survivin expression, p53 overexpression and Ki-67 labeling index were analyzed. RESULTS: Survivin expression was detected in 47 carcinomas (80%) with nuclear immunoreactivity (56%). Survivin nuclear immunoreactivity revealed significantly worse prognosis in NSCLC patients (p=0.003), and correlated with lymph node metastasis (p=0.014), lymphovascular invasion (p=0.032), p53 overexpression, and Ki-67 labeling index (KI 24.2 +/- 6.9, p=0.045). Survivin expression was not correlated with histological type and pT status. CONCLUSIONS: High incidence of survivin overexpression in NSCLC suggests that survivin is involved in lung carcinogenesis, and nuclear expression of survivin can be used as a poor prognostic predictor in NSCLC patients. Expression of mutant p53 seems to be a possible mechanism of survivin up-regulation in NSCLC.


Assuntos
Adulto , Humanos , Biologia , Carcinogênese , Proliferação de Células , Expressão Gênica , Incidência , Pulmão , Linfonodos , Metástase Neoplásica , Prevalência , Prognóstico , Regulação para Cima
18.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-181739

RESUMO

BACKGROUND: Medullary thyroid carcinoma (MTC) that originates from C cells comprises about 10% of all the malignant thyroid tumors. Activating mutations of the RET proto-oncogene have been found to be involved in the anti-apoptotic pathway of MTC that harbors the RET mutation. We investigated the correlation between the clinicopathologic parameters and the expressions of survivin, a novel anti-apoptotic molecule, and the other apoptosis-related proteins, and the known prognostic markers. METHODS: Immunohistochemical staining was performed using antibodies for survivin, Fas, Fas ligand (FasL), bcl-2, calcitonin, CEA and cyclin A in 19 case of MTC; 10 sporadic MTCs, eight multiple endocrine neoplasia (MEN) type 2A MTCs and one familial MTC (FMTC). RESULTS: Survivin protein expression was found in five cases (26%) and this was correlated with the presence of angiolymphatic tumor emboli (p=0.019). FasL was expressed in 14 cases (74%) and it had correlation with the presence of lymph node metastases (p=0.029). The cyclin A-labeling indices were correlated with local invasiveness (p=0.001). CONCLUSIONS: Survivin and FasL might be involved in the lymphatic tumor spread of MTC.


Assuntos
Anticorpos , Calcitonina , Carcinoma Medular , Ciclina A , Ciclinas , Proteína Ligante Fas , Linfonodos , Neoplasia Endócrina Múltipla , Metástase Neoplásica , Proto-Oncogenes , Glândula Tireoide , Neoplasias da Glândula Tireoide
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-675282

RESUMO

Objective To study the expression of survivin protein in primary hepatocellular carcinoma(PHC) and its relationship to the proliferation of the tumor cells and prognosis of PHC. Methods The expression of survivin protein and the proliferation of tumor cells marked by proliferating cell nuclear antigen (PCNA) in 48 cases of PHC were determined by immunohistochemical method. Results The survivin protein was expressed in 31 of 48 cases of PHC (64.6%). The expression of PCNA was significantly higher in hepatocellular carcinoma (HCC) with positive survivin expression than in HCC with negative survivin expression. The patients with positive survivin expression had the worse prognosis than those with negative survivin expression. Conclusion The expression of survivin may play an important role in the proliferation of PHC cells and closely associate with the prognosis of PHC, and probably become the prognostic factor and an important target of therapy.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-590142

RESUMO

Objective To investigate the expressions and correlation between Survivin and PTEN proteins in astrocytoma.Methods The expressions of Survivin and PTEN proteins were examined by immunohistrochemistry in astrocytoma specimens from 65 patients with astrocytoma.Results The positive expression rate of Survivin in astrocytoma grade Ⅱ was significantly lower than that in grade Ⅲ and grade Ⅳ(all P

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