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One of the four transmembrane receptors that belong to the erB family, is the HER2/neu oncoprotein. It forms heterodimers by binding to specific ligands, enhancing cell signaling and assisting in cell growth and differentiation. A variety of human epithelial tumors are characterised by an overexpression and gene amplification of the HER2/neu oncoprotein. This is the case of breast tumors, in which the receptor's overexpression and its gene have been studied extensively and its overexpression has been associated with unfavorable prognosis. In addition, HER2/neu plays a major role in understanding the oncogenesis of prostate adenocarcinoma. For this reason, clarifying the HER2/neu expression is particularly important in androgen independent prostate cancer (PCa), due to the increasing interest in using anti-HER2 targeted therapies for advanced disease treatment. On the other hand, the overexpression of HER2/neu has been reported to release soluble extracellular domain (ECD) in the serum of PCa patients. For this reason, the present review focuses only on studies referring to Serum HER2/neu levels in PCa patients. Serum levels of HER2/neu generally increase with advanced disease state and higher levels have been associated with recurrent or metastatic PCa and a clinically worse outcome. Therefore, it may be concluded that since there is a correlation between increased HER2/neu levels and a poor prognosis in prostate adenocarcinoma, serum HER2/neu could be used in clinical practice and follow up of patients with advanced PCa. Hippokratia 2013, 17, 2: 108-112. [ABSTRACT FROM AUTHOR]

Nineteen haemodialysis (HD) patients with chronic hepatitis C were treated with interferonalpha2b (IFN-α) at a dose of 3 or 1 MU thrice weekly for 6 months and were followed-up for another 14 months without treatment. Six patients discontinued treatment because they either presented severe side-effects to IFN-α or had complications of their primary disease. Levels of AST and ALT were within normal limits on the 2nd month of treatment and remained so throughout the treatment and the follow-up period in all patients except one who showed an elevation of transaminase levels 2 months after the end of treatment. Serum HCVRNA became negative in 10/13 patients at the end of treatment and was negative in all patients on the 6th month and in 12/13 patients on the 14th month during the follow-up period. Levels of 2′5′ oligosynthetase were increased significantly on the 2nd and 4th month of treatment and returned to pretreatment values the 2nd month after treatment. These findings demonstrate that haemodialysis patients with chronic hepatitis C respond well to interferon treatment and that a long-term response is achieved in a high proportion of patients. [ABSTRACT FROM PUBLISHER]

Purpose: Earlier studies have shown that in vitro exposure to single compounds released from composite resins is able to induce cell death via apoptosis and/or necrosis. The purpose of this study was to evaluate the effect of eluates of commercially available composites used for direct (Tetric Ceram/Ivoclar-Vivadent, Simile/Pentron, Filtek Z-250/3M ESPE) and indirect restorations (Adoro/Ivoclar-Vivadent and Conquest Sculpture/Pentron) on the type of cell death of cultured WEHI 13 var fibroblasts. Materials and Methods: Cells exposed to eluates of the materials were assayed by MTT for cytotoxicity, flow cytometry for cell death, biochemically for caspase-3 activation and fluorescent microscopy with Acridine Orange for morphological changes. Results: The 3 direct composite resin eluates induced extensive apoptosis characterized by externalization of phosphatidylserine at the cell surface, activation and positive cytoplasmic expression of caspase-3, and chromatin disintegration. This was accompanied by morphological changes, such as cell enlargement micromultinucleation and membrane blebbing. On the other hand, the other 2 composite resins for indirect restorations were much less cytotoxic in all biological endpoints investigated. Conclusion: These findings suggest that composite resins used for direct and indirect restorations differ extensively in their cytotoxic potential and their ability to induce programmed cell death. This signifies the role of composition and polymerization of these 2 classes of biomaterials with respect to their biologic behavior. [ABSTRACT FROM AUTHOR]

The role of apoptosis in the development and progression of breast cancer is unknown. Recently the bcl-2 gene has been shown to block apoptosis and thus may promote tumour development. From their first results it seems that the two ongogenes are independent prognostic markers for breast cancer and they have no correlation between them. The levels of bcl-2 seems to have increase in half of the patients of our study one year after the operation instead of c-erb-B2 who seems to have decrease.

Introduction. Serotonin receptors are present in osteoblasts and osteoclasts, and serotonin affects bone metabolism. The association of plasma serotonin with markers of bone formation and bone resorption in hemodialysis patients was evaluated. Materials and Methods. Twenty-four hemodialysis patients (11 diabetics) and 22 healthy volunteers were enrolled into the study. Serotonin was assessed in platelet-free plasma, whereas the markers of osteoblastic activity N-terminal midfragment osteocalcin and total procollagen type-1 aminoterminal propeptide as well as the marker of osteoclastic activity beta-isomerized C-terminal cross-linked peptide of collagen type I were measured in serum. Serum intact parathyroid hormone was also assessed. Results. Serotonin did not significantly differ between hemodialysis patients and healthy volunteers. All evaluated markers of bone metabolism and intact parathyroid hormone were much higher in hemodialysis patients. Serotonin was significantly correlated with all evaluated markers of bone metabolism in hemodialysis patients. Serotonin was reversely related to the patients' age. Serotonin, osteocalcin, procollagen type-1 aminoterminal propeptide, and beta-isomerized C-terminal cross-linked peptide of collagen type I were much lower in diabetic hemodialysis patients. Conclusions. Serotonin may increase both bone formation and bone resorption in hemodialysis patients. The reverse relation of serotonin to patients' age as well as its lower levels in diabetic hemodialysis patients indicate that low plasma serotonin may contribute to the higher incidence of low-turnover bone disease that characterizes old and diabetic hemodialysis patients. [ABSTRACT FROM AUTHOR]

Introduction. Angiogenesis plays a role in the pathogenesis of coronary heart disease (CHD) and diabetes mellitus (DM) pathology, and certain angiogenic factors are increased by inflammation. The aim of this study was to evaluate plasma angiogenin and vascular endothelial factor A (VEGFA) levels in hemodialysis patients, as well as the effect of CHD, DM, and inflammation on these markers. Materials and Methods. Sixty-six hemodialysis patients were enrolled in the study, of whom 22 (33.3%) suffered from CHD , 22 (33.3%) from DM, and 28 (42.4%) from inflammation. They were compared with 24 healthy volunteers. Plasma angiogenin and VEGFA were assessed by means of enzyme-linked immunosorbent assay, and serum C-reactive protein was measured with an immunoturbidimetric method. These markers were compared between hemodialysis patients with and without CHD, DM, and inflammation. Results. Compared to healthy volunteers, plasma angiogenin was significantly higher in hemodialysis patients (263.57 ± 65.95 ng/mL versus 499.15 ± 175.68 ng/mL; P < .001). Similarly, plasma VEGFA was markedly increased in hemodialysis patients (median, 60.50 pg/mL; range, 280 pg/mL), compared to healthy volunteers (median, 28.84 pg/mL; range, 59.40 pg/mL; P < .001). Neither angiogenin nor VEGFA levels differed significantly between hemodialysis patients with and without CHD, DM, or inflammation. Conclusions. Plasma angiogenin and VEGFA levels are markedly increased in hemodialysis patients, but not associated with CHD, DM, or inflammation among hemodialysis patients. [ABSTRACT FROM AUTHOR]

Besides extracellular matrix production, fibroblasts are able to produce various cytokines. Their ubiquitous position makes fibroblasts appropriate cells for sensing various noxious stimuli and for attracting immune cells in the affected area. In the present study the effect of lipopolysaccharide (LPS) and cobalt chloride (CoCl2) on the above fibroblasts functions were evaluated in primary human skin fibroblasts cultures. Collagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, transforming growth factor-β1, interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured in fibroblasts culture supernatants. Fibroblasts proliferation and viability were assessed as well. Hypoxia inducible factor-1α and the phosphorylated p65 portion of NF-κB were assessed in fibroblasts protein extracts. LPS and CoCl2 had a minor effect on fibrosis related factors in human primary fibroblasts, possibly due to the absence of interplay with other cell types in the used experimental system. On the contrary both LPS and CoCl2 increased significantly IL-8. LPS also increased considerably MCP-1, but CoCl2 decreased it. Thus LPS and CoCl2 induce a sentinel, nevertheless not identical, phenotype in primary human fibroblasts. The last disparity could result in different body response to infectious or hypoxic noxious stimuli. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals. The triple combination treatment regime (ADR+OCT+DEX) was ineffective for growth inhibition and showed an antagonistic effect on ADR activity in the 4T1 cell line in both proliferation and invasion assays. ADR treatment following the administration of the DEX+OCT regimen decreased the anticancer activity of ADR both on the grading of the bone metastatic lesions and on the overall survival of diseased animals. Moreover, the palliation treatment with OCT+DEX and in combination with ADR rather caused disease progression of the metastatic disease and bone lesions in a 4T1 MBC model in vivo. These results suggest that the administration of the DEX+OCT regimen, although may preserve palliative effects, neutralizes or reverses the anticancer effects of ADR on a 4T1 MBC model in vitro and in vivo. The simultaneous use of these drugs should be considered carefully in clinical practice.

Purpose: Acquired immunity is impaired in hemodialysis (HD) patients, and decreased T cell number may contribute. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are expressed in cells of the immune system and affect T cell development, homeostasis and proliferation. Serum levels of RANKL and OPG and their relation to blood T cell number were evaluated in HD patients., Methods: Thirty-four HD patients and 20 healthy controls participated in the study. Serum RANKL and OPG were measured by ELISA and T cell number was assessed by flow cytometry., Results: Median RANKL concentration did not differ between HD patients and healthy volunteers (300.00 pmol/L; range, 3,340.00 vs. 330.00 pmol/L; range, 440.00 pmol/L; p = 0.528). Median OPG was markedly higher in HD patients than in healthy volunteers (13.12 ± 4.71 vs. 4.71 ± 0.93 pmol/L, p < 0.001). The T cell count was significantly lower in HD patients than in healthy controls (1,177.00 ± 567.71 vs. 1,519.80 ± 594.96 cells/mm(3), p = 0.044). In HD patients, blood T cell number was correlated positively with serum RANKL (ρ = 0.462, p = 0.007) and negatively to serum OPG (r = -0.449, p = 0.008)., Conclusion: Serum OPG concentration is markedly increased in HD patients and may contribute to decreased blood T cell count and impaired acquired immunity that characterizes this population.

Expression of the two gonadotropin-releasing hormone homologue peptides GnRHI and GnRHII and their receptor GnRHR has been demonstrated in a number of malignancies. In hormone-dependent breast cancer, GnRH analogs are used for therapy in premenopausal women. Gene expression of GnRHI, II and R was studied in breast biopsies from primary breast adenocarcinoma obtained from the tumor and the adjacent benign tissue. Levels were evaluated by a multiplex real-time RT-PCR. GnRHI transcripts were detected in 14.7% of the benign and 29.4% malignant biopsies and GnRHII in 21.2% benign and 44.1% malignant biopsies. GnRHR was also more frequent in the malignant (54.2%) than in the benign (24.0%) biopsies, at similar expression levels. No transcripts were detected in biopsies from healthy individuals. There was a strong correlation between the presence of GnRHI and GnRHII transcripts and their receptor in the benign and the malignant biopsies. GnRHI, II and R expression correlated significantly with poor prognosis pathological parameters. Immunohistochemistry for GnRHR revealed expression in malignant cells and in epithelial cells of mammary ducts of the adjacent area with pre-cancerous features. In contrast, GnRH I and II peptides were rarely expressed at low levels in breast cancer cells. In conclusion GnRH peptides and receptor are expressed more frequently in breast tumors than in the adjacent mammary tissue, representing a malignant feature. Their expression correlated to tumor characteristics of poor prognosis and was therefore related to more aggressive malignancies. Concomitant expression of peptides and receptor supports an autocrine/paracrine regulating role., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hemodialysis (HD) patients are characterized by impaired T-cell function at least in part because of T-cell zeta-chain downregulation due to inflammation. Angiogenin responds as an acute phase reactant, is increased in HD patients, suppresses T-cell function and increased angiogenin level is co-localized with T-cell zeta-chain downregulation in various pathologies. Angiogenin can inhibit translation of proteins, which lack internal ribosomal entry sites in the corresponding mRNAs. In this study, the possible effect of angiogenin on T-cell zeta-chain downregulation was evaluated. Thirty HD patients and 21 healthy volunteers participated. T-cell zeta-chain expression was assessed with flow cytometry, plasma angiogenin and serum IL-6 with ELISA and serum C-reactive protein with an immunoturbidimetric method. Two available software tools were used for predicting the presence or not of internal ribosomal entry sites in T-cell zeta-chain mRNA sequence. In silico analysis of T-cell zeta-chain mRNA sequence failed to reveal the presence of internal ribosomal entry sites. T-cell zeta-chain expression was lower in HD patients than in healthy volunteers (1.86 ± 0.63 vs. 4.73 ± 3.22). In HD patients, C-reactive protein as well as IL-6 were higher than in healthy volunteers (10.04 ± 15.13 mg/L vs. 3.43 ± 0.98 mg/L and 15.06 ± 13.08 pg/mL vs. 2.11 ± 2.10 pg/mL respectively). Angiogenin was higher in HD patients than in healthy volunteers (483.20 ± 154.07 ng/mL vs. 259.98 ± 64.15 ng/mL). Neither C-reactive protein, nor IL-6 was associated with angiogenin or T-cell zeta-chain expression. Angiogenin concentration was negatively related to the expression of T-cell zeta-chain (r = -0.410, P = 0.025). Increased angiogenin may contribute to decreased T-cell zeta-chain expression in HD patients., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)

Perilipin-1 surrounds lipid droplets in both adipocytes and in atheroma plaque foam cells and controls access of lipases to the lipid core. In hemodialysis (HD) patients, dyslipidemia, malnutrition, inflammation and atherosclerosis are common. Thirty-six HD patients and 28 healthy volunteers were enrolled into the study. Ten HD patients suffered from coronary heart disease (CHD). Perilipin-1, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), body mass index, albumin, geriatric nutritional risk index, normalized protein catabolic rate, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured. Perilipin-1 did not differ between HD patients and healthy volunteers. IL-6 and TNF-α were higher in HD patients. The evaluated nutritional markers and the markers of inflammation did not differ between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels. Regarding the lipid profile, only HDL-C differed between HD patients with high perilipin-1 levels and HD patients with low perilipin-1 levels, and it was higher in the first subgroup. Perilipin-1 was significantly higher in HD patients without CHD. Perilipin-1 is detectable in the serum of HD patients and it is associated with increased HDL-C and decreased incidence of CHD., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)