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Friday, September 12, 2008

Fwd: New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Tue, Sep 2, 2008 at 8:26 PM
Subject: New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development.
To: mesothelioma77@gmail.com


[1]Biochem Pharmacol. 2008 Aug 5;
Moreno JJ

Lipoxygenase (LOX) pathway leads to the formation of leukotrienes and also catalyses the conversion of arachidonic acid (AA) to hydroperoxyeicosatetraenoic acids that are then reduced to hydroxyeicosatetraenoic acids (HETE) by glutathione peroxidase. There are four mammalian LOXs that produce 5-, 8-, 12- and 15-HETE, respectively. Cytochrome P-450 isozymes are also capable of metabolising AA to HETEs either by bis-allylic oxidation (lipoxygenase-like reaction) to generate 5-, 8-, 9-, 11-, 12- and 15-HETE; or by varpi/varpi-1 hydroxylation to yield 16-, 17-, 18-, 19- and 20-HETEs. It is now widely recognised that HETEs have important physiological and pathological functions that modulate ion transport, renal and pulmonary functions, vascular tone and reactivity, and inflammatory and growth responses. They can be released during the action of growth factors and cytokines, reaching physiological concentrations higher than that of prostanoids and modulating the functions of these factors. Their effects can occur through receptor or non-receptor mechanisms. Recent reviews have summarised the effects of HETEs in vascular homeostasis or lung and renal physiology. The present review focuses on the emerging effects of HETEs on cell signalling and physiological cell growth. It also discusses current observations regarding the role of HETEs in apoptosis, angiogenesis, the proliferation of cancer cells and metastasis, which constitute a potential area for successful therapeutic intervention.



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Source: http://www.hubmed.org/display.cgi?uids=18761324
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Fwd: The ErbB kinase domain: Structural perspectives into kinase activation and inhibition.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Tue, Sep 2, 2008 at 8:26 PM
Subject: The ErbB kinase domain: Structural perspectives into kinase activation and inhibition.
To: mesothelioma77@gmail.com


[1]Exp Cell Res. 2008 Aug 15;
Bose R, Zhang X

Epidermal growth factor receptor (EGFR) and its family members, ErbB2, ErB3 and ErB4, are receptor tyrosine kinases which send signals into the cell to regulate many critical processes including development, tissue homeostasis, and tumorigenesis. Central to the signaling of these receptors is their intracellular kinase domain, which is activated by ligand-induced dimerization of the receptor and phosphorylates several tyrosine residues in the C-terminal tail. The phosphorylated tail then recruits other signaling molecules and relays the signal to downstream pathways. A model of the autoinhibition, activation and feedback inhibition mechanisms for the ErbB kinase domain has emerged from a number of recent structural studies. Meanwhile, recent clinical studies have revealed the relationship between specific ErbB kinase mutations and the responsiveness to kinase inhibitor drugs. We will review these regulation mechanisms of the ErbB kinase domain, and discuss the binding specificity of kinase inhibitors and the effects of kinase domain mutations found in cancer patients from a structural perspective.



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Source: http://www.hubmed.org/display.cgi?uids=18761339
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Fwd: Denaturational Stress Induces Formation of Zinc-Deficient Monomers of Cu,Zn Superoxide Dismutase: Implications for Pathogenesis in Amyotrophic Lateral Sclerosis.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Tue, Sep 2, 2008 at 8:26 PM
Subject: Denaturational Stress Induces Formation of Zinc-Deficient Monomers of Cu,Zn Superoxide Dismutase: Implications for Pathogenesis in Amyotrophic Lateral Sclerosis.
To: mesothelioma77@gmail.com


[1]J Mol Biol. 2008 Aug 22;
Mulligan VK, Kerman A, Ho S, Chakrabartty A

Mutations in the Cu,Zn superoxide dismutase (SOD1) cause a subset of amyotrophic lateral sclerosis cases. SOD1 is a homodimer in which each monomer binds one copper atom and one zinc atom. Mutation is believed to increase the conformational flexibility of SOD1, giving rise to a misfolded SOD1 population with novel cytotoxic properties. While SOD1's metal ligands affect its stability greatly, little is known about the role these metals play in the folding, unfolding, and misfolding processes. Here, we present a method by which we were able to measure the rates of metal release during SOD1 unfolding in guanidine hydrochloride. Rates of dimer dissociation, measured by a time-resolved cross-linking assay, and conformational changes in SOD1's beta-barrel core, monitored by tryptophan fluorescence intensity, were compared with the rates of copper release and zinc release. Correlations were observed across a range of denaturant concentrations, giving rise to a more detailed model of the SOD1 unfolding process than was previously available. According to this model, the major unfolding pathway involves simultaneous dimer dissociation and zinc release as an early step that is followed by a slow conformational change in the protein's core, which, in turn, is followed by rapid copper release. This model establishes a zinc-deficient, copper-loaded SOD1 monomer as a well-populated SOD1 unfolding intermediate and a species likely to be populated under conditions of denaturational stress. Because the cytotoxicity of zinc-deficient SOD1 has been demonstrated previously, this species is a good candidate for the cytotoxic species in SOD1-associated amyotrophic lateral sclerosis.



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Source: http://www.hubmed.org/display.cgi?uids=18761352
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Fwd: Minimally Invasive Surgical Approaches and Management of Prostate Cancer.



---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Tue, Sep 2, 2008 at 8:26 PM
Subject: Minimally Invasive Surgical Approaches and Management of Prostate Cancer.
To: mesothelioma77@gmail.com


[1]Urol Clin North Am. 2008 Aug; 35(3): 489-504
Gonzalgo ML, Patil N, Su LM, Patel VR

For clinically localized prostate cancer, radical prostatectomy remains the "gold standard" treatment. New forms of minimally invasive therapies are sought out by patients, however, because of the potential morbidity associated with open surgery. With quality-of-life aspects influencing patient decision making, minimally invasive therapeutic modalities have generated great interest among patients. Laparoscopic radical prostatectomy, robotic-assisted laparoscopic prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound are all considered to be minimally invasive treatment options for the management of clinically localized prostate cancer.



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Source: http://www.hubmed.org/display.cgi?uids=18761202
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