tbuckley/cabot-search huggingface dataset:
Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness
Authors: H. Gilbert Welch, Philip C. Prorok, A. James O’Malley, Barnett S. Kramer
Journal: New England Journal of Medicine (2016)

The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time.We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002).After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality.Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.
Phosphoglycerate Kinase Deficiency: Characterization of the Wild-Type Enzyme and Three Pathological Variants Generated from C.140T&amp;gt;a, C.491A&amp;gt;T and C.959G&amp;gt;a Mutations
Authors: Simone Morera, Laurent Chiarelli, Stefano Rovida, Paola Bianchi, Elisa Fermo, Alessandro Galizzi, Alberto Zanella, Giovanna Valentini
Journal: Blood (2008)
Erythrocytes as autologous-vaccine carriers in advanced prostate cancer
Authors: E. M. Lasalvia-Prisco, E. Garcia-Giralt, E. M. Lasalvia-Galante, J. Vázquez, S. Cucchi, G. Spera, J. P. Valentine
Journal: Journal of Clinical Oncology (2008)

14017 Background: Malignant tumors condition sentinel lymph nodes to produce permissive immune responses. This local-regional conditioning is decisional because it starts also permissive systemic immunity (Cochran 2006). In some cancer vaccine platforms, immunomodulatory adjuvants counteract this mechanism of tumor progression switching the cell population profile of vaccine sentinel lymph node (VSLN) from permissive to protective (Disis 1996). GM-CSF and etoposide (ETP) showed this activity in the VSLN of a subcutaneous immunotherapeutic site (ITS) where autologous thermostable hemoderivative cancer vaccine (ATH-CV) was also injected (Lasalvia-Prisco 2007). In advanced prostate cancer, we explored to optimize the delivery of ATH-CV to the conditioned VSLN using autologous erythrocytes (AE) as carriers emulating other demonstrated models (Chiarantini 1997). Methods: Thirty M1 prostate cancer patients (Pts), hormone and chemotherapy resistant, performance status ≤2, PSA rising level, were included in this Helsinki Declaration compliant phase I/II trial and 3-group randomized: G1, no additional treatment; G2, ITS with (ATH-CV)+(GM-CSF)+ETP; G3, ITS with ATH-CV encapsulated in AE as it was described (Ihler 1973)+(GM-CSF)+ETP. The procedures were repeated each 30 days, 4 times; 180-day follow-up; end point 180th day. Assessments were performed at 1st and 180th day: (a) delayed hypersensitivity test (DHT) and lymphocyte proliferation assay (LPA) elicited with pre-treatment ATH-CV, (b) 30-day PSA increase and tumor growth. Groups were statistically compared (Student t-test). CTCAE toxicity was assessed. Results: Post-treatment Increase of cases DHT>5mm (G1=0, G2=4, G3=6) and LPA>2.00 (G1=1, G2=5, G3=8) were significantly higher in G2 vs G1 (p<.02, p<.03), G3 vs G2 (p<.05, p<.03). Post-treatment variation (%) of 30-day PSA increase (+8,−16,−34) and tumor growth (+6,−22,−38) were significantly higher in G2 vs G1 (p<.01, p<.01, G3 vs G2 (p<.03, p<.02). No significant toxicity (>2) was registered. Conclusions: In advanced prostate cancer, all other treatments exhausted, the sensitization and tumor anti-progressive effect of ITS with GM-CSF, ETP and ATH-CV were safely potentiated if ATH-CV is carried by autologous erythrocytes. No significant financial relationships to disclose.
GW27-e0695 Value of Tei index and Brain Natriuretic Peptide on Predicting long-term Outcome in Ischemic Cardiomyopathy Patients
Authors: Chang Xuewei, Huifang Ma, Liping Tian, Yidong Wei, Jinghan Wei, Shouyan Zhang
Journal: Journal of the American College of Cardiology (2016)
Adoption of new breast cancer therapies: Is evidence important?
Authors: M. Morrow, J. J. Graff, S. J. Katz
Journal: Journal of Clinical Oncology (2008)

629 Background: The rapid pace of breast cancer research complicates the definition of what treatment options constitute standard therapy. Methods: We surveyed a population-based sample of surgeons from the LA and Detroit SEER registries using case scenarios for breast cancer management. Surgeons defined treatment preferences as strong, moderate, or weak. Therapies were classified as standard if supported by prospective randomized trials. The response rate was 74%. Results from LA are presented here (n=188) and will be updated to include Detroit. Results: See table below. There were no consistent associations between surgeons endorsement of unproven therapies and surgeon characteristics (% practice devoted to breast), practice characteristics (University affiliation, NCI cancer center or American College of Surgeons cancer program status), or delivery system factors such as collaborative clinician communication. Conclusions: We observed wide variation in preference for therapies supported by high quality evidence, coupled with enthusiasm for nonstandard therapies expressed by a significant minority of surgeons. These findings suggest the need for educational strategies that place greater emphasis on the level of evidence supporting standard therapies and less emphasis on what is promising but unproven. Proven Therapies % Strong/Moderate Preference BCT for T1 cancer 97 BCT for T2 cancer 85 Tamoxifen in ER+DCIS 87 RT for 1.2 cm DCIS 82 PMRT, T2 tumor 3 pos nodes 58 Neoadjuvant Ctx to allow BCT for T2 cancer 47 Unproven Therapies No axillary surgery for SN metastasis detected on permanent section 18 Partial breast irradiation for DCIS 18 SN biopsy after neoadjuvant Ctx 69 No significant financial relationships to disclose.
MicroRNA expression in paternal and cisplatin-resistant germ cell tumor cell lines.
Authors: C. Ruf, M. Port, F. Honecker, S. Glaesener, A. Riecke, V. Meineke, C. Bokemeyer, M. Abend
Journal: Journal of Clinical Oncology (2010)

e15029 Background: Resistance to chemotherapy is a potentially deadly and so far poorly understood event in germ cell tumors (GCT). To improve our knowledge on resistance to cisplatin (CDDP) in GCT, we compared the constitutive miRNA gene expression pattern in three CDDP resistant and corresponding paternal GCT cell lines. Methods: Three CDDP resistant cell lines were derived via long term culture under increasing concentrations of CDDP from well established GCT lines (NT2, NCCIT, 2102EP). CDDP resistance was determined using MTT assy. Total RNA was isolated from all 6 cell lines in three independent experiments. Aliquots of individual total RNA were reverse transcribed without preamplification using the so called “Megaplex pools without preamplification protocol for miRNA expression analysis protocol”. RTQ-PCR was performed using two different 384 well low density arrays covering about 800 known miRNA species of human origin. Statistical measures (e.g. coefficient of variation, CV, and 25-75% quantiles) were computed using SAS. Results: CDDP resistance significantly increased in resistant cell lines (range 5-11 fold). In total, 72 genes showed differential expression between paternal and resistant cell lines (NT2=43, NCCIT=53, 2102EP=15), of which 73% (on average) were up- regulated (NT2=95.3%, NCCIT=62.3%, 2102EP=46.7%). One single miRNA, miR-10b, showed 2-3 fold upregulation in all three resistant cell lines. Previously, miR-10b has been associated with cancer progression. miR-371, miR-372, and miR-373 pre-373, which have been identified as oncogenes in GCT, were upregulated in NT2 and NCCIT, but not in 2102EP. Conclusions: To our knowledge, this is the first report on differential expression of miRNAs in CDDP resistent GCT cell lines. Constitutive miRNA gene expression revealed many similarities between NT2 and NCCIT cell lines, whereas 2102EP differed. No significant financial relationships to disclose.
Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer
Authors: Hyun-seok Kim, Christopher B. Umbricht, Peter B. Illei, Ashley Cimino-Mathews, Soonweng Cho, Nivedita Chowdhury, Maria Cristina Figueroa-Magalhaes, Catherine Pesce, Stacie C. Jeter, Charles Mylander, Martin Rosman, Lorraine Tafra, Bradley M. Turner, David G. Hicks, Tyler A. Jensen, Dylan V. Miller, Deborah K. Armstrong, Roisin M. Connolly, John H. Fetting, Robert S. Miller, Ben Ho Park, Vered Stearns, Kala Visvanathan, Antonio C. Wolff, Leslie Cope
Journal: Journal of Clinical Oncology (2016)

Purpose Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor-positive, lymph node-negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and Methods We retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS was similar across sites and to reported clinical practice experience and stable over time. Histopathologic markers alone determined risk category with > 95% confidence in > 55% (616 of 1,113) of cases. Application of the integrated decision model to one site indicated that the frequency of testing would not have changed overall, although ordering patterns would have changed substantially with less testing of estimated clinical risk-high or clinical risk-low cases and more testing of clinical risk-intermediate cases. In the validation set, the model correctly predicted risk category in 52.5% (248 of 472). Conclusion The proposed model accurately predicts high- and low-risk RS categories (> 25 or ≤ 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.
GW27-e0567 Elevation in blood flow and shear stress attenuates endothelial barrier disruption induced by Oxidized Low-Density Lipoprotein
Authors: Zhang Yan, Xiaohong He, Yanling Li, Tingting Zhong, Donghong Liu, Xiaolin Chen, Yafei Jin, Hong Ma, Zhimin Du, Yugang Dong, William E. Lawson, John C.K. Hui, Zhensheng Zheng, Yan Zhang
Journal: Journal of the American College of Cardiology (2016)
Lifetime Duration of Depressive Disorders in Patients With Type 2 Diabetes
Authors: Mary de Groot, Kent A. Crick, Molly Long, Chandan Saha, Jay H. Shubrook
Journal: Diabetes Care (2016)

Depression in patients with type 2 diabetes (T2D) is associated with long-term complications, disability, and early mortality. No studies have systematically examined the length of episodes and remission in adults with major depressive disorder (MDD) and T2D. This study examined the course of depressive disorders in patients with T2D and MDD.Participants (N = 50) enrolled in a behavioral intervention for adults with T2D and MDD were interviewed using the Structured Clinical Interview for DSM-IV-TR to assess history of depressive disorders at baseline (lifetime history), postintervention, and 3-month follow-up. Onset and remission dates were recorded for all Axis I depressive disorders from birth to final interview.Average number of MDD episodes was 1.8 with a mean duration of 23.4 months (SD 31.9; range 0.5-231.3). Over the life course, mean exposure to MDD was 43.1 months (SD 46.5; range 0.5-231.3). Kaplan-Meier survival curve analysis indicated median episode duration decreased with subsequent episodes (14 months, first episode; 9 months, second episode; P < 0.002). In patients with multiple depressive episodes, recovery time was shorter with each subsequent episode (P = 0.002). No differences in length of episode or remission were observed based on chronology of T2D diagnosis.The overall exposure to depression in this sample of adults with T2D represents a substantial period of time that can contribute to negative medical and psychiatric outcomes. Recurrent episodes decrease in duration as do recovery periods, resulting in a waxing and waning pattern. Findings from this study underscore the need to effectively diagnose and treat depression in patients with T2D to minimize risk of future depressive episodes.
Genz-112638 for Gaucher Disease Type 1: Phase 2 Clinical Trial Results After 18 Months of Treatment.
Authors: Judith Peterschmitt, Elena Lukina, Nora Patricia Watman, Elsa Avila Arreguin, Maryam Banikazemi, Gregory Pastores, Marcelo Iastrebner, Marta Dragosky, Hanna Rosenbaum, Mici Phillips, Mathilde Kaper, Tejdip Singh, Ana Cristina Puga
Journal: Blood (2009)
The PTPN22 R620W Polymorphism Is Not Associated With Clinical and Molecular Correlates Of Chronic Lymphocytic Leukemia (CLL) In Patients Originating From a Region With Low Prevalence Of The Autoimmunity Risk Variant
Authors: Irina Panovska-Stavridis, Sanja Trajkova, Aleksandar Eftimov, Martin Ivanovski, Dusko Dukovski, Popova-Simjanovska Marija, Staninova Marija, Lidija Cevreska, Aleksandar Dimovski
Journal: Blood (2013)
Incidence of the JAK2V617F Mutation In Mexican Patients with Myeloproliferative Neoplasms (MPNs)
Authors: Gregorio Ignacio, Rosa María Arana-Trejo, Verónica Gónzalez, Maria Paula Hérnandez, Yolanda Lugo, Luis Solis, Jesús Castellanos, Samuel Celestino, Carlos Váldez, Ramón Rivas
Journal: Blood (2011)
Linguistic representations and memory architectures: The devil is in the details
Authors: Dustin Alfonso Chacón, Shota Momma, Colin Phillips
Journal: Behavioral and Brain Sciences (2016)

Abstract Attempts to explain linguistic phenomena as consequences of memory constraints require detailed specification of linguistic representations and memory architectures alike. We discuss examples of supposed locality biases in language comprehension and production, and their link to memory constraints. Findings do not generally favor Christiansen &amp; Chater's (C&amp;C's) approach. We discuss connections to debates that stretch back to the nineteenth century.
Allogeneic Stem Cell Transplantation Induces Long Term Survival in Pateitns with Advanced Chronic Myeloid Leukaemia:A Study of the British Society for Blood and Marrow Transplantation,
Authors: Gordon Cook, Keiren Kirkland, Julia Lee, Rachel M Pearce, Jane F Apperley, Richard E. Clark, Stephen Mackinnon, David I. Marks
Journal: Blood (2011)
GW27-e0556 Clinical impact of circulating miR-208b, miR-499 and miR-378 in acute myocardial infarction
Authors: Sayed Ali Sheikh, Ke Xia, Fei Li, Peng Liming, Xiaoxiao Mao, Umme Salma, Jun Peng, TianLun Yang
Journal: Journal of the American College of Cardiology (2016)
TCT-337 Intravascular Assessment of Arterial Diseases using Compensated Optical Coherence Tomography: Proof-of-Concept with Comparison with Histology
Authors: Renick D. Lee, Nicolas Foin, Fumiyuki Otsuka, None philip wong, Jean Martial Mari, Michael Joner, Michael J. Girard, Renu Virmani
Journal: Journal of the American College of Cardiology (2015)
Gene Expression Profile in the CML Cell Line K562 Treated with SKI-606, a Dual Inhibitor of Src/Abl Kinase.
Authors: Matteo Renzulli, Tiziana Grafone, Cristian Taccioli, Carolina Terragna, Frank Boschelli, Manuela Mancini, Pasquale Creo, Emanuela Ottaviani, Sabrina Colarossi, Marilina Amabile, Simona Soverini, Angela Poerio, Ilaria Iacobucci, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2005)
PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma
Authors: Xi-wen Bi, Hua Wang, Wen-wen Zhang, Jing-hua Wang, Wen-jian Liu, Zhong-jun Xia, Hui-qiang Huang, Wen-qi Jiang, Yu-jing Zhang, Liang Wang
Journal: Journal of Hematology & Oncology (2016)

Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively. Latent membrane protein 1 (LMP1)-harboring lentiviral vectors were transfected into NK-92 cells to examine the correlation between LMP1 and PD-L1 expression. Proteins in the downstream pathways of LMP1 signaling were measured in NK-92 cells transfected with LMP1-harboring or negative control vectors as well as in SNK-6 cells. PD-L1 expression on tumor specimens and serum concentration of soluble PD-L1 were collected in a retrospective cohort of patients with Ann Arbor stage I~II NKTCL, and their prognostic significance were analyzed. Expression of PD-L1 was significantly higher in SNK-6 cells than in NK-92 cells, at both protein and mRNA levels. Expression of PD-L1 was remarkably upregulated in NK-92 cells transfected with LMP1-harboring lentiviral vectors compared with those transfected with negative control vectors. Proteins in the MAPK/NF-κB pathway were upregulated in LMP1-expressing NK-92 cells compared with the negative control. Selective inhibitors of those proteins induced significant downregulation of PD-L1 expression in LMP1-expressing NK-92 cells as well as in SNK-6 cells. Patients with a high concentration of serum soluble PD-L1 (≥3.4 ng/ml) or with a high percentage of PD-L1 expression in tumor specimens (≥38 %) exhibited significantly lower response rate to treatment and remarkably worse survival, compared with their counterparts. A high concentration of serum soluble PD-L1 and a high percentage of PD-L1 expression in tumor specimens were independent adverse prognostic factors among patients with stage I~II NKTCL. PD-L1 expression positively correlated LMP1 expression in NKTCL, which was probably mediated by the MAPK/NF-κB pathway. PD-L1 expression in serum and tumor tissues has significant prognostic value for early-stage NKTCL.
Changes in FDG- and FLT-PET imaging in patients with non-small cell lung cancer (NSCLC) following treatment with erlotinib (E).
Authors: L. R. Mileshkin, B. G. Hughes, P. Mitchell, V. Charu, B. J. Gitlitz, D. Macfarlane, W. Yu, A. Pirzkall, R. Hicks, B. M. Fine
Journal: Journal of Clinical Oncology (2010)

7567 Background: Assessing the efficacy of molecularly targeted agents, especially in the absence of tumor shrinkage, remains a challenge. The primary objective of this prospective international trial was to evaluate whether on-treatment 18F-deoxyglucose (FDG) and 18F-deoxythymidine (FLT) PET responses predict improved progression-free (PFS) and overall survival (OS) following treatment of 2nd/3rd line NSCLC with E, an epidermal growth factor receptor (EGFR) inhibitor. Methods: Study assessments included FDG- and FLT-PET/CT imaging at baseline (BL), d14 and d56, and diagnostic CT at BL and d56. Detailed uniform protocols were applied for image acquisition and analysis. PET and CT response were determined by central review. Up to 5 target lesions that met RECIST 1.0 and were FDG avid (SUVmax > 2.5) were identified in each pt at BL. Based on EORTC PET response guidelines, partial metabolic response (PMR) was defined as mean decrease >15% in SUVmax across all target lesions. PFS was investigator determined. Results: From October 2006-April 2009, 51 patients (pts) at 8 sites in Australia and United States were treated on study with E at 150 mg PO QD and completed all assessments through d56. Of these 51 pts, 4 showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET while 3 had PMR by d14 FLT-PET; 3 of these 4 CT PR pts had evaluable archival tumor tissue, showing all 3 had EGFR mutations. Among the 47 CT nonresponders, 9 had PMR by d14 FDG-PET; 6 of these 9 pts had evaluable archival tumor tissue showing all 6 were EGFR wildtype with 1 Kras mutation. Both early (d14) and late (d56) PMR by either FDG or FLT were positively associated with PFS. D14 FDG-PET PMR was the only measurement significantly associated with OS. Conclusions: Early (d14) FDG-PET PMR appears to predict improved PFS and OS, even in the absence of later RECIST response. Relationship between PR/PMR and PFS or OS (n=51) CT d56 FDG d14 FDG d56 FLT d14 FLT d56 PFS PR/PMR n (%) 4 (7.8) 13 (25.5) 8 (15.7) 9 (18.0) 8 (16.0) Median (R vs. NR), wks 32 vs. 12 24 vs. 11 28 vs. 12 20 vs. 12 26 vs. 12 HR for R/NR 0.29 0.28 0.32 0.41 0.38 p n/a <0.001 0.01 0.02 0.02 OS Median (R vs. NR), mos 18 vs. 8 12 vs. 8 12 vs. 8 9 vs. 9 10 vs. 9 HR for R/NR 0.24 0.41 0.41 1.01 1.0 p 0.13 0.04 0.13 0.98 0.99 Abbreviations: R, responder; NR, nonresponder. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration DNAVision, Genentech Genentech, Roche Roche Roche Genentech, Roche