tbuckley/cabot-search huggingface dataset:
Signaling pathway-based stratification of clear cell renal cell carcinoma.
Authors: Italia Bongarzone, Mattia Cremona, Virginia A. Espina, Francesca Miccichè, Silvia Veneroni, Maurizio Colecchia, Mariaelena Pierobon, Jianghong Deng, Claudius Mueller, Giuseppe Procopio, Cinzia Lanzi, Emanuel Petricoin, Lance A. Liotta
Journal: Journal of Clinical Oncology (2012)

434 Background: There are marked differences in responses to therapy among patients with clear cell renal cell carcinoma (ccRCC), which makes the outcome difficult to predict. This study is aimed to define a new classification system that would elucidate distinctions between carcinomas in order to facilitate selection of the appropriate treatment. We mapped cell signaling pathways in individual renal cell carcinomas and identified different classes based on commonly shared phosphorylation-driven signaling networks. Methods: Laser capture microdissection and reverse-phase protein arrays were used to profile 75 key nodes in 16 primary clear cell renal cancers. These nodes represent many signaling pathways known to be important in tumorigenesis and progression. Results: Statistical analysis revealed significant differences (p &lt;0.05) in signaling levels between two groups of samples, group A (4 samples) and group B (12 samples), for 27 of the 75 endpoints tested. In group A, high activation levels of EGFR, RET, and RASGFR1 converged to activate AKT/mTOR. Group B, showed high phosphorylation levels of ERK1/2 and STAT transcription factors and samples significantly partitioned in two clusters of 7 and 5 cases designated C and D. Group C showed elevated expression of a regulator of autophagy, LC3B; group D showed activation of Src and STAT transcription factors, suggesting the presence of cytokine-mediated cell survival pathways. A DNA copy number analysis was performed on the same samples and the results showed that group B represents some paradigmatic cases of ccRCC, with VHL loss-of-function mutations. Conclusions: The proteins identified appeared to be linked to pathways that are targeted by drugs typically used to treat clear cell renal cell carcinoma. Thus, this type of analysis could be useful for stratifying patients and selecting the best therapeutic approaches.
Fetal Hemoglobin Expression Is Differentially Affected by Inhibition of the Proposed Dred Complex Constituents, LSD1 and DNMT1
Authors: Tara L Arvedson, Lynn Tran, Sandra L Ross, Sean Yoder, Alexandra Hertz, Kari Hale, John Eschelbach, Tom Dineen, Stephanie Matyas, Cynthia Hartley, Kurt Morgenstern, Dwight Winters, Park Cindy, Graham Molineux, Angela Coxon
Journal: Blood (2012)
Early Consolidation with Myeloablative Radiochemotherapy Followed by Autologous Stem Cell Transplantation in First Remission in Mantle Cell Lymphoma: Long Term Follow up of a Randomized Trial of the
Authors: Martin H. Dreyling, Eva Hoster, Achiel Van Hoof, Bernd Metzner, Christian Gisselbrecht, Michael Pfreundschuh, Marcel Reiser, Lorenz H. Truemper, Hjalmar Steinhauer, Jean-Michel Boiron, Marc Boogaerts, Vittorio Silingardi, J.C. Kluin- Nelemans, Michael Unterhalt, Wolfgang Hiddemann
Journal: Blood (2008)
The JAK2 V617F Mutation Disrupts the Regulatory Activity Exerted By Calreticulin on the Glucocorticoid Receptor in Erythroid Cells
Authors: Mario Falchi, Lilian Varricchio, Fabrizio Martelli, Francesca Masiello, Orietta Piccioni, Agostino Tafuri, Gabriella Girelli, Camelia Iancu-Rubin, Ronald Hoffman, Anna Rita Migliaccio
Journal: Blood (2015)
Resistance of Hematopoietic Stem Cells Lacking the KIR Ligand to Autologous NK Cell Attacks in Patients with Acquired Aplastic Anemia
Authors: Hiroyuki Maruyama, Luis J. Espinoza, Takamasa Katagiri, Yoshitaka Zaimoku, Koichi Kashiwase, Hiroo Saji, Seishi Ogawa, Shinji Nakao
Journal: Blood (2014)
Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis
Authors: Chetasi Talati, Ling Zhang, Ghada Shaheen, Andrew Kuykendall, Markus Ball, Qing Zhang, Jeffrey E. Lancet, Kenneth S. Zuckerman, Alan F. List, Rami Komrokji, Lynn Moscinski, Eric Padron
Journal: Blood (2017)
M200, an integrin α5β1 antibody, promotes apoptosis in proliferating endothelial cells
Authors: V. Ramakrishnan, V. Bhaskar, D. A. Law, M. H.-L. Wong, J. Green, J. Tso, U. Jeffry, B. Finck, R. Murray
Journal: Journal of Clinical Oncology (2004)

3187 Background: The role of VEGF in mediating angiogenesis is well documented, but recent evidence indicates that integrins such as αvβ3 are also important. We identified α5 integrin using a proprietary gene array. The α5β1 integrin mediates the binding of endothelial cells to fibronectin in the extracellular matrix. The growth factors VEGF and bFGF also promote the recruitment of new blood vessels into expanding tumors. We assessed the relative roles of these factors in vitro and in vivo to elucidate the validity of inhibiting integrin α5β1. Methods: We measured affinity of a chimeric antibody, M200, against α5β1 integrin by BIAcore, and assessed the role of α5β1 using an in vitro angiogenesis model and in vivo in a laser-induced model of choroidal neovascularisation (CNV) in cynomolgus monkeys. We compared M200 to an anti-VEGF mAb for effects on endothelial cell survival and proliferation in vitro. Results: M200, and its derivative Fab F200, inhibit binding of fibronectin to α5β1. M200 and F200 have similar potencies by BIAcore (Kd∼0.3nM). Both M200 and F200 show significant inhibition both VEGF and bFGF dependent tube formation in an in vitro angiogenesis model, and of neovascularization in the cynomolgus CNV model. M200 inhibits HUVEC proliferation more effectively than an anti-VEGF mAb (0.40 nM vs. 45 nM) at both low and high VEGF concentrations (2ng-50 ng/ml). No additive affect was observed when cells were challenged with anti-VEGF and M200 together. Thus M200 exerts novel cytotoxic effects in addition to recapitulating the anti-proliferative properties of anti-VEGF. This difference in potency was found to be attributable to the unique ability of M200 to selectively induce apoptosis in proliferating, but not senescent, endothelial cells. Conclusions:Our data shows that M200 is a potent anti-angiogenic with significant activity in vitro and in vivo. Further evaluation of the mechanism in vitro suggests that signaling via α5β1 and VEGF occur through overlapping mechanisms, and that M200 exerts a more significant growth inhibition of HUVEC in vitro than anti-VEGF, independent of growth factor stimulation, and this may translate to better clinical efficacy Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Protein Design Labs, Inc. Protein Design Labs, Inc.
The Histone Deacetylase 1 and 2 (HDAC1/2) Inhibitor ACY-957 Increases Epsilon (HbE) and Gamma (HbG) Globin mRNA in the Peripheral Blood of Non-Anemic Rats and Monkeys
Authors: Jeffrey R Shearstone, Apurva Chonkar, Kailash Bhol, Simon S Jones, Matt Jarpe
Journal: Blood (2015)
Flavopiridol Can Be Safely Dose Escalated in Relapsed CLL Patients: Achievement of Target Cmax Results in Improved Clinical Activity.
Authors: Thomas S. Lin, Mitch Phelps, James T. Dalton, Beth Fischer, Kristie A. Blum, Mollie E. Moran, Michelle B. McEldowney, Sara Broering, Dimitrios Colevas, John C. Byrd, Michael R. Grever
Journal: Blood (2006)
Very Early/Early Relapses of ALL Show Unexpected Changes of Clonal Markers and High Heterogeneity in Initial and Relapse Treatment Response: ALL-BFM 2000 and ALL-REZ BFM 96/2002.
Authors: Cornelia Eckert, Rolf Koehler, Thomas Flohr, Nikola Hagedorn, Anja Moericke, Martin Stanulla, Renate Kirschner-Schwabe, Gunnar Cario, Arend von Stackelberg, Claus R Bartram, Guenter Henze, Martin Schrappe, Andre Schrauder
Journal: Blood (2009)
Abnormal Angiogenesis, Neurogenesis and Lymphangiogenesis in the Skin Underlies Delayed Wound Healing in the Sickle Mouse: Acceleration of Healing by Topical Opioids.
Authors: Kalpna Gupta, Tasneem Poonawala, Brett K. Levay-Young, Marna E. Ericson, Niroop S. Ammbashankar, Robert P. Hebbel
Journal: Blood (2005)
Contribution of poor blood pressure control to strokes
Authors: P G E Kennedy, B I Hoffbrand
Journal: BMJ (1979)

demand expertise.If this is lacking then expert supervision should be at hand.When this is not available, as in practical terms it may not be, then how much wiser it is to stop well short of that critical force.A trial of forceps therefore should still be a laudable and well-recognised procedure, and a "failed forceps" never regarded as an obstetric failure, unless the danger force is exceeded.No amount of experience will always predict the outcome of every instrumental delivery.Perhaps in the electronic age we could design a special type of strain gauge attached to the forceps handles.Failing this, a change in some attitudes towards trials of forceps, and in particular failed forceps, could certainly help.
Mcl-1 Fragment Mcl-1(128–350) Induces Inhibition of Multiple Myeloma Cell Proliferation and Apoptosis Via Both Upregulation of C-Jun as Well as Modulation of Its Transcriptional Activity
Authors: Klaus Podar, Jing Zhang, Alexander Zimmerhackl, Daniela Barila, Sonia Vallet, Martin Sattler, Yu-Tzu Tai, Teru Hideshima, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2008)
Analysis of Genetic Lesions in Atypical B-CLL by Pangenomic CGH-Arrays.
Authors: Christophe Roumier, Olivier Nibourel, Valérie Soenen, Céline Villenet, Sébastien Lignon, Sabine Quief, Fréderic Davi, Florence Cymbalista, Claude Preudhomme, Jean-Pierre Kerckaert, Xavier Troussard
Journal: Blood (2005)
CBM-07SERUM NSE, MMP-9 AND HER2 ARE PREDICTIVE OF BRAIN METASTASES IN METASTATIC BREAST CANCER PATIENTS
Authors: Amélie Darlix, Pierre-Jean Lamy, Evelyne Crapez, Antoine Laurent Braccini, Nelly Firmin, Gilles Romieu, Simon Thezenas, William Jacot
Journal: Neuro-Oncology (2015)

BACKGROUND: Breast cancer (BC) is the second leading cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM in this population. Serum levels of protein S100, an astrocytic marker, are associated with stroke severity. Neuron Specific Enolase (NSE), a neuronal marker, has been associated with BM prognosis in lung cancer. Elevated serum levels of these markers could reflect the brain damages induced by BM. Matrix Metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Finally, it has been shown that HER2-amplified breast tumors have a particular tropism for central nervous system. This study evaluates the predictive value of these four markers for BM in a population of metastatic BC patients. METHODS: In this case-control study, 88 consecutive BC patients with BM (cases) treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor markers determination. Cases were matched by age, tumor biology and number of previous metastatic treatment lines to 162 patients with metastatic BC but without CNS involvement (controls). RESULTS: Serum HER2, NSE and MMP-9 levels were significantly higher in cases than in controls (p= 0.0057, p = 0.0051 and p = 0.0062, respectively). Median HER2 (ng/ml) was 21.1 in cases compared to 12.3 in controls; median NSE (µg/l) was 10.8 compared to 8.70 in controls; median MMP-9 (ng/µl) was 422.9 in cases compared to 320.5 in controls. In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated cases from controls: odd ratio 4.4 (p = 0.000; 95%CI 1.9-9.6) for HER2 and 3.5 (p = 0.005; 95%CI 1.5-8.4) for MMP-9. CONCLUSIONS: Serum HER2 and MMP-9 seem to be predictive of BM in metastatic BC patients. These results need to be validated in further larger prospective studies.
FACS Analysis of Stat3/5 Signaling Reveals Ligand Sensitivity As a Significant Prognostic Factor in Pediatric AML: A Children's Oncology Group Report
Authors: Michele S. Redell, Marcos J. Ruiz, Robert B. Gerbing, Todd A. Alonzo, Beverly Lange, David J. Tweardy, Soheil Meshinchi
Journal: Blood (2011)
IL-22 controls iron-dependent nutritional immunity against systemic bacterial infections
Authors: Kei Sakamoto, Yun-Gi Kim, Hideki Hara, Nobuhiko Kamada, Gustavo Caballero-Flores, Emanuela Tolosano, Miguel P. Soares, José L. Puente, Naohiro Inohara, Gabriel Núñez
Journal: Science Immunology (2017)

Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22-/- mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.
GSA: Genome Sequence Archive
Authors: Yanqing Wang, Fuhai Song, Junwei Zhu, Sisi Zhang, Yadong Yang, Tingting Chen, Bixia Tang, Lili Dong, Nan Ding, Qian Zhang, Zhouxian Bai, Xunong Dong, Huanxin Chen, Mingyuan Sun, Shuang Zhai, Yubin Sun, Lei Yu, Li Lan, Jingfa Xiao, Xiangdong Fang, Hongxing Lei, Zhang Zhang, Wenming Zhao
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract With the rapid development of sequencing technologies towards higher throughput and lower cost, sequence data are generated at an unprecedentedly explosive rate. To provide an efficient and easy-to-use platform for managing huge sequence data, here we present Genome Sequence Archive (GSA; http://bigd.big.ac.cn/gsa or http://gsa.big.ac.cn), a data repository for archiving raw sequence data. In compliance with data standards and structures of the International Nucleotide Sequence Database Collaboration (INSDC), GSA adopts four data objects (BioProject, BioSample, Experiment, and Run) for data organization, accepts raw sequence reads produced by a variety of sequencing platforms, stores both sequence reads and metadata submitted from all over the world, and makes all these data publicly available to worldwide scientific communities. In the era of big data, GSA is not only an important complement to existing INSDC members by alleviating the increasing burdens of handling sequence data deluge, but also takes the significant responsibility for global big data archive and provides free unrestricted access to all publicly available data in support of research activities throughout the world.
Hematopoiesis in Chronic Phase CML emerges from Hematopoietic Stem Cells with a Transcriptional Phenotype Resembling Normal Myeloid Progenitor Cells.
Authors: Ingmar Bruns, Akos Czibere, Patrick Cadeddu, Frederik Roels, Johannes C Fischer, Sebastian Büst, Daniela Brünnert, Ulrich Steidl, Benedict Brors, Norbert Gattermann, Ralf Kronenwett, Rainer Haas
Journal: Blood (2008)
Abstract MP33: Heart Failure Following Cancer Therapy in Patients with Hematological Malignancies Aged 18 Years and Under: A Linked Health Data Analysis (1996-2009)
Authors: Narelle M Berry, Shahid Ullah, Vincent L Versace, Alexandra L McCarthy, John J Atherton, David Roder, Bogda Koczwara, Douglas Coghlan, Munir H Chowdhury, Robyn A Clark
Journal: Circulation (2016)

Introduction: The causal link between chemotherapy treatments and subsequent cardiotoxicity is well established, particularly for children with hematological malignancies. Little information exists on the characteristics and outcomes for patients with heart failure (HF) after chemotherapy. This study aimed to describe the characteristics, survival and mortality of patients who received chemotherapy for hematological cancer (leukemias, lymphomas and related disorders) before 18 years old and subsequently developed HF compared to those who did not. Methods: Linked health data (1996-2009) from the Queensland Cancer Registry, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. From all breast and hematological cancers patients (n=73,158), 15,987 received chemotherapy, including 819 patients aged ≤18 years at time of cancer diagnosis. Patients were categorized as those with an index HF admission (occurred after cancer diagnosis) and those without an index HF admission (non HF). Results: Of the 819 patients, 3.7% (n=30) had an index HF admission. Median age of HF patients at time of cancer diagnosis was 5 years (IQR 3-12) compared to 7 years (IQR 3-14) in the non HF group (p=0.503). Median follow up from cancer diagnosis was 2.5 years in the HF group compared to 5.42 years in the non HF group (p&lt;0.01). Of those who developed HF, 70% (n=21) had the index admission within 12 months of their cancer diagnosis. Of those with HF, 53.3% (n=16) died (all cause) compared to 14.6% (n=115) with no HF. On adjustment for age, sex and chemotherapy admissions, HF patients had an almost 5 fold increased mortality risk compared to non HF patients (HR 4.91 [95% CI, 2.88-8.36]) (Figure 1). Conclusions: This study demonstrated that in children with hematological cancers the onset of HF occurred soon after chemotherapy and mortality risk is almost 5 times that of children who do not develop HF. Innovative strategies are still needed for the prevention and management of cardiotoxicity in this population.
Clinical Research of Autologous Hematopoietic Stem Cell Transplantation for Hematological Malignancies and Solid Tumors.
Authors: Zhen-qian Huang, Dong-hua Zhang, Huo Tan, Cheng-zhi Zhou, Dan Liu, Huan-zhu Zhang, Jie-xia Zhang, Wei Huang, Wen-li Liu
Journal: Blood (2005)
Phase I Study of IMGN901 in Patients with Relapsed and Relapsed/Refractory CD56-Positive Multiple Myeloma
Authors: Asher Alban Chanan-Khan, Mecide Gharibo, Sundar Jagannath, Nikhil C. Munshi, Kenneth C Anderson, Dawn DePaolo, Kelvin P. Lee, Kena Miller, Robin Guild, Sybil Zildjian, Albert Qin
Journal: Blood (2008)
Intrinsic Resistance of Solid Tumors to Immune Checkpoint Blockade Therapy
Authors: Xianda Zhao, Subbaya Subramanian
Journal: Cancer Research (2017)

Abstract Immune checkpoint blockade therapy (ICBT), which blocks negative immune-activating signals and maintains the antitumor response, has elicited a remarkable clinical response in certain cancer patients. However, intrinsic resistance (i.e., insensitivity of the tumors to therapy) remains a daunting challenge. The efficacy of ICBT is tightly modulated by the function of each step in the antitumor immunity cycle. Mechanistically, the number of mutations determines tumor immunogenicity. The properties of the tumor microenvironment control T-cell infiltration, distribution, and function in tumor tissues. Low tumor immunogenicity and a strong immunosuppressive tumor microenvironment cause significant intrinsic resistance to ICBT. With our evolving understanding of intrinsic resistance, people have successfully tested, in preclinical models, treatments targeting specific resistance mechanisms to sensitize ICBT-resistant tumors. Translation of those preclinical findings to the clinical arena will help generate personalized ICBT strategies that target tumor-specific resistance mechanisms. Progress in the new personalized ICBT strategies will expand the reach of immunotherapy to more cancer types, thus enabling more patients to benefit. Cancer Res; 77(4); 817–22. ©2017 AACR.
Heart–Brain Axis
Authors: Pouya Tahsili-Fahadan, Romergryko G. Geocadin
Journal: Circulation Research (2017)

A complex interaction exists between the nervous and cardiovascular systems. A large network of cortical and subcortical brain regions control cardiovascular function via the sympathetic and parasympathetic outflow. A dysfunction in one system may lead to changes in the function of the other. The effects of cardiovascular disease on the nervous system have been widely studied; however, our understanding of the effects of neurological disorders on the cardiovascular system has only expanded in the past 2 decades. Various pathologies of the nervous system can lead to a wide range of alterations in function and structure of the cardiovascular system ranging from transient and benign electrographic changes to myocardial injury, cardiomyopathy, and even cardiac death. In this article, we first review the anatomy and physiology of the central and autonomic nervous systems in regard to control of the cardiovascular function. The effects of neurological injury on cardiac function and structure will be summarized, and finally, we review neurological disorders commonly associated with cardiovascular manifestations.
Patterns of Granulocyte Colony-Stimulating Factor (G-CSF) Use in Elderly Patients with Non-Hodgkin's Lymphoma (NHL) Receiving Myelosuppressive Chemotherapy
Authors: John H Page, Craig Solid, Victoria M Chia, Anne Hudson Blaes, Richard L. Barron, Mi Rim Choi, Thomas J Arneson
Journal: Blood (2012)
Increased Levels of Serum Tissue Inhibitor of Metalloproteinase-1 Correlate with Advanced Stage, Increased Bone Resorption, Lytic Bone Disease and Poor Survival in Newly-Diagnosed Myeloma Patients
Authors: Evangelos Terpos, Meletios A. Dimopoulos, Vikas Shrivastava, Kim Leitzel, Dimitrios Christoulas, Magdalini Migkou, Maria Gavriatopoulou, Konstantinos Anargyrou, Efstathios Kastritis, Allan Lipton
Journal: Blood (2008)
Clinicopathologic characteristics of multiple primary cancers: 377 patients.
Authors: N. A. Babacan, S. Aksoy, B. Cetin, M. A. Kaplan, N. Ozdemir, T. Kos, U. Uyeturk, H. Karaca, D. Uncu, A. Isikdogan, M. Özkan, U. Coskun, M. Benekli, S. Buyukberber, N. Zengin
Journal: Journal of Clinical Oncology (2011)

e19682 Background: Multiple primary cancers (MPC) describe diagnosis of two or more independent primary reportable neoplasms in an individual. Frequency of MPC has been increasing. In this study we aimed to determine the frequency and clinical features of multiple primary cancers in our centers. Methods: From January 1990 to December 2010, patients with multiple primary cancers were screened in 5 centers. Data were obtained from hospital charts retrospectively. Results: Three hundred seventy-seven patients with multiple primary cancers were evaluated. Male to female ratio was 1.44 (M/F; 223/154). The median age of diagnosis was 61 (min-max; 18-88) for initial cancer, 64 (min-max; 20-89) for second cancer. The median time between two cancer diagnoses was 34.5 months (min-max; 2-504). The most frequent initial cancer types were head and neck (54 patients, 14,3%), breast (54 patients, 14,3%), and colorectal (43 patients, 11,4%). The most frequent second cancer types were lung (76 patients, 20,2%), colorectal (39 patients, 10,3%) and breast (33 patients, 8,8%), respectively. The most common cancer couples were breast - gynecologic cancers (15 patients 9,7%), colorectal-breast cancer (9 patients; 5.8%) and breast - colorectal cancers (7 patients; 4.5%) in females. The most common cancer couples were head and neck – lung cancer (29 patients 13%), bladder – lung cancers (9 patients; 4%), bladder-prostate cancers (7 patients; 3%) in males. Conclusions: Physicians should be aware of second primary cancer probability. New developed suspicious lesions should be evaluated rigorously. The histopathologic evaluation of the suspicious lesions for second tumors should be used extensively if needed. In our series most common couples were breast - gynecologic cancer in females and head and neck - lung cancer in males.