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Background Survivin expression is often associated with aggressive tumor behavior and therapy resistance. In this study, we investigated the effect of survivin knockdown by survivin-siRNA lentiviral vector (Svv-Lent) on the response of HNSCC to chemo-radiotherapy, tumor growth and metastasis. Methods Four human HNSCC (OSC19, Cal27, Cal33 and FaDu) and one normal HOK cell lines were included in the study, and survivin knockdown was achieved with Svv-Lent treatment. Cell proliferation and apoptosis were measured by MTT and TUNEL assay, respectively. Transwell assays were performed to measure in vitro cell migration and matrigel invasion. Xenograft tumors were developed in nude mice by injecting Cal27 cells subcutaneously and following tail-vein injection of lung and liver metastasis. Results Knockdown of survivin significantly suppressed HNSCC cell proliferation and induced apoptosis in vitro . Survivin inhibition could also significantly reduce in vitro cell migration and matrigel invasion that might be due to inactivation of matrix metalloproteinases. In vivo studies showed significant repression of Cal27 xenograft tumor growth and tissue metastasis leading to improvement in mice survival in the Svv-Lent treated group compared to controls. Our data indicated that survivin expression in HNSCC cells contributed to chemo-radioresistance, and its down-regulation increased anti-cancer effects of paclitaxel, cisplatin and radiation. Conclusions Our findings suggest that sustained survivin expression facilitates HNSCC tumor growth and confers resistance to chemo-radiotherapy. Svv-Lent therapy may be able to enhance the cytotoxic effect of commonly used anticancer drugs such as cisplatin and paclitaxel, and radiotherapy that could provide a promising strategy for the effective control of resistant head and neck cancer.

Cancer is a class of diseases characterized by uncontrolled cell growth. The development of cancer takes place in a multi-step process during which cells acquire a series of mutations that eventually lead to unrestrained cell growth and division, inhibition of cell differentiation, and evasion of cell death. Dysregulation of oncoapoptotic genes, growth factors, receptors and their downstream signaling pathway components represent a central driving force in tumor development. The detailed studies of signal transduction pathways for mechanisms of cell growth and apoptosis have significantly advanced our understanding of human cancers, subsequently leading to more effective treatments. Oral squamous cell carcinoma represents a classic example of multi-stage carcinogenesis. It gradually evolves through transitional precursor lesions from normal epithelium to a full-blown metastatic phenotype. Genetic alterations in many genes encoding crucial proteins, which regulate cell proliferation, differentiation, survival and apoptosis, have been implicated in oral cancer. As like other solid tumors, in oral cancer these genes include the ones coding for cell cycle regulators or oncoproteins (e.g. Ras, Myc, cyclins, CDKs, and CKIs), tumor suppressors (e.g. p53 and pRb), pro-survival proteins (e.g. telomerase, growth factors or their receptors), anti-apoptotic proteins (e.g. Bcl2 family, IAPs, and NF-kB), pro-apoptotic proteins (e.g. Bax and BH-3 family, Fas, TNF-R, and caspases), and the genes encoding key transcription factors or elements for signal transduction leading to cell growth and apoptosis. Here we discuss the current knowledge of oncoapoptotic regulation in human cancers with special reference to oral cancers.

Genetic variation at 23 microsatellite loci, population structure, and genetic bottleneck hypothesis were examined for Jamunapari goat population found in Etawah, Uttar Pradesh, India. Estimates of genetic variability such as effective number of alleles and gene diversities revealed substantial genetic variation frequently displayed by microsatellite markers. Number of alleles observed across the microsatellite loci varied from 2 to 10 with an overall mean of 4.913 ± 1.905. Average polymorphism across the studied loci and expected gene diversity in the population were 1.066 ± 0.510 and 0.528 ± 0.237, respectively. Population was observed to be significantly differentiated into different groups, and showed fairly high level of inbreeding (f = 0.189 ± 0.049) and global heterozygote deficit. Bottleneck analysis indicated the introduction of unique/rare alleles by immigrants. © 2005 Elsevier B.V. All rights reserved.

Summary Addition of Ni2+, Hg2+ and Cu2+ inhibited the growth, oxygen evolution and oxygen uptake (PS I) in the cells of Cylindrospermum (Hg2+ > Ni2+ > Cu2+). A plot of Vo/V of 2 indicated an increased sensitivity of PS I towards Hg2+ and Ni2+, while Cu2+ exerted an almost similar effect on both PS II and PS I. Hg2+, Ni2+ and Cu2+ induced inhibition of variable fluorescence of Chl a, and DCPIP (50 μM) reduction was reversed by protonophore FCCP (10 μM). Thus, it could be argued that heavy-metal-induced modulation of charge separation (H+ ion movement) across the membrane might be accounting for an increase in the high energy state quenching (qE) of fluorescence and inhibition of Hill activity. Further, addition of electron donors, DPC and H2O2 (25 μM, each), could not release the toxic effect of Hg2+, Ni2+ and Cu2+ on Hill activity. Ascorbic acid (ASC) and ferrocyanide (25 μM, each) supported cytochrome C reduction was greatly stimulated by lethal doses of Hg2+ and Cu2+, but remained unaltered with Ni2+ (I-80 dose of each metal). The same concentrations of Hg2+, Ni2+ and Cu2+ were highly inhibitory to ASC + NADP reduction. However, electron transfer from PMS to NADP was sensitive to Ni2+ only. A corollary of these results suggested that action sites of Hg2+ and Cu2+ were located prior to the electron donation site of PMS, but possibly after the cytochrome reductase level, where Hg2+ and Cu2+ might be accounting for the increased level of reduced cytochrome by preventing the simultaneous oxidation of cytochrome. On the other hand, the inhibition site of Ni2+ was located beyond the site of PMS.