tbuckley/cabot-search huggingface dataset:
Analysis of potential circulating angiogenic biomarkers for bevacizumab in patients with metastatic colorectal cancer.
Authors: Mitsukuni Suenaga, Satoshi Matsusaka, Eiji Shinozaki, Masato Ozaka, Keisho Chin, Mariko Ogura, Toshiharu Yamaguchi, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2014)

e14601 Background: Bevacizumab (BV) plus chemotherapy (chemo) has been shown to improve survival for metastatic colorectal cancer (mCRC). Stromal cell-derived factor-1 (SDF-1) is known as a ligand for CXCR-4. We previously reported that proportion of CXCR4-positive circulating endothelial cells at baseline was correlated with the prognosis of BV plus chemo. The aim of this study was to investigate changes during treatment in serum candidate cytokines including SDF-1 as potential markers of treatment response to BV. Methods: Patients receiving first-line BV plus chemo with mCRC were enrolled in this prospective study. Serum samples were analyzed at pre-treatment and during treatment (on days 14 and 56). Correlation between tumor response and changes in serum levels of the cytokines (such as SDF-1, PDGF, PlGF, etc.) were investigated. Differences in the means of continuous measurements were tested by the Student’s t test. One way analysis of variance (ANOVA) was used to evaluate differences between three measurement points: pre-treatment, day 14 and day 56. Repeated-measures ANOVA was used to evaluate differences between sequential continuous variables. Results: 28 patients were enrolled. Median follow-up time was 352 days. Tumor response was achieved in 53.6% of the patients. SDF-1 levels at pre-treatment (p=0.008) and on days 14 (p=0.002) were significantly lower in tumor responder, while a trend toward higher on days 56 compared to non-responder. The results of one way ANOVA showed significant differences in Ang-1, VEGF-C, PDGF, IL-8, PlGF, and VEGF. Repeated-measures ANOVA to evaluate differences between sequential continuous variables showed significant differences in Ang-1 and -2, VEGF-C, PDGF, IL-8, PlGF, TGF-β and VEGF. SDF-1 was not extracted in these ANOVA. Conclusions: Higher serum levels of SDF-1 at pre-treatment and day 14 might be potential negative predictive surrogate marker. The possibility that sequential continuous variables of serum levels of cytokines reflected anti-angiogenic conditions on BV combined treatment as surrogate markers was suggested.
Amélioration du diagnostic de la métaplasie intestinale gastrique par NBI et magnification: le marqueur de la substance opaque blanche.
Journal: Endoscopy (2017)

La métaplasie intestinale (MI) est un facteur de risque de cancer différencié de l’estomac. La sensibilité de sa détection en lumière blanche est faible, rendant jusqu’alors son diagnostic difficile. La présence d'une crête bleue clair (CBC) à la bordure marginale de l’épithélium des cryptes en NBI avec magnification est un marqueur validé pour le diagnostic endoscopique de la MI.
Molecular and Immunophenotypic Characteristics of Adult Acute Leukemias of Ambiguous Lineage
Authors: Bhumika Patel, Caner Saygin, Bartlomiej P Przychodzen, Cassandra M. Hirsch, Michael J. Clemente, Betty K. Hamilton, Anjali S. Advani, Aziz Nazha, Sarah Lynn Ondrejka, Matt Kalaycio, Mikkael A. Sekeres, Hetty E. Carraway, Jaroslaw P Maciejewski
Journal: Blood (2016)
miR miR on the wall, who’s the most malignant medulloblastoma miR of them all?
Authors: Xin Wang, Borja L Holgado, Vijay Ramaswamy, Stephen Mack, Kory Zayne, Marc Remke, Xiaochong Wu, Livia Garzia, Craig Daniels, Anna M Kenney, Michael D Taylor
Journal: Neuro-Oncology (2017)

microRNAs (miRNAs) have wide-ranging effects on large-scale gene regulation. As such, they play a vital role in dictating normal development, and their aberrant expression has been implicated in cancer. There has been a large body of research on the role of miRNAs in medulloblastoma, the most common malignant brain tumor of childhood. The identification of the 4 molecular subgroups with distinct biological, genetic, and transcriptional features has revolutionized the field of medulloblastoma research over the past 5 years. Despite this, the growing body of research on miRNAs in medulloblastoma has largely focused on the clinical entity of a single disease rather than the molecular subgroups. This review begins by highlighting the role of miRNAs in development and progresses to explore their myriad of implications in cancer. Medulloblastoma is characterized by increased proliferation, inhibition of apoptosis, and maintenance of stemness programs—features that are inadvertently regulated by altered expression patterns in miRNAs. This review aims to contextualize the large body of work on miRNAs within the framework of medulloblastoma subgroups. The goal of this review is to stimulate new areas of research, including potential therapeutics, within a rapidly growing field.
Vaccination Defended against the Attacks of Mr. Brown
Authors: W. Newnham
Journal: BMJ (1842)

a young voman of delicate coIn- stitution and slender frame, after several days com- plaining of lassitude, debility, indispositioif to exertion, and depression of spirits, was seized on the 7th of April with shivering, sickness, pain in the lhead and limbs, stitch in the right side
Mast Cell Leukemia: Clinical Heterogeneity, Molecular Aberrations, Treatment Responses, Survival, and Prognostic Factors
Authors: Mohamad Jawhar, Juliana Schwaab, Manja Meggendorfer, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Torsten Haferlach, Karla Schmitt, Alice Fabarius, Peter Valent, Wolf-Karsten Hofmann, Nicholas C.P. Cross, Georgia Metzgeroth, Andreas Reiter
Journal: Blood (2016)
Association of the polymorphisms of the tandem repeat sequence in the thymidylate synthase gene with tumor stage in colon cancer.
Authors: Samuel Aguiar, Eloisa Olivieri, Dirce Maria Carraro, Celso Lopes Mello, Marcelo Fanelli, Ademar Lopes
Journal: Journal of Clinical Oncology (2013)

e14688 Background: Thymidylate synthase (TS) plays an important role in colorectal carcinogenesis and response to 5FU-based chemotherapy. TS expression can be modified due to polymorphisms in the 5'-untranslated region (5’-UTR) of the gene. The aim of this study is to investigate the association between TS polymorphisms with clinicopathological characteristics of colon carcinomas. Methods: we retrospectively studied 89 individuals with high risk stage II (obstruction, T4 stage, presence of lymphovascular invasion or preoperative CEA &gt; 5.0) and stage III patients submitted to curative intent surgery. DNA was extracted from paraffin embedded tumor tissues and sequenced. The polymorphism studied was the variation of the number of the repeated 28-bp sequences (3 or 2 repeats) of the TS gene 5’-UTR. Results: The frequency of the polymorphisms was: 2R2R in 26 cases (29.2%), 2R3R in 36 cases (40.4%), and 3R3R in 27 cases (30.3%). We did not find associations between the frequencies of these polymorphisms and age, gender, presence of lymphovascular invasion, or level of preoperative CEA. We find a significantly higher proportion of T4 tumors between the 3R3R genotype compared with the 2R2R and 2R3R genotypes (OR=2.69; 95% CI: 1.05 – 6.94; p=0.04). By the other hand, a significantly lower proportion of positive lymph nodes were found among patients with tumors presenting the 3R3R genotype, by comparing with the 2R2R and 2R3R subgroup (OR: 0.28; 95%CI: 0.10 – 0.72; p=0.01). Five-year disease free survival and overall survival were, respectively, 81% and 85% among patients with tumors presenting the 3R3R genotype, and 62% and 67% among patients with tumors presenting 2R2R or 2R3R genotypes. These differences were not statistically significant. Conclusions: in this sample, the TS polymorphic tumor genotype 3R3R was associated with lower risk of lymph node metastases in colon carcinomas.
Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer
Authors: Karim Fizazi, NamPhuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y Alekseev, Mustafa Özgüroğlu, Dingwei Ye, Susan Feyerabend, Andrew Protheroe, Peter De Porre, Thian Kheoh, Youn C Park, Mary B Todd, Kim N Chi
Journal: New England Journal of Medicine (2017)

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival.After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group.The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).
Tailored Approaches for Refined Prognostication in Chronic Lymphocytic Leukemia Patients with Mutated Versus Unmutated Immunoglobulin Receptors
Authors: Panagiotis Baliakas, Theodoros Moysiadis, Anastasia Hadzidimitriou, Aliki Xochelli, Mattias Mattsson, Lesley-Ann Sutton, Eva Minga, Lydia Scarfo, Davide Rossi, Zadie Davis, Andreas Agathangelidis, Neus Villamor, Helen Parker, Jana Kotaskova, Evangelia Stalika, Karla Plevova, Larry Mansouri, Diego Cortese, Alba Navaro Lopez, Julio Delgado, Marta Larrayoz, Emma Young, Achilles Anagnostopoulos, Karin E Smedby, Gunnar Juliusson, Mark Catherwood, Jonathan C Strefford, Niki Stavroyianni, Chrysoula Belessi, Sarka Pospisilova, David Oscier, Gianluca Gaidano, Elias Campo, Paolo Ghia, Richard Rosenquist, Kostas Stamatopoulos, on behalf of ERIC
Journal: Blood (2016)
Targeting chronic myeloid leukemia stem cells with the hypoxia-inducible factor inhibitor acriflavine
Authors: Giulia Cheloni, Michele Tanturli, Ignazia Tusa, Ngoc Ho DeSouza, Yi Shan, Antonella Gozzini, Fréderic Mazurier, Elisabetta Rovida, Shaoguang Li, Persio Dello Sbarba
Journal: Blood (2017)
Approaches for prevention of colon cancer: Role of probiotics
Authors: Seema Nair, Parvathy Varma, Balakrishnan, Vasudevan Dm, Unni Akk
Journal: Clinical Cancer Research (2007)

A4   Lactic Acid Bacteria (LAB) are well known probiotics inhabiting our Gastrointestinal tract, reported to inhibit pathogenic organisms, to stimulate the intestinal immune system and also to produce nutrients such as short-chain fatty acids, vitamins, amino acids, polyamines, growth factors and antioxidants 1 . Recent studies have implicated probiotic bacteria in the prevention of cancers of the colon, modulation of immune function, control of blood cholesterol levels and suppression of allergies 2 . There is evidence that probiotics can interfere at various stages of cancer process such as prevention of DNA damage in the colonic epithelial cells by live bacteria, suppression of pre-neoplastic changes in the colon and suppression of colon tumors in animals 3,4,5 . In the present investigation LAB were isolated from normal and polypoidal human colonic mucosa and characterized for their probiotic potential such as antibacterial activity against enteric pathogens, bile tolerance and acid tolerance. Selected probiotic LAB were studied for their cytotoxicity and adherence capacity to colon cancer cell lines (HCT15) and Intestinal epithelial cell lines (HT29, Caco2). A comparative study of the most efficient anticancerous LAB strains were carried out based on cytotoxicity and bacterial adherence to cell lines. Results show that the anticancerous effect is strain specific. Studies are ongoing to understand the mechanisms of anticancerous activity in individual strains for furthur strain improvement and therapeutic applications. The results provide insights on the optimum probiotic culture and conditions for improved anticancerous potential. Acknowledgements:  Authors wish to acknowledge the financial support from the Science and Engineering Research Council (SERC) of the Department of Science and Technology, Govt. of India.References  Amy C. Brown, Ph.D., R.D. Ana Valiere, M.S. Probiotics and Medical Nutrition Therapy  Nutr Clin Care . 2004 ; 7(2): 56-68.  Daniel C, Roisin H, Colette S, Ian R. The potential mechanisms involved in the anti-carcinogenic action of probiotics  Mutat Res  2005; 591: 276-289  Marteau P, Pochart P, Flourie B .  Effect of chronic ingestion of a fermented dairy product containing  Lactobacillus acidophilus  and  Bifidobacterium bifidum  on metabolic activities of the colonic flora in humans.  Am J Clin Nutr  1990;52:685-688.  Pedrosa MC, Golner BB, Goldin BR, Barakat S, Dallal GE, Russell RM. Survival of yogurt-containingorganisms and  Lactobacillus gasseri  (ADH) and their effect on bacterial enzyme activity in the gastrointestinal tract of healthy and hypochlorhydric elderly subjects.  Am J Clin Nutr  1995;61:353-359.  Orrhage K, Sillerstrom E, Gustafsson JA, Nord CE, Rafter J. Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria.  Mutat Res  1994;311:239-248.
Emerging Data and Current Challenges for Young, Old, Obese, or Male Patients with Breast Cancer
Authors: Rachel A. Freedman, Ann H. Partridge
Journal: Clinical Cancer Research (2017)

There are distinct subgroups of patients who have historically been underrepresented in most prospective clinical trials in breast cancer, including the youngest and oldest patients, male patients, and those struggling with obesity. Herein, we review current and future directions in research for each of these special populations with breast cancer, highlighting significant knowledge gaps and priorities in tumor biology and heterogeneity, therapeutic decision making promotion of adherence, supportive care, and psychosocial and functional well-being. In younger women, future study should focus on the biological underpinnings of aggressive disease and optimizing adherence and treatment decision making while addressing their unique survivorship needs. The latter includes generating a scientific basis for interruption of therapy for pregnancy. Among older patients, interventions should focus on increasing clinical trial accrual, predicting and mitigating toxicity so that functional status can be optimized, tailoring needs for dose modification, and anticipating life expectancy in the context of competing causes of death. For men with breast cancer, we need worldwide collaboration to answer even basic questions on optimal treatment, supportive care, and survivorship strategies. Finally, for those struggling with obesity, we need to better understand the biological associations with cancer incidence, prognosis and outcome, and how we can best intervene to assure weight loss at the "right time." It is only through highly collaborative, far-reaching, prospective, multidisciplinary, patient-centered, and patient-engaged efforts that we can optimize the physical and psychologic outcomes for all patients with breast cancer. Clin Cancer Res; 23(11); 2647-54. ©2017 AACRSee all articles in this CCR Focus section, "Breast Cancer Research: From Base Pairs to Populations."
Sensitive detection of tumor nucleic acids in plasma by mutation-enriched next generation sequencing.
Authors: Andre Marziali
Journal: Journal of Clinical Oncology (2013)

e22041 Background: Next Generation DNA Sequencing (NGS) is becoming the new standard for mutational profiling of tumour tissue, due to its flexibility, speed, and decreasing cost. While generally exceptional in performance, NGS suffers from a sequencing error rate of 0.1% – 1%, largely due to amplification-induced artifacts in its workflow. While this does not constitute a significant problem in application of NGS to sequencing of tumour tissue, it makes NGS impractical as a method to search for low abundance mutation signatures in plasma samples. Numerous publications have shown the presence of tumour signatures in the cell-free DNA (cfDNA) circulating in plasma, but concordance between the tumour signature and the plasma signature has been limited. This is likely due to limitations in the detection technologies used to search for cfDNA in plasma. To maximize concordance between plasma and tissue, it will be essential that sensitivities reaching 0.01% and below (as little as a single tumour mutant allele per sample) be achieved, and ideally that multiple mutational hot spots be analysed to maximize the chance of detection. Current technologies are incapable of such sensitivity over a large number of mutation loci. Methods: We have developed a novel electrophoretic method that can enrich nucleic acid samples over 1,000,000-fold for up to 100 somatic mutations, enabling reliable profiling of samples containing as little as 0.01% mutant. By enriching nucleic acid samples for specific targets prior to amplification and sequencing, we enable the use of NGS in plasma-based mutation detection and profiling. Results: We present technical and clinical data demonstrating highly sensitive multiplexed mutation detection in plasma and tissue samples, demonstrating 0.01% sensitivity over 45 somatic mutations per sample. Conclusions: We have demonstrated a novel somatic mutation enrichment methodology that allows DNA sequencing to work beyond its usual limit of detection to accurately profile solid tumours by detecting their mutation signature in plasma, even when the tumour DNA is present in plasma at abundances below 0.01%.
Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis
Authors: Calum T. Robb, Henry J. McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M. Felton, Nicholas Parkinson, Adane Ayele, Richard M. Breyer, Stephen M. Anderton, Shuh Narumiya, Adriano G. Rossi, Sarah E. Howie, Emma Guttman-Yassky, Richard B. Weller, Chengcan Yao
Journal: Journal of Allergy and Clinical Immunology (2017)
Pluripotent stem cell models of Blau syndrome reveal an IFN-γ–dependent inflammatory response in macrophages
Authors: Sanami Takada, Naotomo Kambe, Yuri Kawasaki, Akira Niwa, Fumiko Honda-Ozaki, Kazuki Kobayashi, Mitsujiro Osawa, Ayako Nagahashi, Katsunori Semi, Akitsu Hotta, Isao Asaka, Yasuhiro Yamada, Ryuta Nishikomori, Toshio Heike, Hiroyuki Matsue, Tatsutoshi Nakahata, Megumu K. Saito
Journal: Journal of Allergy and Clinical Immunology (2017)
Improving childhood cancer care in Latin America and the Caribbean: a PAHO Childhood Cancer Working Group position statement
Authors: Avram Denburg, Cristóbal Cuadrado, Cheryl Alexis, Federico Antillón Klussmann, José Carlos Barrantes Zamora, Curt Bodkyn, Myriam Campbell Bull, Gustavo Dufort y Alvarez, Latoya Gooding, Tezer Kutluk, Silvana Luciani, Jessyca Karina Manner Marcillo, Sandro Martins, Monika Metzger, Anyul Milena Vera, Florencia Moreno, Jabibi Noguera, Armando Pena Hernandez, Karina Quintero Delgado, Michelle-Ann Richards-Dawson, Marcelo Scopinaro, Jaime Shalkow Klincovstein, Corrine Sinquee-Brown, Amaranto Suarez, Julie Torode, Caridad Verdecia, Roberto Franklin Vásquez, Sumit Gupta
Journal: The Lancet Oncology (2017)
Development and Molecular Analysis of Synthetic Lethality By Targeting EZH1 and EZH2 in Non-Hodgkin Lymphomas
Authors: Makoto Yamagishi, Makoto Hori, Dai Fujikawa, Daisuke Honma, Nobuaki Adachi, Takeo Ohsugi, Kazumi Nakano, Makoto Nakashima, Seiichiro Kobayashi, Masako Iwanaga, Atae Utsunomiya, Seiji Okada, Kunihiro Tsukasaki, Kensei Tobinai, Kazushi Araki, Toshiki Watanabe, Kaoru Uchimaru
Journal: Blood (2016)
Richard Paul Hyde Dunnill
Authors: J Alastair Lack
Journal: BMJ (2017)

Richard Dunnill was born in Bexhill, Sussex, where his father was a general practitioner-anaesthetist. He was the youngest of three siblings. He was educated at Charterhouse, Guildford, and then moved on to Guy’s Hospital Medical School to follow in his father’s footsteps. He became a consultant anaesthetist in Poole and Bournemouth in 1977.

At the old Victoria Hospital in Boscombe he established himself as an expert in intensive care. He soon became the lead consultant in …
The High Affinity CXCR4 Inhibitor, BL-8040, Induces Apoptosis of AML Blasts and Their Terminal Differentiation By Blocking AKT/ERK Survival Signals and Downregulating BCL-2, MCL-1 and Cyclin-D1 through Regulation of Mir-15a/16-1 Expression
Authors: Michal Abraham, Shiri Klein, Baruch Bulvik, Hanna Wald, Dvora Holam, Lola Weiss, Katia Beider, Orly Eizenberg, Ori Wald, Abraham Avigdor, Ohad Benjamini, Eithan Galun, Arnon Nagler, Yaron Pereg, Amnon Peled
Journal: Blood (2016)
Predictors of mortality in nursing-home residents with pneumonia: a multicentre study
Authors: M. Falcone, A. Russo, F. Gentiloni Silverj, D. Marzorati, R. Bagarolo, M. Monti, R. Velleca, R. D'Angelo, A. Frustaglia, G.C. Zuccarelli, R. Prina, M. Vignati, M.G. Marnati, M. Venditti, M. Tinelli
Journal: Clinical Microbiology and Infection (2017)
Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura
Authors: Ferras Alwan, Chiara Vendramin, Karen Vanhoorelbeke, Katy Langley, Vickie McDonald, Steve Austin, Amanda Clark, William Lester, Richard Gooding, Tina Biss, Tina Dutt, Nichola Cooper, Oliver Chapman, Tanya Cranfield, Kenny Douglas, H. G. Watson, J. J. van Veen, Keith Sibson, William Thomas, Lynn Manson, Quentin A. Hill, Sylvia Benjamin, Debra Ellis, John-Paul Westwood, Mari Thomas, Marie Scully
Journal: Blood (2017)