bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy
Authors: Dong Xin , Guan Jun , English John C. , Flint Julia , Yee John , Evans Kenneth , Murray Nevin , MacAulay Calum , Ng Raymond T. , Gout Peter W. , Lam Wan L. , Laskin Janessa , Ling Victor , Lam Stephen , Wang Yuzhuo 
Published: February 2010

Abstract
Purpose: Current chemotherapeutic regimens have only modest benefit for non–small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients.
Experimental Design: Pieces (1×3×3 mm3) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area ≤50% of control, P &lt; 0.05) were determined. Clinical outcomes of treated patients were acquired.
Results: Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive.
Conclusions: Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients. Clin Cancer Res; 16(5); 1442–51
Does Lapatinib Work against HER2-negative Breast Cancers?
Authors: Mayer Ingrid A. , Arteaga Carlos L. 
Published: February 2010

Abstract
Aberrant growth factor receptor signaling can augment or suppress estrogen receptor (ER) function in hormone-dependent breast cancer cells and lead to escape from anti-estrogen therapy. Interruption of HER2/ER cross-talk with lapatinib can restore sensitivity to anti-estrogens and thus, should be investigated in combination with endocrine therapy in patients with ER+/HER2-negative breast cancers. Clin Cancer Res; 16(5); 1355–7
Chronic Cyclooxygenase-2 Inhibition Promotes Myofibroblast-Associated Intestinal Fibrosis
Authors: Davids Jennifer S. , Carothers Adelaide M. , Damas Beatrice C. , Bertagnolli Monica M. 
Published: February 2010

AbstractAnti-inflammatory drugs prevent intestinal tumor formation, an activity related to their ability to inhibit inflammatory pathway signaling in the target tissue. We previously showed that treatment of Min/+ mice with the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib induced rapid tumor regression; however, drug-resistant tumors appeared with long-term treatment. In this study, we investigated whole-tissue changes in inflammatory signaling by studying constituents of the tissue stroma and extracellular matrix. We found that celecoxib resistance was associated with changes in factors regulating autocrine transforming growth factor-β (TGFβ) signaling. Chronic drug treatment expanded the population of bone marrow–derived CD34+ vimentin+ αSMA− myofibroblast precursors and αSMA+ vimentin+ F4/80− myofibroblasts in the lamina propria and submucosa, providing a source of increased TGFβ and COX-2 expression. Membrane constituents regulating TGFβ availability, including syndecan-1 and heparanase-1, were also modified by chronic treatment in a manner promoting increased TGFβ signaling. Finally, long-term celecoxib treatment induced tissue fibrosis, as indicated by increased expression of collagen, fibronectin, and laminin in the basement membrane. We conclude that chronic COX-2 inhibition alters TGFβ signaling in the intestinal mucosa, producing conditions consistent with chronic inflammation. Cancer Prev Res; 3(3); 348–58
Loss of Inhibitory Insulin Receptor Substrate-1 Phosphorylation Is an Early Event in Mammalian Target of Rapamycin–Dependent Endometrial Hyperplasia and Carcinoma
Authors: McCampbell Adrienne S. , Harris Heather A. , Crabtree Judy S. , Winneker Richard C. , Walker Cheryl L. , Broaddus Russell R. 
Published: February 2010

Abstract
Insulin-like growth factor-I receptor signaling contributes to the development of endometrial hyperplasia, the precursor to endometrioid-type endometrial carcinoma, in humans and in rodent models. This pathway is under both positive and negative regulation, including S6 kinase (S6K) phosphorylation of insulin receptor substrate-1 (IRS-1) at S636/639, which occurs downstream of mammalian target of rapamycin (mTOR) activation to inhibit this adapter protein. We observed activation of mTOR with a high frequency in human endometrial hyperplasia and carcinoma, but an absence of IRS-1 phosphorylation, despite high levels of activated S6K. To explore when during disease progression mammalian target of rapamycin (mTOR) activation and loss of negative feedback to IRS-1 occurred, we used the Eker rat (Tsc2Ek/+) model, where endometrial hyperplasia develops as a result of loss of Tsc2, a “gatekeeper” for mTOR. We observed mTOR activation early in progression in hyperplasias and in some histologically normal epithelial cells, suggesting that event(s) in addition to loss of Tsc2 were required for progression to hyperplasia. In contrast, whereas IRS-1 S636/639 phosphorylation was observed in normal epithelium, it was absent from all hyperplasias, indicating loss of IRS-1 inhibition by S6K occurred during progression to hyperplasia. Treatment with a mTOR inhibitor (WAY-129327) significantly decreased hyperplasia incidence and proliferative indices. Because progression from normal epithelium to carcinoma proceeds through endometrial hyperplasia, these data suggest a progression sequence where activation of mTOR is followed by loss of negative feedback to IRS-1 during the initial stages of development of this disease. Cancer Prev Res; 3(3); 290–300
Role of Motivation in the Relationship Between Depression, Self-care, and Glycemic Control in Adults With Type 2 Diabetes
Authors: Egede Leonard E. , Osborn Chandra Y. 
Published: February 2010

Purpose The mechanism by which depression influences health outcomes in persons with diabetes is uncertain. The purpose of this study was to test whether depression is related to self-care behavior via social motivation and indirectly related to glycemic control via self-care behavior. Methods Patients with diabetes were recruited from an outpatient clinic. Information gathered pertained to demographics, depression, and diabetes knowledge (information); diabetes fatalism (personal motivation); social support (social motivation); and diabetes self-care (behavior). Hemoglobin A1C values were extracted from the patient medical record. Structural equation models tested the predicted pathways. Results Higher levels of depressive symptoms were significantly related to having less social support and decreased performance of diabetes self-care behavior. In addition, when depressive symptoms were included in the model, fatalistic attitudes were no longer associated with behavioral performance. Conclusions Among adults with diabetes, depression impedes the adoption of effective self-management behaviors (including physical activity, appropriate dietary behavior, foot care, and appropriate self-monitoring of blood glucose behavior) through a decrease in social motivation.
Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-α and Tfr2-β isoforms in different tissues
Authors: Roetto Antonella , Di Cunto Ferdinando , Pellegrino Rosa Maria , Hirsch Emilio , Azzolino Ornella , Bondi Alessandro , Defilippi Ilaria , Carturan Sonia , Miniscalco Barbara , Riondato Fulvio , Cilloni Daniela , Silengo Lorenzo , Altruda Fiorella , Camaschella Clara , Saglio Giuseppe 
Published: February 2010

Abstract
Transferrin receptor 2 (TFR2) is a transmembrane protein that is mutated in hemochromatosis type 3. The TFR2 gene is transcribed in 2 main isoforms: the full-length (α) and a shorter form (β). α-Tfr2 is the sensor of diferric transferrin, implicated in the modulation of hepcidin, the main regulator of iron homeostasis. The function of the putative β-Tfr2 protein is unknown. We have developed a new mouse model (KI) lacking β-Tfr2 compared with Tfr2 knockout mice (KO). Adult Tfr2 KO mice show liver iron overload and inadequate hepcidin levels relative to body iron stores, even though they increase Bmp6 production. KI mice have normal transferrin saturation, liver iron concentration, hepcidin and Bmp6 levels but show a transient anemia at young age and severe spleen iron accumulation in adult animals. Fpn1 is strikingly decreased in the spleen of these animals. These findings and the expression of β-Tfr2 in wild-type mice spleen suggest a role for β-Tfr2 in Fpn1 transcriptional control. Selective inactivation of liver α-Tfr2 in KI mice (LCKO-KI) returned the phenotype to liver iron overload. Our results strengthen the function of hepatic α-Tfr2 in hepcidin activation, suggest a role for extrahepatic Tfr2 and indicate that β-Tfr2 may specifically control spleen iron efflux.
A copy number variation in human NCF1 and its pseudogenes
Authors: Brunson Tiffany , Wang Qingwei , Chambers Isfahan , Song Qing 
Published: February 2010

Abstract

Background
Neutrophil cytosolic factor-1 (NCF1) is a component of NADPH oxidase. The NCF1 gene colocalizes with two pseudogenes (NCF1B and NCF1C). These two pseudogenes have a GT deletion in exon 2, resulting in a frameshift and an early stop codon. Here, we report a copy number variation (CNV) of the NCF1 pseudogenes and their alternative spliced expressions.

Results
We examined three normal populations (86 individuals). We observed the 2:2:2 pattern (NCF1B:NCF1:NCF1C) in only 26 individuals. On average, each African- American has 1.4 ± 0.8 (Mean ± SD) copies of NCF1B and 2.3 ± 0.6 copies of NCF1C; each Caucasian has 1.8 ± 0.7 copies of NCF1B and 1.9 ± 0.4 copies of NCF1C; and each Mexican has 1.6 ± 0.6 copies of NCF1B and 1.0 ± 0.4 copies of NCF1C. Mexicans have significantly less NCF1C copies than African-Americans (p = 6e-15) and Caucasians (p = 3e-11). Mendelian transmission of this CNV was observed in two CEPH pedigrees. Moreover, we cloned two alternative spliced transcripts generated from these two pseudogenes that adopt alternative exon-2 instead of their defective exon 2. The NCF1 pseudogene expression responded robustly to PMA induction during macrophage differentiation. NCF1B decreased from 32.9% to 8.3% in the cDNA pool transcribed from 3 gene copies. NCF1Ψs also displayed distinct expression patterns in different human tissues.

Conclusions
Our results suggest that these two pseudogenes may adopt an alternative exon-2 in different tissues and in response to external stimuli. The GT deletion is insufficient to define them as functionless pseudogenes; this CNV may have biological relevance.
A consensus linkage map of the grass carp (Ctenopharyngodon idella) based on microsatellites and SNPs
Authors: Xia Jun Hong , Liu Feng , Zhu Ze Yuan , Fu Jianjun , Feng Jianbin , Li Jiale , Yue Gen Hua 
Published: February 2010

AbstractBackgroundGrass carp (Ctenopharyngodon idella) belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes.ResultsWe constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs). The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish.ConclusionsThe linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.
Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children
Authors: De Palma Giada , Nadal Inmaculada , Medina Marcela , Donat Ester , Ribes-Koninckx Carmen , Calabuig Miguel , Sanz Yolanda 
Published: February 2010

Abstract

Background
Coeliac disease is a chronic intestinal inflammatory disorder due to an aberrant immune response to dietary gluten proteins in genetically predisposed individuals. Mucosal immune response through IgA secretion constitutes a first line of defence responsible for neutralizing noxious antigens and pathogens. The aim of this study was the characterization of the relationships between immunoglobulin-coated bacteria and bacterial composition of faeces of coeliac disease (CD) patients, untreated and treated with a gluten-free diet (GFD) and healthy controls.

Results
IgA-coated faecal bacterial levels were significantly lower in both untreated and treated CD patients than in healthy controls. IgG and IgM-coated bacterial levels were also significantly lower in treated CD patients than in untreated CD patients and controls. Gram-positive to Gram-negative bacteria ratio was significantly reduced in both CD patients compared to controls. Bifidobacterium, Clostridium histolyticum, C. lituseburense and Faecalibacterium prausnitzii group proportions were less abundant (P < 0.050) in untreated CD patients than in healthy controls. Bacteroides-Prevotella group proportions were more abundant (P < 0.050) in untreated CD patients than in controls. Levels of IgA coating the Bacteroides-Prevotella group were significantly reduced (P < 0.050) in both CD patients in comparison with healthy controls.

Conclusions
In CD patients, reduced IgA-coated bacteria is associated with intestinal dysbiosis, which altogether provide new insights into the possible relationships between the gut microbiota and the host defences in this disorder.
Cellular localization of ROS and NO in olive reproductive tissues during flower development
Authors: Zafra Adoración , Rodríguez-García María Isabel , Alché Juan de Dios 
Published: February 2010

AbstractBackgroundRecent studies have shown that reactive oxygen species (ROS) and nitric oxide (NO) are involved in the signalling processes taking place during the interactions pollen-pistil in several plants. The olive tree (Olea europaeaL.) is an important crop in Mediterranean countries. It is a dicotyledonous species, with a certain level of self-incompatibility, fertilisation preferentially allogamous, and with an incompatibility system of the gametophytic type not well determined yet. The purpose of the present study was to determine whether relevant ROS and NO are present in the stigmatic surface and other reproductive tissues in the olive over different key developmental stages of the reproductive process. This is a first approach to find out the putative function of these signalling molecules in the regulation of the interaction pollen-stigma.ResultsThe presence of ROS and NO was analyzed in the olive floral organs throughout five developmental stages by using histochemical analysis at light microscopy, as well as different fluorochromes, ROS and NO scavengers and a NO donor by confocal laser scanning microscopy. The "green bud" stage and the period including the end of the "recently opened flower" and the "dehiscent anther" stages displayed higher concentrations of the mentioned chemical species. The stigmatic surface (particularly the papillae and the stigma exudate), the anther tissues and the pollen grains and pollen tubes were the tissues accumulating most ROS and NO. The mature pollen grains emitted NO through the apertural regions and the pollen tubes. In contrast, none of these species were detected in the style or the ovary.ConclusionThe results obtained clearly demonstrate that both ROS and NO are produced in the olive reproductive organs in a stage- and tissue- specific manner. The biological significance of the presence of these products may differ between early flowering stages (defence functions) and stages where there is an intense interaction between pollen and pistil which may determine the presence of a receptive phase in the stigma. The study confirms the enhanced production of NO by pollen grains and tubes during the receptive phase, and the decrease in the presence of ROS when NO is actively produced.
The prevalence of hypertension, obesity and dyslipidemia in individuals of over 30 years of age belonging to minorities from the pasture area of Xinjiang
Authors: Yao Xiao-Guang , Frommlet Florian , Zhou Ling , Zu Feiya , Wang Hong-Mei , Yan Zhi-Tao , Luo Wen-Li , Hong Jing , Wang Xin-Ling , Li Nan-Fang 
Published: February 2010

Abstract

Background
The prevalence of population-wide hypertension, obesity and dyslipidemia has not been well studied in the pasture area of Xinjiang. The present epidemiological study was performed to determine the prevalence of hypertension, obesity and dyslipidemia in minority populations from the pasture area of Xinjiang and to discuss the potential risk factors for hypertension.

Methods
A population-based, cross-sectional study in the Xinjiang pasture area was performed which included 2251 participants aged over 30 years (90.33% participation rate) of whom 71.26% were Kazaks. Several risk factors were considered: hypertension (defined as systolic or diastolic blood pressure or both of at least 140/90 mmHg measured on one occasion or treatment for hypertension) overweight/obesity (body mass index ≥ 25 kg/m2) alcohol intake, smoking/tobacco use and dyslipidemia. Outcomes were prevalence of hypertension, obesity and dyslipidemia and the associated risk factors of hypertension detected by multivariate logistic regression analysis taking into account various metabolic and lifestyle characteristics.

Results
The prevalence of hypertension, overweight/obesity and dyslipidemia in all participants from the pasture area of Xinjiang was 51.9%, 47.9% and 49.2% respectively. Independently, the prevalence and awareness of hypertension was 52.6% and 15.3% among Kazaks (n = 1604), 54.6% and 14.1% among Uygurs (n = 418), 39.5% and 16.1% among Mongolians (n = 81) and 43.9% and 18.2% among non-Xinjiang-born Han immigrants (n = 148). The prevalence of overweight/obesity in Kazaks, Uygurs, Mongolians and Han immigrants was 46.7%, 48.9%, 62.5% and 50.3%, respectively. The prevalence of dyslipidemia in the four ethnic groups mentioned was 53.5%, 34.8%, 49.3% and 47.3%, respectively. The mean blood pressure in all participants was 136/86 mmHg (pre-hypertensive), the mean BMI was 24.7 kg/m2. Based on multiple logistic regression analysis, the significant risk factors for hypertension were age [1.07(1.06-1.09), P < 0.0001], overweight/obesity [overweight: 1.61(1.22-2.13), p = 0.0007; obesity: 1.95 (1.33-2.87), p = 0.0007], hypercholesterolemia [1.30(1.15-1.47), p < 0.0001] and an alcohol intake of over 30 g/day [2.22(1.43-3.45), p = 0.0004].

Conclusions
The considerably high prevalence of hypertension, overweight/obesity and dyslipidemia among the minority population aged over 30 from the pasture area of Xinjiang calls for effective preventive measures. Age, increased body mass index, hypercholesterolemia and ≥30 g/d alcohol intake can be counted as risk factors for hypertension, but further genetic or environmental clarification would be desirable to explain the unusually high prevalence of the conditions mentioned above.
Increased shedding of HU177 correlates with worse prognosis in primary melanoma
Authors: Hamilton Heather K , Rose Amy E , Christos Paul J , Shapiro Richard L , Berman Russell S , Mazumdar Madhu , Ma Michelle W , Krich Daniel , Liebes Leonard , Brooks Peter C , Osman Iman 
Published: February 2010

Abstract

Background
Increased levels of cryptic collagen epitope HU177 in the sera of melanoma patients have been shown to be associated with thicker primary melanomas and with the nodular histologic subtype. In this study, we investigate the association between HU177 shedding in the sera and clinical outcome in terms of disease-free survival (DFS) and overall survival (OS).

Methods
Serum samples from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (mean age = 58, mean thickness = 2.09 mm, stage I = 136, stage II = 41, stage III = 32, median follow-up = 54.9 months) were analyzed for HU177 concentration using a validated ELISA assay. HU177 serum levels at the time of diagnosis were used to divide the study cohort into two groups: low and high HU177. DFS and OS were estimated by Kaplan-Meier survival analysis, and the log-rank test was used to compare DFS and OS between the two HU177 groups. Multivariate Cox proportional hazards regression models were employed to examine the independent effect of HU177 category on DFS and OS.

Results
HU177 sera concentrations ranged from 0-139.8 ng/ml (mean and median of 6.2 ng/ml and 3.7 ng/ml, respectively). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. Higher HU177 serum level was associated with an increased rate of melanoma recurrence (p = 0.04) and with increasing mortality (p = 0.01). The association with overall survival remained statistically significant after controlling for thickness and histologic subtype in a multivariate model (p = 0.035).

Conclusions
Increased shedding of HU177 in the serum of primary melanoma patients is associated with poor prognosis. Further studies are warranted to determine the clinical utility of HU177 in risk stratification compared to the current standard of care.