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Protein phosphorylation is a key mechanism by which normal and cancer cells regulate their main transduction pathways. Protein kinases and phosphatases are precisely orchestrated to achieve the (de)phosphorylation of candidate proteins. Indeed, cellular health is dependent on the fine-tune of phosphorylation systems, which when deregulated lead to cancer. Transforming growth factor beta ( TGF-β) pathway involvement in the genesis of prostate cancer has long been established. Many of its members were shown to be hypo- or hyperphosphorylated during the process of malignancy. A major phosphatase that is responsible for the vast majority of the serine/threonine dephosphorylation is the phosphoprotein phosphatase 1 ( PPP1). PPP1 has been associated with the dephosphorylation of several proteins involved in the TGF-β cascade. This review will discuss the role of PPP1 in the regulation of several TGF-β signalling members and how the subversion of this pathway is related to prostate cancer development. Furthermore, current challenges on the protein phosphatases field as new targets to cancer therapy will be addressed. [ABSTRACT FROM AUTHOR]

Abstract: We propose a new design of THz frequency carrier generation for medical applications. The dense wavelength division multiplexing can be generated by using a Gaussian pulse propagating within a modified PANDA ring resonator and add-drop filter. Results obtained have shown that broad region of frequency band can be obtained between 30 and 100THz. This area of frequency band can be useful for medical applications, in which the broad bandwidth of THz signals can be obtained and available for medical applications, for instance, the use of Terahertz pulse imaging (TPI) and signal transduction therapy, especially, for blood vessel extraction are discussed. [Copyright &y& Elsevier]

Abstract: At variance with most oncogenic protein kinases whose malignancy is generally due to genetic alterations conferring constitutive activity, CK2 is a highly pleiotropic Ser/Thr protein kinase naturally endowed with constitutive activity and lacking gain-of-function mutants. Nonetheless CK2 is abnormally elevated in a wide variety of tumors and there is strong evidence that it operates as a cancer driver by creating a cellular environment favorable to neoplasia: notably, CK2 plays a global role as an anti-apoptotic and pro-survival agent, it enhances the multi-drug resistance (MDR) phenotype, it assists the chaperone machinery which protects the “onco-kinome” and it promotes neo-angiogenesis. Based on this scenario we propose that the implication of CK2 in neoplasia is an example of “non oncogene addiction”, i.e. over reliance of the perturbed cellular signaling network on high CK2 level for its own maintenance. Consistent with this, an ample spectrum of diverse types of cancer cells have been already shown to rely on high CK2 level for their survival, as judged from their response to specific CK2 inhibitors and silencing of endogenous CK2 catalytic subunits. Remarkably, among these are cells whose cancer phenotype arises from the genetic alteration of onco-kinases (e.g. Abl and Alk) different from CK2 and insensitive to the CK2 inhibitors used in those experiments. Based on these premises, CK2 could represent a “multi-purpose” target for the treatment of different kinds of tumors. [Copyright &y& Elsevier]

Objective: To determine the potency of TKS050, a new epidermal growth factor receptor (EGFR) inhibitor and genistein, a naturally occurring protein tyrosine kinase inhibitor, to inhibit leiomyoma cell proliferation in vitro. Design: Establishment of paired cultures of leiomyoma and normal myometrial samples. Setting: University clinical research laboratory. Patient(s): Hysterectomy specimens from premenopausal women affected by uterine leiomyomas. Intervention(s): The suppressive effect of TKS050 and genistein on the cells, before and after steroidal hormone treatment, was examined. Main Outcome Measure(s): Cell proliferation, recovery after treatment, cell cycle analysis, and immunochemical analysis of relevant proteins were performed. Result(s): TKS050 (2 μmol/L) and genistein (50 μmol/L) completely suppressed leiomyoma cell proliferation, and the cells did not recover after cessation of treatment. TKS050 induced cell cycle arrest and apoptosis in a dose- and time-dependent manner. Cells accumulated in the G0/G1 phase of the cell cycle at the expense of the S and G2+M phases. Treatment of cells with TKS050 resulted in a dose-dependent inhibition of EGFR autophosphorylation and of phosphorylated signal transducer and activator of transcription 3 (Stat3). Genistein inhibited the phosphorylated Stat3 but did not affect EGFR autophosphorylation. The inhibitory effects of TKS050 or genistein were unaffected by the presence of physiologic concentrations of estradiol-17β. Conclusion(s): Leiomyoma cell growth is effectively blocked by TKS050 and genistein. The inhibitory action of newly developed and natural inhibitors derived from diet may be useful as a possible alternative therapy for leiomyomas. [Copyright &y& Elsevier]

To evaluate the effects of verapamil isomers on in vitro proliferation of bovine choroidal endothelial cells (CECs). CECs were isolated from bovine eyes and cultured in endothelial growth medium (EGM). For the proliferation assays, CECs were exposed to verapamil isomers (0.1–100 μM) in EGM with 2% fetal bovine serum or basic fibroblast growth factor (bFGF) (10 ng/ml). After 72 h of incubation with the desired drug, the cellular proliferation was determined by an MTT assay and a BrdU assay. In addition, the drug toxicity on CECs stimulated with EGM was evaluated by cell counting with trypan blue. All verapamil isomers inhibited the bFGF- or medium-stimulated growth significantly in a concentration range of 10–40 μM without toxicity. No significant differences were seen between the inhibitory effects of the various isomers. Cell toxicity was detected at a concentration of 100 μM verapamil isomers on EGM-stimulated CECs. The results demonstrate the efficacy of all verapamil isomers in inhibiting CEC proliferation involved in the process of choroidal neovascularization. d-(+)-Verapamil may be recommended for further in vivo evaluation in an animal model of exudative AMD; it has fewer systemic and local side effects because calcium channels are not blocked. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of the calcium signaling modulating drug carboxyamido-triazole (CAI) on substeps of exudative age-related macular degeneration (AMD) in vitro. Materials and Methods: Zymography and ELISA determined the effect of CAI on MMP-2 production of choroidal endothelial cells (CECs) stimulated by bFGF and VEGF. The effects of CAI on attachment of retinal pigment endothelial (RPE) cells/CECs onto fibronectin, laminin, collagen IV, and migration toward fibronectin were investigated. Proliferation induced by serum and bFGF (10 μ g/ml) with and without CAI (0.1–10 μ M) was measured by cell counting and [3] H-uptake. Viability and apoptosis of the exposed cells was assessed by an MTT and an apoptosis assay. Results: CAI inhibited serum- and bFGF-induced proliferation, cell attachment onto fibronectin and collagen IV, but only CEC attachment onto laminin. Inhibition of MMP-2 production was observed (10 μ M CAI). CAI reduced the cellular viability by apoptosis induction. Conclusions: CAI inhibits substeps of exudative macular degeneration and may be of value for the treatment of the disease. [ABSTRACT FROM AUTHOR]

A new design of a system for preliminary detection of defective hearts is proposed which is composed of two subsystems, in which one is based on the relationship between the electrocardiogram (ECG) and phonocardiogram (PCG) signals. The relationship between both signals is determined as an impulse response (h(n)) of a system, where the decision is made based on the linear predictive coding coefficients of a heart's impulse response. The other subsystem uses a phase space approach, in which the mean squared error between the distance vectors of the phase space of the normal heart and abnormal heart is judged by the likelihood ratio test (Λ) value, on which the decision is made. The advantage of the proposed system is that a heart's diagnosis system based on the ECG and EPCG signals can lead to high performance heart diagnostics.