tbuckley/cabot-search huggingface dataset:
Cancer susceptibility and the functions of the BRCA2 tumor suppressor
Authors: Ashok R. Venkitaraman
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY09-3 

Inherited mutations affecting the BRCA2 breast cancer susceptibility protein predispose to breast, ovarian and other epithelial cancers at high penetrance (reviewed in 1). BRCA2 inactivation provokes the spontaneous instability of chromosome structure in dividing cells, leading to gross chromosomal rearrangements such as translocations and deletions ([2][1],[3][2]). How BRCA2 protects chromosome structure is incompletely understood. We have elucidated an important function of BRCA2 in the regulation of the enzyme RAD51 in reactions that lead to DNA recombination between homologous DNA strands ([4][3], [5][4]). These reactions might be particularly essential in overcoming blocks to DNA replication by DNA damage, depleted nucleotide pools, or template-bound proteins. Indeed, we find that in BRCA2-deficient cells, DNA intermediates at stalled DNA replication forks are de-stabilized during genome-wide replication arrest, accompanied by the accumulation of genome-wide double-strand DNA breaks ([6][5]). This suggests that in BRCA2 deficiency, it is the breakdown of replication forks, which arrest or pause during normal cell growth, that triggers spontaneous DNA breakage, leading to mutability and cancer predisposition. Besdies chromosomal structural aberrations, BRCA2-deficient cells also exhibit aneuploidy with gains in chromosome number ([2][1]). Suggestive of functions during mitosis, BRCA2 is phosphorylated by the chromosome passenger protein Plk1 during transit through the G2/M phases ([7][6]). Cytokinesis is delayed in BRCA2-deficient cells, with accumulation at the cleavage and abscission steps, accompanied by abnormalities in the distribution of proteins that form the actomyosin contractile ring ([8][7]). These findings link BRCA2 inactivation to cytokinetic abnormalities, and raise the possibility that BRCA2 may have functions at late stages during mitosis.

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Genomic Basis of Adaptive Evolution: The Survival of Amur Ide (<i>Leuciscu</i>s<i>waleckii</i>) in an Extremely Alkaline Environment
Authors: Jian Xu, Jiong-Tang Li, Yanliang Jiang, Wenzhu Peng, Zongli Yao, Baohua Chen, Likun Jiang, Jingyan Feng, Peifeng Ji, Guiming Liu, Zhanjiang Liu, Ruyu Tai, Chuanju Dong, Xiaoqing Sun, Zi-Xia Zhao, Yan Zhang, Jian Wang, Shangqi Li, Yunfeng Zhao, Jiuhui Yang, Xiaowen Sun, Peng Xu
Journal: Molecular Biology and Evolution (2016)

The Amur ide (Leuciscus waleckii) is a cyprinid fish that is widely distributed in Northeast Asia. The Lake Dali Nur population inhabits one of the most extreme aquatic environments on Earth, with an alkalinity up to 50 mmol/L (pH 9.6), thus providing an exceptional model with which to characterize the mechanisms of genomic evolution underlying adaptation to extreme environments. Here, we developed the reference genome assembly for L. waleckii from Lake Dali Nur. Intriguingly, we identified unusual expanded long terminal repeats (LTRs) with higher nucleotide substitution rates than in many other teleosts, suggesting their more recent insertion into the L. waleckii genome. We also identified expansions in genes encoding egg coat proteins and natriuretic peptide receptors, possibly underlying the adaptation to extreme environmental stress. We further sequenced the genomes of 10 additional individuals from freshwater and 18 from Lake Dali Nur populations, and we detected a total of 7.6 million SNPs from both populations. In a genome scan and comparison of these two populations, we identified a set of genomic regions under selective sweeps that harbor genes involved in ion homoeostasis, acid-base regulation, unfolded protein response, reactive oxygen species elimination, and urea excretion. Our findings provide comprehensive insight into the genomic mechanisms of teleost fish that underlie their adaptation to extreme alkaline environments.
Brain-computer interface based motor and cognitive rehabilitation after stroke – state of the art, opportunity, and barriers: summary of the BCI Meeting 2016 in Asilomar
Authors: Floriana Pichiorri, Natalie Mrachacz-Kersting, Marco Molinari, Sonja Kleih, Andrea Kübler, Donatella Mattia
Journal: Brain-Computer Interfaces (2016)

Non-invasive electroencephalographic (EEG) based brain-computer interfaces (BCIs) are a potential tool to support neuronal plasticity after stroke in the sub-acute and even in the chronic state. A few randomized controlled trials have demonstrated the positive effect on motor rehabilitation. Recent data also indicate that BCI training may improve cognitive rehabilitation. However, important questions remain to be addressed for implementing BCI-based rehabilitation in the clinical routine. This translational effort requires an interdisciplinary approach. The current article provides an overview of a stroke rehabilitation workshop of the 6th International Brain-Computer Interface Meeting in Asilomar, Pacific Grove, USA, held from 30 May to 3 June 2016. This workshop provided an overview of the current state of the art in BCI-based motor and cognitive rehabilitation, presented BCI set-ups shown to be effective, and concluded with a discussion of translational issues and barriers.
Time to Leukaemia (TTL) Assessed in NOD/SCID Mice Transplanted with Primary ALL Leukaemia Cells Determines Early Relapse in Patients and Is Identified by a Specific Gene Signature.
Authors: Lüder H. Meyer, Sarah M. Eckhoff, Manon Dammé, Martin Zimmermann, André Schrauder, Georgia Lahr, Karsten Stahnke, Martin Schrappe, Klaus M. Debatin
Journal: Blood (2007)
Absolute Lymphocyte Count at the Time of Relapse Predicts Survival in Patients with Diffuse Large B-Cell Lymphoma.
Authors: Luis F. Porrata, Kay Ristow, Thomas M Haberman, Thomas E Witzig, David James Inwards, Stephen M Ansell, Patrick B Johnston, Ivana N. Micallef, Joseph P Colgan, William L White, Svetomir N Markovic
Journal: Blood (2008)
GW26-e2401 Enhanced levels of miR-122-5p and let-7b-3p in aortas of spontaneously hypertensive rats associated with downregulated levels of Apelin, miR-1-3p, miR-376b-3p and miR-298-5p
Authors: Jiuchang Zhong, Ran Xu, Laijiang Chen, Zhenzhou Zhang, Yingle Xu, Qing Chang, Dingliang Zhu, Pingjin Gao
Journal: Journal of the American College of Cardiology (2015)
Abstract #1202: Mice deficient in the gene for cytochrome P450 (CYP) 1A1 or 1A2 display differential susceptibilities to CYP1A induction and lung tumorigenesis by 3-methylcholanthrene (MC)
Authors: Bhagavatula Moorthy, Lihua Wang, Inayat Fazili, Sudha Kondraganti, Guo-dong Zhou, Weiwu Jiang
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Humans are constantly exposed to environmental polycyclic aromatic hydrocarbons (PAHs). Cytochrome P4501A (CYP1A) enzymes play important roles in the activation of PAHs such as 3-methylcholanthrene (MC) to genotoxic metabolites. We reported earlier that MC elicits persistent induction of hepatic microsomal cytochrome P450 (CYP)1A enzymes for up to 45 days after MC withdrawal. In this study, we tested the hypothesis that Cyp1a2-deficient mice exposed to MC would display persistent induction of CYP1A1 in lung, and be more susceptible to lung tumorigenesis than wild type (WT) mice, while Cyp1a1-null mice will be refractory to CYP1A1 induction and lung tumorigenesis. Eight week-old female WT (C57BL/6J) mice, Cyp1a2-, or Cyp1a1-null mice on the B6 background were treated with a single dose of MC (100 µmol/kg) or vehicle (corn oil), and hepatic and pulmonary CYP1A1 expression was studied at 1, 8, and 15 days after MC treatment. In a separate experiment, 12 week-old WT (A/J) mice, Cyp1a2(-/-), or 1A1 (-/-) mice (A/J back ground) were treated with vehicle corn oil or a single dose of MC (40 µmol/kg), and lung tumors were analyzed 24 week after dosing by histopathology. MC elicited a 8-12-fold augmentation of ethoxyresorufin O-deethlyase (EROD) (CYP1A1) activities, apoprotein levels (western blotting), and mRNA (real time RT-PCR) expression in the livers of WT (C57BL/6J) and Cyp1a2-null animals at the 1 day time point. While induction persisted in the WT animals at 15 days, it declined in the KO animals. In lung, persistent induction of CYP1A1 was observed in the Cyp1a2-null mice. MC did not induce CYP1A1 expression in the Cyp1a1-null mice. In the WT (A/J) mice, twenty four weeks after dosing many MC-treated mice in the WT group had lung adenomas and carcinomas. MC-exposed Cyp1a2-/-) mice displayed much higher rates of incidence and tumor multiplicity than WT mice. On the other hand, the Cyp1a1(-/-) mice were refractory to lung tumorigenesis by MC. The results suggest that hepatic CYP1A2 plays an important role in the persistence of CYP1A1 induction by MC in lung and liver, and that CYP1A2 plays a protective effect against MC-induced tumorigenesis, while CYP1A1 contributes to MC-mediated carcinogenesis. In conclusion, the current observations suggest that Cyp1a1-null and 1a2-null mice could be developed as novel animal models for understanding the molecular mechanisms of carinogenesis by PAHs. (Supported by NIH grant ES009132.) 

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1202.
Characterization of Packed Red Blood Cells Prepared with Experimental Multifunctional Leukocyte and Antibody-Reduction Filters
Authors: Christopher C Silliman, Marguerite R Kelher, Monica LaSarre, Travis H Berry, Kadi Schroeder, Tuan Le, D. Joe Chaffin, Kevin J Land, Barbara Mish, Linda Ceriano, Samuel O. Sowemimo-Coker
Journal: Blood (2011)
Macrophage migration inhibitory factor and long-term survival in gastric cancer
Authors: Y. Mohri, S. Kageyama, T. Mohri, K. Tanaka, M. Ohi, T. Yokoe, M. Kusunoki
Journal: Journal of Clinical Oncology (2009)

e15525 Background: Our study aimed to evaluate whether pretherapeutic serum macrophage migration inhibitory factor (MIF) is an independent factor predicting long-term survival in gastric cancer. Gastric cancer is the second leading cause of cancer-related deaths worldwide, but no satisfactory tumor marker exists. We recently found serum MIF expression was progressively increased in gastric cancer. Methods: One hundred five patients, 73 men and 32 women, mean (±SD) age 63±14 years, with histologically proven gastric adenocarcinoma were included in the study. Pretherapeutic serum was collected and MIF assayed using a commercially available enzyme-linked immunosorbent assay kit. Results: Ninety-three percent of patients received curative surgery. Mean follow up was 53.5±28.3 months, and five-year survival was 65.3 percent. The mean pretherapeutic level of MIF was 72.9ng/ml (range, 2.6 to 852.1). There were no significant correlations between serum MIF level and histopathological findings (Wilcoxon test). Mean pretherapeutic levels of carcinoembryonic antigen, C-reactive protein, and albumin were 27.5ng/ml (range, 0.1 to 778 ng/ml), 0.67mg/dl (range, 0.2 to 7.82mg/dl), and 3.6g/dl (range, 2.4 to 4.4g/dl), respectively. By multivariate analysis, serum MIF was found to be an independent factor predicting long-term survival (Odds ratio, 2.84; 95% C.I. 1.27–6.68). The five-year survival rate for patients with an MIF serum level greater than 23ng/ml was 55 percent, and that for patients with an MIF serum level less than 23ng/ml was 75 percent (p=0.03; log rank test). Conclusions: The serum level of MIF is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer. No significant financial relationships to disclose.
NAD <sup>+</sup> repletion improves muscle function in muscular dystrophy and counters global PARylation
Authors: Dongryeol Ryu, Hongbo Zhang, Eduardo R. Ropelle, Vincenzo Sorrentino, Davi A. G. Mázala, Laurent Mouchiroud, Philip L. Marshall, Matthew D. Campbell, Amir Safi Ali, Gary M. Knowels, Stéphanie Bellemin, Shama R. Iyer, Xu Wang, Karim Gariani, Anthony A. Sauve, Carles Cantó, Kevin E. Conley, Ludivine Walter, Richard M. Lovering, Eva R. Chin, Bernard J. Jasmin, David J. Marcinek, Keir J. Menzies, Johan Auwerx
Journal: Science Translational Medicine (2016)

NAD + treatment can reverse the functional decline in degenerating muscles.
Molecular analysis and clinical outcome of adult APL patients with the type V PML-RARα isoform: results from Intergroup protocol 0129
Authors: James L. Slack, Cheryl L. Willman, Janet W. Andersen, Yun Ping Li, David S. Viswanatha, Clara D. Bloomfield, Martin S. Tallman, Robert E. Gallagher
Journal: Blood (2000)
A phase II study of nilotinib administered to patients with imatinib resistant or intolerant chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast crisis (BC) who also failed dasatinib
Authors: F. J. Giles, P. le Coutre, K. Bhalla, G. Rosti, G. Ossenkoppele, G. Alimena, A. Weitzman, M. Zheng, H. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7038 Background: Nilotinib and dasatinib are two new second generation tyrosine kinase inhibitors used in the treatment of imatinib-resistant/intolerant CML. There is limited data regarding the efficacy and safety of these therapies when given sequentially. Methods: This phase II open-label study was designed to evaluate the safety and efficacy of nilotinib at a dose of 400mg BID in CML-CP, -AP, and -BC pts who previously received and either failed or were intolerant to imatinib and dasatinib. Results: A total of 42 pts are reported - CP (16), AP (9), and BC (17 total; 13 myeloid, 4 lymphoid). Overall 10 (24%) pts had extramedullary disease at baseline. For all pts, median time from first diagnosis was 16.8 (0.6–265) months. The median duration of nilotinib exposure was 81 days with median dose intensity of 800mg/day. A total of 13 (31%) pts with dasatinib failure remain on treatment, 29 (69%) discontinued (6 for AEs, 16 for disease progression). CP: Of the 16 pts, 5 (31%) had a MCyR (3 complete, 2 partial). Complete hematologic response (CHR) was reported in 5/13 (39%) pts without CHR at baseline. Disease progression only occurred in 2 pts. AP: 2/9 (22%) pts had a return to chronic phase (RTC), 6 pts were not evaluable and there was 1 death. Disease progression occurred in 5 pts. BC: 3/17 (18%) achieved CHR, 1 (6%) had RTC, and 4 (24%) pts had disease progression. For all pts, the most common Grade 3/4 AEs reported were thrombocytopenia (26%), neutropenia (24%), and anemia (7%) pts. Conclusions: Nilotinib has significant clinical activity in CML-CP, AP, and BC patients who have failed imatinib and dasatinib. Nilotinib is safe and well tolerated, consistent with its kinase selectivity profile. No significant financial relationships to disclose.
GW26-e2378 Noninvasive Vagus Nerve Stimulation Breaks the Vicious Cycles between Connexin Dysfunction and Early Atrial Electrical Remodeling
Authors: Mingxian Chen, Lilei Yu, Xiaoya Zhuo, Qiming Liu, Songyun Wang, Zhuo Wang, Hong Jiang, Shenghua Zhou
Journal: Journal of the American College of Cardiology (2015)
GW26-e2263 Protein Reprogramming Fibroblasts Into Cardiac Progenitor Cells for Cardiac Repair
Authors: Xiaohong Li, Lin Jiang, Yongheng Fu, Mengzhen Zhang, Honghong Tan, Chunyu Deng, Zhixin Shan, Qingshan Geng, Jianjun Wang, Xi-yong Yu
Journal: Journal of the American College of Cardiology (2015)
Pharmacogenetics of Oral Anticoagulation - VKORC1-Haplotypes Determine the Inter-Individual and Inter-Ethnical Variability.
Authors: Christof Geisen, Matthias Watzka, Katja Sittinger, Beate Luxembourg, Michael Steffens, Clemens R. Müller, Thomas F. Wienker, Edelgard Lindhoff-Last, Erhard Seifried, Johannes Oldenburg
Journal: Blood (2006)
Surgical management and prognostic indicators of uterine leiomyosarcoma
Authors: I. R. Gagua, V. V. Kuznetsov, N. I. Lazareva, V. M. Nechushkina, Z. A. Zavolskaya
Journal: Journal of Clinical Oncology (2007)

16024 Background: Uterine leiomyosarcoma (LMS) is a rare malignant tumor. Preoperative diagnosis is established only in 13.5% patients at our center. Currently, the main method of treatment of LMS is surgery. The efficacy of chemotherapy and radiotherapy are questionable. So, the aim of our study is to establish the optimal treatment modalities and prognostic indicators for this tumor. Methods: A retrospective chart review was done to 163 patients with LMS treated at the NNBRCRC from 1970 to 2002. Multivariate statistical analysis was performed to determine the most important prognostic indicators for LMS. Surgical treatment, as independent method, was performed to 108 patients (66.3 %). Combined treatment, including surgery and postoperative chemotherapy was performed to 30 patients (18.4 %), surgery + radiotherapy - 12 (7.4 %) patients. Complex treatment (surgery + chemotherapy + radiotherapy) was performed to 11 (6.7 %) patients. Results: Histologically, LMS is the most common (41,4%) among all sarcomas of female genital tract. Immunohistochemistry and electronmicroscopy play a major role in establishing the diagnosis. 5 year overall and disease - free survival of patients with LMS is 48.5± 4.2% and 44.3 ± 4.3 %, respectively. We observed association between ovarian preservation and improved survival: overall 5 year survival in patients with ovarian preservation and those who underwent oophorectomy is 87.3 ± 8.4 % and 49.0 ± 5.3 %, respectively (p&lt;0,05). On the basis of multivariate analysis we determined the following prognostic indicators, affecting the outcome of patients with LMS: disease stage, mitotic index, tumor cell necrosis, depth of tumor invasion in myometrium, tumor size, age, menstrual status of the patients and optimal surgery. Conclusions: According to our data, the optimal surgery for LMS is total abdominal hysterectomy in the reproductive age and total abdominal hysterectomy with bilateral salpingo-oophorectomy in the postmenopausal period. The most favorable prognostic indicators are: patient age younger than 30, I stage of disease, tumor size less than 10 cm, less than 10 mitotic figures per 10 high - power fields, submucosal or subserosal location of well-differentiated tumor. No significant financial relationships to disclose.
Abstract B42: Dysregulation of key microRNAs controlling tumor-host interactions triggers escape from osteosarcoma dormancy
Authors: Galia Tiram, Paula Ofek, Taturo Udagawa, Noam Shomron, Maayan Roniger, Batsheva Kerem, Yuval Shaked, Sarit Aviel-Ronen, Iris Barshack, Marcelo Calderon, Rainer Haag, Ronit Satchi-Fainaro
Journal: Cancer Research (2016)

Abstract The presence of dormant, microscopic cancerous lesions possesses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized a human osteosarcoma dormancy model of a pair of cells originating from the same parental tissue; one that remains avascular and non-palpable a year following inoculation into mice and another that generates vascularized palpable tumors one month following inoculation. Using this model of cell lines generating dormant or fast-growing osteosarcomas, we identified three novel regulators of osteosarcoma dormancy: miR-34a, miR-93 and miR-200c. This is the first report showing that loss of these three microRNAs occurs during the switch from dormant avascular into fast-growing angiogenic phenotype. Furthermore, we validated their downregulation in patients' tumor samples compared to normal bone, making them attractive candidates for osteosarcoma therapy. Reconstitution of these microRNAs into Soas-2 and MG-63 cells, which generate fast-growing osteosarcomas, reduced the levels of their target genes, MET proto-oncogene, hypoxia-inducible factor 1α, and moesin, critical to cancer angiogenesis and cancer cells' migration. We further demonstrate that these miRNAs attenuate the angiogenic capabilities of fast-growing osteosarcoma in vitro and in vivo. Moreover, treatment with each of these microRNAs using our novel polyglycerol dendritic nanocarrier significantly prolonged their dormancy period. Taken together, these findings suggest that miR-34a, miR-93 and miR-200c have a key role in osteosarcoma progression, and provide the rationale for the development of novel diagnostic and therapeutic tools for osteosarcoma and other malignancies. Citation Format: Galia Tiram, Paula Ofek, Taturo Udagawa, Noam Shomron, Maayan Roniger, Batsheva Kerem, Yuval Shaked, Sarit Aviel-Ronen, Iris Barshack, Marcelo Calderon, Rainer Haag, Ronit Satchi-Fainaro. Dysregulation of key microRNAs controlling tumor-host interactions triggers escape from osteosarcoma dormancy. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B42.
Scar Homogenization Versus Limited-Substrate Ablation in Patients With Nonischemic Cardiomyopathy and Ventricular Tachycardia
Authors: Yalçın Gökoğlan, Sanghamitra Mohanty, Carola Gianni, Pasquale Santangeli, Chintan Trivedi, Mahmut F. Güneş, Rong Bai, Amin Al-Ahmad, G. Joseph Gallinghouse, Rodney Horton, Patrick M. Hranitzky, Javier E. Sanchez, Salwa Beheiry, Richard Hongo, Dhanunjaya Lakkireddy, Madhu Reddy, Robert A. Schweikert, Antonio Dello Russo, Michela Casella, Claudio Tondo, J. David Burkhardt, Sakis Themistoclakis, Luigi Di Biase, Andrea Natale
Journal: Journal of the American College of Cardiology (2016)
National survey of U.S. oncologists' knowledge, attitudes, and practice patterns regarding herb and supplement use by cancer patients.
Authors: R. T. Lee, L. Cohen, O. I. Olopade, F. C. Curlin
Journal: Journal of Clinical Oncology (2010)

9109 Background: Oncologists commonly encounter the use of herbs and supplement (HS) by their patients during treatment. It is unknown how U.S. oncologists respond to such use, which has implications for clinical outcomes. Methods: National probability sample of 1,000 current ASCO members was contacted by mail and email to complete a survey regarding clinical approaches to HS use by cancer patients. Results: A total of 423 oncologists replied out of 927 delivered surveys for a response rate of 46%. Respondents were 72% male, 76% Caucasian, and had an average age of 48. They reported talking to 41% of patients about HS, and among oncologists that had these discussions, 41% believed this strengthened the doctor-patient relationship. When asked if HS may have anti-cancer properties, 29% indicated yes, and 41% believed that HS are generally safe and have minimal side effects. Twenty percent of oncologists often recommended or encouraged use of HS, whereas 11% often discouraged such use. Nearly two-thirds of oncologists (64%) indicated they lack sufficient knowledge about HS to answer patients' questions. Almost nine out of ten (87%) has provided chemotherapy to patients concurrently using HS, and 35% have done so with >20 patients in the past year. For patients with a curable cancer, 81% of respondents would discourage the use of an unknown herb with chemotherapy, but for a patient with incurable cancer, only 37% would discourage such use. Forty-two percent of oncologists reported they had received some education regarding HS. When given patient scenarios regarding the use of 4 herbs (St. John's Wort, soy, Gingko biloba, and Kava kava), 55-79% of oncologists stated not knowing enough about these topics to answer the question. Age <48, male gender, and non-Caucasian race were correlated with a higher likelihood of providing chemotherapy to curable cancer patients who are also taking an unknown herb. Conclusions: Despite the fact that most U.S. oncologists say they have insufficient knowledge about HS, oncologists commonly provide chemotherapy to patients currently using HS. More education is needed about HS for practicing oncologists to ensure safe and effective cancer treatment. No significant financial relationships to disclose.