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https://www.readbyqxmd.com/read/28732364/a-novel-heterozygous-germline-deletion-in-msh2-gene-in-a-five-generation-chinese-family-with-lynch-syndrome
#1
Bin Wu, Wuyang Ji, Shengran Liang, Chao Ling, Yan You, Lai Xu, Min-Er Zhong, Yi Xiao, Hui-Zhong Qiu, Jun-Yang Lu, Santasree Banerjee
Lynch syndrome (LS) is one of the most common familial forms of colorectal cancer predisposing syndrome with an autosomal dominant mode of inheritance. LS is caused by the germline mutations in DNA mismatch repair (MMR) genes including MSH2, MLH1, MSH6and PMS2. Clinically, LS is characterized by high incidence of early-onset colorectal cancer as well as endometrial, small intestinal and urinary tract cancers, usually occur in the third to fourth decade of the life. Here we describe a five generation Chinese family with LS clinically diagnosed according to the Amsterdam II criteria...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731382/external-validation-and-clinical-utility-of-a-prediction-model-for-6-month-mortality-in-patients-undergoing-hemodialysis-for-end-stage-kidney-disease
#2
Brian Forzley, Lee Er, Helen Hl Chiu, Ognjenka Djurdjev, Dan Martinusen, Rachel C Carson, Gaylene Hargrove, Adeera Levin, Mohamud Karim
BACKGROUND: End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. AIM: We aimed to assess the external validity and clinical utility in an independent cohort in Canada. DESIGN: We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses...
July 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28731225/decreased-levels-of-pdi-and-p5-in-oligodendrocytes-in-alzheimer-s-disease
#3
Yasuyuki Honjo, Takashi Ayaki, Takami Tomiyama, Tomohisa Horibe, Hidefumi Ito, Hiroshi Mori, Ryosuke Takahashi, Koji Kawakami
Protein disulfide isomerase (PDI) is a chaperone protein located in the endoplasmic reticulum (ER). Nitric oxide-induced S-nitrosylation of PDI inhibits its enzymatic activity, leading to protein accumulation and activation of the unfolded protein response. Protein disulfide isomerase P5 (P5) is a member of the PDI family that mostly localizes to the ER lumen. Both S-nitrosylated PDI and S-nitrosylated P5 are found in Alzheimer's disease (AD) brain. Previously, we showed that expression of the ER stress marker, growth arrest, and DNA damage protein (GADD34) was significantly increased in neurons and oligodendrocytes in AD brain...
July 21, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28731173/anacardic-acid-induces-cell-apoptosis-of-prostatic-cancer-through-autophagy-by-er-stress-dapk3-akt-signaling-pathway
#4
Jing Tan, Xianzhen Jiang, Guangming Yin, Leye He, Jianye Liu, Zhi Long, Zhiqiang Jiang, Kun Yao
Anacardic acid, which is commonly seen in plants of Anacardiaceae, is an important composition of cashew, ginkgo leaf and fruit, and it has been suggested in previous research to show antitumor activity. The main aim of the present study was to evaluate the anticancer effects of anacardic acid on cell apoptosis of prostatic cancer and molecular mechanisms of this phenomenon. In this study we found that anacardic acid inhibited cell proliferation, induced apoptosis and caspase-3/9 activities and Bax protein expression of prostatic cancer...
July 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731145/piezo1-protein-induces-the-apoptosis-of-human-osteoarthritis-derived-chondrocytes-by-activating-caspase-12-the-signaling-marker-of-er-stress
#5
Xiao-Fei Li, Zhao Zhang, Zhu-Ke Chen, Zhao-Wei Cui, Hai-Ning Zhang
The present study was carried out to determine whether the mechanically activated cation channel Piezo1 protein plays a role as a signaling pathway which causes the apoptosis of human chondrocytes. The chondrocytes were isolated, cultured, and then subjected to mechanical stretch force for 0, 2, 12, 24 and 48 h, respectively. The expression levels of Piezo1 and the apoptosis-related protein caspase-12 were assessed by reverse transcription-quantitative polymerase chain reaction, as well as the apoptosis-related genes, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-associated X protein (Bax) and Bcl-2-associated death promoter (BAD)...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28731040/er-stress-and-the-unfolded-protein-response-in-neurodegeneration
#6
REVIEW
Claudio Hetz, Smita Saxena
The clinical manifestation of neurodegenerative diseases is initiated by the selective alteration in the functionality of distinct neuronal populations. The pathology of many neurodegenerative diseases includes accumulation of misfolded proteins in the brain. In physiological conditions, the proteostasis network maintains normal protein folding, trafficking and degradation; alterations in this network - particularly disturbances to the function of endoplasmic reticulum (ER) - are thought to contribute to abnormal protein aggregation...
July 21, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28731030/cryo-em-structure-and-biochemical-analysis-reveal-the-basis-of-the-functional-difference-between-human-pi3kc3-c1-and-c2
#7
Meisheng Ma, Jun-Jie Liu, Yan Li, Yuwei Huang, Na Ta, Yang Chen, Hua Fu, Ming-Da Ye, Yuehe Ding, Weijiao Huang, Jia Wang, Meng-Qiu Dong, Li Yu, Hong-Wei Wang
Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking, organelle biogenesis and autophagy. Two class III phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals, the ATG14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2). PI3KC3-C1 is crucial for autophagosome biogenesis, and PI3KC3-C2 is involved in various membrane trafficking events. Here we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer resolution. The two structures share a common L-shaped overall architecture with distinct features...
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28730850/development-and-validation-of-the-heidelberg-form-for-emotion-regulation-strategies-hferst-factor-structure-reliability-and-validity
#8
Shahrzad Izadpanah, Sven Barnow, Andreas B Neubauer, Julia Holl
The Heidelberg Form for Emotion Regulation Strategies (HFERST) was developed to complement previous emotion regulation (ER) questionnaires and addresses some of their limitations by measuring eight ER strategies. An initial item pool was developed in German following expert discussions and adaptation of the items from existing ER scales. Following a stepwise selection based on the experts' judgments, 32 items with the best content validity were chosen. Results of an exploratory factor analysis in Study 1 ( N = 399) and two confirmatory factor analyses in Studies 2 ( N = 715) and 3 ( N = 408) supported the eight-factor structure of the HFERST and provided evidence for its internal consistency, construct and criterion validity, and clinical utility...
July 1, 2017: Assessment
https://www.readbyqxmd.com/read/28730768/modulatory-effect-of-neoadjuvant-chemotherapy-on-the-prognosis-of-patients-with-breast-cancer
#9
Jasna Trifunovic, Numa Memisevic, Borislava Nikolin, Svetlana Salma, Tihomir Dugandzija, Vladimir Vidovic
PURPOSE: To evaluate the changes in biological markers ER, PR, HER2 and Ki67 in residual tumor after surgery for locally advanced breast cancer (LABC), and also to evaluate the outcome of breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: 144 breast cancer patients treated with NAC at the Oncology Institute of Vojvodina, Serbia from 2011 to 2015 were included in this study. Changes in biologic markers ER,PR, HER2/neu and Ki-67 were evaluated at diagnostic core biopsy and at the final surgery tissue specimens...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730767/the-role-of-interleukin-8-and-matrix-metalloproteinases-2-and-9-in-breast-cancer-treated-with-tamoxifen-cell-lines
#10
Jelena Milovanovic, Natasa Todorovic-Rakovic, Zaki Abu Rabi
PURPOSE: To evaluate the role of interleukin 8 (IL8) and matrix metalloproteinase (MMP) 2 and 9 as potential parameters of response to adjuvant tamoxifen and to examine possible associations between biomarkers that might imply possible biological dependence. METHODS: The study included 59 postmenopausal breast cancer patients who received adjuvant tamoxifen. Biomarker levels were determined by ELISA in cytosol tumor extracts. RESULTS: Estrogen receptor (ER) proved as a reliable parameter of response to tamoxifen; patients with ER+ status had significantly longer median relapse-free survival (RFS) compared to those with ER- status (p=0...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28730752/targeted-nanotherapeutics-encapsulating-liver-x-receptor-agonist-gw3965-enhance-antiatherogenic-effects-without-adverse-effects-on-hepatic-lipid-metabolism-in-ldlr-mice
#11
Mikyung Yu, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw, Seung-Joo Lee, Kevin Si, Carleena Angelica Ortega, Won Il Choi, In-Hyun Lee, Yazan Bdour, Jinjun Shi, Morteza Mahmoudi, Sangyong Jon, Edward A Fisher, Omid C Farokhzad
The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized...
July 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28730716/manganese-i-catalyzed-enantioselective-hydrogenation-of-ketones-using-a-defined-chiral-pnp-pincer-ligand
#12
Marcel Garbe, Kathrin Junge, Svenja Walker, Zhihong Wei, Haijun Jiao, Anke Spannenberg, Stephan Bachmann, Michelangelo Scalone, Matthias Beller
A new chiral manganese PNP pincer complex is described. Asymmetric hydrogenation of several prochiral ketones with molecular hydrogen in the presence of this complex proceeds under mild conditions (40 °C, 4 h, 30 bar H₂). Besides high catalytic activity for aromatic substrates, aliphatic ketones are hydrogenated with remarkable selectivities (er up to 92:8). DFT calculations support an outer sphere hydrogenation mechanism as well as the experimentally determined stereochemistry.
July 21, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28730339/breast-cancer-neoplastic-seeding-in-the-setting-of-image-guided-needle-biopsies-of-the-breast
#13
REVIEW
Lumarie Santiago, Beatriz E Adrada, Monica L Huang, Wei Wei, Rosalind P Candelaria
PURPOSE: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy. METHODS: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28730338/jagged1-promotes-aromatase-inhibitor-resistance-by-modulating-tumor-associated-macrophage-differentiation-in-breast-cancer-patients
#14
Hang Liu, Jingxuan Wang, Minghui Zhang, Qijia Xuan, Zhipeng Wang, Xin Lian, Qingyuan Zhang
PURPOSE: Endocrine resistance limits the efficacy of anti-estrogen therapies. Notch signaling is involved in modulating tumor-associated macrophage (TAM) differentiation and is upregulated in endocrine-resistant breast cancer cells. Here, we analyzed the role of Jagged1 in the regulation of TAM polarization to investigate whether the Jagged1-Notch pathway promotes the acquisition of aromatase inhibitor (AI) resistance by upregulating TAM infiltration. METHODS: The Jagged1 expression levels and M2 TAM infiltration density, in 203 tumor samples from ER-positive postmenopausal patients, who received AI treatment, were evaluated by immunohistochemical staining and the results were compared with clincopathological parameters and survival...
July 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28730256/advanced-metastatic-breast-cancer-in-pregnancy-the-imperative-of-physical-breast-examination-in-pregnancy
#15
Anca Angela Simionescu, Claudia Valentina Georgescu, Mirela Corina Ghiluşi, Sabrina Ioana Stoica, Mircea Dragoş Median
Breast cancer is the most frequent cancer diagnosed among women; its association with pregnancy is not encountered. As childbearing age is increasing, the diagnosis of breast cancer associated pregnancy tends to be more often than years ago. Here we report a case of a 37-year-old patient, gravida 7, para 7, diagnosed at 30 weeks gestation with metastatic breast cancer. The patient presented to hospital due to an altered performance status. Obstetrical evaluation was within normal range. A metastatic infiltrating breast cancer poorly differentiated (G3) with satellite skin lesions (T4b), ipsilateral axillary and supraclavicular lymph nodes (N3), lung metastasis bilateral with pleural effusion and hepatic metastasis (M1), were diagnosed...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28729917/autophagy-endoplasmic-reticulum-stress-and-the-unfolded-protein-response-in-intracerebral-hemorrhage
#16
Mingming Niu, Xiaohong Dai, Wei Zou, Xueping Yu, Wei Teng, Qiuxin Chen, Xiaowei Sun, Weiwei Yu, Huihui Ma, Peng Liu
Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729823/administration-of-tauroursodeoxycholic-acid-attenuates-early-brain-injury-via-akt-pathway-activation
#17
Dongdong Sun, Gang Gu, Jianhao Wang, Yan Chai, Yueshan Fan, Mengchen Yang, Xin Xu, Weiwei Gao, Fei Li, Dongpei Yin, Shuai Zhou, Xin Chen, Jianning Zhang
Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28729532/doping-porous-silicon-with-erbium-pores-filling-as-a-method-to-limit-the-er-clustering-effects-and-increasing-its-light-emission
#18
Guido Mula, Tony Printemps, Christophe Licitra, Elisa Sogne, Francesco D'Acapito, Narciso Gambacorti, Nicola Sestu, Michele Saba, Elisa Pinna, Daniele Chiriu, Pier Carlo Ricci, Alberto Casu, Francesco Quochi, Andrea Mura, Giovanni Bongiovanni, Andrea Falqui
Er clustering plays a major role in hindering sufficient optical gain in Er-doped Si materials. For porous Si, the long-standing failure to govern the clustering has been attributed to insufficient knowledge of the several, concomitant and complex processes occurring during the electrochemical Er-doping. We propose here an alternative road to solve the issue: instead of looking for an equilibrium between Er content and light emission using 1-2% Er, we propose to significantly increase the electrochemical doping level to reach the filling the porous silicon pores with luminescent Er-rich material...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729422/o-glycosylation-modulates-the-stability-of-epidermal-growth-factor-like-repeats-and-thereby-regulates-notch-trafficking
#19
Hideyuki Takeuchi, Hongjun Yu, Huilin Hao, Megumi Takeuchi, Atsuko Ito, Huilin Li, Robert S Haltiwanger
Glycosylation in the endoplasmic reticulum (ER) is closely associated with protein folding and quality control. We recently described a non-canonical ER quality control mechanism for folding of thrombospondin type 1 repeats by Protein O-fucosyltransferase 2 (POFUT2). Epidermal Growth Factor-like (EGF) repeats are also small, cysteine rich protein motifs that can be O-glycosylated by several ER-localized enzymes including Protein O-glucosyltransferase 1 (POGLUT1) and POFUT1. Both POGLUT1 and POFUT1 modify the Notch receptor on multiple EGF repeats and are essential for full Notch function...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28729413/breast-cancer-suppression-by-progesterone-receptors-is-mediated-by-their-modulation-of-estrogen-receptors-and-rna-polymerase-iii
#20
Jessica Finlay-Schultz, Austin E Gillen, Heather M Brechbuhl, Joshua J Ivie, Shawna B Matthews, Britta M Jacobsen, David L Bentley, Peter Kabos, Carol A Sartorius
Greater than 50% of estrogen receptor (ER)-positive breast cancers co-express the progesterone receptor (PR), which can directly and globally modify ER action to attenuate tumor growth. However, whether this attenuation is mediated only through PR-ER interaction remains unknown. To address this question, we assessed tumor growth in ER/PR-positive PDX models of breast cancer where both natural and synthetic progestins were found to antagonize the mitogenic effects of estrogens. Probing the genome-wide mechanisms by which this occurs, we documented that chronic progestin treatment blunted ER-mediated gene expression up to 2-fold at the level of mRNA transcripts...
July 20, 2017: Cancer Research
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