tbuckley/cabot-search huggingface dataset:
Long Term Follow-up on the Tretament of High Risk Smoldering Myeloma with Lenalidomide Plus Low Dose Dex (Rd) (phase III spanish trial): Persistent Benefit in Overall Survival
Authors: Maria-Victoria Mateos, Miguel T Hernandez, Pilar Giraldo, Javier De La Rubia, Felipe de Arriba, Lucía López-Corral, Laura Rosiñol, Bruno Paiva, Luis Palomera, Joan Bargay, Albert Oriol, Felipe Prosper, Javier López, Eduardo Olavarría, Nuria Quintana, Jose Luis García, Joan Blade, Juan José Lahuerta, Jesus F. San Miguel
Journal: Blood (2014)
Blast cells from patients treated for secondary AML (sAML) show less P-glycoprotein (Pgp)-mediated efflux of amonafide compared to daunorubicin: Implications for therapy
Authors: A. S. Lundberg, M. R. Baer, M. Chau, H. P. Erba, A. L. Dressel, A. M. Ajami, R. L. Capizzi
Journal: Journal of Clinical Oncology (2008)

13536 Background: Multidrug resistance (MDR) associated with Pgp overexpression in blasts is common in high-risk AML and is associated with poor outcomes. Erba et al (JCO 2007) reported a 42% complete remission (CR) rate in patients (pts) with sAML [prior MDS or treatment-related AML, (tAML)] (N = 88) treated with amonafide and std dose cytarabine. In laboratory studies of Pgp+ human leukemia cells, amonafide was neither a substrate nor an inhibitor of Pgp-mediated efflux, in contrast to daunorubicin (DNR). We sought to correlate the lack of Pgp effect with treatment outcome. Methods: AML blasts from 15 pts from the Phase 2 trial cited above were retrospectively assessed for Pgp expression and function as well as amonafide and DNR uptake and retention in the presence and absence of the Pgp inhibitor cyclosporin A. Pts: median age, 62 yrs (range 51–87); 7 with prior MDS; 8 had tAML; 10 with unfavorable cytogenetics. Pgp-mediated efflux was assessed by comparing uptake of the Pgp substrate DiOC2(3) in the presence and absence of the Pgp inhibitor PSC-833. Pgp- mediated transport (effluxapp) was calculated as differential uptake and retention of amonafide and DNR with (a) and without (b) PSC-833, normalized to apparent influx, using the formula [(a-b)/a]×100, reported as the mean±s.e.m. Results: The 15 sAML samples showed significantly less effluxapp of amonafide (5.2%±3.2) than of DNR (16%±2.1; p=0.0083). The unfavorable cytogenetic subset showed much less effluxapp of amonafide (0.13%±3.7) compared to DNR (16%±2.1; p=0.0015). CR pts also showed less effluxapp of amonafide (4.0%±6.7) than of DNR (21%±2.9; p=0.035). Conclusions: The relative lack of Pgp-mediated efflux of amonafide, compared to DNR, from sAML blasts provides a rationale for its observed clinical efficacy in the Phase 2 trial. Prospective assessment of these MDR parameters is underway in a randomized Phase 3 clinical trial in sAML comparing amonafide to DNR in combination with std dose cytarabine for remission induction. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Xanthus Pharmaceuticals Xanthus Pharmaceuticals Xanthus Pharmaceuticals
Abstract IA19: Microenvironmental regulation of breast cancer invasion, dissemination, and lung colonization
Authors: Andrew J. Ewald
Journal: Cancer Research (2016)

Abstract The majority of cancer deaths are associated with the metastasis of epithelial tumors. This clinical reality presents an interesting conceptual puzzle: homeostatic epithelial cells are tightly adherent to each other and exhibit comparatively modest levels of proliferation and motility. Conversely, metastatic cancer cells must escape from the primary tumor, navigate the local stroma, access the systemic circulation, evade the immune system, and survive in distant sites with molecularly distinct microenvironments. We seek to understand the molecular changes that underlie this large change in epithelial cell behavior. To accomplish this goal, we first developed a series of 3D organotypic assays to elucidate the specific molecular changes downstream of expression of genes associated with metastatic cell behaviors, such as Twist1. We found that Twist1 expression is sufficient to induce mammary cells to disseminate but, surprisingly, its major effectors are proteins that constitute, interpret, or modify the extracellular compartment. We further demonstrated that Twist1 induced dissemination occurs in the presence of membrane localized adherens junction components and requires E-cadherin (Shamir et al, JCB, 2014). We are currently leveraging our bioinformatic analyses to identify molecular targets that can be inhibited to block invasion and dissemination. In addition to candidate gene approaches, we sought to identify invasion and metastasis associated genes in an unbiased fashion. We therefore developed 3D organotypic culture assays using primary and metastatic tumor tissue from mouse models and clinical breast cancer samples (n&amp;gt;150). We discovered a conserved molecular program expressed in the most invasive breast cancer cells across molecular subtypes (Cheung et al, Cell, 2013). We next used lineage analysis in vivo to demonstrate that the majority of metastases in the MMTV-PyMT mouse model are founded by multicellular groups of cancer cells. Importantly, the keratin-14+ (K14+) invasive molecular phenotype is common in invasion strands, locally disseminated cancer cells, CTC clusters, and micrometastases but rare in the macrometastases. We are now focused on understanding how the microenvironment determines the likelihood of dissemination from the primary tumor and metastatic outgrowth in distant organs. Citation Format: Andrew J. Ewald. Microenvironmental regulation of breast cancer invasion, dissemination, and lung colonization. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA19.
Leukemia Derived Dendritic Cells (LDCs) Are Functionally Deficient and Inferior to DC/Leukemia Fusion Cells as a Tumor Vaccine for AML.
Authors: Jacalyn Rosenblatt, Richard Stone, Corrine Lenahan, Zekwui Wu, Baldev Vasir, Daniel J. DeAngelo, Ilene Galinsky, Kenneth Miller, James D. Levine, Robin Joyce, Donald Kufe, David Avigan
Journal: Blood (2005)
추계학술대회 초록집 : 대한간학회 학술연구기금 당선과제 발표 ; 우리나라 급성바이러스 간염의 실태: 역학, 임상 특성 및 바이러스학 특성과 심한 급성 B형간염 및 C형간염환자에서 항바이러스 치료의 효과
Authors: 정숙향 ( Sook Hyang Jeong ), 황성규 ( Seong Gyu Hwang ), 박상종 ( Sang-Jong Park ), 강숙경 ( Sook Kyung Kang ), 지영미 ( Young Mee Jee )
Journal: Clinical and Molecular Hepatology (2006)
The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection
Authors: Feng Su, Pamela K. Green, Kristin Berry, George N. Ioannou
Journal: Hepatology (2016)

Black race and Hispanic ethnicity were associated with lower rates of sustained virologic response (SVR) to interferon‐based treatments for chronic hepatitis C virus infection, whereas Asian race was associated with higher SVR rates compared to white patients. We aimed to describe the association between race/ethnicity and effectiveness of new direct‐acting antiviral regimens in the Veterans Affairs health care system nationally. We identified 21,095 hepatitis C virus–infected patients (11,029 [52%] white, 6,171 [29%] black, 1,187 [6%] Hispanic, 348 [2%] Asian/Pacific Islander/American Indian/Alaska Native, and 2,360 [11%] declined/missing race or ethnicity) who initiated antiviral treatment with regimens containing sofosbuvir, simeprevir + sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ombitasvir/ritonavir/dasabuvir during the 18‐month period from January 1, 2014, to June 30, 2015. Overall SVR rates were 89.8% (95% confidence interval [CI] 89.2‐90.4) in white, 89.8% (95% CI 89.0‐90.6) in black, 86.0% (95% CI 83.7‐88.0) in Hispanic, and 90.7% (95% CI 87.0‐93.5) in Asian/Pacific Islander/American Indian/Alaska Native patients. However, after adjustment for baseline characteristics, black (adjusted odds ratio = 0.77, P &lt; 0.001) and Hispanic (adjusted odds ratio = 0.76, P = 0.007) patients were less likely to achieve SVR than white patients, a difference that was not explained by early treatment discontinuations. Among genotype 1–infected patients treated with ledipasvir/sofosbuvir monotherapy, black patients had significantly lower SVR than white patients when treated for 8 weeks but not when treated for 12 weeks. Conclusion : Direct‐acting antivirals produce high SVR rates in white, black, Hispanic, and Asian/Pacific Islander/American Indian/Alaska Native patients; but after adjusting for baseline characteristics, black race and Hispanic ethnicity remain independent predictors of treatment failure. Short 8‐week ledipasvir/sofosbuvir monotherapy regimens should perhaps be avoided in black patients with genotype 1 hepatitis C virus. (H epatology 2017;65:426‐438).
Deregulation of DUX4 and ERG in acute lymphoblastic leukemia
Authors: Jinghui Zhang, Kelly McCastlain, Hiroki Yoshihara, Beisi Xu, Yunchao Chang, Michelle L Churchman, Gang Wu, Yongjin Li, Lei Wei, Ilaria Iacobucci, Yu Liu, Chunxu Qu, Ji Wen, Michael Edmonson, Debbie Payne-Turner, Kerstin B Kaufmann, Shin-ichiro Takayanagi, Erno Wienholds, Esmé Waanders, Panagiotis Ntziachristos, Sofia Bakogianni, Jingjing Wang, Iannis Aifantis, Kathryn G Roberts, Jing Ma, Guangchun Song, John Easton, Heather L Mulder, Xiang Chen, Scott Newman, Xiaotu Ma, Michael Rusch, Pankaj Gupta, Kristy Boggs, Bhavin Vadodaria, James Dalton, Yanling Liu, Marcus L Valentine, Li Ding, Charles Lu, Robert S Fulton, Lucinda Fulton, Yashodhan Tabib, Kerri Ochoa, Meenakshi Devidas, Deqing Pei, Cheng Cheng, Jun Yang, William E Evans, Mary V Relling, Ching-Hon Pui, Sima Jeha, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Guido Marcucci, Clara D Bloomfield, Jessica Kohlschmidt, Krzysztof Mrózek, Elisabeth Paietta, Martin S Tallman, Wendy Stock, Matthew C Foster, Janis Racevskis, Jacob M Rowe, Selina Luger, Steven M Kornblau, Sheila A Shurtleff, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, John E Dick, Stephen P Hunger, Mignon L Loh, James R Downing, Charles G Mullighan
Journal: Nature Genetics (2016)
Overexpression of SOX5 by a Novel Chromosome Translocation Involving the IGH Locus In a Follicular Lymphoma without BCL2 Expression
Authors: Masayuki Shiseki, Akihiro Masuda, Yan-Hua Wang, Kentaro Yoshinaga, Naoki Mori, Masanao Teramura, Toshiko Motoji
Journal: Blood (2010)
P0376 : Stratification of hepatocellular carcinoma. The prognostic score NIACE, an additional aid to the Barcelona Clinic Liver Cancer (BCLC) staging system? Multicenter study
Authors: X. Adhoute, G. Penaranda, J.-F. Blanc, J. Edeline, S. Naude, H. Perrier, O. Monnet, P. Castellani, V. Oules, O. Bayle, G. Conroy, S. Benali, G. Lefolgoc, B. Pol, J.-P. Bronowicki, J.-L. Raoul, M. Bourliere
Journal: Journal of Hepatology (2015)
Artificial Antigen Presenting Cells (aAPC) Expanded NK-Mediated Enhanced Lysis of Allogeneic Tumor Cells Regardless of HLA Class I/KIR Mismatch and Its Implication of Use in Eradicating Acute Lymphoblastic Leukemia (ALL).
Authors: Hua Zhang, Bruce Levine, Nga Voong, Alan S. Wayne, Carl H. June, Crystal L. Mackall
Journal: Blood (2009)
HER2 status in gastroesophageal cancer: An Irish multicenter experience.
Authors: Aine O'Reilly, Catherine Quinlan, Ciara Marie Kelly, Ciara Ryan, Margaret O'Keeffe, Seamus O'Reilly, Michael William Bennett, Derek G. Power
Journal: Journal of Clinical Oncology (2013)

28 Background: Gastroesophageal cancer is a major cause of cancer-related mortality. The ToGA study, established the benefit of trastuzumab in combination with chemotherapy in HER2 positive metastatic gastroesophageal tumors. We report a multi-centre Irish experience of examining HER2 status by IHC and FISH amongst gastroesophageal adenocarcinomas. Methods: HER2 testing was performed on biopsy or resection specimens of patients with early stage and metastatic gastroesophageal tumors between 2010 and 2012. We defined HER2 positive(+) as IHC3+ or FISH(+) {HER2:17ch ≥2}. All specimens which were IHC2+ or IHC3+, where treatment with trastuzumab was under consideration, went on to have FISH testing. Results: Between 2010 and 2012 HER2 status was established in all patients presenting with biopsy proven gastroesophageal cancers, this amounted to 88 patients (53 gastric, 35 esophageal). Within the population examined 64% of patients had metastatic disease. The majority (51%) had intestinal type adenocarcinomas, the remainder having diffuse type (16%), mixed type (3%) or undetermined (18%). Nineteen patients (21%) were defined as being HER2+ (14 male, 5 female). Four were FISH (+) IHC3+, five were FISH (+) IHC2+ and in ten patients HER2 status was defined by IHC3+ alone as FISH testing was indeterminate (1 patient) or not tested (9 patients). In the subset of HER2+ patients (19 patients), the majority had gastric cancer (63%). Intestinal type adenocarcinoma occurred in 12 patients (63%), the remainder being diffuse type (2 patients), mixed (1 patient) or undetermined (4 patients). Seven patients (36%) had localized disease. In the metastatic cases the distribution of metastases was as follows: 9(47%) liver, 3(15%) lung, 3(15%) peritoneal, 1(5%) adrenal, 1(5%) brain and 1(5%) ovarian. Five patients are receiving trastuzumab for HER2+ disease in combination with cisplatin and fluorouracil based chemotherapy. Conclusions: In a cohort of Irish patients we found similar levels of HER2+ gastroesophageal cancers (21%) as that demonstrated in the ToGA trial (22%). Clinicopathologic characteristics were broadly similar also. Outcome of our experience with HER2 directed therapy will be reported.
Genetic variants in the telomere maintenance pathway as predictors of second primary tumors and recurrence of early-stage head and neck cancer.
Authors: J. Y. Chang, S. M. Lippman, J. Lee, M. Huang, X. Wu
Journal: Journal of Clinical Oncology (2010)

1504 Background: Telomere is critical for chromosome stability. Telomere shortening has been associated with cancer development. In this study, we evaluated genetic variants in the telomere maintenance pathway as predictors for the risk of second primary tumor (SPT) or recurrence in early-stage head and neck squamous cell carcinoma (HNSCC) patients. Methods: We genotyped 427 single nucleotide polymorphisms (SNP) from 41 telomere maintenance pathway genes in a nested 1:2 case-control study of 150 early stage HNSCC patients with SPT/recurrence and 300 patients without. Individual and cumulative effects and interactions of these SNPs on SPT/recurrence were assessed. Results: In the Cox proportional hazards model, patients carrying the variant genotypes of rs9562605, located in the BRCA2 gene, were associated with a 0.5-fold (95% CI 0.4- 0.8) reduced risk of SPT/recurrence, and longer median SPT/recurrence-free survival time (MST) (> 93 months) than those with wild-type genotype (81.6 months) (p = 2.4 × 10-3). A cumulative effect analysis was performed by combining the unfavorable genotypes of the 53 significant SNPs with p < 0.05. A progressively increasing SPT/recurrence risk was observed as the number of unfavorable genotypes increased (p for trend < 0.0001). Specifically, compared to the subjects with fewer than 19 unfavorable genotypes, subjects with more than 30 unfavorable genotypes had 19.7-fold (95% CI 9.6-40.4) increased risk and significantly shorter MST (28.2 months vs. > 93 months, log-rank p = 2.0 × 10-24). From survival tree analysis, rs10849605 was the first split with the smallest p-value (2.5 × 10-3). Node 18 ranked the highest risk group (HR > 3.7, 95% CI 9.6-568.4, MST = 13.4 months) as compared to the reference node, node 1 (MST > 93 months) (log-rank p = 1.1 × 10-23). Conclusions: The study identified several promising SNPs and further demonstrated that the combination of multiple SNPs and their interactions may be useful to predict clinical outcome of early-stage head and neck cancer. No significant financial relationships to disclose.
Myeloid-Derived Suppressor Cells Are Expanded in Patients with AML and Are Dependent on MUC1 Expression
Authors: Athalia Rachel Pyzer, Dina Stroopinsky, Jacalyn Rosenblatt, Kristen Anna Palmer, Maxwell Douglas Coll, Michal Bar-Natan, Hasan Rajabi, Poorvi Somaiya, Katarina Luptakova, Salvia Jain, Malgorzata McMasters, James D. Levine, Jon Arnason, Donald Kufe, David Avigan
Journal: Blood (2014)
Adherence to NCCN treatment guidelines for rectal cancer: Analysis of national practice patterns.
Authors: R. Chagpar, J. N. Cormier, B. W. Feig, G. J. Chang, Y. N. You, Y. Chiang, M. A. Rodriguez-Bigas, J. M. Skibber, Y. Xing
Journal: Journal of Clinical Oncology (2011)

3554 Background: The purpose of this study was to determine current practice trends and factors influencing adherence to the National Comprehensive Cancer Network (NCCN) guidelines for rectal adenocarcinoma. Methods: Retrospective cohort study of patients with rectal cancer identified from the National Cancer Database (2003-2007). Adherence to stage-specific NCCN guidelines was evaluated after individually determining AJCC/TNM stage for each patient (clinical (c) stage for patients receiving neoadjuvant therapy or pathologic (p) stage for those who received surgical resection as a first course of treatment). Stage-specific multivariate analyses were performed to determine factors associated with adherence to NCCN guidelines. Results: 45,876 patients with rectal cancer who met study criteria were analyzed. Overall, adherence to treatment guidelines was observed in 63% of patients; stage I (66%), stage II (57%), stage III (61%) and stage IV (73%). Nonadherence for stage I was largely due to overtreatment (20%) with neoadjuvant therapy. Stage I patients were least likely to be undertreated (14%) compared with stages II (43%), III (39%) and IV (27%), respectively (p<0.001). A primary reason for nonadherence was undertreatment of stage pII (44%) and pIII (40%) patients through lack of adjuvant therapy. Factors associated with adherence across all stages included age, race, comorbidity index, insurance status and type of facility. Conclusions: Young, healthy, clinical stage I rectal cancer patients with insurance are more likely to be overtreated. Conversely, pathologic stage II and III patients who are older, have greater comorbid disease, are underinsured or treated at community hospitals were likely to be undertreated. The impact of these departures from national practice guidelines on patient outcomes remain to be elucidated. Odds ratio for adherence. Stage I Stage II Stage III Stage IV Age <50 - - - - 50-64 1.22 0.84 0.86 0.56 65-74 1.25 0.60 0.70 0.42 >75 1.15 0.24 0.26 0.13 Charlson-Deyo ≥1 vs. 0 1.42 0.77 0.75 0.64 Insurance status Private - - - - Medicare 0.91 0.89 0.84 0.68 Medicaid 0.61 0.79 0.72 0.62 Uninsured 0.51 0.57 0.70 0.42 Facility Teaching - - - - Cancer center 1.01 0.93 1.07 0.92 Community 0.86 0.80 0.90 0.74
Efficacy of Gene Therapy for Wiskott-Aldrich-Syndrome
Authors: Christian J. Braun, Kaan Boztug, Manfred Schmidt, Michael H Albert, Adrian Schwarzer, Anna Paruzynski, Ute Modlich, Rita Beier, Gudrun Göhring, Sonja Naundorf, Klaus Kühlcke, Martina Rose, Christopher Fraser, Liesl A. Mathias, Rudolf Ferrari, Miguel R. Abboud, Waleed Al-Herz, Irina Kondratenko, László Maródi, Brigitte Schlegelberger, Christopher Baum, Christof von Kalle, Christoph Klein
Journal: Blood (2011)
Abstract 17758: Anti-Tachycardia Pacing Has Minimal Impact on Daily Activities Compared to Shocks
Authors: Samuel F Sears, Bruce D Gunderson, Jodi L Koehler
Journal: Circulation (2013)

Introduction: Implantable Cardioverter Defibrillators (ICDs) can deliver either anti-tachycardia pacing (ATP) or shocks to terminate life-threatening ventricular arrhythmias. Multiple studies have shown the negative psychological consequences of multiple shocks as measured through quality of life (QOL) questionnaires. Current ICDs measure and store minutes of daily activity which we hypothesized may be sensitive to ICD therapies and, thus, a possible surrogate for QOL. Our goal was to compare the impact of ATP and shocks on patient (pt) activity.

Methods: We performed a retrospective analysis using 900 pts from the EMPIRIC study to determine the change in weekly hours of activity from pre (baseline) to post ICD therapy for shocks and ATP. Patients with an ICD therapy were separated into two groups based on their initial therapies (shock with or without ATP, ATP-only). We calculated the change in activity from cumulative activity 1 week pre-therapy to 1 week post-therapy. The activity change was compared for one, few (2-4) and many (≥5) therapies.

Results: There were 67 pts with shocks (1 - 13 / pt) and 99 pts with ATP-only (1 to 45 sequences / pt). Activity changed by a median -0.5 weekly hours (range: -41 to 14 hours) for pts with at least 1 shock compared to a median change of +0.1 weekly hours (range: -17 to 14 hours) for patients with ATP-only. Patients receiving ATP-only had a non-significant change in activity (figure). Patients receiving at least 1 shock had a significant activity change for few (p=0.02) and many therapies (p=0.01). Increasing the number of ATP sequences did not significantly impact pt activity (p=0.77). Increasing the number of shocks significantly decreased pt activity (p<0.001).

Conclusions: Patients who received ATP-only therapies had minimal impact on activity while shocked pts had temporal declines in activity. These findings suggest that patient activity may be sensitive to ICD therapies. Further analysis with a larger database is required.

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A 220-Gene Targeted Next-Generation Sequencing Panel for the Detection of Variants in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma: Application to a Cohort of 85 Formalin-Fixed Paraffin-Embedded Diffuse Large B-Cell Lymphoma Biopsies
Authors: Julia Friedman, Asha Guttapalli, Charles Ma, Venkata Thodima, Raghavendra Padmanabhan, Sitharthan Kamalakaran, Imran N Siddiqi, Jane Houldsworth
Journal: Blood (2015)