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Biotech / Medical : TITAN PHARMACEUTICAL (TTP) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (68)	6/15/1999 12:37:00 AM
From: Miljenko Zuanic	Respond to of 362

<<Miljenko follows the science, so maybe he knows of something hidden.>> I will probably be the last one to find what is hidden! One speculation is upcoming PD conference in Vancouver, where TTP may present addition preclinical data on spheramine for PD: parkinson.ca However, may guess is that iloperidone PIII trials are going well (pts enrollment is on schedule), so as each months pass more and more interest will develop. Miljenko

To: scaram(o)uche who wrote (68)	6/20/1999 5:01:00 PM
From: scaram(o)uche	Respond to of 362

just parking something........ Carcinogenesis 1999 Jun;20(6):977-84 Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells in vitro. Rickard KL, Gibson PR, Young GP, Phillips WA University of Melbourne Department of Medicine, Royal Melbourne Hospital and University of Melbourne Department of Surgery, Western Hospital, Melbourne, Victoria, Australia and Department of Medicine, Flinders University of South Australia, Adelai. [Medline record in process] As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 +/- 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol myristate acetate and butyrate were added concurrently, or when other protein kinase C activators were used. Pharmacological inhibition of protein kinase C activity did not alter butyrate-induced alkaline phosphatase activity, but abrogated the augmentation induced by phorbol myristate acetate. We conclude that protein kinase C does not mediate the differentiating effects of butyrate on colon cancer cells, but its activation regulates butyrate-induced cellular differentiation.

To: scaram(o)uche who wrote (68)	6/20/1999 5:07:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 362

more parking....... Br J Cancer 1999 May;80(5-6):705-10 Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-alpha. Hung WC, Chuang LY School of Technology for Medical Sciences, Kaohsiung Medical College, Taiwan, Republic of China. [Medline record in process] Although interferon-alpha (IFN-alpha) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-alpha by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-alpha in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-alpha-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21WAF-1, and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-alpha in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer.