DOCSLIB.ORG

Urine Survivin As a Diagnostic Biomarker for Bladder Cancer: a Systematic Review BJUIBJU INTERNATIONAL Ja Hyeon Ku *† , Guilherme Godoy * , Gilad E

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Urine Survivin As a Diagnostic Biomarker for Bladder Cancer: a Systematic Review BJUIBJU INTERNATIONAL Ja Hyeon Ku *† , Guilherme Godoy * , Gilad E Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review BJUIBJU INTERNATIONAL † ‡ Ja Hyeon Ku * , Guilherme Godoy * , Gilad E. Amiel * and Seth P. Lerner * * Scott Department of Urology, Baylor College of Medicine , and ‡ Michael E. Debakey Veterans Affairs Medical Center, Houston, TX, USA , and † Department of Urology, Seoul National University College of Medicine, Seoul, Korea Accepted for publication 9 November 2011 To determine the clinical utility of urine What ’ s known on the subject? and What does the study add? survivin as a bladder tumour marker we Although many tests for identifying patients with new or recurrent bladder cancer systematically reviewed the available have been used, a reliable method has yet to be established. Recently, increasing evidence. A comprehensive literature review attention has focused on the role of survivin in bladder cancer detection. was performed, from August 1997 to March 2011, using three search engines in Because urine survivin tests have better sensitivity than cytology, urine survivin could English including PubMed, Cochrane potentially replace routine cytology and might be used as an adjunct method for Library, and SCOPUS. Two reviewers cystoscopy. However, the clinical utility of urine survivin as a bladder tumour marker independently evaluated both trial identifi ed in the present study remains to be elucidated. eligibility and methodological quality and data extraction. We included studies that subsets of data. There were 2051 subjects, cytology, but did not match cytology for evaluated urine survivin, used cystoscopy including 1038 in the case group and 1013 specifi city. The clinical utility of urine and/or histopathology as the reference in the control group, and heterogeneity survivin as a bladder tumour marker standard, and allowed the construction of was present among diagnostic studies. The identifi ed in the present study remains to a 2 × 2 contingency table. Bivariate pooled sensitivity and specifi city for urine be elucidated. random effect meta-analyses were used to survivin tests were 0.772 (95% confi dence calculate the summary estimated of interval [ CI ] 0.745 – 0.797) and 0.918 (95% sensitivity and specifi city and to construct CI 0.899 – 0.934), respectively. The area KEYWORDS a summary receiver-operating under the curve of urine survivin tests characteristics curve of urine survivin tests. was 0.9392. When a subgroup analysis bladder neoplasm , survivin , urine , In all, 14 studies were included in the with six studies was performed, urine diagnostic test , systematic review , present review; two studies had two survivin tests had better sensitivity than meta-analysis INTRODUCTION compared with expensive and invasive tests [ 5 ] . Most of these tests have a better cystoscopy procedures. Although urine sensitivity for detecting bladder cancer than Bladder cancers are the second most cytology is highly sensitive in the urinary cytology, but the specifi city is lower. common urological malignancy in the recognition of high-grade urothelial It remains unclear whether or not these Western world, with an estimated 70 530 carcinomas, urine cytology has poor tests offer additional information that is new cases diagnosed each year in the USA sensitivity in low-grade bladder tumours useful for the detection and management of [ 1 ] . Most diagnosed patients (75 – 85%) [ 5 ] . In addition, urine cytology has poor non-muscle invasive bladder tumours [ 5 ] . present with non-muscle invasive disease, inter- and intra-observer reproducibility [ 6 ] . Therefore, a reliable diagnosis and which is characterised by a probability of Cystoscopy is the ‘ gold standard ’ method for surveillance method has yet to be recurrence and progression at 5 years of diagnosing bladder cancer and is also used established. 31 – 78% and 1 – 45%, respectively [ 2 ] . Early in the surveillance of patients with a history diagnosis and postoperative monitoring of of bladder cancer [ 3 ] . However, this method An ideal marker would be offi ce-based, rapid bladder cancer is benefi cial to improve is an invasive and costly procedure, may and inexpensive, and have high specifi city patient prognosis [ 3 ] because detecting miss small papillary tumours and carcinoma and sensitivity in the target population, bladder cancer earlier may decrease the rate in situ , and may be over used particularly in which might reduce the burden of frequent of progression [ 4 ] . patients with low-grade disease. cystoscopy and cost of care. Recently, increasing attention has focused on the role Screening, as well as follow-up of patients Many studies have searched for, developed, of survivin in bladder cancer detection. with bladder cancer, is usually performed and evaluated new tests for identifying Survivin is a structurally unique inhibitor of by urinary cytology as an adjunct to patients with new or recurrent bladder apoptosis protein (IAP) characterized by a cystoscopy. Urine cytology has advantages cancer that are more reliable than cytology highly conserved baculovirus IAP repeat 630 © 2012 BJU INTERNATIONAL | 110, 630–636 | doi:10.1111/j.1464-410X.2011.10884.x URINE SURVIVIN IN DIAGNOSIS OF BLADDER CANCER (BIR) domain. Survivin is a 12-amino acid search criteria. We then determined the fi nal version of the Quality Assessment of protein (16.5 kDa) encoded at chromosomal studies included in the meta-analysis after Diagnostic Accuracy Studies (QUADAS) tool region 17q25, and acts as an IAP by applying the same inclusion and exclusion [ 11 ] , which has 14 items. Every included inhibiting caspases 3, 7, and 9 [ 7 ] . Survivin criteria to the remaining content of the study was assessed by ‘ yes ’ , ‘ no ’ , and is almost exclusively expressed in malignant articles. To be enrolled in the present study, ‘ unclear ’ from the variations (items 1 and 2), epithelium and can be measured in urine at retrieved studies had to fulfi l the following the bias (items 3 – 7, 10 – 12, and 14) and the mRNA and protein level [ 8 ] . Survivin is inclusion criteria: provide a 2 × 2 the report quality (items 8, 9, and 13), expressed in human and rat embryogenesis contingency table; detect survivin in urine; respectively, and the causes of bias and tissues and most human tumours, but not in published in English; include a per patient variations were identifi ed. normal adult tissues (except the thymus analysis; and use cystoscopy and/or gland) [ 9 ] , which makes survivin especially histopathology as the reference standard. HOMOGENEITY TEST signifi cant compared with other IAP Exclusion criteria were as follows: non- members broadly distributed in normal adult human study; review articles; letters; Heterogeneity was explored using the tissues. Given the sharp differential editorial comments; case reports; articles chi-square test and likelihood ratio (LR) I2 . expression of survivin in cancerous vs that did not include raw data; and studies LR I2 measures the percentage of the total normal tissues, the detection of survivin on cancer not arising in the bladder. When variation across studies that are due to appears to be a suitable tool for cancer data or subsets of data were presented in heterogeneity rather than chance. LR I 2 is diagnosis. As a member of IAPs, survivin is more than one article, only the largest series evaluated as follows: I 2 = (Q – df)/Q × 100%, overexpressed in undifferentiated cells were included in the analysis. A cohort of where Q is Cochran ’ s heterogeneity statistic associated with a high potential of cell patients was not included more than once and df is the degrees of freedom. An I 2 proliferation [ 10 ] . in the same analysis. Included studies met > 50% may be considered to represent the quality criteria for studies of diagnosis substantial heterogeneity [ 12 ] . For the We performed a systematic review of the of the Oxford Centre for Evidence-Based LR chi-square test, we judged that diagnostic accuracy of trials of urine Medicine. Briefl y, the studies had clearly heterogeneity was signifi cant for P < 0.05. survivin tests for bladder cancer. The present identifi ed different groups of patients (with When there was evidence of heterogeneity, study sought to evaluate and compare the and without disease, and positive and data were analysed using a random effects detection validity (sensitivity and specifi city) negative tests). All included studies had a meta-analysis to obtain a summary estimate of urine survivin tests in the diagnosis of true-negative group that was free of the for the test sensitivity with 95% CIs. Studies bladder cancer and to construct a summary disease according to the defi nition used in in which positive results were confi rmed receiver-operating characteristic (ROC) the present study. were conducted using a pooled specifi city curve. with 95% CIs. EXTRACTION OF DATA THRESHOLD EFFECT ANALYSIS MATERIALS AND METHODS One reviewer (J.H.K) screened the titles and abstracts identifi ed by the search strategy A different threshold may be used in SEARCH STRATEGY and then two reviewers (J.H.K. and G.G.) included studies to defi ne positive test independently assessed the full tests for results due to lack of standardisation. A A comprehensive computer literature search inclusion. The database was designed to differential threshold effect may be the for abstracts was performed to identify ensure the most relevant data with respect reason for detectable sensitivities and articles about the diagnostic performance of to author, year of publication, demographics specifi cities of test accuracy studies. urine survivin for the detection of bladder of the patients, tumour characteristics, Summary ROC curves were constructed to cancer. We did a systematic review of geographic location, period of recruitment, see the variation between studies and original articles published between August study design, adoption of the ‘ blind ’ method, summarise the results quantitatively. A 1997 and March 2011 that analysed the and reference standard. The data extracted threshold effect was suspected with the diagnostic role of urine survivin in patients from articles comprised the number of ROC space graph if the points aligned in a with bladder cancer.
Load more

Recommended publications
  • Survivin Expression in Glioblastomas Correlates with Proliferation, but Not with Apoptosis
    ANTICANCER RESEARCH 28: 109-118 (2008) Survivin Expression in Glioblastomas Correlates with Proliferation, but not with Apoptosis MARTA MELLAI, VALENTINA CALDERA, ALESSIA PATRUCCO, LAURA ANNOVAZZI and DAVIDE SCHIFFER Neuro-bio-oncology Center of Policlinico di Monza Foundation and Department of Neuroscience, University of Turin, Via Pietro Micca, 29, 13100 Vercelli, Italy Abstract. Background: Survivin is expressed in proliferating The subcellular distribution of survivin has been tissues and in tumors. It is a member of the inhibitory controversial: is it a microtubule-associated protein or a apoptosis protein (IAP) family known to regulate mitosis and chromosomal passenger protein? It has been observed that to inhibit apoptosis. It has therefore been regarded as a target the sequence Ala3-Ile19 identifies the nuclear pool of for therapies. In malignant gliomas it increases with survivin and segregates with nucleoplasmic proteins; based malignancy, even though in glioblastomas it does not seem to upon fluorescence, it localizes to the kinetochores of correlate with outcome. Materials and Methods: Survivin was metaphase chromosomes and to the central spindle midzone immunohistochemically studied in 39 selected viable during anaphase. The sequence Cys57-Trp67 characterizes glioblastoma areas belonging to 20 cases which were assayed the cytosolic pool associated with microtubules, centrosomes, for apoptosis, using a TUNEL assay, caspase-3, poly(ADP- spindle poles and mitotic spindle microtubules during ribose)polymerase 1 (PARP-1), Bid (BH3-interacting domain metaphase and anaphase. A polyclonal antibody recognizes death agonist) and with the proliferation index Ki-67/MIB-1 both pools within the same mitotic cells. The predominant and mitotic index (ªπ). Results: A positive linear correlation survivin pool is associated with microtubules and participates was found between the survivin labelling index (LI) and the in the assembly of a bipolar mitotic spindle (8).
    [Show full text]
  • Overexpression of Survivin and XIAP in MDR Cancer Cells Unrelated to P-Glycoprotein
    969-976 24/2/07 14:24 Page 969 ONCOLOGY REPORTS 17: 969-976, 2007 969 Overexpression of Survivin and XIAP in MDR cancer cells unrelated to P-glycoprotein ZHI SHI1,2, YONG-JU LIANG1, ZHE-SHENG CHEN2,3, XIAO-HONG WANG1, YAN DING1, LI-MING CHEN1 and LI-WU FU1,3 1State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, P.R. China; 2Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA Received November 30, 2006; Accepted January 29, 2007 Abstract. Cancer cells developing multidrug resistance (MDR) P-gp. In summary, our study suggested that the overexpression is one of the most serious clinical problems responsible for of Survivin and XIAP in MDR cancer cells does not directly the failure of cancer chemotherapy. P-glycoprotein (P-gp) interact with P-gp. overexpression and inhibitor of apoptosis proteins (IAPs) overexpression in cancer cells are the two common mechanisms Introduction of MDR. However, the relationship between IAPs and P-gp in MDR cancer cells is unknown. We investigated the expression Cancer cells developing resistance to chemotherapeutic drugs levels of two IAPs, Survivin and XIAP, and their interaction is a frequent clinical problem encountered in the treatment of with P-gp in MDR cancer cells. We have found that the human human cancers. After obtaining resistance to a single drug or epidermoid carcinoma cells KBv200 and breast cancer cells a class of drugs, cancer cells show cross-resistance to other MCF-7/Adr overexpress not only P-gp but also XIAP and functionally and structurally unrelated drugs which include Survivin, and showed high resistance to chemotherapeutic the anthracyclines, vinca alkaloids, taxanes, topoisomerase I drugs doxorubicin, docetaxel and vincristine, in contrast to inhibitors, and other natural products.
    [Show full text]
  • Combination of the Natural Compound Periplocin and TRAIL Induce
    Han et al. Journal of Experimental & Clinical Cancer Research (2019) 38:501 https://doi.org/10.1186/s13046-019-1498-z RESEARCH Open Access Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy Lujuan Han1†, Suli Dai1†, Zhirong Li1, Cong Zhang1, Sisi Wei1, Ruinian Zhao1, Hongtao Zhang2, Lianmei Zhao1* and Baoen Shan1* Abstract Background: Esophageal cancer is one of the most common malignant tumors in the world. With currently available therapies, only 20% ~ 30% patients can survive this disease for more than 5 years. TRAIL, a natural ligand for death receptors that can induce the apoptosis of cancer cells, has been explored as a therapeutic agent for cancers, but it has been reported that many cancer cells are resistant to TRAIL, limiting the potential clinical use of TRAIL as a cancer therapy. Meanwhile, Periplocin (CPP), a natural compound from dry root of Periploca sepium Bge, has been studied for its anti-cancer activity in a variety of cancers. It is not clear whether CPP and TRAIL can have activity on esophageal squamous cell carcinoma (ESCC) cells, or whether the combination of these two agents can have synergistic activity. Methods: We used MTS assay, flow cytometry and TUNEL assay to detect the effects of CPP alone or in combination with TRAIL on ESCC cells. The mechanism of CPP enhances the activity of TRAIL was analyzed by western blot, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. The anti-tumor effects and the potential toxic side effects of CPP alone or in combination with TRAIL were also evaluated in vivo.
    [Show full text]
  • XIAP's Profile in Human Cancer
    biomolecules Review XIAP’s Profile in Human Cancer Huailu Tu and Max Costa * Department of Environmental Medicine, Grossman School of Medicine, New York University, New York, NY 10010, USA; [email protected] * Correspondence: [email protected] Received: 16 September 2020; Accepted: 25 October 2020; Published: 29 October 2020 Abstract: XIAP, the X-linked inhibitor of apoptosis protein, regulates cell death signaling pathways through binding and inhibiting caspases. Mounting experimental research associated with XIAP has shown it to be a master regulator of cell death not only in apoptosis, but also in autophagy and necroptosis. As a vital decider on cell survival, XIAP is involved in the regulation of cancer initiation, promotion and progression. XIAP up-regulation occurs in many human diseases, resulting in a series of undesired effects such as raising the cellular tolerance to genetic lesions, inflammation and cytotoxicity. Hence, anti-tumor drugs targeting XIAP have become an important focus for cancer therapy research. RNA–XIAP interaction is a focus, which has enriched the general profile of XIAP regulation in human cancer. In this review, the basic functions of XIAP, its regulatory role in cancer, anti-XIAP drugs and recent findings about RNA–XIAP interactions are discussed. Keywords: XIAP; apoptosis; cancer; therapeutics; non-coding RNA 1. Introduction X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3), baculoviral IAP repeat-containing protein 4 (BIRC4), and human IAPs like protein (hILP), belongs to IAP family which was discovered in insect baculovirus [1]. Eight different IAPs have been isolated from human tissues: NAIP (BIRC1), BIRC2 (cIAP1), BIRC3 (cIAP2), XIAP (BIRC4), BIRC5 (survivin), BIRC6 (apollon), BIRC7 (livin) and BIRC8 [2].
    [Show full text]
  • Survivin-3B Potentiates Immune Escape in Cancer but Also Inhibits the Toxicity of Cancer Chemotherapy
    Published OnlineFirst July 15, 2013; DOI: 10.1158/0008-5472.CAN-13-0036 Cancer Molecular and Cellular Pathobiology Research Survivin-3B Potentiates Immune Escape in Cancer but Also Inhibits the Toxicity of Cancer Chemotherapy Fred erique Vegran 1,5, Romain Mary1, Anne Gibeaud1,Celine Mirjolet2, Bertrand Collin4,6, Alexandra Oudot4, Celine Charon-Barra3, Laurent Arnould3, Sarab Lizard-Nacol1, and Romain Boidot1 Abstract Dysregulation in patterns of alternative RNA splicing in cancer cells is emerging as a significant factor in cancer pathophysiology. In this study, we investigated the little known alternative splice isoform survivin-3B (S-3B) that is overexpressed in a tumor-specific manner. Ectopic overexpression of S-3B drove tumorigenesis by facilitating immune escape in a manner associated with resistance to immune cell toxicity. This resistance was mediated by interaction of S-3B with procaspase-8, inhibiting death-inducing signaling complex formation in response to Fas/ Fas ligand interaction. We found that S-3B overexpression also mediated resistance to cancer chemotherapy, in this case through interactions with procaspase-6. S-3B binding to procaspase-6 inhibited its activation despite mitochondrial depolarization and caspase-3 activation. When combined with chemotherapy, S-3B targeting in vivo elicited a nearly eradication of tumors. Mechanistic investigations identified a previously unrecognized 7-amino acid region as responsible for the procancerous properties of survivin proteins. Taken together, our results defined S-3B as an important functional actor in tumor formation and treatment resistance. Cancer Res; 73(17); 1–11. Ó2013 AACR. Introduction that can induce the expression of five different transcripts with D Alternative splicing is an important mechanism for the different functions: survivin, survivin- Ex3, survivin-2B (5), a generation of the variety of proteins indispensable for cell survivin-3B (S-3B; ref.
    [Show full text]
  • Identification of a Variant Form of Cellular Inhibitor of Apoptosis Protein (C-IAP2) That Contains a Disrupted Ring Domain
    Identification of a Variant Form of Cellular Inhibitor of Apoptosis Protein (c-IAP2) That Contains a Disrupted Ring Domain Sun-Mi Park, Ji-Su Kim, Ji-Hyun Park, Seung-Goo Kang and Tae Ho Lee Department of Biology and Protein Network Research Center, Yonsei University, Seoul, Korea ABSTRACT Among the members of the inhibitor of apoptosis (IAP) protein family, only Livin and survivin have been reported to have variant forms. We have found a variant form of c-IAP2 through the interaction with the X protein of HBV using the yeast two-hybrid system. In contrast to the wild-type c-IAP2, the variant form has two stretches of sequence in the RING domain that are repeated in the C-terminus that would disrupt the RING domain. We demonstrate that the variant form has an inhibitory effect on TNF-mediated NF-κB activation unlike the wild-type c-IAP2, which increases TNF- mediated NF-κB activation. These results suggest that this variant form has different activities from the wild-type and the RING domain may be involved in the regulation of TNF-induced NF-κB activation. (Immune Network 2002;2(3):137-141) Key Words: c-IAP2, TNF, NF-κB, TRAF2, TRAF6 Introduction involved in TNF signaling and exerts positive feed- Members of the inhibitor of apoptosis (IAP) back control on NF-κB via an IκBα targeting protein family have been reported to be involved in mechanism. signaling that prevent cell death induced by TNFR There have been reports that have shown variant (1), Fas signaling (2) and etoposide (3).
    [Show full text]
  • Survivin, Versatile Modulation of Cell Division and Apoptosis in Cancer
    Oncogene (2003) 22, 8581–8589 & 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00 www.nature.com/onc Survivin, versatile modulation of cell division and apoptosis in cancer Dario C Altieri*,1 1Department of Cancer Biology and the Cancer Center, LRB-428, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA Survivin is a member of the inhibitor of apoptosis (IAP) spliced survivin transcripts (Figure 1). In addition to gene family that has attracted attention from several wild-type survivin (142 amino acids), two survivin viewpoints of basic and translational research. Its cell isoforms are generated by insertion of an alternative cycle-regulated expression at mitosis and association with exon 2 (survivin-2B, 165 amino acids) or removal of the mitotic apparatus have been of interest to cell exon 3 (survivin-DEx-3, 137 amino acids) (Mahotka biologists studying faithful segregation of sister chroma- et al., 1999). In survivin-DEx-3, the splicing event tids and timely separation of daughter cells. Investigators introduces a frame shift that generates a unique – interested in mechanisms of apoptosis have found survivin COOH terminus of potential functional significance an evolving challenge:while survivin inhibits apoptosis in (Mahotka et al., 2002) (Figure 1). vitro and in vivo, this pathway may be more selective as A unique property of survivin is a sharp cell-cycle- compared to cytoprotection mediated by other IAPs. dependent expression at mitosis. This is largely, but not Finally, basic and translational researchers in cancer exclusively, controlled at the level of gene transcription biology have converged on survivin as a pivotal cancer and involves canonical CDE/CHR boxes (Badie et al., gene, not simply for its sharp expression in tumors and not 2000) in the survivin promoter (Kobayashi et al., 1999; in normal tissues, but also for the potential exploitation of Li and Altieri, 1999b), acting as potential G1-repressor this pathway in cancer diagnosis and therapy.
    [Show full text]
  • Human RPE Expression of Cell Survival Factors
    Human RPE Expression of Cell Survival Factors Ping Yang,1 Jessica L. Wiser,1 James J. Peairs,1 Jessica N. Ebright,1 Zachary J. Zavodni,1 Catherine Bowes Rickman,1,2 and Glenn J. Jaffe1 PURPOSE. To determine basal and tumor necrosis factor (TNF)- etinal pigment epithelial (RPE) cells form a monolayer of ␣–regulated expression of retinal pigment epithelial (RPE) cell Rcuboidal cells located between the photoreceptors of the survival factors and whether regulation is dependent on nu- neurosensory retina and the choroidal capillary bed. The RPE clear transcription factor (NF)-␬B. comprises an important blood–retinal barrier component and performs many important functions essential to the visual pro- METHODS. Cultured human RPE cells were infected with ade- novirus encoding either mutant inhibitory (I)-␬Bor␤-galacto- cess. Normally, RPE cells remain in a quiescent state and survive over an individual’s lifetime.1,2 sidase and treated with TNF-␣ for various times. Freshly pre- Age-related macular degeneration (AMD) is an idiopathic pared RPE/choroid and RPE samples were isolated from human retinal degenerative disease that is the leading cause of irre- donor eyes. Real-time reverse transcription-polymerase chain versible vision loss in the Western world among persons older reaction, Western blot, and immunocytochemistry were used than 65 years.3 AMD is characterized by clinical signs, ranging to determine survival factor gene expression, cellular protein from a few soft drusen and pigmentary changes in the macular levels, and localization,
    [Show full text]
  • Correlation of Survivin and B‑Cell Lymphoma 2 Expression with Pathological Malignancy and Anti‑Apoptotic Properties of Glial Cell Tumors
    396 BIOMEDICAL REPORTS 6: 396-400, 2017 Correlation of survivin and B‑cell lymphoma 2 expression with pathological malignancy and anti‑apoptotic properties of glial cell tumors IN-SUK BAE, CHOONG-HYUN KIM, JAE-MIN KIM, JIN-HWAN CHEONG, JE-IL RYU and MYUNG-HOON HAN Department of Neurosurgery, Hanyang University Guri Hospital, Guri-si, Gyeonggi-do 11923, Republic of Korea Received December 15, 2016; Accepted January 27, 2017 DOI: 10.3892/br.2017.861 Abstract. Apoptosis, whose mechanism remains unclear, is properties in gliomas. Thus, survivin or Bcl-2 may serve as regulated by multiple factors. B-cell lymphoma 2 (Bcl-2) is a potential targets for inducing the apoptosis of gliomas. well-known anti-apoptotic mediator. Survivin is also a recently recognized novel family inhibitor of apoptosis protein, which Introduction inhibits apoptosis via a pathway distinct from Bcl-2 family members. Survivin and Bcl-2 are expressed in various types Glial cell tumors form the most common group of primary of human cancer. In the present study, survivin and Bcl-2 brain tumors, accounting for 40% of all central nervous expression were characterized in glial cell tumors, and the system (CNS) neoplasms (1). Despite marked efforts to correlation with pathological malignancy and anti-apoptotic improve the clinical outcome of glioma patients, very properties were investigated. Fifty-eight patients who had little progress has been made, particularly in patients with undergone surgical resection for glial cell tumors were high-grade gliomas (2). As in other types of cancer, malig- evaluated. The pathological types of glial cell tumors were nant progression of glial cell tumors is accompanied by categorized according to the World Health Organization abnormal molecular changes (3).
    [Show full text]
  • Chemotherapy-Induced Survivin Regulation in Acute Myeloid Leukemia Cells
    applied sciences Article Chemotherapy-Induced Survivin Regulation in Acute Myeloid Leukemia Cells Petra Otevˇrelová and Barbora Brodská * Department of Proteomics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 12820 Prague, Czech Republic; [email protected] * Correspondence: [email protected] Abstract: Survivin is a 16.5 kDa protein highly expressed in centrosomes, where it controls proper sister chromatid separation. In addition to its function in mitosis, survivin is also involved in apopto- sis. Overexpression of survivin in many cancer types makes it a suitable target for cancer therapy. Western blotting and confocal microscopy were used to characterize the effect of chemotherapy on acute myeloid leukemia (AML) cells. We found enhanced survivin expression in a panel of AML cell lines treated with cytarabine (Ara-C), which is part of a first-line induction regimen for AML therapy. Simultaneously, Ara-C caused growth arrest and depletion of the mitotic cell fraction. Subsequently, the effect of a second component of standard therapy protocol, idarubicin, and of a known survivin inhibitor, YM-155, on cell viability and survivin expression and localization in AML cells was investigated. Idarubicin reversed Ara-C-induced survivin upregulation in the majority of AML cell lines. YM-155 caused survivin deregulation together with a viability decrease in cells resistant to idarubicin treatment, suggesting that YM-155 might be efficient in a specific subset of AML patients. Expression levels of other apoptosis-related proteins, in particular X-linked inhibitor of apoptosis (XIAP), Mcl-1, and p53, and of the cell-cycle inhibitor p21 considerably changed in almost all cases, confirming the off-target effects of YM-155.
    [Show full text]
  • Effect of Protein Kinase C Alpha, Caspase-3, and Survivin on Apoptosis of Oral Cancer Cells Induced by Staurosporine1
    Acta Pharmacologica Sinica 2005 Nov; 26 (11): 1365–1372 Full-length article Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine1 Yu-xia ZHANG 2, 4, Shi-bin YU3, 4, Jing-ping OU-YANG2, 5, Dong XIA2, Min WANG2, Jin-rong LI3 2Department of Pathology and Pathophysiology, School of Medicine; 3The First Department of Oral and Maxillofacial Surgery, School of Stomatology, Wuhan University, Wuhan 430071, China Key words Abstract protein kinase C alpha; caspase-3; survivin Aim: To elucidate inhibition of protein kinase C α (PKC α) activity by staurosporine protein; apoptosis; staurosporine; carci- on apoptosis of oral cancer cell line tongue squamous cell carcinoma (TSCCa) noma, squamous cell; mouth cells and to clarify the role of survivin and caspase-3 in mediating apoptosis. 1 Project supported in part by Natural Science Methods: TSCCa cell viability was measured by MTT assay after 100 nmol/L Foundation of Hubei Province (No 304130550). staurosporine treatment. Apoptotic cells were identified by using phase contrast 4 Who contributed equally to this article. 5 Correspondence to Prof Jing-ping OU-YANG. microscopy, acridine orange/ethidium bromide staining, and flow cytometry. Level Phn 86-27-8733-1241. of PKC α and its subcellular location were investigated using Western blot analysis. Fax 86-27-8733-1077. Expression of survivin and caspase-3 were evaluated using immunocytochemistry. E-mail [email protected] Results: Staurosporine significantly inhibited the cell viability of TSCCa cells in a Received 2005-03-11 dose- and time-dependent manner. Marked cell accumulation in G2/M phase was Accepted 2005-07-22 observed after 100 nmol/L staurosporine exposure for 6 h and 12 h.
    [Show full text]
  • XIAP and Survivin As Therapeutic Targets for Radiation Sensitization in Preclinical Models of Lung Cancer
    Oncogene (2004) 23, 7047–7052 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $30.00 www.nature.com/onc XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer Carolyn Cao1,YiMu1, Dennis E Hallahan1 and Bo Lu*,1 1Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, 1301 22nd Avenue South, B-902 The Vanderbilt Clinic, Nashville, TN 37232-5671, USA Survivin and XIAP are members of inhibitors of apoptosis pathway (Salvesen and Duckett, 2002).In addition, (IAPs) family. They are upregulated in various malig- survivin plays an important role in mitosis by interact- nancies. Inactivation of these molecules has resulted in ing with other chromosomal passenger proteins such as chemosensitization. The purpose of this study was to INCEPT and AURORA B (Adams et al., 2001). An determine whether inhibition of survivin, XIAP, or both important feature of these molecules is that there are enhances radiotherapy in a lung cancer model. Transient upregulated in various malignancies (Bao et al., 2002). transfection of H460 cells with antisense oligonucleotides Clinically, high levels of XIAP or survivin have been (ASOs) against either molecule has specifically reduced associated with decreased overall survival, increased their expression, by Western analysis. Results from 3-(4,5- recurrence and resistance to radiotherapy (Holcik et al., methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and 2000; Rodel et al., 2003). Several reports demonstrated clonogenic assays suggest that inhibition of survivin or an association between high levels of survivin and poor XIAP greatly decreased cell survival following irradiation.
    [Show full text]