Transduction of p27 to Induce Apoptosis in Tumor Cells

Transduction is a biochemical technique for the introduction of full-length proteins into the cells. It has the potential to be used in the development of a new therapeutic strategy for cancer therapy. Different forms of p27 (TAT-p27, TAT-Mp27, TAT-p23) were transduced into tumor cell lines, lymphocytes and B-CLL cells, and their influence on proliferation and apoptosis was investigated. The metabolism of transduced proteins differed between the cell types. TAT-p27 protein is metabolized faster than the mutated form. Furthermore, the half-life of TAT-p27 depended on the type of cells. All forms of TAT-p27 fusion protein moderately decreased the proliferation of different types of the cells and induced apoptosis. The cells from some B-CLL patients were sensitive to TAT fusion proteins, and the sensitivity was increased with the addition of Fluda. This study provides valuable results for further development of TAT technology as the potential tool for a specially targeted therapy of tumors

Drug Delivery by TAT-technology

TAT technology is a biochemical technique for introduction of full-length peptides or proteins into cells. This process occurs in a rapid, concentration-dependent fashion that appears to be independent of receptors and transporters. It has broad implications in experimental systems for regulating intracellular processes and has the potential to be used in the development of new therapeutic strategies for cancer, infectious diseases, and development of vaccines. It has been shown that different forms of TAT-p27 protein can modulate the cell cycle of cultured cell lines, depending on the concentration and type of cells. Transfer of TAT-proteins/peptides use from cell culture systems to animal disease models has been slow, but the ability of TAT conjugates to protect mice against ischemia, inhibit tumor growth, and enhance gene delivery suggests that they offer wide ranging pharmaceutical applications for treating a whole range of diseases

Expression of Sirtuin 1 and 2 Is Associated with Poor Prognosis in Non-Small Cell Lung Cancer Patients

Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biology

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity

Clinicopathological features of 105 NSCLC patients.

<p>ADC, adenocarcinomas; SCC, squamous cell carcinoma; WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated; SD, standard deviation.</p><p>Clinicopathological features of 105 NSCLC patients.</p

Combination of high levels of SIRT1 and SIRT2 proteins predicts shorter RFS and OS.

<p>Kaplan-Meier curves of RFS (A, C, E) and OS (B, D, F) for SIRT1 (A, B), SIRT2 (C, D) and the combination of SIRT1 and SIRT2 (E, F) as assessed by immunohistochemical staining.</p