tbuckley/cabot-search huggingface dataset:
Abstract P2-01-31: Validation of novel diagnostic kits using the semi-dry dot-blot method for detecting metastatic lymph nodes in breast cancer; distinguishing macrometastases and micrometastases
Authors: R Otsubo, H Hirakawa, M Oikawa, E Inamasu, M Baba, M Matsumoto, H Yano, N Kinoshita, K Abe, J Fukuoka, T Nagayasu
Journal: Cancer Research (2017)

Abstract Background: The semi-dry dot-blot (SDB) method is a diagnostic procedure for detecting lymph node (LN) metastases. Metastases are confirmed by the presence of cytokeratin (CK) in lavage fluid of sectioned LNs that contain anti-pancytokeratin antibody, based on the theory that epithelial components such as CK are not found in normal LNs. We evaluated two novel SDB kits that use the newly developed anti-CK19 antibody for diagnosing LN metastases in breast cancer. Methods: We obtained 159 LNs dissected from 93 breast cancer patients from July 2013 to December 2015 at Nagasaki University Hospital, including 38 dissected axillary LNs and 121 sentinel LNs, sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage fluid of sliced LNs were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. The washed LNs were blindly diagnosed by pathologists using hematoxylin and eosin (H&amp;E) stain. Diagnoses based on the kit were compared with their H&amp;E counterparts. Results: Of the 159 LNs, 68 were assessed as positive and 91 as negative by permanent pathological examination with H&amp;E. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. In 11 false-negative cases, there were nine micrometastases, producing a sensitivity of 96.4% for detecting macrometastases. Sensitivity, specificity, and accuracy of the high-power kit for detecting LN metastases was 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, sensitivity, specificity and accuracy for distinguishing macrometastases from micrometastases was 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 min using the kits, at a cost of less than 25 USD. Conclusions: The kits in our study were accurate, quick, and cost-effective in diagnosing LN metastases without the loss of LN tissue. The kits' ability to distinguish macrometastases from micrometastases was excellent, which is important, clinically. Citation Format: Otsubo R, Hirakawa H, Oikawa M, Inamasu E, Baba M, Matsumoto M, Yano H, Kinoshita N, Abe K, Fukuoka J, Nagayasu T. Validation of novel diagnostic kits using the semi-dry dot-blot method for detecting metastatic lymph nodes in breast cancer; distinguishing macrometastases and micrometastases [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 P2-01-31.
Prostaglandin-mediated inhibition of serotonin signaling controls the affective component of inflammatory pain
Authors: Anand Kumar Singh, Joanna Zajdel, Elahe Mirrasekhian, Nader Almoosawi, Isabell Frisch, Anna M. Klawonn, Maarit Jaarola, Michael Fritz, David Engblom
Journal: Journal of Clinical Investigation (2017)

Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E2 that is synthesized by cyclooxygenase 2 in neural cells. Further, mice lacking the prostaglandin E2 receptor EP3 selectively on serotonergic cells or selectively in the area of the dorsal raphe nucleus failed to form an aversion to formalin-induced pain, as did mice lacking the serotonin transporter. Chemogenetic manipulations revealed that EP3 receptor activation elicited conditioned place aversion to pain via inhibition of serotonergic neurons. In contrast to their role in inflammatory pain aversion, EP3 receptors on serotonergic cells were dispensable for acute nociceptive behaviors and for aversion induced by thermal pain or a κ opioid receptor agonist. Collectively, our findings show that prostaglandin-mediated modulation of serotonergic transmission controls the affective component of inflammatory pain.
NLRP3 Inflammasome Deficiency Protects against Microbial Sepsis via Increased Lipoxin B<sub>4</sub>Synthesis
Authors: Seonmin Lee, Kiichi Nakahira, Jesmond Dalli, Ilias I. Siempos, Paul C. Norris, Romain A. Colas, Jong-Seok Moon, Masakazu Shinohara, Shu Hisata, Judie Ann Howrylak, Gee-Young Suh, Stefan W. Ryter, Charles N. Serhan, Augustine M. K. Choi
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern with high mortality and morbidity. Although inflammatory responses triggered by infection are crucial for host defense against invading microbes, the excessive inflammation often causes tissue damage leading to organ dysfunction. Resolution of inflammation, an active immune process mediated by endogenous lipid mediators (LMs), is important to maintain host homeostasis.We sought to determine the role of the nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome in polymicrobial sepsis and regulation of LM biosynthesis.We performed cecal ligation and puncture (CLP) using mice lacking NLRP3 inflammasome-associated molecules to assess mortality. Inflammation was evaluated by using biologic fluids including plasma, bronchoalveolar, and peritoneal lavage fluid. Local acting LMs in peritoneal lavage fluid from polymicrobacterial septic mice were assessed by mass spectrometry-based metabololipidomics.Genetic deficiency of NLRP3 inhibited inflammatory responses and enhanced survival of CLP-induced septic mice. NLRP3 deficiency reduced proinflammatory LMs and increased proresolving LM, lipoxin B4 (LXB4) in septic mice, and in macrophages stimulated with LPS and ATP. Activation of the NLRP3 inflammasome induced caspase-7 cleavage and pyroptosis. Caspase-7 deficiency similarly reduced inflammation and mortality in CLP-induced sepsis, and increased LXB4 production in vivo and in vitro. Exogenous application of LXB4 reduced inflammation, pyroptosis, and mortality of mice after CLP.Genetic deficiency of NLRP3 promoted resolution of inflammation in polymicrobial sepsis by relieving caspase-7-dependent repression of LXB4 biosynthesis, and increased survival potentially via LXB4 production and inhibition of proinflammatory cytokines.
Cytokine Inhibition in Patients With Chronic Fatigue Syndrome
Authors: Megan E. Roerink, Sebastian J.H. Bredie, Michael Heijnen, Charles A. Dinarello, Hans Knoop, Jos W.M. Van der Meer
Journal: Annals of Internal Medicine (2017)

Background: Interleukin-1 (IL-1), an important proinflammatory cytokine, is suspected to play a role in chronic fatigue syndrome (CFS). Objective: To evaluate the effect of subcutaneous anakinra versus placebo on fatigue severity in female patients with CFS. Design: Randomized, placebo-controlled trial from July 2014 to May 2016. Patients, providers, and researchers were blinded to treatment assignment. (ClinicalTrials.gov: NCT02108210) Setting: University hospital in the Netherlands. Patients: 50 women aged 18 to 59 years with CFS and severe fatigue leading to functional impairment. Intervention: Participants were randomly assigned to daily subcutaneous anakinra, 100 mg (n = 25), or placebo (n = 25) for 4 weeks and were followed for an additional 20 weeks after treatment (n = 50). Measurements: The primary outcome was fatigue severity, measured by the Checklist Individual Strength subscale (CIS-fatigue) at 4 weeks. Secondary outcomes were level of impairment, physical and social functioning, psychological distress, and pain severity at 4 and 24 weeks. Results: At 4 weeks, 8% (2 of 25) of anakinra recipients and 20% (5 of 25) of placebo recipients reached a fatigue level within the range reported by healthy persons. There were no clinically important or statistically significant differences between groups in CIS-fatigue score at 4 weeks (mean difference, 1.5 points [95% CI, −4.1 to 7.2 points]) or the end of follow-up. No statistically significant between-group differences were seen for any secondary outcome at 4 weeks or the end of follow-up. One patient in the anakinra group discontinued treatment because of an adverse event. Patients in the anakinra group had more injection site reactions (68% [17 of 25] vs. 4% [1 of 25]). Limitation: Small sample size and wide variability in symptom duration; inclusion was not limited to patients with postinfectious symptoms. Conclusion: Peripheral IL-1 inhibition using anakinra for 4 weeks does not result in a clinically significant reduction in fatigue severity in women with CFS and severe fatigue. Primary Funding Source: Interleukin Foundation and an independent donor who wishes to remain anonymous.
Involvement of STAT3 Transcription Factor in Disseminated Nasal-Type Natural Killer Cell Lymphomas.
Authors: Paul Coppo, Valérie Gouilleux-Gruart, Sandrine Bouchet, Yenlin Huang, Peggy Dartigues, Philippe Gaulard, Felix Agbalika, Luc Douay, Kaiss Lassoued, Norbert C. Gorin
Journal: Blood (2007)
A Replication Study of Gene Variants Associated with Venous Thrombosis. Results From a Population-Based Nested Case-Cohort Study.
Authors: Willem M Lijfering, Irene D Bezemer, Sverre C Christiansen, Inger-Anne Naess, Frits Rosendaal, Jens Hammerstrøm, Suzanne C Cannegieter
Journal: Blood (2009)
Treatment refusal greater for drug therapy than psychotherapy
Authors: Jacqui Wise
Journal: BMJ (2017)

Patients with mental health problems are more likely to refuse treatment or not complete the recommended course if it consists of drug therapy alone than if it comprises psychotherapy alone, a meta-analysis published in the journal Psychotherapy has found.

The rates of treatment refusal were about two times higher for pharmacotherapy alone than for psychotherapy alone, particularly for the treatment of social anxiety disorder, depressive disorders, …
Low-Dose Cyclophosphamide Plus Granulocyte Colony-Stimulating Factor As an Efficacious and Safe Peripheral Blood Stem Cell Mobilizing Regimen in Patients with Hematologic Malignancies
Authors: Arun Sendilnathan, Jaskirat Singh Randhawa, Changchun Xie, Rebecca Bolt, Thomas Leemhuis, Nora Buzek, Kitty Tierney, Susan Pinkard, Saulius Girnius, Stephen Medlin
Journal: Blood (2015)
Phase I Study of Decitabine and Rapamycin in Relapsed/Refractory Acute Myelogenous Leukemia
Authors: Jane L. Liesveld, Kristen O'Dwyer, Michael W. Becker, Deborah Mulford, Alison Walker, Rui Chen, Jeremy Bechelli, Karen Rosell, Craig T. Jordan, Mohammad Minhajuddin, Gordon L. Phillips
Journal: Blood (2012)
Stage Adjusted International Prognostic Index (St-IPI) Is a Simple and Better Prognostic Model in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Nationwide Multi-Institutional Registry in Thailand
Authors: Lalita Norasetthada, Weerasak Nawarawong, Udomsak Bunworasate, Kitsada Wudhikarn, Noppadol Siritanaratanakul, Archrob Khuhapinant, Arnuparp Lekhakula, Jakrawadee Julamanee, Chittima Sirijerachai, Kanchana Chansung, Suporn Chuncharunee, Pimjai Niparuck, Tontanai Numbenjapon, Kannadit Prayongratana, Tawatchai Suwanban, Rachanid Pornvipavee, Peerapon Wong, Nonglak Kanitsap, Nisa Makruasi, Tanin Intragumtornchai
Journal: Blood (2015)
2 Chlorodeoxyadenosine (2-CdA) and Cytarabine (ara-C) Combination Is Effective and Safe in Idiopathic Hypereosinophilic Syndrome (HES).
Authors: Elias Jabbour, Srdan Verstovsek, Varsha Gandhi, Jorge Cortes, Francis Giles, Charles Koller, Susan O’Brien, William Plunkett, Guillermo Garcia-Manero, Ellen Jackson, Hagop Kantarjian, Michael Andreeff
Journal: Blood (2004)
Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future
Authors: Peter Valent, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Wolfgang R. Sperr, Luis Escribano, Tracy I. George, Hanneke C. Kluin-Nelemans, Celalettin Ustun, Massimo Triggiani, Knut Brockow, Jason Gotlib, Alberto Orfao, Lawrence B. Schwartz, Sigurd Broesby-Olsen, Carsten Bindslev-Jensen, Petri T. Kovanen, Stephen J. Galli, K. Frank Austen, Daniel A. Arber, Hans-Peter Horny, Michel Arock, Dean D. Metcalfe
Journal: Cancer Research (2017)

Abstract Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. Cancer Res; 77(6); 1261–70. ©2017 AACR.
US reproductive health and rights: beyond the global gag rule
Authors: Rachel Benson Gold, Ann M Starrs
Journal: The Lancet Public Health (2017)

As one of his first actions as president, Donald Trump imposed and expanded the global gag rule, a sweeping policy that will cripple highly successful US family planning programmes in developing countries and seriously damage broader US global health efforts.1 This callous policy—ostensibly meant to counter abortion—might shock observers abroad, but is only the opening salvo in what is expected to be a broad-based assault on sexual and reproductive health and rights. President Trump has vowed to "put America first"; however, his policies would put the health of women last, around the world and most certainly in the USA.
Ibrutinib Is an Irreversible Molecular Inhibitor of Interleukin-2 Inducible Kinase: Expanding Therapeutic Potential and Modulating a Th1 Selective Pressure in CD4 T-Cells
Authors: Jason A Dubovsky, Kyle A Beckwith, Jennifer A. Woyach, Samantha M. Jaglowski, Joshua Hessler, Betty Y. Chang, Karilyn Larkin, Matthew R Stefanovski, Frank W Frissora, Lisa L. Smith, Kelly A Smucker, Joseph M. Flynn, Jeffrey A. Jones, Leslie A Andritsos, Kami Maddocks, Amy Lehman, Richard R. Furman, Jeff Sharman, Anjali Mishra, Michael A. Caligiuri, Joseph J. Buggy, Natarajan Muthusamy, Amy J Johnson, John C. Byrd
Journal: Blood (2012)
Abstract PR08: Mutant KRAS decouples glycolysis from cell mechanics in non-small cell lung cancer
Authors: Jin Suk Park, Jessica Sudderth, Boning Gao, Robert Bachoo, Gaudenz Danuser
Journal: Cancer Research (2017)

Abstract Reprogramming of the cellular metabolism is an accepted hallmark of cancer. On the other hand, increasing evidence suggests the importance of the microenvironment, including its mechanical properties, in tumor development and metastasis. Whether cellular metabolism and cell mechanics are interdependent has been relatively unexplored, although recent works from several labs seem to suggest a direct link between microenvironment and metabolic state of cells. My project focuses on this mechano-metabolism in cancer. Using metabolic flux analysis, we show that the metabolism of untransformed human bronchial epithelial cells (HBECs) responds to the stiffness of the extracellular matrix. Relative to the cells on soft substrates, the cells on stiff substrates had elevated rates of glycolysis by 2.8-fold and of oxidative respiration by 1.2-fold. However, this mechano-sensitivity is lost in hTert/p53/myc/Kras-transformed lung epithelial cells, as well as non-small cell lung cancer (NSCLC) that harbors the KRAS mutations. Interestingly, these cells assume overall higher rates of glycolysis and oxidative respiration, independent of cell substrate stiffness. Thus far I have been able to identify that the mechano-desensitization is driven by the Kras mutations, which constitutively activate downstream signal cascades including the MAPK pathway. In addition, isotope tracing shows that mutant KRAS is required to generate citrate from glucose on soft substrates, and the absence of KRAS mutations significantly hinder glycolysis upon the treatment with blebbistatin. This study subsequently establishes the novel insight that the metabolic stabilization due to the mechano-insensitivity of cancer cells is driven by mutant KRAS, which may be advantageous when out-competing the surrounding cells over the course of tumorgenesis. This abstract is also being presented as Poster A55. Citation Format: Jin Suk Park, Jessica Sudderth, Boning Gao, Robert Bachoo, Gaudenz Danuser. Mutant KRAS decouples glycolysis from cell mechanics in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr PR08.
Prelimenary results of a phase I/II of a combination of cetuximab and taxane for triple negative breast cancer patients
Authors: H. Nechushtan, H. Steinberg, T. Peretz
Journal: Journal of Clinical Oncology (2009)

e12018 Background: The triple negative subtype of breast cancer is currently only treated with chemotherapeutic agents. It has been demonstrated that over 50% of this kind of tumors express EGFR (HER-1). Cetuximab is a humanized antiEGFR IgG1 antibody. In colon cancer there are also high percentage of EGFR expression and addition of Cetuximab to chemotherapy results in renewed sensitivity to treatments. We therefore hypothesized that in a similar manner addition of Cetuximab to taxanes which are among the most potent anti breast cancer drugs will result in increased effectiveness in this subset of breast cancer patients. Methods: From January 2007 to January 2009, we treated 12 breast cancer patients with either paclitaxel 80 mg/m2, (10 patients) or docetaxel (30 mg mg/m2) (2 patients), with cetuximab weekly. Patients had a pathology sample of breast cancer with triple negative components, metastatic disease and up to two prior chemotherapy lines in the metastatic settings. Results: Patient characteristics (median): age 60 (31–69) years, prior taxane therapy 9/12 pts. Toxicity: Dermatologic grade 2 9/12 grade 3 3/12, nail disease grade 2 10/12 evaluable patients. One patient developed severe swallowing difficulties after 19 month of therapy which may or may not be linked to the treatment. Response is evaluable for 11/12 patients. Response which includes clinical response, tumor marker decrease, and a metastasis size decrease was noted in 9/11 patients. Including tumor marker normalization and nearly a roentgoenolgic CR in a young patient previously treated with several chemeotherapietic lines. Three patients developed brain metastasis during treatments. Molecular pathology is now performed. We continue accrual. Conclusions: Administration of taxane-cetuximab weekly therapy for triple negative breast cancer patients is possible. Toxicity is the cumulated expected toxicity of each of the agents — special care should be taken for nail disease which occurred in most of the patients. Some impressive clinical responses were obtained even in taxane pretreated patients. [Table: see text]
Variation in DNA Repair Genes XRCC3, XRCC4, and XRCC5 and Risk of Myeloma.
Authors: Patrick Hayden, Prerna Tewari, Anthony Staines, Derek Morris, Dominique Crowley, Alexandra Nieters, Nicholas Becker, Silvia de Sanjose, L. Foretova, Mark Maynardie, Pier Luigi Coco, Paolo Boefetta, Paul Brennan, Paul V. Browne, Mark Lawler
Journal: Blood (2006)
Sigmund Freud - Zum 100. Geburtstag - On his 100th Birthday - Pour son 100e anniversaire
Authors: O.H. Arnold, J. Cremerius, Gustav Hans Graber, E.A.D.E. Carp, Igor A. Caruso, Karl Wucherer-Huldenfeld, R. Laforgue, Oluf Brüel, Jeanne Lampl-De Groot, Charles Baudouin, Berthold Stokvis
Journal: Psychotherapy and Psychosomatics (1956)
LEF-1は慢性リンパ球性白血病における生存促進的因子であり,単クローン性B細胞リンパ球増加症の前白血病状態で発現する
Authors: Gutierrez Albert, C Tschumper Renee, WU Xiaosheng, D Shanafelt Tait, Eckel-Passow Jeanette, Huddleston Paul M., L Slager Susan, E Kay Neil, F Jelinek Diane
Journal: Blood (2010)
The Experience of the International Registry for Chronic Myeloid Leukemia (CML) in Children and Adolescents (I-CML-Ped Study): Pronostic Consideration
Authors: Frédéric Millot, Joelle Guilhot, Meinolf Suttorp, Petr Sedlacek, Eveline S.J.M. de Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Culic Srdjana, Marie-Francoise Dresse, Andrea Biondi, Andre Baruchel
Journal: Blood (2014)