tbuckley/cabot-search huggingface dataset:
Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants
Authors: Vahid Bahrambeigi, Xiaofei Song, Karen Sperle, Christine R. Beck, Hadia Hijazi, Christopher M. Grochowski, Shen Gu, Pavel Seeman, Karen J. Woodward, Claudia M. B. Carvalho, Grace M. Hobson, James R. Lupski
Journal: Genome Medicine (2019)

Abstract Background We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 ( PLP1 ) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). We then compared our new data to previous structural variant mutagenesis studies involving the Xq22 region of the human genome. The aggregate data from 159 sequenced join-points (discontinuous sequences in the reference genome that are joined during the rearrangement process) were studied. Analysis of these data from 150 individuals enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated. Methods Genomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array or clinical chromosomal microarray analysis and breakpoint junction sequence analysis. Results High-density customized array showed that the majority of cases (33/50; ~ 66%) present with single duplications, although complex genomic rearrangements (CGRs) are also frequent (17/50; ~ 34%). Breakpoint mapping to nucleotide resolution revealed further previously unknown structural and sequence complexities, even in single duplications. Meta-analysis of all studied rearrangements that occur at the PLP1 locus showed that single duplications were found in ~ 54% of individuals and that, among all CGR cases, triplication flanked by duplications is the most frequent CGR array CGH pattern observed. Importantly, in ~ 32% of join-points, there is evidence for a mutational signature of microhomeology (highly similar yet imperfect sequence matches). Conclusions These data reveal a high frequency of CGRs at the PLP1 locus and support the assertion that replication-based mechanisms are prominent contributors to the formation of CGRs at Xq22. We propose that microhomeology can facilitate template switching, by stabilizing strand annealing of the primer using W-C base complementarity, and is a mutational signature for replicative repair.
Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement
Authors: Kris M Mahadeo, Rajinder Bajwa, Hisham Abdel-Azim, Leslie E Lehmann, Christine Duncan, Nicole Zantek, Jennifer Vittorio, Joseph Angelo, Jennifer McArthur, Keri Schadler, Sherwin Chan, Priti Tewari, Sajad Khazal, Jeffery J Auletta, Sung Won Choi, Basirat Shoberu, Krzysztof Kalwak, Avis Harden, Partow Kebriaei, Jun-ichi Abe, Shulin Li, Jerelyn Roberson Moffet, Susan Abraham, Francesco Paolo Tambaro, Katharina Kleinschmidt, Paul G Richardson, Selim Corbacioglu
Journal: The Lancet Haematology (2019)
IT-008. OVERCOMING BRAIN TUMOR IMMUNE-EVASION BY DISRUPTING THE CD47-SIRPa INTERACTION AXIS TO TREAT HIGH GRADE PEDIATRIC AND ADULT BRAIN TUMORS
Authors: Sharareh Gholamin, Siddhartha Mitra, Chase Richard, Achal Achrol, Suzana Kahn, Anne Volkmer, Jens Volkmer, Stephen Willingham, Doosik Kong, Jun Shin, Michelle Monje-Deisseroth, Yoon-Jae Cho, Irving Weissman, Samuel Cheshier
Journal: Neuro-Oncology (2013)

INTRODUCTION: Adult and pediatric brain tumors are among the most fatal cancers. Current standard treatments are palliative at best and in children cause long-term neurocognitive impairments, which necessitates developing new therapeutic modalities. One of the key tumor features facilitating its gro
Abstract 17241: Impact of Excessive Birth Weight on Body Mass Index Growth Trajectories Over the Life Course: The Bogalusa Heart Study
Authors: Yajun Guo, Camilo Fernandez, Alexander Razavi, Rupert Barshop, Lydia A Bazzano
Journal: Circulation (2019)

Introduction: Excessive long-term weight gain is an independent risk factor for cardiovascular disease (CVD). However, the association between birth weight and weight gain over the life course is u...
Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study
Authors: Brian I Rini, Sumanta K Pal, Bernard J Escudier, Michael B Atkins, Thomas E Hutson, Camillo Porta, Elena Verzoni, Michael N Needle, David F McDermott
Journal: The Lancet Oncology (2019)
HIV-1 Protease Inhibitor Ritonavir Potentiates the Effect of 1,25-Dihydroxyvitamin D3 to Induce Growth Arrest and Differentiation of Human Myeloid Leukemia Cells Via Inhibition of CYP24.
Authors: Takayuki Ikezoe, Yang Yang, Kentaro Bandobashi, Nobuo Sekiguchi, Shuichi Sakai, H. Phillip Koeffler, Hirokuni Taguchi
Journal: Blood (2004)
The molecular and immune characteristics, antitumor activity of crizotinib in non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping alterations.
Authors: Jiadi Gan, Wenfeng Fang, Weineng Feng, Jiexia Zhang, Huojin Deng, Lei Zhang, Yadan Li, Juanjuan Qian, Hongli Luo, Yanhui Chen, Ying Yang, Henghui Zhang, Li Zhang
Journal: Journal of Clinical Oncology (2019)

e20588 Background: MET exon 14 ( METex14) skipping caused by certain mutations in splice sites of METex14 has been regarded as a promising target for non-small cell lung cancer (NSCLC) treatment with crizotinib, and was observed with lower responsiveness to immunotherapy (Joshua K. et al ASCO 2017). The molecular and immune characteristics, antitumor activity of crizotinib for Chinese NSCLC patients harboring METex14 skipping alterations remain to be elucidated. Methods: Tumor genomic profiling was performed by next-generation sequencing (NGS) assay (GeneCast Biotechnology Co., Beijing) on 9722 samples (FFPE and/or peripheral blood derived from 9289 Chinese NSCLC patients). PD-L1 expression was determined by qualitative immunohistochemical assay. Multiplex immunohistochemistry (mIHC) analysis was adopted to evaluate the immune microenvironment of selected samples. Retrospective analysis was performed to explore antitumor activity of crizotinib monotherapy in 10 patients harboring METex14 skipping alterations. Results: A total of 62 (0.67%) patients with somatic mutations occurred in METex14 splice sites (± 3bp) were identified. Median age of these patients is 64.5 years and 39% patients are female. Main histologic types are adenocarcinoma (81%, 50/62) and squamous carcinoma (13%, 8/62). 30 patients harbored high frequency METex14 mutations ranged from 1.34% to 79.49% nearly without co-existed known driver variants. Other 32 patients had low frequency mutations (below 1%) with some crucial oncogenic mutations such as EGFR 19del/L858R. In addition, very few CD8 + T cells were observed in tumor region and significantly less infiltrated than in stroma region ( P&lt; 0.01). The overall response rate of crizotinib monotherapy on the ten patients with METex14 skipping alterations was 70% (7/10 achieved partial response), with progression free survival range from 3 to 20 months. Conclusions: The occurrence rate of METex14 skipping mutations in Chinese NSCLC patients is low. Low frequency ( &lt; 1%) METex14 mutations usually co-exist with other driver mutations while high frequency METex14 mutations do not. That little infiltration of CD8 + T cells in tumor region might be associated with poor responsiveness of NSCLC patients carrying METex14 skipping alterations to immunotherapy. Our clinical cases exhibited promising antitumor activity of crizotinib in Chinese NSCLC patients harboring METex14 skipping alterations.
The impact of obesity on time to recurrence in ovarian cancer: A retrospective study.
Authors: Karina E Hew, Arvind Bakhru, Evan Harrison, Mehmet Ozhan Turan, Neil B. Rosenshein
Journal: Journal of Clinical Oncology (2012)

5055 Background: There has been conflicting data regarding the relationship between obesity and progression free survival in patients with ovarian cancer. There has been some evidence to suggest that obesity results in altered tumor biology and a poorer prognosis in these patients. The aim of this study was to examine whether obesity is a risk factor for time to recurrence in primary epithelial ovarian cancer. Methods: A multicenter retrospective chart review was performed at Mercy Medical Center and University of Michigan Medical Center. 591 patients were diagnosed with primary epithelial ovarian cancer between 2004-2009. However, 221 patients were excluded from the analysis because of persistent or progressive disease, treatment with neoadjuvant chemotherapy, presence of synchronous tumors or incomplete follow-up data. 370 patients were eligible for analysis. Data collected included: height and weight at the time of surgery, age, race, medical co-morbid illnesses, tumor stage, grade and histology. Treatment related data such as number of cycles of adjuvant chemotherapy; and optimal versus suboptimal tumor debulking was also collected. Body mass index (BMI) was defined according to WHO 2004 criteria. Women with a BMI greater than 30 were categorized as obese. The diagnosis of recurrence was made by positive radiological or pathological diagnosis of cancer recurrence after patient had surgery, received adjuvant chemotherapy and had no clinical, radiological or serological evidence of recurrence during this time. The time to recurrence was then quantified in terms of months from the initial surgery. Survival analyses were performed with the Kaplan-Meier method and compared using log-rank testing. Time to recurrence was analyzed using Mann-Whitney U and Wilcox W tests. Results: 130 (35%) obese patients were compared with 240 (65%) non obese patients. A recurrence was documented in 125 (47.9%) non obese patients and 49 (37.7%) obese patients. Time to recurrence between both BMI groups was found to be identical, at 15 months (p=1.0). The progression free survival was similar in both obese and non obese subjects (p=0.118). Conclusions: Obesity does not impact the time to recurrence in patients with primary ovarian cancer.
YKL-40 and P53 expressions in anal carcinoma predict shorther overall and disease free survival
Authors: M. Mistrangelo, Isabella Castellano, Paola Cassoni, C. Crudo, L. Chiusa, R. Lupo, Umberto Ricardi, E. Milanesi, P. Racca, L. Ciuffreda, G. Beltramo, Antonio Mussa, Mario Morino
Journal: Annals of Oncology (2009)
Pretreatment Cytogenetic Abnormalities Are Predictive of Induction Success, Cumulative Incidence of Relapse and Overall Survival in Patients &amp;gt;60 Years of Age with Newly Diagnosed Acute Myeloid Leukemia.
Authors: Richard F. Schlenk, Sabine Kayser, Martina Morhardt, Konstanze Döhner, Hartmut Döhner, Stefan Fröhling
Journal: Blood (2005)
Comprehensive analysis integrating both clinicopathological and gene expression data in more than 1,500 samples: Proliferation captured by gene expression grade index appears to be the strongest prognostic factor in breast cancer (BC)
Authors: C. Sotiriou, P. Wirapati, S. Loi, B. Haibe-Kains, C. Desmedt, A. Tutt, P. Ellis, M. Buyse, M. Delorenzi, M. Piccart
Journal: Journal of Clinical Oncology (2006)

507 Background: Although, the development of high-throughput gene expression technologies has allowed the identification of several “molecular signatures” predicting clinical outcome, no attempt has been made yet to perform a comprehensive analysis integrating both clinicopathological, and gene expression data. Here, we aim to elucidate the relationship between clinical parameters and tumor markers, with gene expression patterns and their interaction with prognosis. Methods: We analyzed gene expression and clinical data from several published studies, including more than 1500 BC patients. We developed several gene expression indices associated with different biological stages of disease characterized by the expression of hormone receptors, HER2 amplification, p53 mutation, angiogenesis, tumor invasion and proliferation. Multivariable analyses were used to characterize the dependency patterns between these indices and their impact on survival. Results: Estrogen receptor (ER) and HER2 indices were the most prominent discriminators dichotomizing tumor samples into two main subsets in agreement with the previously proposed BC subtypes. Tumor proliferation, assessed by our previously reported gene expression index (GGI), was the most strongly associated with prognosis (HR 2.29, CI 1.88–2.78, p&lt;0.0001). Almost all ER- and HER2+ tumors were associated with high GGI scores. In contrast, ER+ and HER2- tumors showed a whole range of GGI values. Within the high proliferation subset, ER- and HER2+ indices did not have any prognostic value. Similar results were found with relation to p53 mutation index. Nodal status and tumor size, which essentially measure the duration of disease, retained prognostic value in addition to proliferation. Conclusions: Proliferation captured by the GGI appears to be a key biological factor, downstream of ER, HER2 and p53. Although understanding the upstream factors is important for advancing biological knowledge and therapeutic interventions, GGI seems to be the most important factor predicting clinical outcome in BC and deserves consideration as stratification factor in clinical trials. No significant financial relationships to disclose.
NaClまたはKClの注入時に、ラット脳内ミオイノシトール(INO)含有量およびNa + /ミオイノシトール共輸送体(スミット)mRNAを減少させるカリウム減少(Kd)
Authors: Nakanishi T, Yamauchi A, Miyai A, Imai E, Shimada S, Tohyama M, Takamitsu Y
Journal: Journal of the American Society of Nephrology (1996)
FIP1L1/PDGFRa Synergizes with SCF/c-Kit Signaling To Induce Systemic Mastocytosis in a Chronic Eosinophilic Leukemia Murine Model
Authors: Yoshiyuki Yamada, Jose A. Cancelas, Eric B. Brandt, Abel Sanchez-Aguilera, Melissa McBride, Nabel J.H. Al-Moamen, Fred Finkelman, David A. Williams, Marc E. Rothenberg
Journal: Blood (2007)
Protease−Activated Receptor 2 (PAR−2) as a Novel Target To Prevent Inhibitor Formation to FIX.
Authors: Stefano Baila, Christian Furlan Freguia, Nicholas Iacobelli, Danielle Dunn, Joerg Schuettrumpf, Federico Mingozzi, Patricia Andrade-Gordon, Valder R. Arruda
Journal: Blood (2006)
化学療法歴のないPS2の進行非小細胞肺癌患者の治療におけるpaclitaxel poliglumex(CT-2103、PPX)+カルボプラチン併用療法vsパクリタキセル標準製剤+カルボプラチン併用療法の第3相比較試験
Authors: Corey J. Langer
Journal: Journal of Thoracic Oncology (2008)
Abstract 15034: Predictors of Healthy Arterial Aging in Persons With Metabolic Syndrome and Diabetes: The Multi-Ethnic Study of Atherosclerosis
Authors: Alexander C Razavi, Nathan D Wong, Matthew J Budoff, Lydia A Bazzano, Tanika N Kelly, Jiang He, Camilo Fernandez Alonso, Joao A Lima, Joseph F Polak, Morgana L Mongraw-Chaffin, Moyses Szklo, Alain G Bertoni, Roger S Blumenthal, Michael J Blaha, Seamus P Whelton
Journal: Circulation (2019)

Introduction: Overall, individuals with metabolic syndrome (MetS) and diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Long-term persistent CAC=0 is a marker of he...
Treosulfan Compared to Total Body Irradiation-Based Preparative Regimens Before Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia : A Retrospective Long-Term Study.
Authors: Dietrich Wilhelm Beelen, Tanja Gromke, Rudolf Trenschel, Inken Hilgendorf, Daniel Wolff, Ahmet Elmaagacli, Mathias Freund, Jochen Casper
Journal: Blood (2008)
Early Interim FDG-PET Scan Predicts Outcome in Non-Bulky Limited Stage Hodgkin Lymphoma, but may Not Guide Use of Consolidative Radiotherapy.
Authors: Jeffrey A. Barnes, Ann S. LaCasce, Christiana E. Toomey, Ephraim Hochberg, Alfred I. Lee, George P. Canellos, Jeremy S. Abramson
Journal: Blood (2008)
Inhibiting eicosanoid degradation exerts antifibrotic effects in a pulmonary fibrosis mouse model and human tissue
Authors: Thomas Bärnthaler, Anna Theiler, Diana Zabini, Sandra Trautmann, Elvira Stacher-Priehse, Ilse Lanz, Walter Klepetko, Katharina Sinn, Holger Flick, Stefan Scheidl, Dominique Thomas, Horst Olschewski, Grazyna Kwapiszewska, Rufina Schuligoi, Akos Heinemann
Journal: Journal of Allergy and Clinical Immunology (2019)

Idiopathic pulmonary fibrosis (IPF) is a disease with high 5-year mortality and few therapeutic options. Prostaglandin (PG) E2 exhibits antifibrotic properties and is reduced in bronchoalveolar lavage from patients with IPF. 15-Prostaglandin dehydrogenase (15-PGDH) is the key enzyme in PGE2 metabolism under the control of TGF-β and microRNA 218.We sought to investigate the expression of 15-PGDH in IPF and the therapeutic potential of a specific inhibitor of this enzyme in a mouse model and human tissue.In vitro studies, including fibrocyte differentiation, regulation of 15-PGDH, RT-PCR, and Western blot, were performed using peripheral blood from healthy donors and patients with IPF and A549 cells. Immunohistochemistry, immunofluorescence, 15-PGDH activity assays, and in situ hybridization as well as ex vivo IPF tissue culture experiments were done using healthy donor and IPF lungs. Therapeutic effects of 15-PGDH inhibition were studied in the bleomycin mouse model of pulmonary fibrosis.We demonstrate that 15-PGDH shows areas of increased expression in patients with IPF. Inhibition of this enzyme increases PGE2 levels and reduces collagen production in IPF precision cut lung slices and in the bleomycin model. Inhibitor-treated mice show amelioration of lung function, decreased alveolar epithelial cell apoptosis, and fibroblast proliferation. Pulmonary fibrocyte accumulation is also decreased by inhibitor treatment in mice, similar to PGE2 that inhibits fibrocyte differentiation from blood of healthy donors and patients with IPF. Finally, microRNA 218-5p, which is downregulated in patients with IPF, suppressed 15-PGDH expression in vivo and in vitro.These findings highlight the role of 15-PGDH in IPF and suggest 15-PGDH inhibition as a promising therapeutic approach.
Prognostic Determinants in Adult AML Patients with Intermediate Risk Karyotype.
Authors: Francesco Buccisano, Luca Maurillo, Del Poeta Giovanni, Del Principe Maria Ilaria, Cox Maria Christina, Panetta Paola, Tamburini Anna, Irno Consalvo Maria, Mazzone Carla, Neri Benedetta, Ottaviani Licia, Fraboni Daniela, Lo Coco Francesco, Amadori Sergio, Venditti Adriano
Journal: Blood (2005)
CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Prognosis in Patients With Breast Cancer
Authors: Wei He, Felix Grassmann, Mikael Eriksson, Erik Eliasson, Sara Margolin, Linda Thorén, Per Hall, Kamila Czene
Journal: Journal of Clinical Oncology (2019)

PURPOSE To examine the association between CYP2D6 genotype, discontinuation of tamoxifen therapy, and prognosis for breast cancer. PATIENTS AND METHODS We conducted a prospective-retrospective study linking data from a clinical breast cancer register, the Swedish Prescribed Drug Register, and self-reported questionnaires. We genotyped CYP2D6 in 1,309 patients with breast cancer who were treated with tamoxifen and were diagnosed from 2005 to 2012; they were categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. We investigated whether metabolizer status was associated with tamoxifen discontinuation and prognosis for breast cancer using Cox regression analysis. RESULTS The 6-month discontinuation rates of tamoxifen among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 7.1%, 7.6%, 6.7%, and 18.8%, respectively. A U-shaped association was found between CYP2D6 metabolizer status and breast cancer–specific mortality, with adjusted hazard ratios of 2.59 (95% CI, 1.01 to 6.67) for poor, 1.48 (95% CI, 0.72 to 3.05) for intermediate, 1 (reference) for normal, and 4.52 (95% CI, 1.42 to 14.37) for ultrarapid CYP2D6 metabolizers. CONCLUSION Both poor and ultrarapid CYP2D6 metabolizers of tamoxifen have a worse prognosis for breast cancer compared with normal metabolizers after receiving a standard dose of tamoxifen. This U-shaped association might call for individualized tamoxifen dosage.
Effects of Darbepoetin Alfa Administered Once Per Cycle for the Prevention of Anemia on the Incidence of Transfusions, Neurocognitive Functions, and Symptom Assessment.
Authors: Saroj Vadhan-Raj, Jon Trent, Shreyaskumar Patel, Mindy Collard, Carlos E. Bueso-Ramos, Charles Cleeland, Robert Benjamin, Christina Meyers
Journal: Blood (2006)
Association of High Mortality With Postoperative Myocardial Infarction After Major Vascular Surgery Despite Use of Evidence-Based Therapies
Authors: Robert J. Beaulieu, Danielle C. Sutzko, Jeremy Albright, Erin Jeruzal, Nicholas H. Osborne, Peter K. Henke
Journal: JAMA Surgery (2019)

Patients undergoing vascular surgery are at high risk of postoperative myocardial infarction (POMI). Postoperative myocardial infarction is independently associated with significant risk of in-hospital mortality.To examine the association of patient and procedural characteristics with the risk of POMI after vascular surgery and determine the association of evidence-based therapies with longer-term outcomes.A retrospective cohort study of prospectively collected data within a statewide quality improvement collaborative database between January 2012 and December 2017. Patient demographics, comorbid conditions, and perioperative medications were captured. Patients were grouped according to occurrence of POMI. Univariate analysis and logistic regression were used to identify factors associated with POMI. The collaborative collects data from private and academic hospitals in Michigan. Patients undergoing major vascular surgery, defined as endovascular aortic aneurysm repair, open abdominal aortic aneurysm, peripheral bypass, carotid endarterectomy, or carotid artery stenting were included. Analysis began December 2018.The presence of a POMI and 1-year mortality.Of 26 231 patients identified, 16 989 (65.8%) were men and the overall mean (SD) age was 69.35 (9.89) years. A total of 410 individuals (1.6%) experienced a POMI. Factors associated with higher rates of POMI were age (odds ratio [OR], 1.032 [95% CI, 1.019-1.045]; P < .001), diabetes (OR, 1.514 [95% CI, 1.201-1.907]; P < .001), congestive heart failure (OR, 1.519 [95% CI, 1.163-1.983]; P = .002), valvular disease (OR, 1.447 [95% CI, 1.024-2.046]; P = .04), coronary artery disease (OR, 1.381 [95% CI, 1.058-1.803]; P = .02), and preoperative P2Y12 antagonist use (OR, 1.37 [95% CI, 1.08-1.725]; P = .009). Procedurally, open abdominal aortic aneurysm (OR, 4.53 [95% CI, 2.73-7.517]; P < .001) and peripheral bypass (OR, 2.375 [95% CI, 1.818-3.102]; P < .001) were associated with the highest risk of POMI. After POMI, patients were discharged and received evidence-based therapy with high fidelity, including β-blockade (296 [82.7%]) and antiplatelet therapy (336 [95.7%]). A high portion of patients with POMI were dead at 1 year compared with patients without POMI (113 [37.42%] vs 993 [5.05%]; χ2 = 589.3; P < .001).Despite high rates of discharge with evidence-based therapies, the long-term burden of POMI is substantial, with a high mortality rate in the following year. Patients with diabetes mellitus, coronary artery disease, congestive heart failure, and valvular disease warrant additional consideration in the preoperative period. Further, aggressive strategies to treat patients who experience a POMI are needed to reduce the risk of postoperative mortality.
Long-Term Survival Is Comparable between Palifermin-Treated and Placebo-Treated Patients (Pts) with Hematologic Malignancies (HM) Undergoing High-Dose Chemotherapy and Total Body Irradiation Followed by Autologous Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Ricardo Spielberger, Christos Emmanouilides, William Bensinger, Alan Rong, Alessandra Cesano, Patrick Stiff
Journal: Blood (2005)
호암상 수상 기념특강 : B형간염 예방접종 시행 후, 우리나라 B형간염 관련 질환의 변화와 추이
Authors: 안윤옥 ( Yoon Ok Ahn ), 김정룡 ( Chung Yong Kim ), 배상혁 ( Sang Hyuck Bae ), 장현갑 ( Hyun Gab Chang )
Journal: Clinical and Molecular Hepatology (2010)