Search results for "survivin"

Expression of IAPs and alternative splice variants in hepatocellular carcinoma tissues and cells.

2005

IAPs (inhibitors of apoptosis proteins) might have a major role in the apoptotic resistance that marks many cancers. The studies on IAPs in human HCC have focused on survivin or XIAP, indicating that their new or increased expression in this tumor is associated with a more unfavorable prognosis. The present results corroborate these findings, emphasizing the role that the coordinated expression of different IAPs and alternative splice variants might play in the adverse biology of hepatocellular carcinoma.

The Synthetic Cannabinoid WIN 55,212-2 Sensitizes Hepatocellular Carcinoma Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-I…

2010

In this article, we demonstrate that the synthetic cannabinoid R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate (WIN 55,212-2) sensitizes human hepatocellular carcinoma (HCC) cells to apoptosis mediated by tumor necrosis-related apoptosis inducing ligand (TRAIL). The apoptotic mechanism induced by treatment with WIN/TRAIL combination involved the loss of the mitochondrial transmembrane potential and led to the activation of caspases. In HCC cells, WIN treatment induced the up-regulation of TRAIL death receptor DR5, an effect that seemed to be related to the increase in the level of p8 and CHOP, two factors implicat…

Survivin’s Dual Role: An Export’s View

2007

Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor during development and pathogenesis. As such, survivin has aroused keen interest in disparate areas of basic and translational research. Survivin acts as a subunit of the chromosomal passenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin and INCENP, and is essential for proper chromosome segregation and cytokinesis. Our recent findings indicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionary conserved in all mammalian survivin proteins. In addition, the survivin/…

Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsenti…

2014

A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G 2 /M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr 34 and to increase the cytotoxic activity of paclit…

Nuclear and Cytoplasmic Survivin: Molecular Mechanism, Prognostic, and Therapeutic Potential.

2007

Abstract Survivin's proposed dual role as an apoptosis inhibitor and a mitotic effector positioned it in the front line of cancer research. Notably, survivin is detected as a cytoplasmic and nuclear protein in cancer patients, which stimulated numerous studies to investigate and to speculate on the functional and prognostic significance of its dynamic localization. Recent evidence shows that the direct interaction of survivin with the nuclear export receptor Crm1 is critically involved in its intracellular localization and cancer-relevant functions. Here, we review our current understanding of the Crm1/survivin interface and discuss its potential prognostic and therapeutic relevance. [Cance…

Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker

2007

Survivin functions as an apoptosis inhibitor and a regulator of cell division in many tumours. The intracellular localization of survivin in tumours has been suggested as a prognostic marker. However, current reports are inconsistent and the underlying molecular mechanisms are not understood. The present study has examined the localization and prognostic value of nuclear and cytoplasmic survivin in the pre-therapeutic biopsies from 71 oral and oropharyngeal squamous carcinoma (OSCC) patients. Statistical analysis indicated that preferential nuclear versus cytoplasmic survivin correlated with favourable versus unfavourable disease outcome. Uni- and multi-variate analysis showed that in contr…

DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis

2011

DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O(6)-methylguanine adducts that are converted by mismatch repair into DNA dou…

Survivin detection in saliva samples from patients with oral squamous cell carcinoma

2007

USE OF FUZZY NEURAL NETWORKS IN MODELING RELATIONSHIPS OF HPV INFECTION WITH APOPTOTIC AND PROLIFERATION MARKERS IN POTENTIALLY MALIGNANT ORAL LESIONS

2005

To evaluate in oral leukoplakia the relationship between HPV infection and markers of apoptosis (bcl-2, survivin) and proliferation (PCNA), also conditionally to age, gender, smoking and drinking habits of patients, by means of Fuzzy neural networks (FNN) system 21 cases of oral leukopakia, clinically and histologically diagnosed, were examined for HPV DNA presence, bcl-2, survivin and PCNA expression. HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR: MY09-MY11/GP5-GP6), and the HPV genotype determined by direct DNA sequencing. All markers were investigated by means of standardised immunohistochemistry procedure. Data were analysed by chi-square test, crude OR an…

HPV DNA and survivin expression in epithelial oral carcinogenesis: a relationship?

2004

Abstract HPV has been thought to be involved in the development of several oral diseases, such as premalignant mucosal lesions and oral carcinoma. Survivin is a recently characterized IAP protein, which is abundantly expressed in most solid and haematological malignancies, but undetectable in normal adult tissues. Aim of this study was to investigate survivin expression and HPV presence in oral premalignant lesions and oral carcinoma. 47 samples of oral tissue including 11 squamous cell carcinomas (OSCC), 16 oral leukoplakias (OL) and 20 normal oral mucosa specimens, after investigation of HPV presence by nested PCR (consensus MY/GP primers) and viral genotype identification by direct seque…