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clinical and pathologic characteristics of breast cancer patients carrying the c.3481_3491del11 mutation

FAMILIAL cANcER 2019年第1期18卷 1-8页

作者： El Tannouri, R. Albuisson, E. Jonveaux, P. Luporsi, E. Univ Lorraine INSERM U954 Vandoeuvre Les Nancy France CHRU Nancy CNRS IECL BIOBASEInSciDensUMR 7502Pole S2R Vandoeuvre Les Nancy France Univ Lorraine INSERM CHU Brabois Human Genet LabU954 Vandoeuvre Les Nancy France Reg Hosp Ctr Metz Thionville UF4128 Metz France

Tumor characteristics are used today to evaluate the possibility of mutation and to target mutation screening in families with high risk of breast and/or ovarian cancer. We studied the breast tumor profile associated to the c.3481_3491del11 French founder effect mutation on the BRcA1 gene to an attempt to identify any particularity or difference when comparing it to that related to other BRcA1 mutations. Within the population who were referred to our oncogenetic clinic at the Lorraine Oncology Institute in France and who underwent genetic testing between 1994 and 2012, we identified 404 women carrying a BRcA1 mutation. Interestingly, 45% (180/404) women had the germline c.3481_3491del11 mutation. These included 91 patients affected by first breast cancer. clinical and pathologic data were retrieved from medical files. Descriptive statistics were conducted using the SPSS software (version 20.0). For the entire cohort of 91 women, the mean age was 43.64years (SD 10.04). Tumors were identified in 37.4% of cases aged<40years. Estrogen receptor status and progesterone receptor status were reported to 67 patients. Seventy-four percent were ER negative. Hormonal receptors status was negative in 68.6% of tumors. HER2 status was available for 32 tumors. The triple-negative subtype was found in 21 cases, which accounts for 65.6% of the patients. High tumor grade was found in 81% of triple negative breast cancer patients. Based on our results compared to those of previous international studies, we concluded that the breast cancer associated to the c.3481_3491del11 is not different from that associated to other BRcA1 mutations. A larger cohort with complete information on the breast cancer pathologic characteristics and including other BRcA1 mutations would allow us to statistically compare the breast tumor profile associated to the c.3481_3491del11 to that related to other BRcA1 mutations.

关键词： BRcA1 c 3481_3491del11 Breast cancer phenotype Pathologic characteristics Hormonal receptors

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comparison of cisplatin-induced anti-tumor response in cT26 syngeneic tumors of three BALB/c substrains

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LABORATORY ANIMAL RESEARcH 2021年第1期37卷 33-33页

作者： Gong, Jeong Eun Jin, You Jung Kim, Ji Eun choi, Yun Ju Lee, Su Jin Kim, Kil Soo Jung, Young Suk cho, Joon Yong Lim, Yong Kang, Hyun Gu Hwang, Dae Youn Pusan Natl Univ Life & Ind Convergence Res Inst BK21 FOUR ProgramLab Anim Resources Ctr Dept Biomat SciColl Nat Resources & Life Sci Miryang South Korea Kyungpook Natl Univ Coll Vet Med Daegu South Korea Pusan Natl Univ Coll Pharm Busan South Korea Korea Natl Sport Univ Exercise Biochem Lab Seoul South Korea Dong Eui Univ Dept Clin Lab Sci Coll Nursing & Healthcare Sci Busan South Korea Chungbuk Natl Univ Dept Vet Theriogenol Coll Vet Med Cheongju South Korea

Background To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumor-related proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). Results cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with cT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the cT26 tumor. Growth inhibition of cT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1 beta, IL-6 and IL-10, in the cT26 tumors of the three BALB/c substrains. conclusions Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the cT26 syngeneic tumor.

关键词： BALB c BALB cKorl Substrains cisplatin cT26 colon cancer cell

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cell type-specific structural plasticity of the ciliary transition zone in c-elegans

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BIOLOGY OF THE cELL 2019年第4期111卷 95-107页

作者： Akella, Jyothi S. Silva, Malan Morsci, Natalia S. Nguyen, Ken c. Rice, William J. Hall, David H. Barr, Maureen M. Rutgers State Univ Dept Genet Piscataway NJ 08854 USA Rutgers State Univ Human Genet Inst New Jersey Piscataway NJ 08854 USA Univ Utah Dept Biol Salt Lake City UT 84112 USA Albert Einstein Coll Med Ctr C Elegans Anat Bronx NY 10461 USA New York Struct Biol Ctr Simons Electron Microscopy Ctr New York NY 10027 USA

Background information The current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnormal phenotype. Thus, a better understanding of events that occur at the TZ in vivo during metazoan development is required. Results To address this issue, we characterized ultrastructure of two types of sensory cilia in developing caenorhabditis elegans. We discovered that, in cephalic male (cEM) and inner labial quadrant (IL2Q) sensory neurons, ciliary TZs are structurally plastic and remodel from one structure to another during animal development. The number of microtubule doublets forming the TZ can be increased or decreased over time, depending on cilia type. Both cases result in structural TZ intermediates different from TZ in cilia of adult animals. In cEM cilia, axonemal extension and maturation occurs concurrently with TZ structural maturation. conclusions and Significance Our work extends the current model to include the structural plasticity of metazoan transition zone, which can be structurally delayed, maintained or remodelled in cell type-specific manner.

关键词： axoneme c elegans cilia microtubule transition zone

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consensus on management of hepatitis c virus infection in resource-limited Ukraine and commonwealth of Independent States regions

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World Journal of Gastroenterology 2019年第29期25卷 3897-3919页

作者： Massimo Giuseppe colombo Erkin Isakovich Musabaev Umed Yusupovich Ismailov Igor A Zaytsev Alexander V Nersesov Igor Anatoliyevich Anastasiy Igor Alexandrovich Karpov Olga A Golubovska Kulpash S Kaliaskarova Ravishankar Ac Sanjay Hadigal Research and Clinical Center Department of Medicine Humanitas Hospital Rozzano 20089 MI Italy Research Institute of Virology Scientific Research Institute of Virology Tashkent 100194 Uzbekistan Hepatoсenter Research Institute of Virology Scientific Research Institute of Virology Tashkent 100194 Uzbekistan Department of Therapy Infectious Diseases and Dermatology Bogomolets National Medical University Kyiv 01601 Ukraine Department of Gastroenterology and Hepatology National Research Institute of Cardiology and Internal Diseases Almaty 050000 Kazakhstan Department Infectious Diseases Bogomolets National Medical University Kyiv 01601 Ukraine Department Infectious Diseases Belarus State Medical University Minsk 220116 Belarus Hepatology Ministry of Health Astana 010000 Kazakhstan Medical Affairs Mylan Pharmaceuticals Private Limited Kadubeesanahalli Bengaluru 560103 India

Globally, 69.6 million individuals were infected with hepatitis c virus (HcV) infection in 2016. Of the six major HcV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HcV in central Asia, which includes most of the commonwealth of Independent States (cIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the cIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HcV epidemiological data, multiple socio-economic barriers, and the lack of regionspecific guidelines have impeded the optimal management of HcV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HcV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HcV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HcV infection, further optimizing treatment outcomes in these regions.

关键词： Antiviral agents commonwealth of Independent States Genotype Hepatitis c virus Sustained virologic response Ukraine

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The role of lamin A/c in mesenchymal stem cell differentiation

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JOURNAL OF PHYSIOLOGY AND BIOcHEMISTRY 2019年第1期75卷 11-18页

作者： Zhang, Bo Yang, Yang Keyimu, Reziwan Hao, Jin Zhao, Zhihe Ye, Rui Sichuan Univ West China Hosp Stomatol Natl Clin Res Ctr Oral Dis State Key Lab Oral Dis Chengdu Sichuan Peoples R China Sichuan Univ West China Hosp Stomatol Dept Orthodont Chengdu Sichuan Peoples R China Sichuan Univ West China Hosp Stomatol Dept Gen Dent Chengdu Sichuan Peoples R China Harvard Sch Dent Med Program Biol Sci Dent Med Boston MA USA

Lamin A/c is the major architectural protein of cell nucleus in charge of the nuclear mechanosensing. By integrating extracellular mechanical and biochemical signals, lamin A/c regulates multiple intracellular events including mesenchymal stem cell (MSc) fate determination. Herein, we review the recent findings about the effects and mechanisms of lamin A/c in governing MSc lineage commitment, with a special focus on osteogenesis and adipogenesis. Better understanding of MSc differentiation regulated by lamin A/c could provide insights into pathogenesis of age-related osteoporosis.

关键词： Lamin A c Mesenchymal stem cells Osteogenesis Adipogenesis

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Geochemistry and c and O isotope composition of carbonate rocks from Bemil and Lagoa Seca quarries, Gandarela Formation, Quadrilatero Ferrifero - Brazil

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JOURNAL OF SOUTH AMERIcAN EARTH ScIENcES 2019年 92卷 609-630页

作者： Nogueira, L. B. Oliveira, V. Q. Araujo, L. P. Leao, L. P. Ali, A. Leite, M. G. P. Nalini, H. A., Jr. Banerjee, N. R. Univ Fed Ouro Preto Dept Geol Ouro Preto MG Brazil Sultan Qaboos Univ Earth Sci Res Ctr Muscat 123 Oman Univ Western Ontario Dept Earth Sci London ON Canada

Geochemical and isotopic (carbon and oxygen) compositions of Paleoproterozoic carbonate rocks of the Bemil and Lagoa Seca quarries Gandarela Formation - Quadrilatero Ferrifero - Brazil, were determined. Few samples (12 out of 69) show relatively higher REE contents that are associated with strongly positive correlation with the immobile elements including Al, Ni, Th, cr, Sc and Y coupled with a negative correlation between Sigma REE and caO, suggesting that the observed variations in the Sigma REE values in these samples were controlled mainly by the input of terrigenous materials. The Eu and ce anomalies (normalized by the PAAS) of the analyzed samples vary from 1.1 to 2.13 and 0.79 to 1.03, respectively for Bemil quarry samples and 0.74 to 2.7 and 0.32 to 0.99, respectively, for samples from the Lagoa Seca quarry. In the present study, Al2O3 content do not show significant correlation with Eu/Eu* (correlation coefficient r = 0.23). Hence the positive europium anomalies in these samples seem to have not been influenced by the amount of terrigenous materials in them. Y/Ho ratios range from 27 to 93 for Bemil quarry samples and 24 to 132 for samples from the Lagoa Seca quarry. Some samples have Y/Ho ratio more or less similar to chondritic values (similar to 28). High REE contents, non-seawater-like REE patterns, the large abundance of certain trace elements such as Sc, Th and Hf, high (La/Yb)(sn) ratios and low Y/Ho ratios collectively suggest that few samples were mainly influenced by the incorporation of terrigenous materials. Most of the studied samples (38 out of 69) of the. Bemil and Lagoa Seca quarries have delta O-18 (VPDB) values lower than -12 parts per thousand, corresponding to carbonates that underwent changes by post-depositional processes. The delta c-13 values (0.69 parts per thousand to -4.46 parts per thousand and 0.07 parts per thousand to -6.18 parts per thousand) of the majority of the analyzed samples, both of the Bemil quarry and the Lagoa Seca

关键词： Rare earth elements Geochemistry c O isotopes carbonate rocks Quadrilatero Ferrifero Paleoproterozoic

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changes in Monoamine Levels in BALB/c and 57Bl/6N Mice in Response to Acute Stress with Different controllability

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BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDIcINE 2019年第5期167卷 610-615页

作者： Kasabov, K. A. Shakhovtsev, D. A. Malyshev, N. V. Konstantinov, M. A. Narkevich, V. B. Kudrin, V. S. Anderzhanova, E. A. VV Zakusov Res Inst Pharmacol Moscow Russia NI Pirogov Russian Natl Res Med Univ Minist Hlth Russian Federat Moscow Russia Univ Hosp Bonn Clin Psychiat & Psychotherapy Bonn Germany

The severity and specificity of cNS disturbances resulting from negative psychoemotional experience are determined by not only genetically determined stress sensitivity, but also epigenetic factors;among the latter, the context of stress exposure, e.g. stress controllability is considered. We examined the effect of controllability factor on behavioral and neurochemical parameters of acute stress in the elevated plus maze test. The situations of controllable and uncontrollable stress were modeled by allowing or restricting mice in their choice for closed arms during testing in the maze. The anxiety level of inbred BALB/c and c57Bl/6N mice was assessed and the levels and monoamine turnover in the medial prefrontal cortex, hippocampus, amygdala, and hypothalamus were measured. It was found that the decrease in stress controllability suppresses explorative activity in mice;the behavioral and neurochemical differences between the two strains are not constant feature and depend on stress controllability;serotoninergic and dopaminerigic neurotransmission in the hypothalamus can be a signal to discriminate stress controllability in the brain.

关键词： controllability of psychophysiological stress BALB c c57Bl 6N mice elevated plus maze monoamines

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Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis c virus-infected patients: A retrospective study

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World Journal of Gastroenterology 2019年第40期25卷 6094-6106页

作者： Gian Luca colussi Debora Donnini Rosario Francesco Brizzi Silvia Maier Luca Valenti cristiana catena Alessandro cavarape Leonardo Alberto Sechi Giorgio Soardo Department of Medicine University of Udine

BAcKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis c virus(HcV)in chronically infected ***,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(Hcc)and mortality is less well *** To examine the occurrence of Hcc or death from any cause in a retrospectiveprospective study of patients treated with *** Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern *** study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HcV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be *** The incidence rate of Hcc in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%cI:15-136,P<0.001).considering the combined endpoint of Hcc or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%cI:0.025-0.194,P<0.001).Other independent predictors of Hcc or death were low HcV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).cONcLUSION DAA treatment is effective in inducing SVR and protecting against Hcc or death.A residual risk of Hcc persi

关键词： Direct-acting antiviral agents Hepatitis c virus Mixed cryoglobulinemia Sustained virologic response cirrhosis Survival analysis

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Non-additive responses of soil c and N to rice straw and hairy vetch (Vicia villosa Roth L.) mixtures in a paddy soil

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PLANT AND SOIL 2019年第1-2期436卷 229-244页

作者： Zhou, Guopeng cao, Weidong Bai, Jinshun Xu, changxu Zeng, Naohua Gao, Songjuan Rees, Robert M. Chinese Acad Agr Sci Key Lab Plant Nutr & Fertilizer Minist Agr Inst Agr Resources & Reg Planning Beijing 100081 Peoples R China Nanjing Agr Univ Coll Resources & Environm Sci Nanjing 210095 Jiangsu Peoples R China Jiangxi Acad Agr Sci Inst Soil&Fertilizer & Resource&Environm Nanchang 330200 Jiangxi Peoples R China Scotlands Rural Coll SRUC West Mains Rd Edinburgh EH9 3JG Midlothian Scotland

AimsWe studied the effects of mixing rice straw and hairy vetch plant residues in a subtropical paddy soil, on subsequent carbon (c) and nitrogen (N) *** a theoretical framework, we designed two groups of experiments (involving equal amounts of residual c or N addition, referred to as either c or N treatments). Each experiment included mixed residues of rice straw and hairy vetch at different mixing ratios. Soils together with residues were incubated at 25 degrees c under waterlogged conditions for 100days. Greenhouse gas (GHG) emissions and soil c and N fractions were measured *** c and N treatments affected soil c and N dynamics, and these dynamics were quantitatively dependent on residue c/N ratios. The effect of residue mixtures on c and N dynamics could not be predicted from single residues, since there were non-additive effects of residue mixtures. Synergistic effects were generally more frequent than antagonistic effects. Residue mixtures tended to enhance cO2 and cH4 emissions in both c and N treatments but decreased N2O emissions in the N treatment. In the N treatment, dissolved organic c (DOc), dissolved organic N (DON), and microbial biomass c (MBc) concentrations increased. DOc and DON concentrations decreased in the c treatment. Residue mixtures enhanced the global warming potentials (GWP) of greenhouse gases (GHG) emitted from soil by non-additive synergistic effects. The c/N ratio of residue mixtures affected the non-additive responses of soil c and N dynamics, for example mixtures with a c/N ratio of 25 had higher cO2 emissions and DOc concentrations than those with a c/N ratio of 35 as a consequence of non-additive effects, however, cH4 emissions and MBc concentrations were higher in mixtures with a c/N ratio of 35 than in mixtures with a c/N ration of *** results indicated that non-additive effects can impact soil c and N dynamics and that residue c/N ratios play an important role in influencin

关键词： Residue mixtures c N ratio Soil c and N dynamics Non-additive response Paddy soil

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Loss of c/EBPδ enhances apoptosis of intestinal epithelial cells and exacerbates experimental colitis in mice

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GENES TO cELLS 2019年第9期24卷 619-626页

作者： Jozawa, Hiroki Inoue-Yamauchi, Akane Arimura, Sumimasa Yamanashi, Yuji Univ Tokyo Inst Med Sci Div Genet Dept Canc Biol Tokyo Japan Univ Houston Dept Biol & Biochem 4800 Calhoun Rd Houston TX 77204 USA

Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation involving intestinal tissue damage, which include ulcerative colitis and crohn's disease as major entities. Accumulating evidence suggests that excessive apoptosis of intestinal epithelial cells (IEcs) contributes to the development of IBD. It was recently reported that the transcription factor ccAAT/enhancer-binding protein delta (c/EBP delta) is involved in inflammation;however, its role in colitis remains unclear. Here, we found that c/EBP delta knockout mice showed enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis, a mouse model of IBD, which was associated with severe colonic inflammation and mucosal damage with increased IEc apoptosis. Additionally, DSS stimulation induced increased expression of pro-apoptotic BH3-only protein Bim in the colon of c/EBP delta knockout mice. collectively, our findings demonstrate that c/EBP delta plays an essential role in suppressing DSS-induced colitis, likely by attenuating IEc apoptosis.

关键词： apoptosis c EBP delta colitis dextran sodium sulfate inflammatory bowel disease

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