Comparative Efficacy Analysis of Mobilization and Collection of Autologous Hematopoietic Stem Cells in Patients with Lymphoproliferative Disorders and Multiple Sclerosis

Aim. Comparative efficacy analysis of autologous hematopoietic stem cells (HSC) prior to auto-HSCT in patients with lymphoproliferative disorders (LPDs) and multiple sclerosis (MS). Materials & Methods. The trial included 237 patients: 103 LPD and 134 MS patients. In 225 patients HSC mobilization involved only colony-stimulating factors (CSFs), in 12 patients chemotherapy (cyclophosphamide, etoposide) was combined with CSFs. On the intended date of cytapheresis all the patients were tested for CD34+ marker expression. Сytapheresis followed in the patients with CD34+ count more than 0.01 × 106/mL. Results. In 23 (22 %) LPD patients CD34+ count was too low for auto-HSCT (‘collection failure group’). Within this group 19 patients received CSF mobilization, and 4 patients received chemotherapy + CSF. Plerixafor was administered in 5 patients, in 4 of them a repeated mobilization also failed to collect enough cells. In 80 LPD patients the number of mobilized and collected CD34+ cells was sufficient for auto-HSCT (‘collection success group’). Within this group 77 patients received auto-HSCT, 74 patients were treated with CSF mobilization, 6 patients received chemotherapy + CSF, and in 11 patients plerixafor was administered. Median total number of CD34+ cells in the ‘collection success group’ was 2.7 × 106/kg. All 134 MS patients had enough CD34+ cells for auto-HSCT. All of them received CSF mobilization. Median total number of CD34+ cells in the MS group was 2.34 × 106/kg. Potential risk factors for HSC mobilization failure in LPDs were evaluated. They included age, gender, prior radiotherapy, number of antitumor treatment lines prior to auto-HSCT, clinical response prior to auto-HSCT (complete/partial remission or stabilization), and HSC mobilization regimen. These factors with the exception of gender were not associated with mobilization failure parameters. The worst mobilization outcomes were reported in male patients. Conclusion. In 22 % of LPD patients the planned high-dose chemotherapy and auto-HSCT failed due to insufficient counts of autologous CD34+ cells in apheresis product. Male gender can be considered to be a prognostic factor of mobilization failure in LPDs

Outcome of Classical Hodgkin’s Lymphoma Treatment Based on High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation: The Experience in the NI Pirogov Russian National Medical Center of Surgery

Aim. To estimate the long-term outcome of the programmed treatment of classical Hodgkin’s lymphoma (cHL) including high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of various factors on the achieved results in a single-center study. Materials & Methods. In the A.A. Maksimov Clinical Center of Hematology and Cellular Therapy of the NI Pirogov Russian National Medical Center of Surgery 260 cHL patients received HDCT combined with auto-HSCT within the period from December 2006 to March 2017. The median age was 29 years (range 17–62). The study included 40 % men (n = 104), and 60 % women (n = 156). The median pretransplantation chemotherapy line was 3 (range 2–9). At this stage, prior to auto-HSCT, complete remission (CR) rate was 26.5 %, partial remission (PR) rate was 52.3 %, disease stabilisation rate was 13.5 %. HDCT with auto-HSCT was applied beyond progression as a salvage therapy in 7.7 % of patients. In 79.6 % of patients the standard BEAM and CBV conditioning regimens were used. Results. After HDCT combined with auto-HSCT overall 5-year survival (OS) of 260 cHL patients was 74 %, and 5-year progression-free survival (PFS) was 48 %, which corresponds to the results of some international studies. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during the first CR or PR (85 %) vs the second and subsequent CR and PR (71 %). Neither gender (p = 0.4) nor ECOG status (p = 0.2) effects on OS and PFS were revealed. 5-year OS rates were significantly higher after HDCT and auto-HSCT performed during CR or PR (82 %) vs disease stabilisation and progression (54 %) as well as upon achieving CR (93 %) vs PR (77 %). Conclusion. In cHL tumor sensitivity to chemotherapy is the essential indication for HDCT combined with auto-HSCT. The optimal time for HDCT and auto-HSCT in cHL is the first CR/PR, and the best treatment outcome is achieved in patients with complete response prior to HDCT and auto-HSCT

Protective Effects of Platycodon grandiflorum Aqueous Extract on Thioacetamide-induced Fulminant Hepatic Failure in Mice

The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure

A comparative population-based study of prostate cancer incidence and mortality rates in Singapore, Sweden and Geneva, Switzerland from 1973 to 2006

10.1186/1471-2407-12-222BMC Cancer12-BCMA

P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation

BACKGROUND: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. CONCLUSIONS/SIGNIFICANCE: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis

Incidences of obesity and extreme obesity among US adults: findings from the 2009 Behavioral Risk Factor Surveillance System

<p>Abstract</p> <p>Background</p> <p>No recent national studies have provided incidence data for obesity, nor have they examined the association between incidence and selected risk factors. The purpose of this study is to examine the incidence of obesity (body mass index [BMI] ≥ 30.0 kg/m²) and extreme obesity (BMI ≥ 40.0 kg/m²) among US adults and to determine variations across socio-demographic characteristics and behavioral factors.</p> <p>Methods</p> <p>We used a weighted sample of 401,587 US adults from the 2009 Behavioral Risk Factor Surveillance System. Incidence calculations were based on respondent's height and current and previous weights. Logistic regression was used to examine associations between incidence and selected socio-demographic characteristics and behavioral factors.</p> <p>Results</p> <p>The overall crude incidences of obesity and extreme obesity in 2009 were 4% and 0.7% per year, respectively. In our multivariable analyses that controlled for baseline body mass index, the incidences of obesity and extreme obesity decreased significantly with increasing levels of education. Incidences were significantly higher among young adults, women, and adults who did not participate in any leisure-time physical activity. Incidence was lowest among non-Hispanic whites.</p> <p>Conclusions</p> <p>The high incidence of obesity underscores the importance of implementing effective policy and environmental strategies in the general population. Given the significant variations in incidence within the subgroups, public health officials should prioritize younger adults, women, minorities, and adults with lower education as the targets for these efforts.</p

Tumor Cell Plasticity and Angiogenesis in Human Melanomas

Recent molecular studies provide evidence for a significant transcriptional plasticity of tumor cell subpopulations that facilitate an active contribution to tumor vasculature. This feature is accompanied by morphological changes both in vitro and in vivo. Herein, we investigated the morphological plasticity of tumor cells with special focus on vasculogenic mimicry and neovascularisation in human melanoma and mouse xenografts of human melanoma cell lines. In melanoma xenograft experiments, different vessel markers and green fluorescent protein expression were used to show how melanoma cells contribute to neovascularization. Additionally, we analyzed neovascularization in 49 primary melanomas and 175 melanoma metastases using immunostaining for blood (CD34) and lymphatic (D2–40) vessel-specific markers. We found significantly more lymphatic vessels in primary melanomas than in melanoma metastases (p<0.0001). In contrast to the near absence of lymphatic vessels within metastases, we found extensive blood micro-neovascularization. Blood micro-neovascularization was absent in micro metastases (less than 2 mm). A significant inverse correlation between Glut-1 expression (implying local hypoxia) and the presence of microvessels indicates their functional activity as blood vessels (p<0.0001). We suggest that the hypoxic microenvironment in metastases contributes to a phenotype switch allowing melanoma cells to physically contribute to blood vessel formation