Growth inhibition and chemo-radiosensitization of head and neck squamous cell carcinoma (HNSCC) by survivin-siRNA lentivirus.

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.

Modern approaches to a rapid diagnosis of tuberculosis: promises and challenges ahead.

The limitations of the conventional methods for diagnosing tuberculosis have spurred multi-faceted research activities in this field throughout the world. Chromatographic methods appear promising but may not be widely available in the developing countries. Immuno-diagnostic methods using combinations ("cocktails") of antigens have high sensitivity and specificity and can easily be applied in the peripheral laboratories and in the field settings. Though expensive, molecular methods for diagnosis of tuberculosis have advantages of speed, sensitivity, and specificity. Adequate training of the eligible personnels in molecular methods and prevention of laboratory-dependent contamination may help reduce false positive results. Although, there are no clear guidelines, so far on how to make out the best from the gene amplification methods, yet their use may be encouraged with adequate quality controls, because of the inherent ingenuity and promises of these methods. Phage-based molecular methods provide rapid results in susceptibility tests for anti-tubercular drugs. In future, many sophisticated techniques are expected to hit the market for a rapid diagnosis of tuberculosis. In the developing countries, it is necessary to evaluate availability of suitable infrastructure and trained personnels before adopting modern diagnostic methods.