bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced antiproliferative and proapoptotic effects on prostate cancer cells by simultaneously inhibiting androgen receptor and cAMP‐dependent protein kinase A
Authors: Desiniotis Andreas , Schäfer Georg , Klocker Helmut , Eder Iris E. 
Published: August 2009

AbstractThe androgen‐signaling pathway with the androgen receptor (AR) as its key molecule is widely understood to influence prostate tumor growth significantly even after androgen ablation. Under androgen‐deprived conditions, the AR may be activated inappropriately through interaction with other molecules, including cyclic AMP‐dependent protein kinase A (PKA). In a previous study, we have shown that knocking down the AR significantly inhibits prostate tumor growth. In this study, we show that combined inhibition of the AR and the regulatory subunit I alpha of PKA (RIα) with small interference RNAs significantly increased the growth‐inhibitory and proapoptotic effects of AR knockdown. This treatment strategy was effective in androgen‐sensitive and in androgen ablation‐resistant prostate cancer cells. In addition, we report that downregulating PKA RIα was sufficient to inhibit PKA signaling and interestingly also impaired AR expression and activation. Vice versa, AR knockdown induced a decline in PKA RIα, associated with reduced PKA activity. This mutual influence on expression level was specific, because siRNAs against the AR did not affect expression of PKA RIα in AR negative DU‐145 cells and a siRNA control did not affect protein expression. Another important finding of our study was that depletion of PKA RIα also potentiated the antiproliferative effect of the antiandrogen bicalutamide in androgen‐sensitive LNCaP. We therefore concluded that combined inhibition of PKA RIα and AR may be a promising new therapeutic option for prostate cancer patients and might be superior to solely preventing AR expression.
Validation of predictive models for germline mutations in DNA mismatch repair genes in colorectal cancer
Authors: Monzon Jose G. , Cremin Carol , Armstrong Linlea , Nuk Jennifer , Young Sean , Horsman Doug E. , Garbutt Kristy , Bajdik Chris D. , Gill Sharlene 
Published: August 2009

AbstractLynch syndrome is defined by the presence of germline mutations in mismatch repair (MMR) genes. Several models have been recently devised that predict mutation carrier status (Myriad Genetics, Wijnen, Barnetson, PREMM and MMRpro models). Families at moderate‐high risk for harboring a Lynch‐associated mutation, referred to the BC Cancer Agency (BCCA) Hereditary Cancer Program (HCP), underwent mutation analysis, immunohistochemistry and/or microsatellite testing. Seventy‐two tested cases were included. Twenty‐five patients were mutation positive (34.7%) and 47 were mutation negative (65.3%). Nineteen of 43 patients who were both microsatellite stable and normal on immunohistochemistry for MLH1 and MSH2 were also genotyped for mutations in these genes; all 19 were negative for MMR gene mutations. Model‐derived probabilities of harboring a MMR gene mutation in the proband were calculated and compared to observed results. The area under the ROC curves were 0.75 (95%CI; 0.63–0.87), 0.86 (0.7–0.96), 0.89 (0.82–0.97), 0.89 (0.81–0.98) and 0.93 (0.86–0.99) for the Myriad, Barnetson, Wijnen, MMRpro and PREMM models, respectively. The Amsterdam II criteria had a sensitivity and specificity of 0.76 and 0.74, respectively, in this cohort. The PREMM model demonstrated the best performance for predicting carrier status based on the positive likelihood ratios at the >10%, >20% and >30% probability thresholds. In this referred cohort, the PREMM model had the most favorable concordance index and predictive performance for carrier status based on the positive LR. These prediction models (PREMM, MMRPro and Wijnen) may soon replace the Amsterdam II and revised Bethesda criteria as a prescreening tool for Lynch mutations.
Primary gene‐engineered neural stem/progenitor cells demonstrate tumor‐selective migration and antitumor effects in glioma
Authors: Mercapide Javier , Rappa Germana , Anzanello Fabio , King Judy , Fodstad Oystein , Lorico Aurelio 
Published: August 2009

AbstractThe prognosis of patients with glioblastoma multiforme (GBM) is generally poor after surgical tumor resection. With the aim of developing new adjuvant therapeutic strategies, we have investigated primary neural stem/progenitor cells (NSPC) in co‐cultures with glioma cells, and in a model of gene therapy on aggressively growing malignant glioma. NSPC exhibited tropism towards medium conditioned by glioma cells, and in adherent low‐cell density co‐culture, were attracted to, and fused with, tumor cells. Similarly, within 24–48 hr of co‐culture in suspension, NSPC‐tumor hybrids were observed, representing 2–3% of the total cell population. NSPC were then coinjected into mouse brain with GBM cells, employing NSPC expressing cyclophosphamide (CPA)‐activating enzyme cytochrome p450 2B6 (CYP2B6), which catalyzes CPA prodrug transformation into membrane diffusible DNA‐alkylating metabolites. Upon CPA administration, NSPC containing CYP2B6 elicited substantial impairment of tumor growth. When implanted intracerebrally at a distant site from the tumor, gene‐engineered NSPC specifically targeted GBM grafts, after traveling through brain parenchyma, and hindered tumor growth through local activation of CPA. Directed migration of primary NSPC corresponded closely with intracerebral and tumoral pattern of expression of vascular endothelial growth factor, which is a motility factor for NSPC. Overall, these findings indicate that therapeutic gene delivery mediated by primary NSPC is a potentially valid strategy for treatment of high‐grade gliomas.
Modulation of murine innate and acquired immune responses following in vitro exposure to electrospun blends of collagen and polydioxanone
Authors: Smith Matthew J. , Smith Donna C. , Bowlin Gary L. , White Kimber L. 
Published: August 2009

AbstractIn light of cell sourcing issues and the lack of a bioreactor comparable to the body, many in the field of tissue engineering have focused their efforts on designing biomaterials capable of in situ regeneration. The theory is that, by using the body as both the bioreactor and the source for cell infiltration, scaffolds composed of bioresorbable materials can be remodeled into native tissue. Thus, research into the effects of such materials on the host immune response is increasingly important. This study applies an immunotoxicological approach to evaluate the effects of electrospun blends of polydioxanone (PDO) and collagen type I on murine innate and acquired immune responses. Results indicated that these materials had few effects on innate immune responses, yet they produced significant immunomodulatory effects in multiple endpoints evaluating both branches of acquired immunity (i.e., cell‐mediated and humoral immunity). Specifically, collagen content appeared to be responsible for suppression of cell‐mediated immunity, while blends of PDO and collagen appeared to be more suppressive of antibody‐forming cell responses than either PDO or collagen alone. These results demonstrate the importance of completing evaluations into the immunotoxicological effects of biomaterials, and they suggest that such testing should become a primary focus when evaluating a material's potential foruse in tissue engineering applications. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Development and biocompatibility of a novel corrodible fluoride‐coated magnesium‐calcium alloy with improved degradation kinetics and adequate mechanical properties for cardiovascular applications
Authors: Drynda Andreas , Hassel Thomas , Hoehn René , Perz Angela , Bach Friedrich‐Wilhelm , Peuster Matthias 
Published: August 2009

AbstractRecently, corrodible magnesium‐based alloys have been introduced for use as cardiovascular stents and orthopedic implants. However, rapid corrosion rates have raised questions about their biocompatibility. Therefore, we developed a binary fluoride‐coated magnesium‐calcium alloy with improved degradation kinetics. Biocompatibility of the alloys was evaluated with metabolic assays (colorimetric WST‐1 test). Furthermore, five different probes of magnesium‐calcium alloys (MgCa 0.4, 0.6, 0.8, 1.2, and 2.0 wt %) were cocultivated with human smooth muscle cells and endothelial cells. To investigate the decomposition kinetics in a physiological environment the alloys were used untreated and fluoride coated (MgF2). Mg and Ca decreased the metabolic activity in vascular cells dose‐dependently, with cytotoxic effects only at unphysiological concentrations. Uncoated magnesium alloys showed signs of decomposition after a short incubation time of 24 h in contrast to MgF2 coated alloys. After 10 days smooth muscle and endothelial cells around the alloys were still alive, whereas colonization of the surfaces was only observed for smooth muscle cells. The fluoride‐coated MgCa alloys exhibited good results concerning mechanical properties, degradation kinetics, and biocompatibility in vitro. We conclude that a binary fluoride magnesium‐calcium alloy is a promising candidate for the production of cardiovascular stents. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Leptin attenuates hypoxia/reoxygenation‐induced activation of the intrinsic pathway of apoptosis in rat H9c2 cells
Authors: Shin Eyun‐Jung , Schram Kristin , Zheng Xi‐long , Sweeney Gary 
Published: August 2009

AbstractCardiomyocyte apoptosis is a component of cardiac remodeling that can contribute to heart failure in obesity. A role for leptin in mediating this process has been suggested and the objective of this work was to investigate the effect of leptin on apoptosis and associated mechanisms in H9c2 cells which were subjected to hypoxia/reoxygenation (HR) to mimic myocardial ischemia/reperfusion. Qualitative immunofluorescent and quantitative laser scanning cytometry approaches demonstrated that exposure of cells to HR increased DNA fragmentation (TUNEL staining) which was attenuated by leptin (6 nM, 1 h) pretreatment. We also found increased annexin‐V binding and caspase‐3 activity in cells exposed to HR, both of which were attenuated by leptin pretreatment. Leptin reduced HR‐induced translocation of the pro‐apoptotic protein Bax to the mitochondrial membrane, which provides a mechanism to explain its protective effect. Consequently, leptin attenuated the HR‐induced decrease in mitochondrial membrane potential and increase in cytochrome c release from mitochondria. Leptin treatment increased the phosphorylation of p38 MAPK and AMPK and respective inhibitors of these kinases, SB203580 and Compound C, prevented the ability of leptin to decrease HR‐induced caspase‐3 activity. In conclusion, we establish mechanisms via which leptin exerts anti‐apoptotic effects that may be of significance in understanding the development of heart failure in obesity. J. Cell. Physiol. 221: 490–497, 2009. © 2009 Wiley‐Liss, Inc.
Growth inhibition of bovine pulmonary artery smooth muscle cells following long‐term heparin treatment
Authors: Mrabat Hicham , Garg Hari G. , Hales Charles A. 
Published: August 2009

AbstractHeparin (HP) inhibits pulmonary artery smooth muscle cell (PASMC) growth in vitro and vascular remodeling in vivo. Bârzu et al. (1994) suggested that the antiproliferative effect of HP on rat aortic smooth muscle cell in vitro diminishes with prolonged exposure to heparin. We exposed cultured bovine PASMC (BPASMC) to prolonged pretreatment with 20 µg/ml of 0‐hexanoylated HP from passages 3 to13 and compared them to control (no pretreatment) cultures of identical passages. The pretreated BPASMC and control groups were growth arrested for 48 h, followed by treatment of 0‐hexanoylated HP at different doses. On day 5, the growth inhibition of BPASMC was determined. The percent inhibition by 1 µg/ml of 0‐hexanoylated HP was 46 ± 14% versus 62 ± 13%, for control and pretreated BPASMC, respectively. At 10 µg/ml the inhibition was 62 ± 7% versus 84 ± 6%. For 100 µg/ml the inhibition increased to 92 ± 5% versus 100% and at 200 µg/ml the inhibition was 95 ± 3% versus 100%. BPASMC (with or without preexposure to 0‐hexanoylated HP), at passage 13, were sensitive to the growth inhibitory effect of 0‐hexanoylated HP with no significant difference among the groups (95 ± 3% inhibition vs. 100% for pretreated BPASMC). We found that 0‐hexanoylated HP‐induced necrosis as shown by flow cytometry and only minor apoptosis. Caspase‐3 and PARP detection was insignificant between the groups. In summary, no cell subpopulation at long‐term treatment exhibited resistance to 0‐hexanoylated HP. The HP antiproliferative effect on SMC is potentially important in defining new approaches to the treatment of the remodeled vasculature of pulmonary hypertension. J. Cell. Physiol. 221: 603–608, 2009. © 2009 Wiley‐Liss, Inc.
Immobilized HIV‐1 Tat protein promotes gene transfer via a transactivation‐independent mechanism which requires binding of Tat to viral particles
Authors: Nappi Filomena , Chiozzini Chiara , Bordignon Valentina , Borsetti Alessandra , Bellino Stefania , Cippitelli Marco , Barillari Giovanni , Caputo Antonella , Tyagi Mudit , Giacca Mauro , Ensoli Barbara 
Published: August 2009

AbstractBackgroundRetroviral transduction of cells is improved upon virus adsorption onto immobilized fibronectin (FN) fragments. Because HIV‐1 Tat possesses the same functional domains that lead to increased transduction efficiency in FN by colocalization of bound virus and cells, we hypothesized that Tat could enhance gene transfer by a similar mechanism.MethodsSingle‐cycle replication retro‐ or lentivirus carrying green fluorescent protein or cloramphenicol acetyltransferase as reporter genes were added to wells coated with Tat or Tat peptides. Wells were extensively washed to remove unbound virus and levels of transduction were detected by measuring reporter gene expression. Virus adsorption to immobilized Tat was measured using a p24 antigen capture assay.ResultsImmobilized Tat efficiently binds retro‐ and lentiviral particles and mediates virus transmission at virus input doses that were otherwise unable to transduce susceptible cells. Virus adsorption to Tat is not mediated by envelope glycoprotein (Env) because immobilized Tat binds and retains vesicular stomatitis virus G (VSV‐G) pseudotypes as well as envelope‐free particles. HIV‐1 Env or VSV‐G are required for Tat‐assisted transduction, which is abrogated by an antibody blocking the HIV‐1 Env–CD4 interaction. Tat‐assisted transduction is mediated by the cysteine‐rich region of Tat, which is known to be essential for Tat transactivation activity. However, Tat transactivation is not required for Tat‐assisted transduction, as indicated by the enhancement of transduction by transactivation‐silent Tat mutants.ConclusionsImmobilized Tat promotes virus transduction by a transactiva‐ tion‐independent mechanism, which requires binding of virus to Tat. Recombinant Tat or Tat fragments provide a new method to increase efficiency of retro‐ and lentiviral based gene transfer and gene therapy. Copyright © 2009 John Wiley & Sons, Ltd.
Afraid in the hospital: Parental concern for errors during a child's hospitalization
Authors: Tarini Beth A. , Lozano Paula , Christakis Dimitri A. 
Published: August 2009

AbstractOBJECTIVE:(1) To determine the proportion of parents concerned about medical errors during a child's hospitalization; and (2) the association between this concern and parental self‐efficacy with physician interactions.STUDY DESIGN:Cross‐sectional survey.SETTING:Tertiary care children's hospital.PARTICIPANTS:Parents of children admitted to the general medical service.OUTCOME MEASURE:Parental concern about medical errors.METHODS:Parents were asked their agreement with the statement “When my child is in the hospital I feel that I have to watch over the care that he/she is receiving to make sure that mistakes aren't made.” We used multivariate logistic regression to examine the association between parents' self‐efficacy with physician interactions and the need “to watch over a child's care,” adjusting for parent and child demographics, English proficiency, past hospitalization, and social desirability bias.RESULTS:Of 278 eligible parents, 130 completed surveys and 63% reported the need to watch over their child's care to ensure that mistakes were not made. Parents with greater self‐efficacy with physician interactions were less likely to report this need (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72‐0.92). All parents who were “very uncomfortable” communicating with doctors in English reported the need to watch over their child's care to prevent mistakes.CONCLUSIONS:Nearly two‐thirds of surveyed parents felt the need to watch over their child's hospital care to prevent mistakes. Parents with greater self‐efficacy with physician interactions were less likely to report the need to watch over their child's care while parents with lower English proficiency were more likely to report this need. Journal of Hospital Medicine 2009;4:521–527. © 2009 Society of Hospital Medicine.
Synthesis of [13C4]Baraclude® (entecavir)
Authors: Tran Scott B. , Ekhato Ihoezo V. , Rinehart J. Kent 
Published: August 2009

AbstractEntecavir, labeled as 1H‐[13C4]purin‐6(9H)‐one, was prepared from commercially available [13C]guanidine HCl, 1 and diethyl [1,2,3‐13C3]malonate, 2. The reagents were condensed together to give 2‐amino‐4,6‐dichloro[2,4,5,6‐13C4]pyrimidine 3, which in turn was coupled to an optically active amino cyclopentanol derivative, 9. A further sequence of eight reaction steps completed the constructions of the purine ring system and the exocyclic olefin attachment on the cyclic pentyl portion, 18. The removal of the methoxide and benzyl protecting groups gave [13C4]entecavir, 20 in an overall yield of 6.8%. The chemical purity of the title compound was determined by HPLC to be 99.23%. The percent isotopic [13C4] abundance was found by mass spectral analysis to be 96.7%. No detectable level of the unlabeled entecavir was found by LC‐MS analysis. Copyright © 2009 John Wiley & Sons, Ltd.
Lack of prognostic significance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non‐small cell lung cancer
Authors: Hoffmann A.C. , Kaifi J.T. , Vallböhmer D. , Yekebas E. , Grimminger P. , Leers J.M. , Izbicki J.R. , Hölscher A.H. , Schneider P.M. , Metzger R. , Brabender J. 
Published: August 2009

AbstractBackground and ObjectivesTo further improve the screening, diagnosis and therapy of patients with non‐small cell lung cancer (NSCLC) additional diagnostic tools are desperately warranted. Aim of this study was to investigate the potential of the DNA methylation of DAPK, MGMT, and GSTPI in serum of patients with NSCLC as a prognostic molecular marker in this disease.MethodsSeventy‐six patients with NSCLC were included in this study. The analysis of DNA methylation in serum of patients was performed on pre‐operative samples. Following DNA isolation and bisulfite‐treatment, DNA methylation was analyzed by quantitative‐methylation‐specific real‐time PCR with β‐actin as the internal reference gene.ResultsDNA methylation was detectable with following frequencies: DAPK 68.4%, MGMT 7.9%, GSTPI 0%. There were no associations between DNA methylation status and histology, tumor stage, grading or gender detectable. With a mean follow‐up of 19.7 months the median survival was 26.3 months. There were no associations between the status of DNA methylation in patient's serum and prognosis detectable.ConclusionThe analysis of DNA methylation in serum of patients with NSCLC by quantitative‐methylation‐specific real‐time PCR is technically feasible. Although our results suggest quantification of DNA methylation in serum not of prognostic significance in this disease, further studies are warranted to determine the future potential of this molecular approach. J. Surg. Oncol. 2009;100:414–417. © 2009 Wiley‐Liss, Inc.
Short length of stay and rapid recovery to normal function after surgery for metastatic melanoma to abdominal and retroperitoneal viscera
Authors: Dengel Lynn T. , Slingluff Jr. Craig L. 
Published: August 2009

AbstractBackgroundMetastatic melanoma to abdominal and retroperitoneal viscera carries a poor prognosis possibly resulting in reluctance to offer surgical management. There is value in defining the morbidity of such surgery.MethodsReview of a prospectively maintained database identified patients with metastatic melanoma to abdominal or retroperitoneal viscera who underwent surgery from 9/99 to 8/06.ResultsNineteen patients underwent surgery for metastasis to abdominal or retroperitoneal viscera detected by clinical symptoms (80%), or imaging (20%). The median length of stay was 7 days. There was no perioperative mortality. Surgical complications occurred in four patients. At initial follow‐up, 13 patients (68%) had returned to baseline function, 7 of which reported improvement. Four patients (21%) had minimal symptoms, and only two patients (11%) had significantly limited function. Median follow‐up was 35 months, at which time 9 of the 19 patients (47%) were still alive, with 3‐ and 5‐year Kaplan–Meier survival estimates of 53% (SE 12) and 45% (SE 12), respectively, and 2 of the 19 patients are alive at over 8 years since surgery.ConclusionIn selected cases, surgery may have both palliative benefit and curative potential for patients with visceral metastases of melanoma. Surgical management of such patients should be encouraged in appropriate clinical settings. J. Surg. Oncol. 2009;100:481–483. © 2009 Wiley‐Liss, Inc.
Clinical and histopathological features of remnant gastric cancers, after gastrectomy for synchronous multiple gastric cancers
Authors: Fujita Takeo , Gotohda Naoto , Takahashi Shinichiro , Nakagohri Toshio , Konishi Masaru , Kinoshita Taira 
Published: August 2009

AbstractBackgroundRemnant gastric cancers have been extensively investigated; however, little has been unveiled the features of remnant gastric cancers with regard to the existence of synchronous multiple lesions. We evaluated the clinicopathological features of remnant gastric cancers, after initial gastrectomy for both single and multiple gastric cancers.MethodsWe retrospectively analyzed 3,042 patients diagnosed with gastric cancers who underwent gastrectomy. Of these, total gastrectomy cases were excluded, and remaining 2,120 cases were investigated.ResultsAmong the 2,120 patients, 1,967 patients were histopathologically diagnosed with solitary lesion and 153 patients with multiple lesions. The incidence of remnant gastric cancers was higher in patients with multiple lesions at initial surgery than those with solitary lesion (P < 0.05). Moreover, remnant cancers developed within shorter duration of follow‐up after treatment of synchronous multiple lesions compared to those that developed after treatment of solitary lesions (P = 0.05). Among the patients treated for synchronous multiple lesions, distance from the oral margin was a potential risk factor for the development of secondary cancers in the remnant stomach.ConclusionsPatients with synchronous multiple gastric cancers are more susceptible to the development of secondary cancers in their remnant stomach. These patients need careful follow‐up after initial gastrectomy. J. Surg. Oncol. 2009;100:466–471. © 2009 Wiley‐Liss, Inc.