Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent

<p>Abstract</p> <p>Background</p> <p>Despite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.</p> <p>Methods</p> <p>We focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.</p> <p>Results</p> <p>It was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer cell lines <it>in vitro</it>. In contrast, Antp-TPR peptide did not affect the viability of normal cells. Moreover, analysis <it>in vivo </it>revealed that Antp-TPR peptide displayed a significant antitumor activity in a xenograft model of human pancreatic cancer in mice.</p> <p>Conclusion</p> <p>These results indicate that Antp-TPR peptide would provide a potent and selective anticancer therapy to cancer patients.</p

Influence of an artificial pleural effusion technique on cardio-pulmonary function and autonomic activity

Objective : Percutaneous treatment of hepatocellular carcinoma (HCC) located directly under the diaphragm is problematic because ultrasonic imaging is difficult, and the lung may be injured during the procedure. It has been reported that an infusion of 5% glucose solution into the thoracic cavity enables percutaneous treatment in such cases. However, the safety aspects of this have not been investigated. In this study, variations in heart rate and changes in circulatory and respiratory dynamics were examined during the infusion of artificial pleural effusion directly under the diaphragm in patients with HCC. Method : The subjects were 13 patients with an HCC directly under the diaphragm. About 500 ml of a 5% glucose solution was infused into the thoracic cavity, and mean blood pressure, heart rate, and oxygen saturation were measured. Holter electrocardiography was simultaneously recorded to evaluate autonomic nerve function. To analyze variations in heart rate, the low-frequency waves (LF : 0.04-0.15 Hz), high-frequency waves (HF : 0.15-0.40 Hz, an index of parasympathetic nerve activity), and the LF/HF ratio (index of sympathetic nerve activity) were examined. The above parameters were measured before, during (when infusion of the half the planned volume was complete), and after infusion were compared. Results : No significant changes in the mean blood pressure or heart rate were found. Oxygen saturation was significantly decreased during and after the infusion. The HF value was slightly higher after infusion and the LF value was significantly increased during infusion. The LF/HF ratio was significantly increased during infusion, and this increase persisted after infusion. Conclusions : The infusion of artificial pleural effusion had no effect on circulatory dynamics, but transiently affected respiratory functions. It was also revealed that infusion stimulated the parasympathetic nerves

Enhancement of the NH2 + NO → OH + H + N2 Reaction by Vibrational Excitation of NH2

LIF detection of H, OH and NH2 in the NH2 + NO reaction system. Enhancement of the NH2 + NO → OH + H + N2 reaction by vibrational excitation of NH2. (Observation of the significant reduction of the yield of OH by an addition of CF4.)学会名:22nd International Symposium on Gas Kinetics ; 会期:2012年6月18日(月)～22日(金) ; 開催地:アメリカ,コロラド州,ボールダー(Boulder) ; 発表者:Nanase Kohno ; 発表形式:ポスター ; 備考:JPC Poster Award受