tbuckley/cabot-search huggingface dataset:
Predictive biomarkers of invasive carcinoma on excision in patients with a diagnosis of ductal carcinoma in situ of the breast by needle biopsy.
Authors: Miki Mori, Gregor Krings, Loretta Chan, Denise Wolf, Yunn-Yi Chen, Karla Kerlikowske, Thea D. Tlsty, Jean-Philippe Coppe, Naoko Matsuda, Koyu Suzuki, Seigo Nakamura, Laura van't Veer
Journal: Journal of Clinical Oncology (2014)

e12029 Background: DCIS diagnosed on needle biopsy may underestimate the presence of invasive cancer identified on subsequent excision. This study aims to identify clinicopathologic factors from pre-operative needle biopsies that are predictive of invasive cancer on subsequent surgical excision. Methods: The study population consisted of 69 breasts from 67 women initially diagnosed with only DCIS on needle biopsy at St. Luke’s International Hospital, Japan from 2006 until 2008. Parameters analyzed included presenting clinical features, biopsy device, DCIS nuclear grade and morphology, and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67, p16, p53 and cyclooxygenase-2 (COX2) in biopsy specimens. Associations between clinical, pathological, and immunohistochemical findings in initial biopsy specimens and the presence of invasive cancer on subsequent excision were analyzed for significance using univariate and multivariate analysis. Results: Of 69 breasts with only DCIS on initial needle biopsy, subsequent surgical excision revealed pure DCIS in 46 (66.7%) and invasive carcinoma in 23 (33.3%). By univariate analysis, pre-operative factors significantly associated with invasive disease on surgical excision included sampling by core needle biopsy rather than vacuum assisted biopsy (p<0.05), p53 positivity (p<0.01), and low ER expression (p<0.05) in needle biopsy samples. Multivariate analysis revealed two significant independent pre-operative predictors of invasive cancer on final pathology, namely age under 50 (p<0.05) and p53 positivity (p<0.05), with sampling by core needle biopsy trending toward significance (p=0.097). A regression model including age<50, p53 positivity, and sampling method predicted invasive disease with AUC=0.8 in the training set by ROC analysis. Conclusions: Age<50, sampling by core needle biopsy instead of a vacuum assisted device, and p53 positivity were associated .with subsequent invasive cancer on surgical excision. Women with these factors should consider excisional biopsy prior to deciding on definitive treatment.
Prevalence and Dynamics of BCR-ABL Independent Gene Mutations in Patients with Chronic Myeloid Leukemia
Authors: Thomas Ernst, Jenny Rinke, Melinda Busch, Jana Ernst, Ellen Obstfelder, Mathias Schmidt, Vivien Schäfer, Anja Waldau, Nils Winkelmann, Bernd Gruhn, Andreas Hochhaus
Journal: Blood (2016)
PULMONARY HYPERTENSION IS ASSOCIATED WITH A HIGHER RISK OF HEART FAILURE AND MORTALITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE JACKSON HEART STUDY
Authors: Senthil Selvaraj, Sanjiv Shah, Mark Ommerborn, Cheryl Clark, Michael Hall, Robert Mentz, Saadia Qazi, Jeremy Robbins, Jiaying Chen, Thomas Skelton, J. Michael Gaziano, Luc Djousse
Journal: Journal of the American College of Cardiology (2017)
A Phase 1 Study of Nivolumab in Combination with Ipilimumab for Relapsed or Refractory Hematologic Malignancies (CheckMate 039)
Authors: Stephen Ansell, Martin E Gutierrez, Margaret A. Shipp, Douglas Gladstone, Alison Moskowitz, Ivan Borello, Mihaela Popa-Mckiver, Benedetto Farsaci, Lili Zhu, Alexander M. Lesokhin, Philippe Armand
Journal: Blood (2016)
Immunosuppression for Patients with Low and Intermediate Risk Myelodysplastic Syndrome: A Prospective Randomized Multicenter Trial Comparing Antithymocyte Globulin + Cyclosporine with Best Supportive Care: SAKK 33/99.
Authors: Jakob R. Passweg, Aristoteles Giagounidis, Mathew Simcock, Carlo Aul, Christiane Dobbelstein, Michael Stadler, Gert Ossenkoppele, Wolf K. Hofmann, Andre Tichelli, Arnold Ganser
Journal: Blood (2007)
Current Status and Future Potential of Transcatheter Interventions in Congenital Heart Disease
Authors: Damien P. Kenny, Ziyad M. Hijazi
Journal: Circulation Research (2017)

Percutaneous therapies for congenital heart disease have evolved rapidly in the past 3 decades. This has occurred despite limited investment from industry and support from regulatory bodies resulting in a lack of specific device development. Indeed, many devices remain off-label with a best-fit approach often required, spurning an innovative culture within the subspecialty, which had arguably laid the foundation for many of the current and evolving structural heart interventions. Challenges remain, not least encouraging device design focused on smaller infants and the inevitable consequences of somatic growth. Data collection tools are emerging but remain behind adult cardiology and cardiac surgery and leading to partial blindness as to the longer-term consequences of our interventions. Tail coating on the back of developments in other fields of adult intervention will soon fail to meet the expanding needs for more precise interventions and biological materials. Increasing collaboration with surgical colleagues will require development of dedicated equipment for hybrid interventions aimed at minimizing the longer-term consequences of scar to the heart. Therefore, great challenges remain to ensure that children and adults with congenital heart disease continue to benefit from an exponential growth in minimally invasive interventions and technology. This can only be achieved through a concerted collaborative approach from physicians, industry, academia, and regulatory bodies supporting great innovators to continue the philosophy of thinking beyond the limits that has been the foundation of our specialty for the past 50 years.
Absence of Band 3 in Severe Dyserythropoietic/Hemolytic Anemia with Complete Distal Renal Acidosis and a Novel Homozygous Exon 12 C.1430C&gt;a (p.Ser477X) SLC4A1 Gene Mutation
Authors: Leo Kager, Lesley J Bruce, Joanna F Flatt, Petra Zeitlhofer, Gerhard Fritsch, Bernhard Fahrner, Oskar A. Haas
Journal: Blood (2015)
INVESTIGATION OF NOVEL DRUG TARGETS IMPLICATED IN HIGH-DOSE STATIN THERAPY FROM YELLOW-II TRIAL: TOWARDS PERSONALIZED LIPID LOWERING THERAPIES
Authors: Annapoorna Subhash Kini, Khader Shameer, Yuliya Vengrenyuk, Benjamin Glicksberg, Kipp Johnson, Aparna Divaraniya, Ben Readhead, Meerarani Purushothaman, Brian Kidd, Samin Sharma, Jagat Narula, Joel Dudley
Journal: Journal of the American College of Cardiology (2017)
ACTIVATING STIMULI MODULATE PRE-MRNA MATURATION IN PLATELETS: A NOVEL MECHANISM THAT REGULATES PLATELET FUNCTION?
Authors: Giovanni Cimmino, Roberta Tarallo, Giovanni Nassa, Giorgio Giurato, Stefano Conte, Grazia Pellegrino, Giuseppina Bruno, Francesca Rizzo, Luca Ricciardi, Annamaria Salvati, Giovanna Marchese, Plinio Cirillo, Alessandro Weisz, Paolo Golino
Journal: Journal of the American College of Cardiology (2017)
Asia-Pacific colorectal screening score and colorectal cancer screening in asymptomatic Asian population.
Authors: Joseph JY Sung, Hyun S Kim, Khean Lee Goh, Jose Sollano, Khay Guan Yeoh, Han Mo Chiu, Deng Chiang Wu, Rungsun Rerknimitr, Takahisa Matsuda, Vui Heng Chong, Furqaan Ahmed, Jingnan Li, Rupert Leong, Kelvin KF Tsoi, Martin CS Wong
Journal: Journal of Clinical Oncology (2014)

3545 Background: There has been a rapid rise in colorectal cancer (CRC) incidence in recent decades in many Asian countries. Age, gender, smoking, and family history are the significant risk factors of CRC. This study would like to develop an Asia-Pacific Colorectal Screening (APCS) score to identify subjects with high-risk for colorectal advanced neoplasia (AN) in Asia. Methods: A multicentre study was in 11 Asian cities. A total of 7,463 asymptomatic subjects underwent screening colonoscopy. The first 2,000 subjects were used as a derivation cohort. AN was defined as advanced adenoma and CRC. A multiple logistic regression was applied to the derivation cohort identifying significant risk factors for AN; odds ratios of significant risk factors were then utilized to develop APCS score ranging from 0-6, including age (0=40-49, 1=50-59, 2=60+), gender (0=female, 1=male), family history (0=absent, 1=present), smoking (0=no, 1=current or past), and Body Mass Index (BMI) (0= <23kg/m2, 1= >23kg/m2). Three tiers of risk were defined: 0 ‘average risk’ (AR); 1-3 ‘moderate risk’ (MR); and 4–6 ‘high risk’ (HR). The APCS score was applied to the validation cohort as performance assessment. Results: The baseline prevalence of AN were 4.9% and 5.4% in the derivation and validation cohorts. In the validation cohort, 110 subjects (2.0%) were in AR, 4,148 subjects (75.9%) in MR, and 1,205 (22.1%) subjects in HR. Prevalence of AN in AR, MR and HR were 0.9%, 4.1% and 10.5% respectively. Compared with AR, subjects in MR and HR had 4.5-fold and 11.5-fold increased prevalence of AN. Conclusions: The APCS score based on age, gender, family history, smoking and BMI is a useful tool in stratifying asymptomatic Asians for priority of CRC screening.
Abstract 15505: Elevated Plasma Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and Myeloperoxidase in Patients With Takotsubo Cardiomyopathy
Authors: Tsukasa Matsushita, Yoshiki Matsumura, Tomotaka Yoshiyama, Kenji Shimeno, Ryo Matsumoto, Yukio Abe, Kimio Kamimori, Takahiko Naruko, Kenichi Sugioka, Masashi Nakagawa, Minoru Yoshiyama, Makiko Ueda
Journal: Circulation (2016)

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) are recognized as a useful biomarker for acute coronary syndrome. In addition, myeloperoxidase (MPO), a member of the heme peroxidase superfamily, may play a key role in plaque instability. The aim of this study was to compare plasma sLOX-1 and MPO levels between TC patients and patients with coronary artery disease.

Methods: Plasma sLOX-1 and MPO levels were measured in patients with TC (n=30), stable angina pectoris (SAP, n=66) and unstable angina pectoris (UAP, n=72) using a sandwich ELISA method.

Results: Plasma sLOX-1 levels and MPO levels were significantly higher in TC patients compared with SAP patients ( P <0.0001) or UAP patients ( P <0.01). In TC patients, plasma sLOX-1 levels were positively correlated with neutrophil count and NT-BNP levels (neutrophil count, R=0.49, P<0.01; NT-BNP, R=0.69, P<0.0002). Moreover plasma sLOX-1 levels were positively correlated with plasma MPO levels (R=0.53, P=0.0053). However they were not correlated with serum C-reactive protein levels. Additionally, there was a tendency for plasma sLOX-1 levels to be negatively correlated with left ventricular ejection fraction (R=0.38, P=0.052).

Conclusions: This study demonstrates for the first time that plasma sLOX-1 levels and MPO levels, two markers of oxidative stress, are elevated in TC patients compared with SAP and UAP patients. These findings strongly suggest that oxidative stress plays an important role in the pathophysiology of Takotsubo cardiomyopathy.
INCREMENTAL UTILITY OF CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY BEYOND CORONARY ARTERY CALCIUM SCORING FOR PREDICTING MAJOR ADVERSE CARDIAC EVENTS ACCORDING TO IMPAIRED RENAL FUNCTION: THE CONFIRM REGISTRY
Authors: Ji Hyun Lee, Mahn Won Park, Briain O. Hartaigh, Asim Rizvi, Donghee Han, Hadi Mirhedayati Roudsari, Subhi Al'Aref, Khalil Anchouche, Ashley Beecy, Heidi Gransar, Hyung Bok Park, Jessica M. Peña, James Min, Fay Lin
Journal: Journal of the American College of Cardiology (2017)
CARDIO-FEMORAL VASCULAR INDEX: A NEW MARKER OF ARTERIAL AGING
Authors: Timothy S. Phan, Harry Garett Oldland, Khuzaima Javaid, Uzma Kewan, Izzah Vasim, Swapna Varakantam, Scott R. Akers, Julio A. Chirinos
Journal: Journal of the American College of Cardiology (2017)
Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk Factors and Scope of the Problem
Authors: Adam L. Green, Elissa Furutani, Karina Braga Ribeiro, Carlos Rodriguez Galindo
Journal: Journal of Clinical Oncology (2017)

Purpose Despite advances in childhood cancer care, some patients die soon after diagnosis. This population is not well described and may be under-reported. Better understanding of risk factors for early death and scope of the problem could lead to prevention of these occurrences and thus better survival rates in childhood cancer. Methods We retrieved data from SEER 13 registries on 36,337 patients age 0 to 19 years diagnosed with cancer between 1992 and 2011. Early death was defined as death within 1 month of diagnosis. Socioeconomic status data for each individual's county of residence were derived from Census 2000. Crude and adjusted odds ratios and corresponding 95% CIs were estimated for the association between early death and demographic, clinical, and socioeconomic factors. Results Percentage of early death in the period was 1.5% (n = 555). Children with acute myeloid leukemia, infant acute lymphoblastic leukemia, hepatoblastoma, and malignant brain tumors had the highest risk of early death. On multivariable analysis, an age younger than 1 year was a strong predictor of early death in all disease groups examined. Black race and Hispanic ethnicity were both risk factors for early death in multiple disease groups. Residence in counties with lower than median average income was associated with a higher risk of early death in hematologic malignancies. Percentages of early death decreased significantly over time, especially in hematologic malignancies. Conclusion Risk factors for early death in childhood cancer include an age younger than 1 year, specific diagnoses, minority race and ethnicity, and disadvantaged socioeconomic status. The population-based disease-specific percentages of early death were uniformly higher than those reported in cooperative clinical trials, suggesting that early death is under-reported in the medical literature. Initiatives to identify those at risk and develop preventive interventions should be prioritized.
Avoidance of On-Target Off-Tumor Activation Using a Co-stimulation-Only Chimeric Antigen Receptor
Authors: Jonathan Fisher, Pierre Abramowski, Nisansala Dilrukshi Wisidagamage Don, Barry Flutter, Anna Capsomidis, Gordon Weng-Kit Cheung, Kenth Gustafsson, John Anderson
Journal: Molecular Therapy (2017)

Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR. An anti-GD2 CAR containing a solitary endodomain derived from the NKG2D adaptor DAP10 was expressed in Vγ9Vδ2+ T cells. Differential ligation of the CAR and/or TCR using antibody-coated beads showed that pro-inflammatory cytokine response depended on activation of both receptors. Moreover, in killing assays, GD2-expressing neuroblastoma cells that engaged the Vγ9Vδ2 TCR were efficiently lysed, whereas cells that expressed GD2 equivalently but did not engage the Vγ9Vδ2 TCR were untouched. Differentiation between X-on tumor and X-off tumor offers potential for safer immunotherapy and broader target selection. Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR. An anti-GD2 CAR containing a solitary endodomain derived from the NKG2D adaptor DAP10 was expressed in Vγ9Vδ2+ T cells. Differential ligation of the CAR and/or TCR using antibody-coated beads showed that pro-inflammatory cytokine response depended on activation of both receptors. Moreover, in killing assays, GD2-expressing neuroblastoma cells that engaged the Vγ9Vδ2 TCR were efficiently lysed, whereas cells that expressed GD2 equivalently but did not engage the Vγ9Vδ2 TCR were untouched. Differentiation between X-on tumor and X-off tumor offers potential for safer immunotherapy and broader target selection.
Predictive value of CTCs biomarkers status in patients with metastatic breast cancer (MBC) receiving anti-HER2 therapy.
Authors: Zefei Jiang, Lei Li, Shaohua Zhang, Tao Wang, Yi Liu, Li Bian, Yang Yuan, Fan Qi, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2014)

628 Background: The value of circulating tumor cells (CTCs) enumeration has been widely accepted, but the predictive value of enumeration and the detection of HER-2 expression in CTCs (CTCs-HER2) in patients with HER2 positive disease treated with HER-2 targeted therapy has still not been prospectively demonstrated. Methods: One hundred one HER-2 positive (IHC HER2+++ or FISH+) patients were enrolled from Oct 2010 to Nov 2013. All of the patients received a new line of treatment with chemotherapy plus trastuzumab or lapatinib. CTC isolation, enumeration and characterization were performed by using the CellSearch technology. HER2 expression intensity in CTC was given a score of 0, 1+, 2+, or 3+, according to the trial we have conducted previously, the CTCHER2 positive criterion was defined as >30% of CTCs over-expressing HER2 (3+). Hormone receptor positive(HR+) was defined as ER or PR positive and hormone receptor negative(HR-) was defined as ER or PR negative. Results: 56(55.4%) out of 101 patients were detected with CTC≥1. For the patients who detected CTC, 29(51.8%) patients were CTCHER2-positive, 27(48.2%) were CTCHER2-negative. There was a statistically difference in PFS between the groups of CTCHER2-positive and the CTCHER2-negative (P=0.014). For the patients with ≥5 CTC, HR- patients benefit a longer PFS compared with HR+ patients (7m vs 4m). The PFS for CTCHER2-positive and hormone receptor negative patients versus CTCHER2- negative and hormone receptor positive patients were 8.5 months versus 2.5 months(P=0.003). Conclusions: This analysis demonstrates that the baseline enumeration of CTC for HER2 positive MBC patients with different HR statuses who received chemo plus anti-HER2 therapy lacks of predictive value, whereas the detection of baseline CTCHER2 status is associated with significant prediction of therapeutic benefit. Moreover, the CTCHER2 positive and HR- patients can benefit most from chemo plus anti-HER2 therapy. Routine CTCs biomarkers assessment should be prospectively evaluated in patients candidates for molecularly targeted therapies.
Synergistic Anti-Tumor Effect of KPT-8602, a Second Generation Selective Inhibitor of Nuclear Export (SINE) Compound, and Panobinostat, a Pan-Histone Deacetylase (HDAC) Inhibitor in Multiple Myeloma
Authors: Christian Argueta, Hua Chang, Trinayan Kashyap, Sivan Elloul, Sharon Friedlander, Margaret S. Lee, Michael Kauffman, Sharon Shacham, William Senapedis, Erkan Baloglu
Journal: Blood (2016)
CD34+ Selected Cells "Boost" for Poor Graft Function Post Allogeneic Stem Cell Transplantation
Authors: Razan Mohty, Annalisa Ruggeri, Giorgia Battipaglia, Florent Malard, Eolia Brissot, Ramdane Belhocine, Sandra Eder, Federica Giannotti, Remy Dulery, Mohamad Mohty
Journal: Blood (2016)
In vivo activity of rituximab-CpG oligodeoxynucleotide conjugate against rituximab-resistant human CD20+ B-cell lymphoma
Authors: J. Timmerman, D. Betting, R. Yamada, S. Hurvitz, K. Steward, J. Said, N. van Rooijen, K. Kafi
Journal: Journal of Clinical Oncology (2009)

8529 Background: The anti-CD20 monoclonal antibody rituximab (R) is a mainstay in the treatment of B cell non-Hodgkin's lymphoma (NHL), exerting anti-tumor effects via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and apoptosis induction. Toll-like receptor 9 agonist CpG oligodeoxynucleotides (CpG) are potent activators of ADCC and T cell immunity, and have been studied for anti-NHL effects when administered by systemic or intratumoral routes. We sought to optimize the delivery of CpG to sites of NHL to improve R efficacy. Methods: We utilized an aggressive syngeneic human CD20-expressing murine B cell lymphoma (38C13-huCD20) to study the in vivo augmentation of R efficacy by CpG. Established tumors in immunocompetent mice were treated with R plus CpG given systemically, intratumorally, or chemically linked to antibody using maleimide-sulfhydryl chemistry (D. Betting et al, J. Immunol. 2008; 181: 4131). Results: 5- to 7-day established tumors were completely resistant to single agent R. Combining intratumoral, but not systemic administration of CpG with R resulted in tumor eradication from up to 42% of mice (p &lt; 0.0003 vs. R alone, CpG alone, R + systemic CpG). Mechanistic studies indicated that both natural killer cells and complement participated in the cure of tumors by intratumoral CpG + R, by increasing tumor cell sensitivity to complement and ADCC lysis, and by augmenting the cytotoxicity of ADCC effectors. To overcome the need for repeated direct intratumoral injections and allow precise targeting of CpG to tumor cells, we chemically linked CpG to R using a cleavable linker. A single i.v. injection of this R-CpG conjugate achieved eradication of established tumors from 100% of mice. In contrast, equivalent doses of unlinked i.v. R + CpG, CpG alone, or R alone cured only 8% of mice. Thus, combining CpG with R was most effective using direct conjugation to the antibody. Conclusions: In conclusion, enhancement of R efficacy required sustained intratumoral delivery of CpG to maximize anti-tumor responses. R-CpG conjugate efficiently eradicated an established B cell lymphoma that is fully resistant to single-agent R. Clinical testing of anti-CD20-CpG conjugates against B cell NHL is thus warranted. [Table: see text]
Inhibition of Sialic Acid Loss Greatly Improves Survival of Refrigerated Platelets
Authors: Gerard Jansen, Emma C Josefsson, Qiyong Peter Liu, Viktoria Rumjantseva, Herve Falet, Renata Grozovsky, Wolfgang Bergmeier, Denisa D. Wagner, John H. Hartwig, Karin M. Hoffmeister
Journal: Blood (2011)