tbuckley/cabot-search huggingface dataset:
Targeting histone‐acetyltransferase Tat‐interactive protein 60 inhibits intestinal allergy
Authors: G. Yang, B.‐H. Cheng, S.‐B. Yang, Z.‐Q. Liu, S.‐Q. Qiu, L.‐T. Yang, R.‐D. Xie, X.‐R. Geng, M.‐G. Li, L. Gao, Z.‐G. Liu, P.‐C. Yang
Journal: Allergy (2017)

Abstract Background The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone‐acetyltransferase ( HAT ) activities are required in gene transcription of a large number of molecules in the immune system of the body. Objectives This study tests a hypothesis that HAT Tat‐interactive protein 60 (Tip60) plays an important role in the initiation of IgE‐mediated allergy. Methods The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE‐mediated allergic inflammation. Results High levels of Tip60 were observed in the peripheral B cells of patients with FA . Tat‐interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 ( STAT 6), and nuclear factor‐κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa. Conclusions Tat‐interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti‐allergy drug.
Prostate Cancer: Self-Normalized Detection of ANXA3 from Untreated Urine of Prostate Cancer Patients without Digital Rectal Examination (Adv. Healthcare Mater. 17/2017)
Authors: Minhong Jeun, Sungwook Park, Yongdeok Kim, Jaewon Choi, Sang Hoon Song, In Gab Jeong, Choung-Soo Kim, Kwan Hyi Lee
Journal: Advanced Healthcare Materials (2017)

In article number 1700449, Kwan Hyi Lee and co-workers describe an ion-responsive urine sensor for analyzing minuscule amounts of prostate cancer biomarkers. Patients' untreated urine samples are loaded onto the sensor, and the resulting signals are proportional to the amount of the urine cancer biomarker within the patients' urine. The resulting signals are also confirmed to be proportional to the size of the tumor volume measured from patients' magnetic resonance images.
同時血液脳関門開口と局所遺伝子デリバリーのための集束超音波を用いた葉酸抱合遺伝子搬送マイクロバブル【Powered by NICT】
Authors: Fan Ching-Hsiang, Chang En-Ling, Ting Chien-Yu, Lin Yu-Chun, Liao En-Chi, Huang Chiung-Yin, Chang Yuan-Chih, Chan Hong-Lin, Wei Kuo-Chen, Yeh Chih-Kuang
Journal: Biomaterials (2016)
修復ウサギ軟骨損傷へのキトサンヒドロゲル脱灰骨マトリックスハイブリッド足場を用いた同種異系軟骨細胞の移植【Powered by NICT】
Authors: Man Zhentao, Hu Xiaoqing, Liu Zhenlong, Huang Hongjie, Meng Qingyang, Zhang Xin, Dai Linghui, Zhang Jiying, Fu Xin, Duan Xiaoning, Zhou Chunyan, Ao Yingfang
Journal: Biomaterials (2016)
Testing and linkage to HIV care in China: a cluster-randomised trial
Authors: Zunyou Wu, Zhenzhu Tang, Yurong Mao, Paul Van Veldhuisen, Walter Ling, David Liu, Zhiyong Shen, Roger Detels, Guanghua Lan, Lynda Erinoff, Robert Lindblad, Diane Gu, Houlin Tang, Lian Hu, Qiuying Zhu, Li Lu, Neal Oden, Albert L Hasson, Yan Zhao, Jennifer M McGoogan, Xianmin Ge, Nanci Zhang, Keming Rou, Jinhui Zhu, Hui Wei, Cynthia X Shi, Xia Jin, Jian Li, Julio S G Montaner
Journal: The Lancet HIV (2017)
Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer
Authors: M Cecilia Caino, Jae Ho Seo, Yuan Wang, Dayana B Rivadeneira, Dmitry I Gabrilovich, Eui Tae Kim, Ashani T Weeraratna, Lucia R Languino, Dario C Altieri
Journal: Journal of Clinical Investigation (2017)

Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II–dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility. Conversely, introduction of stress stimuli to the microenvironment, including hypoxia, acutely lowered SNPH levels, resulting in bioenergetics defects and increased superoxide production. In turn, this suppressed tumor cell proliferation but increased tumor cell invasion via greater mitochondrial trafficking to the cortical cytoskeleton. Loss of SNPH or expression of an SNPH mutant lacking the mitochondrial localization sequence resulted in increased metastatic dissemination in xenograft or syngeneic tumor models in vivo. Accordingly, tumor cells that acquired the ability to metastasize in vivo constitutively downregulated SNPH and exhibited higher oxidative stress, reduced cell proliferation, and increased cell motility. Therefore, SNPH is a stress-regulated mitochondrial switch of the cell proliferation-motility balance in cancer, and its pathway may represent a therapeutic target.
標的化癌治療のための遺伝子操作と自己組織化腫瘍溶解性蛋白質ナノ粒子【Powered by NICT】
Authors: Lee Joong-jae, Kang Jung Ae, Ryu Yiseul, Han Sang-Soo, Nam You Ree, Rho Jong Kook, Choi Dae Seong, Kang Sun-Woong, Lee Dong-Eun, Kim Hak-Sung
Journal: Biomaterials (2017)
Final efficacy results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer
Authors: Richard Bell, Julia Brown, Mahesh Parmar, Mark Toi, Thomas Suter, Guenther Steger, Xavier Pivot, John Mackey, Christian Jackisch, Rebecca Dent, Peter Hall, Almut Mecke, Leilani Morales, Louise Provencher, Elzbieta Staroslawska, Roberto Hegg, Laurence Vanlemmens, Andreas Kirsch, Andreas Schneeweiss, Norikazu Masuda, Friedrich Overkamp, David Cameron
Journal: Cancer Research (2015)
Sixty seconds on . . . brisk walking
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Perhaps in 19th century novels. But these days, more than four in 10 adults in England aged 40 to 60 are not even managing 10 minutes of continuous brisk walking a month, according to Public Health England.

Well, believe it. PHE’s evidence summary concludes that 10 minutes of walking at a brisk intensity each …
Correction: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia
Authors: S. Degryse, C. E. de Bock, S. Demeyer, I. Govaerts, S. Bornschein, D. Verbeke, K. Jacobs, S. Binos, D. A. Skerrett-Byrne, H. C. Murray, N. M. Verrills, P. Van Vlierberghe, J. Cools, M. D. Dun
Journal: Leukemia (2018)
運動効果:ヘパトカインであるセレノプロテインPの欠損は,筋での活性酸素種およびAMPKの上方制御によりマウスの運動応答性を増強する
Authors: Misu Hirofumi, Takayama Hiroaki, Kikuchi Akihiro, Ishii Kiyo‐aki, Takamura Toshinari, Chikamoto Keita, Kanamori Takehiro, Tajima Natsumi, Lan Fei, Takeshita Yumie, Honda Masao, Kaneko Shuichi, Saito Yoshiro, Mita Yuichiro, Yoshioka Yuya, Noguchi Noriko, Matsugo Seiichi, Tanaka Mutsumi, Kato Seiji, Matsuyama Naoto, Iwayama Kaito, Tokuyama Kumpei, Akazawa Nobuhiko, Maeda Seiji, Takekoshi Kazuhiro
Journal: Nature Medicine (2017)
Post-translational Regulation of Radioactive Iodine Therapy Response in Papillary Thyroid Carcinoma
Authors: Moran Amit, Shorook Na'ara, Demilza Francis, Wisam Matanis, Sagit Zolotov, Birgit Eisenhaber, Frank Eisenhaber, Michal Weiler Sagie, Leonid Malkin, Salem Billan, Tomer Charas, Ziv Gil
Journal: JNCI Journal of the National Cancer Institute (2017)

Radioactive iodine (RAI) is the mainstay of treatment for differentiated thyroid carcinoma (DTC). Nevertheless, the mechanism of RAI resistance that occurs in many patients with DTC remains unknown. We aimed to elucidate the role of post-translational regulation of radioiodine uptake.We analyzed the expression pattern of the ribosomal glycosylphosphatidylinositol transamidase (GPIT) complex in freshly excised tumors from 10 patients with DTC. We used functional RAI uptake assays to assess the role of GPIT in iodine uptake both in vivo and in vitro. The effects of MEK inhibition on the GPIT subunit PIGU and the sodium iodide symporter (NIS) were assessed in three DTC cell lines and in four human DTC biopsies. We used a multivariable logistic regression model to study the role of PIGU in the response to RAI treatment in advanced DTC. All statistical tests were two-sided.Expression profiling of different GPIT complex subunits revealed statistically significantly lower expression of PIGU in papillary carcinomas than in matched normal thyroid tissue (P < .001). Expression of PIGU in the K1 human papillary carcinoma cell line resulted in a robust increase in NIS glycosylation and trafficking to the cell membrane, accompanied by a robust increase in I125 uptake both in vitro (465 200 ± 56 343 vs 1236 ± 156 counts per million, P < .001) and in vivo (128 945 ± 28 556 vs 7963 ± 192 counts per million, P < .001, n = 5 mice per group). Treatment with the MEK inhibitors U0126 and PD302 rescued PIGU expression. Finally, the PIGU expression levels in tumors of 18 patients with recurrent DTC were associated with a biochemical response to RAI treatment (hazard ratio = 8.06, 95% confidence interval = 3.72 to 12.3, P = .001).We showed that downregulation of PIGU in DTC determines NIS function and RAI avidity. This represents a novel mechanism for RAI resistance.
Statistical modeling of CALGB 80405 (Alliance) to identify influential factors in metastatic colorectal cancer (CRC) dependent on primary (1o) tumor side.
Authors: Leon Furchtgott, David Swanson, Boris Hayete, Iya Khalil, Diane Wuest, Kelly Rich, Andrew B. Nixon, Donna Niedzwiecki, Jeffrey A. Meyerhardt, Eileen Mary O'Reilly, Fang-Shu Ou, Heinz-Josef Lenz, Federico Innocenti, Alan P. Venook
Journal: Journal of Clinical Oncology (2017)

3528 Background: CALGB 80405 is a phase III clinical trial of FOLFOX and FOLFIRI w/ randomly assigned cetuximab or bevacizumab. Novel machine learning approaches to the study dataset provide valuable insights into CRC prognosis and management of CRC progression. Methods: Using a Monte Carlo Bayesian Generalized Linear Model analytical platform, we built an ensemble of models for overall survival (OS). We used 99 baseline and demographic variables, including 1904 patients w/ 1 o side and 949 w/ KRAS wild-type status. Building an ensemble of predictive models reduces risk of overfitting, estimates model uncertainty and identifies key variables by model consensus as measured by ensemble frequency (freq). We fit gender and 1 o side (L vs R) stratum-specific models to examine differences in drivers of disease in those strata. Results: 1 o side (avg Cox hazard ratio = 0.89, R side reference), ECOG performance status (1.30, reference level 0), AST concentration (1.01), peripheral neutrophil percentage (1.01) and local primary and abdominal site of disease indicators (1.22; 1.26) were key variables predictive of OS ( &gt; 75% freq). In 1 o side stratum-specific models, urine protein level (1.61), treatment intent (0.75, nonpalliative as reference) and hemoglobin concentration (0.85) were more associated w/ L side progression (freq &gt; 85% in L stratum model, &lt; 20% in R), while liver and lung sites of disease (2.3; 1.09) were more associated w/ R side progression (freq &gt; 65% in R stratum model, &lt; 20% in L). Predictors of 1 o left-sidedness included age (avg log odds ratio = 0.02), hemoglobin (0.41), and abdominal (3.79) and liver (0.68) sites of disease. Modest differences in disease prognostic factors existed between genders: women more influenced by metastatic status, age, liver site of disease and creatinine level; men more influenced by urine protein level and prior diabetes. Conclusions: 1 o side plays a central role in potentially explaining both variation in OS and differences in drivers of OS. Availability of these measures at baseline enables better sense of disease course at initiation of treatment. Support: U10CA180821, U10CA180882, Eli Lilly &amp; Co., Genentech, Pfizer Clinical trial information: NCT00265850.
ウサギにおけるGLP-1受容体およびPI3キナーゼAkt-eNOS経路の刺激を通してボグリボースは心筋梗塞サイズを縮小する
Authors: Iwasa Masamitsu, Kobayashi Hiroyuki, Yasuda Shinji, Bao Naren Two Ya, Yamaki Takahiko, Sumi Shohei, Ushikoshi Hiroaki, Nishigaki Kazuhiko, Takemura Genzou, Fujiwara Takako, Fujiwara Hisayoshi, Minatoguchi Shinya
Journal: Circulation (2009)
Deficiency in Kelch protein Klhl31 causes congenital myopathy in mice
Authors: James B. Papizan, Glynnis A. Garry, Svetlana Brezprozvannaya, John R. McAnally, Rhonda Bassel-Duby, Ning Liu, Eric N. Olson
Journal: Journal of Clinical Investigation (2017)

Maintenance of muscle structure and function depends on the precise organization of contractile proteins into sarcomeres and coupling of the contractile apparatus to the sarcoplasmic reticulum (SR), which serves as the reservoir for calcium required for contraction. Several members of the Kelch superfamily of proteins, which modulate protein stability as substrate-specific adaptors for ubiquitination, have been implicated in sarcomere formation. The Kelch protein Klhl31 is expressed in a muscle-specific manner under control of the transcription factor MEF2. To explore its functions in vivo, we created a mouse model of Klhl31 loss of function using the CRISPR-Cas9 system. Mice lacking Klhl31 exhibited stunted postnatal skeletal muscle growth, centronuclear myopathy, central cores, Z-disc streaming, and SR dilation. We used proteomics to identify several candidate Klhl31 substrates, including Filamin-C (FlnC). In the Klhl31-knockout mice, FlnC protein levels were highly upregulated with no change in transcription, and we further demonstrated that Klhl31 targets FlnC for ubiquitination and degradation. These findings highlight a role for Klhl31 in the maintenance of skeletal muscle structure and provide insight into the mechanisms underlying congenital myopathies.
Re: Giorgio Gandaglia, Stephen A. Boorjian, William P. Parker, et al. Impact of Postoperative Radiotherapy in Men with Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy for Prostate Cancer: A Long-term Survival Analysis. Eur Urol 2017;72:910–7
Authors: Alan Dal Pra, Stephane Supiot, Pirus Ghadjar
Journal: European Urology (2017)
Abstract 138: Inhibition of Stress-inducible Genes That Distinguish Pathological Cardiac Hypertrophy via Targeting Acidic Nuclear Protein 32e
Authors: Hyewon Shin, Zhi Yang, Minzhen He, Danish Sayed, Maha Abdellatif
Journal: Circulation Research (2016)

Cardiac hypertrophy is a manifestation of an increase in the workload imposed on the heart. The cause, duration, and extent of the workload dictate the physiological vs. pathological nature of the hypertrophy and its likelihood to transition into cardiac failure. Our goal is to identify differences between these 2 forms of hypertrophy by examining the binding patterns of key basic transcription factors and regulators in a genome-wide fashion. Our data show that a pause-release mechanism of RNA polymerase II (pol II) bound to the transcriptional start site (TSS) induces housekeeping/essential genes (~ 63% of expressed genes), in a synchronous and incremental fashion that is proportional to the increase in myocyte size and does not require de novo pol II binding. This mechanism is responsible for the increase in cell size and mass that constitute hypertrophy in both physiological and pathological forms. Superimposed on this is a second and critical group of genes (~3.5%) that are stress-induced in the pathological form of hypertrophy but are minimally, if at all, expressed in the postnatal and adult heart (e.g. Acta1, Ankrd1, Xirp2, Nppa, Col1a1 ..etc). In contrast to the housekeeping genes, these genes require de novo pol II recruitment and exhibit a robust increase in expression. To further identify the transcriptional mechanisms that distinguish these sets of genes, we performed chromatin immunoprecipitation-deep sequencing (ChIP-Seq) analysis for cyclin-dependent kinase 9 (Cdk9) and histone H2A.z. The results reveal an increase in Cdk9 at the TSS of paused genes vs. an increase at TSS and throughout the gene body of inducible genes. In contrast, H2A.z levels remained constant. However, we found that Acidic Nuclear Protein 32e (Anp32e), a nuclear protein phosphatase 2A (PP2A) inhibitor, interacted with H2A.z and regulated phosphorylation of Cdk9. Interestingly, knockdown of Anp32e during pressure overload hypertrophy resulted in 70-90% inhibition of stress-inducible genes, but only an incremental inhibition of the increase in cardiac size. Thus, we propose that targeting Anp32e may partially revert pathological hypertrophy to a more physiological form via specifically inhibiting the stress-induced genes while preserving the increase in cardiac mass.
Low-Dose Cyclophosphamide Induces Antitumor T-Cell Responses, which Associate with Survival in Metastatic Colorectal Cancer
Authors: Martin Scurr, Tom Pembroke, Anja Bloom, David Roberts, Amanda Thomson, Kathryn Smart, Hayley Bridgeman, Richard Adams, Alison Brewster, Robert Jones, Sarah Gwynne, Daniel Blount, Richard Harrop, Robert Hills, Awen Gallimore, Andrew Godkin
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Anticancer T-cell responses can control tumors, but immunosuppressive mechanisms in vivo prevent their function. The role of regulatory T cells (Tregs) in metastatic colorectal cancer is unclear. We have previously shown depletion of Tregs enhances colorectal cancer–specific effector T-cell responses. Low-dose cyclophosphamide targets Tregs in animal models and some human studies; however, the effect of cyclophosphamide in metastatic colorectal cancer is unknown. Experimental Design: Fifty-five patients with metastatic colorectal cancer were enrolled in a phase I/II trial and randomly assigned to receive 2-week-long courses of low-dose (50 mg twice a day) cyclophosphamide or not. The absolute number, phenotype, and antitumor function of peripheral blood–derived lymphocyte subsets were monitored throughout treatment, as well as during 18-month follow-up. Results: Initially, cyclophosphamide reduced proliferation in all lymphocyte subsets; however, a rapid mobilization of effector T cells overcame this decrease, leading to increased absolute T-cell numbers. In contrast, a reduction in proportional and absolute Treg, B-cell, and NK-cell numbers occurred. The expansion and subsequent activation of effector T cells was focused on tumor-specific T cells, producing both granzyme B and IFNγ. Cyclophosphamide-treated patients demonstrating the most enhanced IFNγ+ tumor-specific T-cell responses exhibited a significant delay in tumor progression [HR = 0.29; 95% confidence interval (CI), 0.12–0.69; P = 0.0047), compared with nonresponders and no-treatment controls. Conclusions: Cyclophosphamide-induced Treg depletion is mirrored by a striking boost in antitumor immunity. This study provides the first direct evidence of the benefit of naturally primed T cells in patients with metastatic colorectal cancer. Our results also support the concept that nonmutated self-antigens may act as useful targets for immunotherapies. Clin Cancer Res; 23(22); 6771–80. ©2017 AACR.
The spatiotemporal characteristics of influenza A and B in the WHO European Region: can one define influenza transmission zones in Europe?
Authors: Saverio Caini, Wladimir J Alonso, Clotilde El-Guerche Séblain, François Schellevis, John Paget
Journal: Eurosurveillance (2017)

We aimed to assess the epidemiology and spatiotemporal patterns of influenza in the World Health Organization (WHO) European Region and evaluate the validity of partitioning the Region into five influenza transmission zones (ITZs) as proposed by the WHO. We used the FluNet database and included over 650,000 influenza cases from 2000 to 2015. We analysed the data by country and season (from July to the following June). We calculated the median proportion of cases caused by each virus type in a season, compared the timing of the primary peak between countries and used a range of cluster analysis methods to assess the degree of overlap between the WHO-defined and data-driven ITZs. Influenza A and B caused, respectively, a median of 83% and 17% cases in a season. There was a significant west-to-east and non-significant (p = 0.10) south-to-north gradient in the timing of influenza activity. Typically, influenza peaked in February and March; influenza A earlier than influenza B. Most countries in the WHO European Region would fit into two ITZs: 'Western Europe' and 'Eastern Europe'; countries bordering Asia may be better placed into extra-European ITZs. Our findings have implications for the presentation of surveillance data and prevention and control measures in this large WHO Region.
極性疎水性による脂質二分子層へのバクテリオファージSPP1DNAパッケージングモーターのナノチャンネルの配向単方向性挿入【Powered by NICT】
Authors: Zhou Zhi, Ji Zhouxiang, Wang Shaoying, Haque Farzin, Guo Peixuan
Journal: Biomaterials (2016)
Regulation of Macrophage Apoptosis and Atherosclerosis by Lipid-Induced PKCδ Isoform Activation
Authors: Qian Li, Kyoungmin Park, Yu Xia, Motonobu Matsumoto, Weier Qi, Jialin Fu, Hisashi Yokomizo, Mogher Khamaisi, Xuanchun Wang, Christian Rask-Madsen, George L. King
Journal: Circulation Research (2017)

Activation of monocytes/macrophages by hyperlipidemia associated with diabetes mellitus and obesity contributes to the development of atherosclerosis. PKCδ (protein kinase C δ) expression and activity in monocytes were increased by hyperlipidemia and diabetes mellitus with unknown consequences to atherosclerosis.To investigate the effect of PKCδ activation in macrophages on the severity of atherosclerosis.PKCδ expression and activity were increased in Zucker diabetic rats. Mice with selective deletion of PKCδ in macrophages were generated by breeding PKCδ flox/flox mice with LyzM-Cre and ApoE-/- mice (MPKCδKO/ApoE-/- mice) and studied in atherogenic (AD) and high-fat diet (HFD). Mice fed AD and HFD exhibited hyperlipidemia, but only HFD-fed mice had insulin resistance and mild diabetes mellitus. Surprisingly, MPKCδKO/ApoE-/- mice exhibited accelerated aortic atherosclerotic lesions by 2-fold versus ApoE-/- mice on AD or HFD. Splenomegaly was observed in MPKCδKO/ApoE-/- mice on AD and HFD but not on regular chow. Both the AD or HFD increased macrophage number in aortic plaques and spleen by 1.7- and 2-fold, respectively, in MPKCδKO/ApoE-/- versus ApoE-/- mice because of decreased apoptosis (62%) and increased proliferation (1.9-fold), and not because of uptake, with parallel increased expressions of inflammatory cytokines. Mechanisms for the increased macrophages in MPKCδKO/ApoE-/- were associated with elevated phosphorylation levels of prosurvival cell-signaling proteins, Akt and FoxO3a, with reduction of proapoptotic protein Bim associated with PKCδ induced inhibition of P85/PI3K.Accelerated development of atherosclerosis induced by insulin resistance and hyperlipidemia may be partially limited by PKCδ isoform activation in the monocytes, which decreased its number and inflammatory responses in the arterial wall.