tbuckley/cabot-search huggingface dataset:
A Randomised Phase II Study of Pegylated Liposomal Doxorubicine in Elderly Patients with Acute Lymphoblastic Leukemia (ALL): The GRAALL-SA1 Study.
Authors: Mathilde hunault-Berger, Thibaut Leguay, Xavier Thomas, Ollivier Legrand, Francoise Huguet, Francis Witz, Martine Escoffre-Barbe, Laurence Legros, Pascal Turlure, Patrice Chevallier, Fabrice Larosa, jean-Yves Cahn, Oumedaly Reman, Philippe Rousselot, Andre Delannoy, Nathalie Dhedin, Marina Pochitaloff, marie-Christine Béné, Norbert Ifrah, Hervé Dombret
Journal: Blood (2008)
Phase II multicenter proof of concept study of AZD4547 in<i> FGFR</i> amplified tumours.
Authors: Elizabeth Catherine Smyth, Nicholas C. Turner, Clare Peckitt, Alex Pearson, Gina Brown, Sue Chua, Angela Gillbanks, Stephen R. D. Johnston, NOELIA TARAZONA, Ros Cutts, Elaine Kilgour, Claire Rooney, Neil R. Smith, Katherine Anne Sumpter, Mazhar A. Ajaz, Anne L. Thomas, David Watkins, Ian Chau, Sanjay Popat, David Cunningham
Journal: Journal of Clinical Oncology (2015)

2508 Background: FGFR1/2 amplification acts as an oncogenic driver in multiple cancers. We investigated the efficacy of AZD4547, a potent orally available selective inhibitor of FGFR 1,2 & 3 receptor tyrosine kinases, in FGFR1/2 amplified cancers. Methods: This is a phase II Simon 2 stage design for patients (pts) with FGFR1 (HER2 negative breast/NSCLC) or FGFR2 (gastroesophageal) amplified tumors treated with AZD4547 80mg twice daily on an intermittent (2 weeks (wks) on, 1 wk off) or continuous schedule. Eligible pts had progressed following ≥ 1 line of prior therapy. FGFR1/2 amplification was determined centrally using FISH. Primary endpoint is centrally reviewed confirmed response rate (RR), with the study concluding efficacy if ≥ 3/17 patients in a cohort had a confirmed response. PET-CT was performed at baseline, D14 and 8 wks, biopsy at baseline and D14 and optionally on progression. Biomarker assessment included phospho-immunohistochemistry, FGFR copy number variation in tumor and plasma, and whole exome sequencing. Results: We screened 285 pts with advanced cancer, identifying FGFR1 amplification in 18% (20/111) HER2 negative breast cancer (BC), 9.5% (4/42) NSCLC, and FGFR2 amplification in 7.6% (10/132) gastroesophageal (GC). Confirmed RR was 33% (3/9) in FGFR2 amplified GC, and 12.5% (1/8) FGFR1 amplified BC. All 3 GC responders had a PET response on D14 PET. GC responses were durable; time on treatment was 45, 29 and 27 wks with the last pt ongoing. Common toxicities (all grades and schedules) included fatigue (71%), mucositis (41%), nausea (35%), and nail changes (24%). Asymptomatic retinal pigmented epithelial detachment occurred in 1 pt. Phosphate was elevated in most pts. Exploratory analysis revealed all GC pts with PR had FGFR2 FISH ratio > 8. Elevated FGFR2 copy number was detected in free plasma DNA of all GC pts with PR, and no non-responding pt. Analysis of progression biopsies in a responding GC pt identified acquired KRAS amplification in progressing disease. Conclusions: AZD4547 demonstrated high activity in FGFR2 amplified GC and lower activity in FGFR1 amplified BC. Assessment of FGFR2 copy number in cell free plasma DNA may provide a screening tool to identify FGFR2 amplified GC. Clinical trial information: NCT01795768. Clinical trial information: NCT01795768.
Duration of Immunosuppressive Therapy for Chronic Graft-vs.-Host Disease (cGVHD) Following Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation (HCT).
Authors: Andrew R. Rezvani, Wendy Leisenring, Paul L. Martin, Mary E.D. Flowers, David G. Maloney, Thomas R. Chauncey, Brenda M. Sandmaier, Rainer F. Storb
Journal: Blood (2007)
Natural history of<i>Mycobacterium avium</i>complex lung disease in untreated patients with stable course
Authors: Ji An Hwang, Sunyoung Kim, Kyung-Wook Jo, Tae Sun Shim
Journal: European Respiratory Journal (2017)

Little is known about the long-term natural history of Mycobacterium avium complex lung disease (MAC-LD) in untreated patients with stable course.The aim of this study was to investigate the natural course of untreated stable MAC-LD, with a focus on factors associated with clinical deterioration, spontaneous sputum conversion and prognosis.Of 488 patients diagnosed with MAC-LD between 1998 and 2011, 305 patients (62.5%) showed progressive MAC-LD resulting in treatment initiation within 3 years of diagnosis and 115 patients (23.6%) exhibited stable MAC-LD for at least 3 years with a median follow-up duration of 5.6 years. Patients with stable MAC-LD were more likely to have higher body mass index and less systemic symptoms at initial diagnosis compared with patients with progressive MAC-LD, while positive sputum acid-fast bacilli smear, fibrocavitary type and more extensive disease in radiological findings were more associated with progressive MAC-LD. Of the untreated patients with stable MAC-LD, 51.6% underwent spontaneous sputum conversion, with younger age, higher body mass index and negative sputum acid-fast bacilli smear at initial diagnosis found to be predictors of this occurrence.Advanced age, fibrocavitary type and abnormal pulmonary function were negative prognostic factors for survival in patients with stable MAC-LD.
Correlation of HER2/neu expression by real-time qRT-PCR in the peripheral blood of locoregional breast cancer patients with time to progression.
Authors: Renata Kelly Kuniyoshi, Viviane Vilas Boas, Beatriz da Costa Aguiar Alves, Patricia Hikari Maeda, Anna Estela Luiza Colo, Flavia de Sousa Gehrke, Fernando L. A. Fonseca, Auro Del Giglio
Journal: Journal of Clinical Oncology (2012)

e11059 Background: HER2/neu is a membrane receptor overexpressed in about 20% of Breast Cancer (BC) patients which can be targeted by several agents. As an epithelial marker it can also be detected by qRT-PCR in the peripheral blood (PB) of BC patients reflecting the presence of circulating tumor cells (CTCs). Objectives: Evaluate the prognostic impact of Her2/neu expression detection in the PB of BC patients. Methods: We performed qRT-PCR for HER2/neu serially at entry into the study and at every 3 months intervals for up to 2 years in every patient. Our qRT-PCR used primers described in Ferreira et al, 2010. In our hands this method could detect 1 MCF-7 cell diluted in 1x104 mononuclear cells and had a specificity of 83% (4/22 normal women controls had a positive test). Results: from 02/20/08 to 02/09/10 we included 41 patients with a histopathological diagnosis of BC with a mean age of 54 years (range 29 to 83 years); 55% post-menopausal; stages I:12%, II:41% and III:46%; 58% and 51% were ER+, 64% PR+, and 25% cerb2 positive (+++). The patients were treated with adjuvant and 41% with neoadjuvant chemotherapy with anthracycline regimens including anthracyclines in 88% and taxanes in 75%. With a mean follow up of 28 months, only HER2/neu expression at study entry as a continuous variable (HR = 1.125 95% CI: 1.021 – 1.238) and disease stage (HR = 6.34 95% CI 1.30 – 30.82) correlated significantly with time to progression by multivariate analysis. HER2/neu expression did not correlate with HER2/neu tissue expression. Conclusions: HER2/neu expression by Real Time RT-PCR in the PB of BC patients is a potential new prognostic factor for BC patients with locorregional disease.
圧迫されたヒトの心臓における前負荷動員一回仕事量(PRSW)と収縮期末圧容積関係(ESPVR)の線形性および変力性反応の比較
Authors: Mori M, Takeuchi M, Takaoka H, Hayashi Y, Yokoyama M
Journal: Circulation (1992)
City on Fire
Authors: Michel Sauve
Journal: Annals of Internal Medicine (2017)

On Being a Doctor7 March 2017City on FireMichel Sauve, MD, MScMichel Sauve, MD, MScFrom Alberta Health Services, Fort McMurray, Alberta, Canada.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-1384 Audio Reading - "City on Fire" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "City on Fire," by M. Sauve. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail "All staff must remain in the building."The hospital overhead speakers crackled with urgency. It was 3 p.m. on May 3, 2016.I had left my Fort McMurray home that morning thinking it was just another workday. The smell of the forest fire was in the air, but such smells were not that unusual, working in a city that is essentially carved out of the Canadian boreal forest.I never dreamed that forest fires would reach downtown Fort McMurray, my home for the last 25 years. Thanks to the development of the nearby oil sands, the northern Alberta city had ... Author, Article, and Disclosure InformationAffiliations: From Alberta Health Services, Fort McMurray, Alberta, Canada.Corresponding Author: Michel Sauve, MD, MSc, Alberta Health Services, 10-9914 Morrisson Street, Fort McMurray, AB T9H 4A4, Canada; e-mail, [email protected]ca. PreviousarticleNextarticle Advertisement Audio Reading - "City on Fire" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "City on Fire," by M. Sauve. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byEffects of the Fort McMurray wildfires on the health of evacuated workers: follow-up of 2 cohorts 7 March 2017Volume 166, Issue 5Page: 373-375KeywordsChartsCyclic adenosine monophosphateHeart rateMedical servicesOilsOxygenSmellTemperatureVomitingWheelchairs ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hematopoietic Progenitors with Slow Divisional Kinetics Give Rise to T Cell Precursors in the Thymus of the SCID Mouse Transplantation Model and Represent the Subset with Primitive Function.
Authors: Mario Schubert, Margot Zoeller, Wolfgang Wagner, Patrick Wuchter, Volker Eckstein, Anthony D. Ho
Journal: Blood (2007)
Ion channels or aquaporins as novel molecular targets in gastric cancer
Authors: Jianling Xia, Hongqiang Wang, Shi Li, Qinghui Wu, Li Sun, Hongxiang Huang, Ming Zeng
Journal: Molecular Cancer (2017)

Gastric cancer (GC) is a common disease with few effective treatment choices and poor prognosis, and has the second-highest mortality rates among all cancers worldwide. Dysregulation and/or malfunction of ion channels or aquaporins (AQPs) are common in various human cancers. Furthermore, ion channels are involved in numerous important aspects of the tumor aggressive phonotype, such as proliferation, cell cycle, apoptosis, motility, migration, and invasion. Indeed, by localizing in the plasma membrane, ion channels or AQPs can sense and respond to extracellular environment changes; thus, they play a crucial role in cell signaling and cancer progression. These findings have expanded a new area of pharmaceutical exploration for various types of cancer, including GC. The involvement of multiple ion channels, such as voltage-gated potassium and sodium channels, intracellular chloride channels, 'transient receptor potential' channels, and AQPs, which have been shown to facilitate the pathogenesis of other tumors, also plays a role in GC. In this review, an overview of ion channel and aquaporin expression and function in carcinogenesis of GC is presented. Studies of ion channels or AQPs will advance our understanding of the molecular genesis of GC and may identify novel and effective targets for the clinical application of GC.
SB431542, a TGF-Beta Receptor Kinase Inhibitor, Restores Bone Formation Which Ameliorates Myeloma-Induced Microenvironment.
Authors: Kyoko Takeuchi, Masahiro Abe, Asuka Oda, Hiroe Amou, Masahiro Hiasa, Jin Asano, Kenichi Kitazoe, Toshihiro Hashimoto, Shuji Ozaki, Shinsuke Kido, Daisuke Inoue, Toshio Matsumoto
Journal: Blood (2006)
Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial
Authors: Isabelle Gingras, Eileen Holmes, Evandro De Azambuja, David H A Nguyen, Miguel Izquierdo, Jo Anne Zujewski, Moshe Inbar, Bjorn Naume, Gianluca Tomasello, Julie R Gralow, Antonio C Wolff, Lyndsay Harris, Michael Gnant, Alvaro Moreno-Aspitia, Martine J Piccart, Hatem A Azim
Journal: JNCI Journal of the National Cancer Institute (2016)

Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown.This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS.One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29).Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials.
Age-related characteristics of ambulatory blood pressure load and mean blood pressure in normotensive subjects
Authors: P. K. Zachariah
Journal: JAMA (1991)

Ambulatory blood pressure monitoring has become increasingly popular for diagnosing and treating hypertension. However, data from normotensive subjects are needed for interpretation of hypertensive readings. Ambulatory blood pressure was monitored in 126 normotensive subjects (age range, 20 to 84 years). Mean systolic and diastolic blood pressures and blood pressure loads (percentage of systolic readings &gt;140 mm Hg and diastolic readings &gt;90 mm Hg) were obtained and interpreted. Mean awake systolic and diastolic pressures ranged from 125 ± 10 to 137 ± 17 mm Hg and 70 ± 8 to 71 ± 9 mm Hg, respectively. The systolic and diastolic trends of subjects' blood pressures taken during office visits and the 24-hour measurements were similar. Ranges for systolic and diastolic blood pressure loads from youngest to oldest ages were 9%± 14% to 25%±20% and 3%±7% to 4%±7%, respectively. A comparison of blood pressure means from our sample that were taken during office visits and blood pressure means from a 2122-patient community survey demonstrated that our sample was reflective of an unselected population. (<i>JAMA</i>. 1991;265:1414-1417)
FLT3 Mutations in Pediatric Acute Promyelocytic Leukemia; A Report from the Children's Oncology Group AAML0631 Trial
Authors: Matthew A. Kutny, Todd A. Alonzo, Robert Gerbing, Yi-Cheng Wang, Cecilia Fu, Alan S. Gamis, E. Anders Kolb, James H. Feusner, John Gregory, Soheil Meshinchi
Journal: Blood (2016)
MUC1 Inhibition Reverses the Poor Immunogenicity of Leukemia Stem Cells Rendering Them Susceptible to Immunotherapy
Authors: Dina Stroopinsky, Jacalyn Rosenblatt, Heidi Mills, Katarina Luptakova, Brett Glotzbecker, Baldev Vasir, Robin Joyce, James Levine, Dimitrios Tzachanis, Jon E. Arnason, Ilene Galinsky, Richard M. Stone, Donald Kufe, Yoram Reiter, David Avigan
Journal: Blood (2011)
Use of single polymorphism arrays (SNP-A) to modify prognostic scoring systems for myelodysplastic syndromes.
Authors: Manojkumar Bupathi, Paul Elson, Visconte Valeria, Fabiola Traina, Christine O' Keefe, Ali Tabarroki, Edy Hasrouni, Anjali S. Advani, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Lukasz Gondek, Ramon Velasquez Tiu
Journal: Journal of Clinical Oncology (2012)

6521 Background: MDS are hematologic neoplasms characterized by dysplasia and cytopenias. Two commonly used risk stratifications, IPSS (Greenberg et al Blood 1997) and IPSS-R are based on clinical factors (marrow blasts, number of cytopenias and genetic abnormalities determined by conventional karyotyping), with the IPSS based on 4 cytogenetic risk groups and the IPSS-R based on 5 cytogenetic risk groups defined by Schanz et al JCO 2012. A drawback to metaphase cytogenetics (MC) is its inability to detect small cryptic chromosomal defects and uniparental disomy (UPD). SNP-A can identify these small cytogenetic lesions/UPD and has been shown to be of prognostic value in MDS. The goal of this investigation was to determine if SNP-A detected defects could be used to refine the IPSS and IPSS-R. Methods: SNP-A karyotyping was performed as previously described (Tiu et al, Blood, 2011). We reviewed data from 327 patients idenfitying SNP-A results, MC, and the IPSS/IPSS-R-related clinical factors were identified. Overall survival (OS) measured from the date of sampling for SNP-A karyotyping was the primary endpoint. Data were analyzed using Cox proportional hazards models. Results: SNP-A lesions not detected by MC were grouped as 1) none or only gains/losses; 2) UPD only or gains+losses but no UPD; and 3) UPD+other defects. The frequencies/median os in months (mo) of the groups were: 66%/20.0, 23%/12.7 and 11%/5.8, respectively, p&lt;.0001 for OS. Combining the SNP-A groups with MC resulted in revised definitions of cytogenetic risk that had better discrimination than the underlying models; and when combined with the relevant clinical factors resulted in refined IPSS (IPSS SNP-A ) and IPSS-R (IPSS-R SNP-A ) risk stratifications (Table). Conclusions: Detection of chromosomal gains, losses, and UPD by SNP-A has prognostic value in MDS and can be used to refine current risk stratifications. [Table: see text]
Abstract P5-13-01: Sociodemographic and economic factors are essential determinants of weight gain between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort
Authors: P Fassier, L Zelek, V Partula, L Lecuyer, B Srour, P Bachmann, M Touillaud, N Druesne-Pecollo, P Galan, S Hercberg, P Cohen, H Hoarau, P Latino-Martel, R Gonzalez, M Deschasaux, M Touvier
Journal: Cancer Research (2017)

Abstract Background: While many cancer patients are affected by weight loss, others tend to gain weight, which may impact prognosis and risk of recurrence and of second cancer. The aim of this prospective study was to investigate weight variation between before and after cancer diagnosis and socio-demographic, economic, lifestyle and clinical factors associated with moderate-to-severe weight gain. Methods: 1051 incident cases of first primary cancer were diagnosed in the NutriNet-Santé cohort between 2009 and 2015. Weight was prospectively collected every 6 months since subjects' inclusion (i.e. an average of 2y before diagnosis). Mean weights before and after cancer diagnosis were compared with paired Student's t-test. Factors associated with moderate-to-severe weight gain (≥5% of initial weight) were investigated by multivariable logistic regression. Results: Weight loss was observed in men (-3.54kg in those who lost weight, p=0.0002) and in colorectal cancer patients (-3.94kg, p=0.0012). Weight gain was observed in breast and skin cancers (2.83kg, p=0.047, and 2.96kg, p=0.03 respectively). Women (OR=1.99[1.18-3.35]), younger patients (OR=1.78[1.05-3.03]), those with lower education (OR=2.17[1.07-4.37]), those with excess weight before diagnosis (OR=1.53[1.02-2.30]) and those who stopped smoking after diagnosis (OR=4.60[2.06-10.25]) were more likely to experience moderate-to-severe weight gain. In breast cancer patients, induced menopause was associated with weight gain (OR=4.12[1.76-9.67]), but no association was detected for tumor characteristics or treatments. Conclusion: This large prospective cohort provided original results on weight variation between before and after cancer diagnosis, highlighting different weight trajectories. Socio-demographic and economic factors appeared to strongly influence the risk of weight gain, illustrating social inequalities in health. Citation Format: Fassier P, Zelek L, Partula V, Lecuyer L, Srour B, Bachmann P, Touillaud M, Druesne-Pecollo N, Galan P, Hercberg S, Cohen P, Hoarau H, Latino-Martel P, Gonzalez R, Deschasaux M, Touvier M. Sociodemographic and economic factors are essential determinants of weight gain between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-13-01.
Cytogenetic Abnormalities and Appearance of Multiple Myeloma in Whole Body-MRI.
Authors: Jens Hillengass, Kerstin Fechtner, Anna Jauch, Tobias Baeuerle, Thomas Hielscher, Christiane Heiss, Sofia Ayyaz, Dirk Hose, Marc-André Weber, Hartmut Goldschmidt, Kai Neben
Journal: Blood (2009)
Clinical Efficacy of BK Virus Specific T-Cells in Treatment of Severe Refractory Hemorrhagic Cystitis after HLA Haploidentical Transplantation
Authors: Oscar M. Pello, Anne Bradshaw, Andrew Innes, Sally-Anne Finn, Emma Bray, Shab Uddin, Eduardo Olavarria, Jane F. Apperley, Jiří Pavlů
Journal: Blood (2016)
RFUSIN2 - a Clinical Grade Lentiviral Vector Co-Expressing CD80/IL-2 Manufactured Under GMP for a Phase I Clinical Trial Study of Immune Gene Therapy for Poor Prognosis Acute Myeloid Leukaemia
Authors: Lucas Chan, Wendy Ingram, Nicola Hardwick, David Darling, Joti Bhalla, Aytug Kizilors, Shahram Y Kordasti, Ghulam J Mufti, Farzin Farzaneh
Journal: Blood (2008)