bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: Risk and prognosis prediction
Authors: Hassan Manal M. , Kaseb Ahmed , Etzel Carol J. , El‐Serag Hashem , Spitz Margaret R. , Chang Ping , Hale Katherine S. , Liu Mei , Rashid Asif , Shama Mohamed , Abbruzzese James L. , Loyer Evelyne M. , Kaur Harmeet , Hassabo Hesham M. , Vauthey Jean‐Nicolas , Wray Curtis J. , Hassan Basmah S. , Patt Yehuda Z. , Hawk Ernest , Soliman Khalid M. , Li Donghui 
Published: June 2013

AbstractNonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome‐wide association studies had reported that a variation in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case−control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68–6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13–71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05–5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26–3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3. © 2013 Wiley Periodicals, Inc.
Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory Ewing sarcoma
Authors: Raciborska Anna , Bilska Katarzyna , Drabko Katarzyna , Chaber Radoslaw , Pogorzala Monika , Wyrobek Elżbieta , Polczyńska Katarzyna , Rogowska Elżbieta , Rodriguez‐Galindo Carlos , Wozniak Wojciech 
Published: June 2013

ABSTRACTBackgroundPatients with metastatic, progressive or recurrent Ewing sarcoma (ES) have a dismal outcome. The combination of irinotecan and temozolomide has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination with vincristine for patients with relapsed and refractory ES.Materials and MethodsTwenty‐two patients with relapsed or refractory ES were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2/day i.v. days 1–5) and temozolomide (125 mg/m2/day p.o. days 1–5) (VIT) during the period 2008–2012. All toxicities were documented.ResultsA total of 91 cycles (median 4.1 cycles/patient) were administered. A complete response (CR) was achieved in five patients, partial response (PR) in seven patients, stable disease (SD) in three patients, and progression disease (PD) in seven patients, with an overall response rate of 68.1%. Median time to progression was 3.0 months (range 1.1–37.1 months). Five patients (22.7%) are alive with no evidence of disease with a median follow‐up of 10.3 months (range 2.1–46.5); four of them received consolidation with high‐dose chemotherapy and autologous hematopoietic stem cell transplant after responding to VIT. Outcome was better for patients with relapsed ES compared with patients who progressed to initial therapy (estimated 2 year overall survival 36.4% vs. 0%, respectively). There were no significant toxicities.ConclusionsThe shorter, 5‐day VIT regimen is an active and well‐tolerated regimen in refractory ES. This combination deserves further investigation in the upfront management of patients with metastatic disease. Pediatr Blood Cancer 2013;60:1621–1625. © 2013 Wiley Periodicals, Inc.
Pulmonary disease after treatment for wilms tumor: A report from the national wilms tumor long‐term follow‐up study
Authors: Green Daniel M. , Lange Jane M. , Qu Annie , Peterson Susan M. , Kalapurakal John A. , Stokes Dennis C. , Grigoriev Yevgeny A. , Takashima Janice R. , Norkool Pat , Friedman Debra L. , Breslow Norman E. 
Published: June 2013

AbstractPurposeThis study was undertaken to evaluate the incidence of pulmonary disease among patients treated with radiation therapy (RT) for pulmonary metastases (PM) from Wilms tumor (WT).Patients and MethodsWe reviewed records of 6,449 patients treated on National Wilms Tumor Studies‐1, ‐2, ‐3, and ‐4 whose flow sheets or annual status reports documented one of several pulmonary conditions. Cases were fully evaluable if pulmonary function test (PFT) results were available, pulmonary fibrosis was identified on a chest radiograph or was listed as the primary or a contributing factor to death. Partially evaluable cases were those for whom PFT results could not be obtained. We evaluated the relationship between RT factors and the occurrence of pulmonary disease using hazard ratios (HRs) and cumulative incidence, treating death as a competing risk.ResultsSixty‐four fully evaluable and 16 partially evaluable cases of pulmonary disease were identified. The cumulative incidence of pulmonary disease at 15 years since WT diagnosis was 4.0% (95% confidence interval [CI] 2.6–5.4%) among fully evaluable and 4.8% (95% CI 3.3–6.4%) among fully and partially evaluable patients who received lung RT for PM at initial diagnosis. Rates of pulmonary disease were substantially higher among those who received lung RT for PM present at initial diagnosis or relapse compared to those who received no RT or only abdominal RT (HR 30.2, 95% CI 16.9–53.9).ConclusionThe risk of pulmonary disease must be considered in evaluating the risk:benefit ratio of lung RT for the management of PM from WT. Pediatr Blood Cancer 2013;60:1721–1726. © 2013 Wiley Periodicals, Inc.
Fluorescent probe for high‐throughput screening of membrane protein expression
Authors: Backmark A. E. , Olivier N. , Snijder A. , Gordon E. , Dekker N. , Ferguson A. D. 
Published: June 2013

AbstractScreening of protein variants requires specific detection methods to assay protein levels and stability in crude mixtures. Many strategies apply fluorescence‐detection size‐exclusion chromatography (FSEC) using green fluorescent protein (GFP) fusion proteins to qualitatively monitor expression, stability, and monodispersity. However, GFP fusion proteins have several important disadvantages; including false‐positives, protein aggregation after proteolytic removal of GFP, and reductions in protein yields without the GFP fusion. Here we describe a FSEC screening strategy based on a fluorescent multivalent NTA probe that interacts with polyhistidine‐tags on target proteins. This method overcomes the limitations of GFP fusion proteins, and can be used to rank protein production based on qualitative and quantitative parameters. Domain boundaries of the human G‐protein coupled adenosine A2a receptor were readily identified from crude detergent‐extracts of a library of construct variants transiently produced in suspension‐adapted HEK293‐6E cells. Well expressing clones of MraY, an important bacterial infection target, could be identified from a library of 24 orthologs. This probe provides a highly sensitive tool to detect target proteins to expression levels down to 0.02 mg/L in crude lysate, and requires minimal amounts of cell culture.
Knockdown of lipocalin‐2 suppresses the growth and invasion of prostate cancer cells
Authors: Tung Min‐Che , Hsieh Shu‐Ching , Yang Shun‐Fa , Cheng Chun‐Wen , Tsai Rong‐Tzong , Wang Shao‐Chuan , Huang Min‐Hsien , Hsieh Yi‐Hsien 
Published: June 2013

AbstractBACKGROUNDLipocalin‐2 (LCN2) is a member of the lipocalin superfamily, and it has an important role in the regulation of cellular oncogenesis and apoptosis. However, the role for LCN2 in prostate cancer remains unclear.METHODLCN2 expression has been determined by Western blotting, qRT‐PCR, and immunohistochemistry in the human prostate cell lines PC3, DU145, LNCaP, and 22Rv, and in human prostate tissue array. In this study, we identified shRNA‐LCN2 to determine the role of LCN2 in prostate‐cancer cell proliferation, migration, and invasion. Cell proliferative ability was measured by MTT, colony‐formation, and cell‐cycle analysis. The role of LCN2 in prostate‐cancer cell migration and invasion was analyzed by cell‐migration assay and Matrigel invasion assay. The effect of LCN2 knockdown on prostate tumor growth was assessed in a subcutaneous xenograft model.RESULTSLCN2 protein and mRNA expression are higher in PC3 and DU145 cells than in LNCaP and 22Rv cells, and prostate cancer tissue correlated significantly with tumor differentiation (P < 0.017) and Gleason's grade (P < 0.02). LCN2 knockdown in PC3 and DU145 cells decreased cell proliferation, colony formation, cell cycle arrest, migration, and invasion. Conversely, LCN2 overexpression in 22Rv cells produced the opposite effect. Subcutaneous xenografts in mice models showed decreased tumor growth in the LCN2‐knockdown mice.CONCLUSIONSOur results suggest that LCN2 might play an important role in regulation of proliferation and invasion of human prostate cancer, and that it can be a valuable marker of prostate cancer progression. Prostate 73:1281–1290. © 2013 Wiley Periodicals, Inc.
Androgen receptor enhances entosis, a non‐apoptotic cell death, through modulation of Rho/ROCK pathway in prostate cancer cells
Authors: Wen Simeng , Shang Zhiqun , Zhu Shimiao , Chang Chawnshang , Niu Yuanjie 
Published: June 2013

AbstractBACKGROUNDCell‐in‐cell phenomenon has been found for more than a century. Entosis, which is a newly found homogeneous cell‐in‐cell phenomenon and a non‐apoptosis cell death progress, has unclear function in prostate cancer progression. Here, we dissected mechanism of AR signaling related to entosis incidence in PCa progression.METHODSTwo stable PCa cell lines, named LNCaP‐ARsi and C4‐2‐ARsi were established with stably transfected AR‐shRNA to knockdown AR mRNA expression in LNCaP and C4‐2 cells, respectively. PC3‐AR9 cell line was also established after stably transfecting full‐length AR‐cDNA into PC3 cells. All these cells were cultured in poly‐HEME‐coated plates to induce entosis, which is demonstrated via double staining.RESULTSAndrogen‐DHT could enhance entosis in LNCaP, C4‐2 and PC3‐AR9 PCa cells in a dose dependent manner. Knock‐down of AR in LNCaP and C4‐2 significantly suppressed entosis as compared to LNCaP‐ARsc and C4‐2‐ARsc cells at both 1 and 10 nM DHT condition (P < 0.05). And suppression of Rho/ROCK expression resulted in interruption of AR‐mediated entosis. Human PCa samples surveys demonstrated that entosis was found only in CRPC but not in BPH and ADPC where AR was less expressed as compared to CRPC.CONCLUSIONSThese results indicated that AR might play a negative role during PCa progression via influencing entosis by modulating Rho/ROCK pathway. This newly identified AR role of enhancing entosis might help us to better understand the multiple and opposite roles of AR, which could either promote or suppress PCa cell progression via different mechanisms. Prostate 73:1306–1315. © 2013 Wiley Periodicals, Inc.
Of mice and men‐warning: Intact versus castrated adult male mice as xenograft hosts are equivalent to hypogonadal versus abiraterone treated aging human males, respectively
Authors: Sedelaar J.P. Michiel , Dalrymple Susan S. , Isaacs John T. 
Published: June 2013

AbstractBACKGROUNDImmune deficient male mice bearing human prostate cancer xenografts are used to evaluate therapeutic response to novel androgen ablation approaches and the results compared to surgical castration based upon assumption that testosterone microenvironment in intact and castrated adult male mice mimics eugonadal and castrated aging adult human males.METHODSTo test these assumptions, serum total testosterone (TT) and free testosterone (FT) were determined longitudinally in groups (n > 20) of intact versus castrated adult male nude, NOG, and immune competent C57BL/6 mice.RESULTSIn adult male mice, TT and FT varies by 30‐ to 100‐fold within the same animal providing a microenvironment that is only equivalent to hypogonadal, not eugonadal, adult human males (TT is 1.7 ± 1.2 ng/ml [5.8 ± 4.1 nM] in nude and 2.5 ± 1.3 ng/ml [8.7 ± 4.4 nM] in NOG mice versus >4.2 ng/ml [14.7 nM] in eugonadal humans). This was confirmed based upon enhanced growth of androgen dependent human prostate cancer xenografts inoculated into mice supplemented with exogenous testosterone to elevate and chronically maintain serum TT at a level (5 ng/ml [18 nM]) equivalent to a 50‐year‐old eugonadal human male. In castrated mice, TT and FT range from 2 to 20 pg/ml (7–70 pM) and <0.8 pg/ml (<2.6 pM), respectively, which is equivalent to castrate resistant prostate cancer (CRPC) patients treated with abiraterone. This was confirmed based upon the inability of another CYP17A1 inhibitor, ketoconazole, to inhibit the growth of CRPC xenografts in castrated mice.CONCLUSIONSAdult male mice supplemented with testosterone mimic eugonadal human males, while unsupplemented animals mimic standard androgen ablation and castrated animals mimic abiraterone treated patients. These studies confirm what is claimed in Robert Burns' poem “To a Mouse” that “The best laid schemes of mice and men/often go awry.” Prostate 73:1316–1325. © 2013 Wiley Periodicals, Inc.
Function of mutant and wild‐type plexinB1 in prostate cancer cells
Authors: Damola Adebiyi , Legendre Anne , Ball Stephen , Masters John R. , Williamson Magali 
Published: June 2013

AbstractBACKGROUNDSemaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumors, indicating a role for plexinB1 in the pathogenesis of prostate cancer. However, the effect of semaphorin/plexin signaling is highly context dependent and whether plexinB1 acts as an inducer or inhibitor of prostate tumor progression in this context is not known.METHODSThe response of prostate cancer cell lines to plexinB1 activation was assessed in migration, invasion, proliferation and protein phosphorylation assays. Expression was assessed by quantitative RTPCR and immunoblotting.RESULTSDifferent prostate cancer cell lines respond to Sema4D (the ligand for plexinB1) in diverse ways. Activation of endogenous plexinB1 enhances migration, invasion and anchorage‐independent growth of LNCaP prostate cancer cells via activation of ErbB2 and Akt. In contrast, Sema4D‐stimulation decreased the motility and proliferative capacity of PC3 cells. LNCaP has a missense mutation (Thr1697Ala) in the plexinB1 gene while LNCaP‐LN3, a derivative of LNCaP, expresses high levels of wild‐type plexinB1 only. Sema4D stimulation increases the motility and anchorage independent growth of both cell lines, showing that these responses are not dependent on the presence of the Thr1697Ala form of plexinB1. ErbB2 and plexinB1 are expressed in primary prostate epithelial cells.CONCLUSIONSPlexinB1 signals via ErbB2 to increase the invasive phenotype of prostate cancer cells. Both wild‐type and mutant forms of plexinB1 are potential targets for anti‐cancer therapy in prostate tumors that express ErbB2. Prostate 73:1326–1335, 2013. © 2013 The Authors. The Prostate published by Wiley Periodicals, Inc.
A study of caloric restriction versus standard diet in overweight men with newly diagnosed prostate cancer: A randomized controlled trial
Authors: Wright Jonathan L. , Plymate Stephen , D'Oria‐Cameron Andrea , Bain Carolyn , Haugk Kathy , Xiao Liren , Lin Daniel W. , Stanford Janet L. , McTiernan Anne 
Published: June 2013

ABSTRACTINTRODUCTIONObese men have an increased risk of prostate cancer (PCa)‐specific mortality. Potential mechanisms include insulin and related proteins. We investigate whether a short‐term caloric restriction diet in overweight/obese men with newly diagnosed PCa can lead to measurable changes in patient anthropometrics and insulin‐related proteins.METHODSOverweight and obese PCa patients choosing active surveillance or radical prostatectomy were randomized to a 6‐week, caloric‐restricted diet or to continue their current diet. Changes from baseline to end of study in anthropometrics, dietary constituents and serum proteins (insulin, c‐peptide, IGF‐1, adiponectin, IGF‐BP3) were compared between the intervention and control groups using a Generalized Estimating Equation model.RESULTSNineteen patients were randomized to the intervention (N = 10) or control (N = 9) group. Men in the intervention group had a 1.7% (3.7 lbs) mean decline in weight versus 1.0% (2.0 lbs) in controls (P < 0.05), and a reduced intake of calories, total and saturated fat, protein and starch (all P < 0.1 compared to controls). There was a significant difference (P = 0.002) in mean serum IGFBP‐3 between the intervention (+2.8%) and control group (−6.9%). Other biomarkers changed with the diet intervention to a degree similar to previous weight loss studies but were not statistically significant compared with controls.CONCLUSIONIn this small pilot study, a 6‐week caloric restricted diet in men with newly diagnosed PCa produced changes in weight, diet and serum proteins possibly related to prognosis. These results support larger‐scale trials testing longer‐term weight loss effects on potential PCa progression biomarkers. Prostate 73:1345–1351, 2013. © 2013 Wiley Periodicals, Inc.
Tests of marginal homogeneity and special cases
Authors: Dunnigan Keith 
Published: June 2013

AbstractThe analysis of two‐way contingency tables is common in clinical studies. In addition to summary counts and percentages, statistical tests or summary measures are often desired. If the data can be viewed as two categorical measurements on the same experimental unit (matched pair data) then a test of marginal homogeneity may be appropriate. The most common clinical example is the so called ‘shift table’ whereby a quantity is tested for change between two time points. The two principal marginal homogeneity tests are the Stuart Maxwell and Bhapkar tests. At present, SAS software does not compute either test directly (for tables with more than two categories) and a programmatic solution is required. Two examples of programmatic SAS code are found in the current literature. Although accurate in most instances, they fail to produce output for certain tables (‘special cases’). After summarizing the mathematics behind the two tests, a SAS macro is presented, which produces correct output for all tables. Finally, several examples are coded and presented with resultant output. Copyright © 2013 John Wiley & Sons, Ltd.
Detecting pygmy rabbits (Brachylagus idahoensis) using DNA extracted from fecal pellets of mixed‐species groups
Authors: Torstrom Shannon M. , Adams Jennifer R. , Waits Lisette P. 
Published: June 2013

ABSTRACTNoninvasive genetic sampling is an essential tool for studying elusive and endangered species. However, the DNA from noninvasive genetic sampling tends to be low in quantity and quality, which leads to poor DNA amplification. Using fecal pellets of pygmy rabbits (Brachylagus idahoensis) collected in February, March, and November 2011, we tested a possible solution of increasing the amount of sample by combining multiple pellet groups during DNA extraction. One potential drawback of this approach is accidental mixing of samples from multiple species. This study evaluates the mitochondrial DNA (mtDNA) species identification success rate for pygmy rabbit (PY) fecal DNA when mixed with eastern cottontail (Sylvilagus floridanus; EC) fecal pellet DNA at lower frequencies (1PY:3EC and 2PY:6EC) and eastern cottontail or mountain cottontail (S. nuttalli) pellet samples at an equal frequency (4:4). We found that successful detection of pygmy rabbit DNA using a species‐specific mtDNA polymerase chain reaction (PCR) test varies from 0% to 95% depending on the competing species and PCR protocol. From these results, we conclude that if samples are unintentionally mixed, the species with a greater number of pellets within the sample will be more likely to be detected. Also, if pellet piles are intentionally mixed to reduce sampling cost, the protocol should be optimized to maximize DNA amplification for the focal species; however, there will be reduced detection rates depending on the quality and quantity of the focal species DNA within the sample. © 2013 The Wildlife Society.
Beliefs, attitudes, and intentions for allowing elephants in group ranches around amboseli national park, Kenya
Authors: Browne‐Nuñez Christine , Jacobson Susan K. , Vaske Jerry J. 
Published: June 2013

ABSTRACTWildlife authorities and conservationists are working to improve attitudes toward elephants (Loxodonta africana) among residents of the Greater Amboseli Ecosystem in southern Kenya; yet information on existing attitudes and their antecedents is lacking. In 2005, we conducted a survey of 569 randomly selected residents of group ranches—communally held lands around Amboseli National Park—to 1) identify intentions to allow elephants in group ranches, 2) examine attitudes toward this behavior, 3) explore underlying beliefs that influence attitudes, and 4) identify socio‐demographic predictors of residents for and against elephants in group ranches. A slight majority (53%) supported elephants in the group ranches and 47% were opposed. Residents who favored elephants in group ranches were more likely to believe that allowing elephants would increase opportunities to see elephants and attract more tourists to visit group ranches. Those opposed believed that it would cause conflict between people, increase dangerous human–elephant interactions, and increase costs to local people. Both groups believed allowing elephants in the group ranches would cause elephants to increase in number, but those in favor gave this outcome a positive evaluation, whereas those opposed felt this was a negative outcome. Women were less positive than men toward allowing elephants outside the park. Information on beliefs and evaluations of outcomes associated with allowing elephants in group ranches can assist stakeholder groups in addressing concerns of local people and developing interventions to facilitate the continued coexistence of people and elephants. © 2013 The Wildlife Society.