tbuckley/cabot-search huggingface dataset:
Abstract 17925: Genetic Testing of 440 Chinese Aortopathy Patients Using a Panel Assay
Authors: Yanyun Ma, Hang Yang, Mingyao Luo, Yinhui Zhang, Kun Zhao, Kun Fang, Chang Shu, Zhou Zhou
Journal: Circulation (2017)

Introduction: Aortopathy which is characterized by aneurysms, dissection, dilation of the aorta, can occur secondarily to several syndromes. Because of the genetic heterogeneity, we designed a gene panel containing 15 genes responsible for inherited aortopathy, to identify genetic mutations and help make a precise diagnosis. Methods: Here we tested 440 probands with aortopathy using panel assay. Variants were screened by bioinformatics analysis and confirmed using Sanger sequencing. Multiplex ligation-dependent probe amplification(MLPA) was used to detect exonic deletions/duplications. Results: The results showed that 136 individuals (31%) tested positive for a (likely) pathogenic mutation, 123 (28%) had a variant of uncertain significance (VUS). Most of the (likely) pathogenic mutations (124/136) were located in the fibrillin-1 (FBN1) gene. Also, we found that patients with a FBN1 truncating or splicing mutation were more prone to have a severe aortic disease. Among the selected 76 MLPA individuals, 5(6....
Genome landscapes of rectal cancer before and after preoperative chemoradiotherapy
Authors: Jie Yang, Yuan Lin, Ying Huang, Jing Jin, Shuangmei Zou, Xiaolong Zhang, Hongmin Li, Ting Feng, Jinna Chen, Zhixiang Zuo, Jian Zheng, Yexiong Li, Ge Gao, Chen Wu, Wen Tan, Dongxin Lin
Journal: Theranostics (2019)

Resistance to preoperative chemoradiotherapy (CRT) is a major obstacle to cancer treatment in patients with locally advanced rectal cancer.This study was to explore genome alterations in rectal cancer under CRT stress.Methods: Whole-exome sequencing (WES) was performed on 28 paired tumors collected before and after CRT from the same patients who did not respond to CRT treatment.Somatic point mutations and copy number variations were detected by VarScan2 and Exome CNVs respectively using paired tumor and blood samples.Somatic alterations associated with CRT resistance were inferred considering differences in significantly mutated genes, mutation counts and cancer cell fraction between matched pre-and post-CRT tumors.We employed SignatureAnalyzer to infer mutation signatures and PyClone to decipher clonal evolution and examine intratumoral heterogeneity in tumors before and after CRT.The associations between intratumoral heterogeneity and patients' survival were analyzed using the log-rank test and the Cox regression model.Results: (i) Recurrent mutations in CTDSP2, APC, KRAS, TP53 and NFKBIZ confer selective advantages on cancer cells and made them resistant to CRT treatment.(ii) CRT alters the genomic characteristics of tumors at both the somatic mutation and the copy number variation levels.(iii) CRT-resistant tumors exhibit either a branched or a linear evolution pattern.(iv) Different recurrent mutation signatures in pre-CRT and post-CRT patients implicate mutational processes underlying the evolution of CRT-resistant tumors.(v) High intratumoral heterogeneity in pre-or post-CRT is associated with poor patients' survival.Conclusion: Our study reveals genome landscapes in rectal cancer before and after CRT and tumors evolution under CRT stress.The treatment-associated characteristics are useful for further investigations of CRT resistance in rectal cancer.
First Canadian interim analysis from the phase IIIb CompLEEment-1 ribociclib + letrozole HR+ HER2- advanced breast cancer trial
Authors: C. Ferrario, E. Warner, N. Califaretti, A.A. Joy, S. Chia, J. Wu, J.P. Zarate, M. Lakshmi, S.R. Perri, S. Haftchenary, S.F. Dent
Journal: Annals of Oncology (2019)
MIRACLE: Green tea extract versus placebo for the prevention of colorectal adenomas: A randomized, controlled trial
Authors: T. Seufferlein, T.J. Ettrich, S. Menzler, H. Messmann, G. Kleber, A. Zipprich, S. Frank-Gleich, H. Algül, K. Metter, F. Odemar, T. Heuer, U. Hügle, R. Behrens, L. Perkhofer, C. Scholl, K.L. Schneider, F. Rohlmann, R. Muche, J.C. Stingl
Journal: Annals of Oncology (2019)
Class(y) Dissection of <i>BRAF</i> Heterogeneity: Beyond Non-V600
Authors: Elisa Fontana, Nicola Valeri
Journal: Clinical Cancer Research (2019)

Abstract Different classes of BRAF mutations are present in colorectal and other cancers. Non-V600 mutations are rare; however, their detection rate will increase as the use of next-generation sequencing ramps up quickly in clinical practice. Different biochemical signaling pathways are active in non-V600 BRAF–mutant cancers and may affect treatment response. See related article by Yaeger et al., p. 7089
Phase II study of lenvatinib plus pembrolizumab for disease progression after PD-1/PD-L1 immune checkpoint inhibitor in metastatic clear cell renal cell carcinoma (mccRCC): Results of an interim analysis
Authors: C.-H. Lee, A.Y. Shah, V. Makker, M.H. Taylor, D. Shaffer, J.J. Hsieh, A.L. Cohn, C. DiSimone, A Pinto Marin, D.W. Rasco, S.G. Ribe, D.A. Richards, D.E. Stepan, C.E. Dutcus, J. Wu, E.V. Schmidt, R.F. Perini, R.J. Motzer
Journal: Annals of Oncology (2019)
Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Authors: Y. Matsubara, T. Yamanaka, T. Yamashita, S. Okamoto, S. Toda, K. Kohagura, Y. Sugawara, A. Yamanaka, N. Suganuma, H. Nakayama, T. Yoshida, H. Iwasaki, Y. Rino, M. Masuda
Journal: Annals of Oncology (2019)
Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Authors: V. Voronova, K. Peskov, P. Glybochko, A. Svistunov, V. Fomin, P. Kopylov, D. Enikeev, E. Gitel, A. Ragimov, E. Poddubskaya, M. Sekacheva
Journal: Annals of Oncology (2019)
Striking a balance in an antibody network: A roadmap for HIV-1 vaccines
Authors: Tysheena P. Charles, Cynthia A. Derdeyn
Journal: Journal of Clinical Investigation (2019)

With almost 2 million new HIV-1 infections in 2018, a highly effective vaccine is imperative. Vaccine-elicited HIV-1 antibodies contribute to protection through multiple nonneutralizing activities, but the exact mechanisms remain unknown. In this issue of the JCI, Neidich and associates sought to determine how antibodies contributed to reducing the risk of HIV-1 acquisition in a phase IIb preventative vaccine efficacy trial, HVTN 505. Their studies revealed that antibody-dependent cellular phagocytosis (ADCP) and FcγRIIa binding were strongly associated with reduced HIV-1 risk; however, HIV-1 envelope-specific IgG3, IgA; and host FcγRIIa genotype also influenced risk. This study highlights the intricate interactions between antibodies and innate immune functions in humans.
Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Authors: J. Jarczyk, R. Wirtz, F. Roghmann, H. Juette, M.C. Kriegmair, T.S. Worst, D. Sikic, S. Wach, H. Taubert, B. Wullich, V. Weyerer, R. Stoehr, F. Zengerling, C. Bolenz, J. Breyer, M. Burger, S. Porubsky, A. Hartmann, P. Erben, M. Eckstein
Journal: Annals of Oncology (2019)
Patient-reported outcomes of palbociclib plus exemestane with GnRH agonist versus capecitabine in premenopausal women with hormone receptor-positive metastatic breast cancer from the YoungPearl phase ll trial (KCSG-BR 15-10, NCT02592746)
Authors: S. Lee, Y.H. Park, S.-A. Im, K.H. Jung, I.H. Park, S.Y. Kang, J.H. Kim, G.M. Kim, K.-E. Lee, H. Ahn, M.H. Lee, H.J. Kim, S. Koh
Journal: Annals of Oncology (2019)
Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Authors: X. Wang, Y. Liu, Z. Meng, Y. Wu, S. Wang, G. Jin, Y. Qin, F. Wang, J. Wang, L. Wang, J. Bai, X. Shi, Z. Wen, X. Jia, X. Fu, X. Wang, Q. Qin, Y. Gao, W. Guo, S. Lu
Journal: Annals of Oncology (2019)
Planned organ preservation for T2 T3 M0 rectal adenocarcinoma: A possible option using chemoradiotherapy (CRT) and contact X-ray brachytherapy (CXB). A French multicenter study
Authors: J.-P. Gérard, K. Benezery, N. Barbet, L. Montagne, J.-M. Hannoun-Levi, E. Francois
Journal: Annals of Oncology (2019)
Prognostic and predictive impact on FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer
Authors: H. Hasegawa, H. Taniguchi, T. Kato, S. Fujii, H. Ebi, M. Shiozawa, S. Yuki, T. Masuishi, K. Kato, N. Izawa, T. Moriwaki, Y. Kagawa, Y. Sakamoto, W. Okamoto, Y. Nakamura, K. Yamazaki, T. Yoshino
Journal: Annals of Oncology (2019)
Abstract 306: Deficiency of ROCK1 in Macrophages Protects Against Atherosclerosis
Authors: Hong-Wei Wang, Naotsugu Oyama, Yoshiyuki Rikitake, Shiro Kitamoto, Jonathan Gitlin, Ping-Yen Liu, James K Liao, William A Boisvert
Journal: Circulation (2007)

Background: Rho kinases (ROCKs) are serine-threonine protein kinases that regulate various cellular functions. There is increasing evidence that the RhoA/ROCK pathway plays an important pathophysiological role in cardiovascular diseases. However, direct evidence of which ROCK isoforms or target tissues are involved in the atherogenic process is still lacking. Objective: The aim of this study was to determine the effect of ROCK1 deficiency on atherogenesis and how ROCK1 affects key atherosclerosis-related macrophage function such as lipid uptake and chemotaxis. Methods: We utilized ROCK1 −/− mice and the atherosclerosis-prone apolipoprotein E knockout (apoE −/− ) mice or low-density lipoprotein receptor knockout (LDLR −/− ) mice to investigate the role of ROCK1 in the pathogenesis of atherosclerotic plaque formation. Bone marrow-derived macrophages from ROCK1 −/− and ROCK1 +/+ mice were used to investigate acetylated (Ac)LDL-mediated foam cell formation and chemotaxis. Results: Compared to atherosclerosis-prone apoE −/− mice, apoE −/− ROCK1 +/− mice had substantially less fatty streaks foam cells and atherosclerosis (77.0 ± 12.9 × 10 3 μm 2 versus 166.4 ± 14.6 × 10 3 μm 2 , P &lt; 0.01). Atherosclerotic lesions were reduced also in LDLR −/− mice, whose bone marrow were replaced with bone marrow derived from ROCK1 −/− mice compared to ROCK1 +/+ recipients (181.5 ± 15.6 × 10 3 μm 2 versus 448.5 ± 33.3 × 10 3 μm 2 , P &lt; 0.05). Bone marrow-derived ROCK1-deficient macrophages exhibited impaired chemotaxis to monocyte chemotactic protein-1 and showed reduced ability to take up lipids and to develop into foam cells when exposed to modified low density lipoprotein. Conclusion: These findings indicate that ROCK1 in macrophages is a critical mediator of foam cell formation, macrophage chemotaxis and atherogenesis, and suggest that macrophage ROCK1 may be an important therapeutic target for vascular inflammation and atherosclerosis.
The Need for Innovation in Health Care Systems to Improve Suicide Prevention
Authors: Barbara Stanley, J. John Mann
Journal: JAMA Psychiatry (2019)

Suicide rates have continued to rise in the United States. Speculations for this rise proliferate but the causes for the increase remain unknown. While research focuses on identifying causes, the health care system is an important site for identification of patients at risk. Forty percent of individuals who die by suicide were seen in primary care in the month prior to suicide. The Zero Suicide model describes a comprehensive approach for health care systems to aid in identification and intervention of suicidal patients. While this model promises to improve care of suicidal patients, the need for innovation in our approach to understanding and caring for suicidal patients is pressing. Use of technology to enhance moment-to-moment monitoring of at-risk individuals offers promise and the possibility of intervening close to escalation of acute suicidal states. Further, once identified, suicidal individuals are often difficult to engage in treatment. Novel approaches to engagement and treatment that are effective and acceptable to suicidal patients ought to be developed. Specifically, males are much more likely than females to die by suicide. At the same time, males are less likely to seek and remain in the treatments we have to offer. Innovation should seek to identify strategies that are acceptable to males. Additionally, while about half of psychiatric inpatient admissions are suicide related, there is a paucity of suicide-specific psychosocial interventions available for inpatient settings. Innovation in monitoring and treatment offer promise in helping to reduce suicidal behavior in the United States.
Driving in the Minivan—Life as a Pediatrician and Parent of a Child With Disabilities
Authors: Megan H. Pesch
Journal: JAMA (2019)

In this narrative medicine essay, a developmental and behavioral pediatrician shares her experience parenting her youngest daughter, deaf from exposure to congenital cytomegalovirus (CMV) and the joys and struggles guiding the care and development of a child with hearing impairment.
Mechanisms of bacillary dysentery: lessons learnt from infant rabbits
Authors: Lauren K. Yum, Hervé Agaisse
Journal: Gut Microbes (2019)

The bacterial pathogen Shigella flexneri causes more than 250 million cases of bacillary dysentery (blood in stool) every year across the world. This human-specific disease is characterized by profuse bloody diarrhea, dramatic ulceration of the colonic epithelium and immune cell infiltration of the colonic tissue. A major challenge in understanding the mechanisms supporting bacillary dysentery is the reliance on animal models that do not fully recapitulate the symptoms observed in humans, including bloody diarrhea. Here we outline advances provided by a recently developed infant rabbit model of bacillary dysentery. The infant rabbit model defines bacillary dysentery as a critical combination of massive vascular lesions and dramatic epithelial fenestration due to intracellular infection and cell-to-cell spread, respectively. The infant rabbit model provides an unprecedented framework for understanding how the cell biology of Shigella flexneri infection relates to pathogenesis.
Adjuvant or salvage radiotherapy for the treatment of localised prostate cancer? A prospectively planned aggregate data meta-analysis
Authors: C.L. Vale, M. Brihoum, S. Chabaud, A. Cook, D. Fisher, S. Forcat, C. Fraser-Browne, A. Herschtal, A. Kneebone, S. Nénan, C. Parker, M.K.B. Parmar, M. Pearse, P. Richaud, E. Rogozińska, P. Sargos, M.R. Sydes, J.F. Tierney
Journal: Annals of Oncology (2019)
ctDNA in Gastric and Gastroesophageal Cancer: Prognostic, Predictive, or Preliminary?
Authors: Alexander M. Frankell, Elizabeth C. Smyth
Journal: Clinical Cancer Research (2019)

Abstract In gastric and gastroesophageal adenocarcinoma, circulating tumor DNA identifies molecular drivers missed using routine tumor biopsy, can refine patient selection for targeted therapy, and may be prognostic following surgical resection. However, lack of standardization could impede adoption of this technology as a clinically useful tool; prospective validation in clinical trials is required. See related article by Maron et al., p. 7098
ERBB2 mRNA as a predictor in HER2-positive (HER2+)/hormone receptor-positive (HR+) metastatic breast cancer (BC) treated with HER2 blockade in combination with endocrine therapy (ET): A retrospective analysis of the ALTERNATIVE and SOLTI-PAMELA trials
Authors: N. Chic, T. Pascual, F. Brasó-Maristany, P. Villagrasa Gonzalez, L. Pare Brunet, F. Schettini, B. Conte, B. Adamo, M. Vidal, M. Muñoz, O. Martínez, B. Gonzalez-Farre, J. Cortés, A. Llombart-Cussac, V. Rodrik-Outmezguine, M.A. Izquierdo Delso, R. Schiff, C.K. Osborne, M. Rimawi, A. Prat
Journal: Annals of Oncology (2019)
Prevention of Childhood Aspirin Poisoning
Authors: Robert G. Scherz
Journal: New England Journal of Medicine (1971)

ACCIDENTAL poisoning of young children after uncontrolled aspirin ingestion is a common problem in the United States. Aspirin continues to be the most frequent medicine involved in accidental childhood poisoning, accounting for 19.0 to 25.8 per cent of all poisonings of children under the age of five years reported to the National Clearinghouse for Poison Control Centers from 1963–1969.1 Owing to its special attraction to children, 0.08 g (1 1/4 gr) flavored aspirin accounts for 85 to 90 per cent of the reported ingestions.The purpose of this paper is to compare the effects of three forms of safety packaging . . .
Assessing cancer therapeutic agents across fifteen human tumor cell line panel
Authors: Yulia Ovechkina, Phuong Nguyen, Robert Keyser, Rod Shively, Karen Marcoe, Christine ODay
Journal: Cancer Research (2008)

1550  Human cancer cell lines are a useful in vitro model to investigate the efficacy of anticancer drugs. We have assembled a fifteen human tumor cell line panel to examine the mechanism of cytotoxicity. The cell line panel was assembled with five common human tumor types including breast, lung, colon, melanoma and leukemia. Cell lines were chosen based on available published mutation profiling data and represent the major mutations occurring in cancer genes. A set of cancer therapeutic agents were tested for proliferative, apoptotic and cell cycle arrest responses using a novel multiplexed cell image based technology. We generated cell line profiles to reveal drug sensitivity and resistance patterns using multiplexed cellular response phenotypes. The combination of mutation profiling data with cellular response phenotypes allowed us to investigate mechanisms of enhanced susceptibility to anti-cancer agents. Confirmation of this approach was clearly demonstrated in the K562 cell line. K562 cells contain a Philadelphia chromosome which forms due to translocation between chromosomes 22 and 9. This translocation leads to fusion of the bcr and abl genes to generate a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In our study, Bcr-Abl inhibitor treatment led to a ten fold higher cell proliferation inhibition and apoptosis induction in the K562 cell line than that in the other fourteen tested cell lines. This finding demonstrated that the high selectivity of the Bcr-Abl inhibitor for the K562 cancer cell line growth inhibition could be directly attributed to inhibition of the activated oncogene product found in this particular cell line.  In addition, the time course of growth inhibition, apoptosis and cell cycle arrest detection were evaluated for all fifteen tumor cell lines. Detection of cell cycle arrest was found to be most sensitive at 24 hours. Taxol-mediated mitotic block was present at 24 hours and often not observed at 72 hours in all tested cell lines. Doxorubicin caused a G1 block in all cell lines tested at 24 hours. Only one half of the cell lines retained the G1 block at 72 hours. In contrast, apoptosis detection was much more sensitive at 72 hours than at the 24 hour time point. The number of apoptotic cells increased at 72 hours in all cases. The apoptotic signal of activated caspase-3 was prolonged and increased with time.  Cellular responses from continuous culture and cryo-preserved cells in regards to growth inhibition, number of doublings, apoptosis and cell cycle arrest were compared for all fifteen cell lines. Our results demonstrated that cellular response profiles in cryo-preserved cells were similar to those generated with continuous cultured cells.  In conclusion, our study demonstrates that using multiplexed cell image based technology coupled with genetic analysis is a robust and sensitive approach to assess the mechanism of action and sensitivity to chemotherapeutics agents.
Association of Lifetime Indoor Tanning and Subsequent Risk of Cutaneous Squamous Cell Carcinoma
Authors: Simon Lergenmuller, Reza Ghiasvand, Trude E. Robsahm, Adele C. Green, Eiliv Lund, Corina S. Rueegg, Marit B. Veierød
Journal: JAMA Dermatology (2019)

No study, to our knowledge, has prospectively investigated a dose-response association between lifetime indoor tanning and risk of cutaneous squamous cell carcinoma (SCC).To investigate the dose-response association between lifetime indoor tanning and SCC risk, the association between duration of use and age at initiation with SCC risk, and the association between age at initiation and age at diagnosis.This cohort study included data from women born from 1927 to 1963 from the Norwegian Women and Cancer study, established in 1991 with follow-up through December 31, 2015. Baseline questionnaires were issued to participants from 1991 to 2007, with follow-up questionnaires given every 5 to 7 years. Data analysis was performed from January 2, 2018, to March 2, 2019.Participants reported pigmentation factors. Sunburns, sunbathing vacations, and indoor tanning were reported for childhood, adolescence, and adulthood.Information on all cancer diagnoses and dates of emigration or death were obtained through linkage to the Cancer Registry of Norway, using the unique personal identification number of Norwegian citizens.A total of 159 419 women (mean [SD] age at inclusion, 49.9 [8.3] years) were included in the study. During follow-up (mean [SD], 16.5 [6.4] years), 597 women were diagnosed with SCC. Risk of SCC increased with increasing cumulative number of indoor tanning sessions. The adjusted hazard ratio (HR) for highest use vs never use was 1.83 (95% CI, 1.38-2.42; P < .001 for trend). A significantly higher risk of SCC was found among women with 10 years or less of use (HR, 1.41; 95% CI, 1.08-1.85) and more than 10 years of use (HR, 1.43; 95% CI, 1.16-1.76) and among women with age at initiation of 30 years or older (HR, 1.36; 95% CI, 1.11-1.67) and younger than 30 years (HR, 1.51; 95% CI, 1.18-1.92) vs never users. No significant association was found between age at initiation and age at diagnosis (estimated regression coefficient, -0.09 [95% CI, -1.11 to 0.94] for age at initiation of ≥30 years and -0.02 [95% CI, -1.27 to 1.22] for <30 years vs never use).The findings provide supporting evidence that there is a dose-response association between indoor tanning and SCC risk among women. The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation. These results support development of policies that regulate indoor tanning.
Classification of thyroid nodule using DNA methylation profiling on tissue and circulating tumor DNA
Authors: S. Hong, J. Li, L. Cheng, S. Yu, Z. Zhang, B. Lin, Z. Su, Z. Ke, R. Liu, S. Peng, Q. Li, Q. Zhang, Z. Guo, W. Lv, H. Xiao
Journal: Annals of Oncology (2019)
Results of the TAPPAS trial: An adaptive enrichment phase III trial of TRC105 and pazopanib (P) versus pazopanib alone in patients with advanced angiosarcoma (AS)
Authors: R.L. Jones, V. Ravi, A.S. Brohl, S.P. Chawla, K. Ganjoo, A. Italiano, S. Attia, M. Burgess, K. Thornton, L. Cranmer, L. Liu, C. Theuer, R. Maki
Journal: Annals of Oncology (2019)
A phase I/Ib, multi-center trial of ARQ-761 (Beta-Lapachone) with gemcitabine/nab-paclitaxel in patients with advanced pancreatic cancer
Authors: M.S. Beg, D. Boothman, L. Khosama, Y. Arriaga, U. Verma, A. Sanjeeviaiah, S. Kazmi, F. Fattah, S. Pilarski, M. Rodriguez, D. Lindsey, S. Linden, B. Schwartz, D. Laheru
Journal: Annals of Oncology (2019)