bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effectiveness of crisis resolution/home treatment teams for older people with mental health problems: a systematic review and scoping exercise
Authors: Toot Sandeep , Devine Mike , Orrell Martin 
Published: February 2011

AbstractObjectiveTo assess the effectiveness of crisis resolution/home treatment services for older people with mental health problems.DesignA systematic review was conducted to report on the effectiveness of crisis resolution/home treatment teams (CRHTTs) for older people with mental health problems. As part of the review, we also carried out a scoping exercise to assess the typologies of older people's CRHTTs in practice, and to review these in the context of policy and research findings.ResultsThe literature contains Grade C evidence, according to the Oxford Centre of Evidence Based Medicine (CEBM) guidelines, that CRHTTs are effective in reducing numbers of admissions to hospitals. Outcomes such as length of hospital stay and maintenance of community residence were reviewed but evidence was inadequate for drawing conclusions. The scoping exercise defined three types of home treatment service model: generic home treatment teams; specialist older adults home treatment teams; and intermediate care services. These home treatment teams seemed to be effectively managing crises and reducing admissions.ConclusionThis review has shown a lack of evidence for the efficacy of crisis resolution/home treatment teams in supporting older people with mental health problems to remain at home. There is clearly a need for a randomised controlled trial to establish the efficacy of crisis resolution/home treatment services for older people with mental health problems, as well as a more focussed assessment of the different home treatment service models which have developed in the UK. Copyright © 2011 John Wiley & Sons, Ltd.
Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection
Authors: Schurich Anna , Khanna Pooja , Lopes Ross A. , Han Ki Jun , Peppa Dimitra , Micco Lorenzo , Nebbia Gaia , Kennedy Patrick T.F. , Geretti Anna-Maria , Dusheiko Geoffrey , Maini Mala K. 
Published: February 2011

Abstract

An excess of coinhibitory signals has been proposed to drive the T-cell exhaustion characteristic of persistent viral infections. In this study we examined the contribution of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) to CD8 T cell tolerance in chronic hepatitis B virus (HBV) infection (CHB). CD8 T cells in patients with CHB have an increased propensity to express the coinhibitory receptor CTLA-4 and this correlates with viral load. CTLA-4 is up-regulated on those HBV-specific CD8 T cells with the highest levels of the proapoptotic protein Bim, which we have previously shown mediates their premature attrition; abrogation of CTLA-4-mediated coinhibition can reduce Bim expression. Longitudinal study of CHB patients beginning antiviral therapy reveals that HBV DNA suppression induces transient reconstitution of HBV-specific CD8 T cells but does not reprogram their CTLA-4hiBimhi tolerogenic phenotype. Blocking CTLA-4 is able to increase the expansion of interferon gamma (IFN-γ)-producing HBV-specific CD8 T cells in both the peripheral and intrahepatic compartments. The rescue of anti-HBV responses by either CTLA-4 or PD-L1 blockade is nonredundant.

Conclusion:

CTLA-4 is expressed by HBV-specific CD8 T cells with high levels of Bim and helps to drive this proapoptotic phenotype. CTLA-4 blockade could form one arm of a therapeutic approach to modulate the diverse patterns of coregulation of T-cell exhaustion in this heterogeneous disease. (Hepatology 2011;)
Sorafenib inhibits transforming growth factor β1-Mediated Epithelial-Mesenchymal Transition and apoptosis in mouse hepatocytes
Authors: Chen Yue-Lei , Lv Jing , Ye Xiao-Lei , Sun Ming-Yu , Xu Qin , Liu Cheng-Hai , Min Li-Hua , Li Hui-Ping , Liu Ping , Ding Xiaoyan 
Published: February 2011

Abstract

Epithelial-mesenchymal transition (EMT) is a physiological process that has been recognized to occur during the progression of an increasingly large number of human diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. The activation of transforming growth factor β (TGF-β) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-β signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-β signaling. When applied to AML12 cells and primary hepatocytes, sorafenib strikingly suppressed TGF-β1-induced EMT and apoptosis. Additionally, sorafenib inhibited TGF-β1-induced signal transducer and activator of transcription 3 phosphorylation. We further present

in vitro

evidence that sorafenib ameliorates the proapoptotic and profibrotic effects of TGF-β1 in mouse primary hepatocytes, suggesting that this drug exerts a protective effect on hepatocytes and has therapeutic potential for the treatment of liver fibrosis. (Hepatology 2011;)
Invasive breast cancer incidence trends by detailed race/ethnicity and age
Authors: Liu Lihua , Zhang Juanjuan , Wu Anna H. , Pike Malcolm C. , Deapen Dennis 
Published: February 2011

AbstractRacial/ethnic disparities in breast cancer incidence may contain important evidence for understanding and control of the disease. Monitoring the incidence trends of breast cancer by race/ethnicity allows identification of high risk groups and development of targeted prevention programs. Using population‐based cancer registry data from the Los Angeles Cancer Surveillance Program, we examined the invasive female breast cancer incidence trends among the diverse racial/ethnic populations in Los Angeles County, California, from 1972 to 2007. Age‐adjusted incidence rates (AAIRs) and age‐specific incidence rates (ASIRs) were calculated and examined respectively for non‐Hispanic (NH) white, black, Hispanic, Chinese, Filipina, Japanese and Korean women by calendar year and time period. Rising trends of AAIRs were found in all racial/ethnic groups during the 1980s and 1990s. The breast cancer risk increased more substantially in Japanese and Filipinas than in Chinese and Koreans. During 2000–2007, the trends of AAIRs declined significantly among NH white women and slightly in blacks, remained unchanged for Hispanics and continued to rise significantly among all Asian subgroups. The patterns of ASIRs by race/ethnicity changed dramatically over time. By 2000–2007, younger Hispanic women had the lowest breast cancer risk, replacing the Chinese and Koreans who formerly had the lowest risk. Rapidly increasing breast cancer incidence trends among Asian–Americans underline the importance of behavioral and lifestyle changes as a result of acculturation on the development of the disease. The unique trends of breast cancer incidence by race/ethnicity suggest the need for targeted breast cancer control programs for different racial/ethnic populations.
MKK4 suppresses metastatic colonization by multiple highly metastatic prostate cancer cell lines through a transient impairment in cell cycle progression
Authors: Szmulewitz Russell Z. , Clark Robert , Lotan Tamara , Otto Kristen , Taylor Veneris Jennifer , Macleod Kay , Rinker‐Schaeffer Carrie 
Published: February 2011

AbstractMetastatic dissemination in prostate cancer is often early, but not all cancer cells form clinical metastases. Map kinase kinase 4 (MKK4) suppresses metastasis in a preclinical prostate cancer model. We hypothesize that MKK4 will specifically inhibit metastatic colonization through impaired proliferation. Three highly metastatic rat prostate cancer cell lines (AT6.1, Mat‐Lu and AT3.1) were employed. Stably over‐expressing HA‐MKK4 or vector control lines were injected into immunocompromised mice. These experiments validated that HA‐MKK4 specifically affects metastatic colonization and increases survival. Median survival (days) with HA‐MKK4 vs. vector was 42 vs. 28 (p < 0.0001) for AT6.1, 25 vs. 19 (p < 0.0001) for Mat‐Lu and 27 vs. 20 (p < 0.0001) for AT3.1. HA‐MKK4 suppresses colonization within 14 days post dissemination, after which exponential proliferation resumes. Although overt metastases retain HA‐MKK4, it is inactive within these lesions. Nonetheless, metastasis‐derived cell lines were shown to retain functional HA‐MKK4 and like their parental HA‐MKK4 line are suppressed for experimental metastasis formation in vivo. Disseminated AT6.1‐HA‐MKK4 cells were analyzed and were found to have an alteration in cell cycle. Specifically, there was an accumulation of cells in G1‐phase (p = 0.024) and decrease in S‐phase (p = 0.037) compared with vector. In multiple prostate cancer lines, HA‐MKK4 suppresses an early step in metastatic colonization. These data support a model in which MKK4 activation at the metastatic site causes a cell‐cycle arrest, which is eventually overcome despite presence of functional HA‐MKK4. Further studies will specifically interrogate the regulation of MKK4 activation within the metastatic microenvironment and the down‐stream molecular events critical for metastasis suppression.
Association of superoxide dismutases and NAD(P)H quinone oxidoreductases with prognosis of patients with breast carcinomas
Authors: Hubackova Miluse , Vaclavikova Radka , Ehrlichova Marie , Mrhalova Marcela , Kodet Roman , Kubackova Katerina , Vrána David , Gut Ivan , Soucek Pavel 
Published: February 2011

AbstractAssociations of transcript levels of oxidative stress‐modifying genes SOD2, SOD3, NQO1 and NQO2 and their functional single nucleotide polymorphisms (SNPs) rs4880, rs1799895, rs2536512, rs699473, rs1800566 and rs1143684 with prognosis of breast cancer patients were studied. SNPs were assessed by allelic discrimination in a cohort of 321 breast cancer patients from the Czech Republic. Transcript levels were determined by real‐time polymerase chain reaction (PCR) with absolute quantification in tumor and adjacent non‐neoplastic control tissues. Both genotypes and transcript levels were then compared with available clinical data on patients. Patients carrying low activity allele Leu in NQO2 rs1143684 had a greater incidence of stage 0 or I disease (i.e., better prognosis) than patients with the Phe/Phe genotype. This association was more evident in patients without expression of progesterone receptors (p = 0.031). Patients carrying the Thr allele in SOD3 rs2536512 SNP had a significantly greater incidence of tumors expressing estrogen receptors than patients carrying the Ala/Ala genotype (p = 0.007). SOD3 transcript level was significantly higher in grade 1 or 2 tumors than in grade 3 tumors (p = 0.006). Patients carrying T allele in SOD3 rs699473 SNP had significantly poorer progression‐free survival (PFS) than patients carrying the CC genotype (p = 0.038). The same applied to the subgroup of patients treated by hormonal regimens (p = 0.021). Patients carrying the high activity Ala/Ala genotype in SOD2 (rs4880) had significantly poorer PFS than Val allele carriers in the group treated by cyclophosphamide but not hormonal regimens (p = 0.004). Our results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients and that their significance should be further characterized.
Krebs von den Lungen‐6 (KL‐6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer
Authors: Tanaka Sonosuke , Hattori Noboru , Ishikawa Nobuhisa , Shoda Hiroyasu , Takano Atsushi , Nishino Ryohei , Okada Morihito , Arihiro Koji , Inai Kouki , Hamada Hironobu , Yokoyama Akihito , Kohno Nobuoki 
Published: February 2011

AbstractBy immunizing mice with a lung adenocarcinoma cell line, we previously established a murine IgG1 monoclonal antibody that recognizes a sialylated sugar chain designated Krebs von den Lungen‐6 (KL‐6). KL‐6 is a high–molecular‐weight glycoprotein classified as a human MUC1 mucin. The aim of this study was to determine whether KL‐6 expression in tumors correlates with circulating KL‐6 levels and whether circulating KL‐6 has any prognostic value in patients with surgically resected non‐small cell lung cancer (NSCLC). Immunohistochemical analysis of KL‐6 expression was performed on 103 NSCLC tissues, and its associations with serum KL‐6 levels and survival were examined. We also evaluated whether KL‐6 expression patterns and/or serum KL‐6 levels could predict prognosis in these NSCLC patients. Immunohistochemical analysis of KL‐6 in NSCLC tissues showed that a depolarized KL‐6 expression pattern was associated with a high level of circulating KL‐6 and a poor prognosis in NSCLC patients who underwent curative surgery. Furthermore, a high circulating KL‐6 level was associated with both poorer progression‐free survival (PFS) and overall survival (OS), and multivariate analyses confirmed its independent prognostic value for both PFS and OS (p = 0.041 and 0.023, respectively). Our data suggest that preoperative serum KL‐6 level reflects KL‐6 expression patterns in NSCLC tissue, and can serve as a useful prognostic biomarker in NSCLC patients who undergo curative surgery.
The importance of integrin‐linked kinase in the regulation of bladder cancer invasion
Authors: Matsui Yoshiyuki , Assi Kiran , Ogawa Osamu , Raven Peter A. , Dedhar Shoukat , Gleave Martin E. , Salh Baljinder , So Alan I. 
Published: February 2011

AbstractIt is important to understand the molecular mechanisms of bladder cancer progression not only to prevent cancer progression but also to detect new therapeutic targets against advanced bladder cancer. The integrin‐linked kinase (ILK) is a major signaling integrator in mammalian cells and plays an important role in epithelial–mesenchymal transition (EMT) of human cancers, but its mechanisms are not completely understood. In this study, we investigated the importance and mechanisms of ILK in bladder cancer progression. When the expression of ILK in bladder cancer cell lines and N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN)‐induced murine bladder cancer was evaluated, ILK has a tendency to be overexpressed in invasive cell lines and invasive BBN‐induced murine bladder cancer. Overexpression of ILK in 253J bladder cancer cells suppressed E‐cadherin expression, resulting in the promotion of cell invasion. Conversely, ILK knockdown by siRNA suppresses cell invasion in invasive bladder cancer cells through the regulation of E‐cadherin or matrix metalloprotease 9 (MMP‐9). To regulate E‐cadherin expression, our results showed that the glycogen synthase kinase 3β (GSK3β)‐Zeb1 pathway may play an important role downstream of ILK. Finally, the results of a human bladder tissue microarray (TMA) showed that ILK expression correlates with the invasiveness of human bladder cancer. Our study suggests that ILK is overexpressed in invasive bladder cancer and plays an important role in the EMT of bladder cancer via the control of E‐cadherin and MMP‐9 expression. ILK may be a new molecular target to suppress tumor progression in advanced and high‐risk bladder cancer patients.
Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells
Authors: Liby Tiera A. , Spyropoulos Perry , Buff Lindner Haley , Eldridge Juanita , Beeson Craig , Hsu Tien , Muise‐Helmericks Robin C. 
Published: February 2011

AbstractThe PI3 kinase/Akt pathway is commonly deregulated in human cancers, functioning in such processes as proliferation, glucose metabolism, survival and motility. We have previously described a novel function for one of the Akt isoforms (Akt3) in primary endothelial cells: the control of VEGF‐induced mitochondrial biogenesis. We sought to determine if Akt3 played a similar role in carcinoma cells. Because the PI3 kinase/Akt pathway has been strongly implicated as a key regulator in ovarian carcinoma, we tested the role of Akt3 in this tumor type. Silencing of Akt3 by shRNA did not cause an overt reduction in mitochondrial gene expression in a series of PTEN positive ovarian cancer cells. Rather, we find that blockade of Akt3, results in smaller, less vascularized tumors in a xenograft mouse model that is correlated with a reduction in VEGF expression. We find that blockade of Akt3, but not Akt1, results in a reduction in VEGF secretion and retention of VEGF protein in the endoplasmic reticulum (ER). The reduction in secretion under conditions of Akt3 blockade is, at least in part, due to the down regulation of the resident golgi protein and reported tumor cell marker, RCAS1. Conversely, over‐expression of Akt3 results in an increase in RCAS1 expression and in VEGF secretion. Silencing of RCAS1 using siRNA inhibits VEGF secretion. These findings suggest an important role for Akt3 in the regulation of RCAS1 and VEGF secretion in ovarian cancer cells.
Low‐dose docetaxel enhances the sensitivity of S‐1 in a xenograft model of human castration resistant prostate cancer
Authors: Hasegawa Masanori , Miyajima Akira , Kosaka Takeo , Yasumizu Yota , Tanaka Nobuyuki , Maeda Takahiro , Shirotake Suguru , Ide Hiroki , Kikuchi Eiji , Oya Mototsugu 
Published: February 2011

AbstractS‐1 is a recently developed dihydropyrimidine dehydrogenase inhibitor fluoropyrimidine and has demonstrated high maximum plasma 5‐Fluorouracil (5‐FU) levels with mild toxicity, and an oral formulation has resulted in an improvement in patient quality of life. The aims of the present study were to determine the efficacy of S‐1 or S‐1 combined with docetaxel (DOC) using castration resistant prostate cancer (CRPC) cells and to explore their clinical potential for treating CRPC patients. LNCaP cells, androgen dependent prostate cancer (ADPC) cells and C4‐2 cells, which are a CRPC subline of LNCaP cells, were used. Specimens obtained from ADPC and CRPC patients were also evaluated. The CRPC specimens and C4‐2 cells exhibited significantly lower thymidylate synthase (TS) expression, a target of 5‐FU, than the ADPC specimens and LNCaP cells. In vitro, C4‐2 cells exhibited higher sensitivity to 5‐FU than LNCaP cells. In C4‐2 xenograft model, S‐1 monotherapy suppressed tumor growth and low‐dose DOC enhanced the anti‐tumor effect of S‐1. In vitro, low‐dose DOC, which did not induce G2/M arrest, increased p53 and p21 and resulted in down‐regulation of TS in C4‐2 cells, and down‐regulation of TS is considered to be responsible for the synergistic effect of S‐1 in vivo. The present findings indicate that CRPC patients with androgen ablation may be good candidates for 5‐FU based chemotherapy, and these regimens have attractive therapeutic potential for clinical practice, and they may have a significant impact on therapeutic options.
Potentiation of tumor radiotherapy by a radiation‐inducible oncolytic and oncoapoptotic adenovirus in cervical cancer xenografts
Authors: Wang Haibo , Song Xin , Zhang He , Zhang Jianjun , Shen Xiaodi , Zhou Yixiong , Fan Xianqun , Dai Liyan , Qian Guanxiang , Hoffman Andrew R. , Hu Ji‐Fan , Ge Shengfang 
Published: February 2011

AbstractThe p53 tumor suppressor pathway is impaired in more than 90% of cervical cancers and cancer‐derived cell lines as a result of infection by human papillomavirus (HPV). The HPV E6 oncoprotein forms complexes with p53 and promotes its degradation via ubiquitin‐dependent mechanism. In our study, we attempted to improve the clinical outcomes of this combined therapy by modifying the p53‐targeted adenovirus to become radiation‐responsive. The antitumor adenovirus was constructed by inserting a radiation‐responsive expression cassette composed of the promoter of early growth response‐1 (Egr‐1) and the proapoptotic protein TRAIL. We showed that the addition of adenovirus containing Egr‐1/TRAIL significantly increased cell death and apoptosis caused by radiotherapy. In mice bearing xenograft tumors, intratumoral administration of the Egr‐1/TRAIL adenovirus followed by radiation significantly reduced tumor growth and enhanced tumor survival. Our Egr‐1/TRAIL adenoviral gene product may offer a novel “one‐two punch” tumor therapy for cervical cancers not only by potentiating radiation treatment but also by preserving p53 defect‐specific tumor killing of the oncolytic adenovirus.
Effect of hypoxia on the expression of iron regulatory proteins 1 and the mechanisms involved
Authors: Luo Qian‐Qian , Wang Dan , Yu Min‐Yan , Zhu Li 
Published: February 2011

AbstractIron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Iron regulatory proteins (IRPs, IRP1 and IRP2) are master regulators of cellular iron metabolism. Hypoxia triggers a broad range of gene responses that are primarily mediated by hypoxia‐inducible factor‐1 (HIF‐1). In this study, we have shown that hypoxia could not only upregulate the expression of hypoxia inducible factor‐1 but also downregulate the expression of IRP1. However, the molecular mechanisms that govern the IRP1 response to hypoxia are not known. Herein we suggested that HIF/HRE system was an essential link between IRP1 and hypoxia. The HRE of IRP1 5′‐regulation regions could combine with HIF‐1 in vitro. Dual‐luciferase reporter assay showed that IRP1 was directly downregulated by HIF/HRE system. © 2011 IUBMB IUBMB Life, 63(2): 120–128, 2011
Heparin plays a key regulatory role via a p53/FAK‐dependent signaling in melanoma cell adhesion and migration
Authors: Chalkiadaki Georgia , Nikitovic Dragana , Berdiaki Aikaterini , Katonis Pavlos , Karamanos Nikos K. , Tzanakakis George N. 
Published: February 2011

AbstractHeparin and its various derivatives affect cancer progression in humans. In this study, we show that heparin uptaken intracellularly by melanoma cells activated a signaling cascade, which in turn inhibited melanoma cell adhesion and migration. The reduced ability of M5 cells to adhere onto the fibronectin (FN) substrate was directly correlated to a decrease in the expression of focal adhesion kinase (FAK), which is a key regulator of melanoma motility. Cell treatment with heparin caused a marked downregulation in FAK expression (P ≤ 0.01). This is followed by an analogous inhibition of both constitutive and FN‐induced FAK Y397‐phosphorylation (P ≤ 0.01). Moreover, heparin stimulated the p53 expression (P ≤ 0.001) of M5 cells and its increased accumulation in the nucleus. This favors a decrease in FAK promoter activation and explains the reduced FAK transcript and protein levels. In conclusion, the results of this study clearly demonstrate that the action of heparin in the regulation of melanoma cell adhesion and migration involves a p53/FAK/signaling pathway, which may be of importance in molecular targeted therapy of the disease. © 2011 IUBMB IUBMB Life, 63(2): 109–119, 2011
The mammalian zinc finger transcription factor Krüppel‐like factor 3 (KLF3/BKLF)
Authors: Pearson Richard C.M. , Funnell Alister P.W. , Crossley Merlin 
Published: February 2011

AbstractKLF3 is a member of the Krüppel‐like factor (KLF) family of transcription factors. These proteins are classified by the presence of three C‐terminal C2H2 zinc fingers that allow sequence‐specific binding to CACCC boxes and GC‐rich motifs found in the promoters, enhancers, and other control regions of target genes. KLFs have diverse biological roles, regulating proliferation, differentiation, and apoptosis in many tissues throughout development. KLF3 is a transcriptional repressor that binds the cofactor C‐terminal binding protein, which in turn recruits a large repressor complex to mediate transcriptional silencing. In addition to an understanding of the molecular mechanisms that allow KLF3 to regulate the expression of its target genes, the biological roles of this transcription factor are now being defined. In agreement with the widespread expression pattern of this transcription factor, it is becoming clear that KLF3 is an important regulator of several biological processes, including adipogenesis, erythropoiesis, and B cell development. © 2011 IUBMB IUBMB Life, 63(2): 86–93, 2011