tbuckley/cabot-search huggingface dataset:
Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up
Authors: A. R. Zander, N. Kroeger, C. Schmoor, W. Krueger, V. Moebus, N. Frickhofen, B. Metzner, W. Schultze, W. Berdel, M. Koenigsmann, E. Thiel
Journal: Journal of Clinical Oncology (2006)

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m 2 ), Cyclophosphamide (600 mg/m 2 ) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m 2 ), Thiotepa (150 mg/m 2 ) and Mitoxantrone (10 mg/m 2 ) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m 2 ), Methotrexate (40 mg/m 2 ) and Fluoruracil (600 mg/m 2 ) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.
Healthy eating and active living program level 1 (HEAL) for breast cancer survivors.
Authors: C. E. Lee, B. Szuck, Y. Lau
Journal: Journal of Clinical Oncology (2010)

e19645 Background: Breast cancer survivors often suffer treatment-related side effects, including fatigue, reduced physical function, and physical fitness. We designed a Healthy Eating and Active Living Level 1 (HEAL-1) program to introduce breast cancer survivors with self-management strategies to improve their physical and dietary lifestyle to achieve better cancer-related outcomes. Methods: We assess the effect of a multidisciplinary 6-week program on functional outcomes of breast cancer survivors. Women (N=10) with breast cancer who completed radiation and/or chemotherapy were assessed at three time points: 6 weeks prior to (pre-program), immediately before (baseline), and immediately after the program (post-program). The program involves a dietitian, fitness instructor, psychologist and physical therapist. All participants were evaluated on their fatigue (FACIT-Fatigue), physical function (6-Minute Walk Test (6MWT), Tandem Walk Test, 8-foot walk speed test), physical fitness (blood pressure, resting heart rate, strength, and flexibility), physical activity (7-day Physical Activity Recall), and food intake (3-day food diary). Each participant was provided with a pedometer and a log to record their daily steps counts. Results: The participants' mean age was 52.5 years (43 to 65). All had completed radiation and/or chemotherapy within one year. There was a significant improvement over time in fatigue (p<0.004), 6MWT (p<0.004), blood pressure (p<0.021), and resting heart rate (p<0.001), with fatigue having continued significant improvement between baseline and post-program compared to between pre-program and baseline. All other variables demonstrated an improvement trend over time. Conclusions: Preliminary findings show overall improvement trend in all aspects of functional outcome. Interestingly, fatigue, some physical function and physical fitness improve even within a short duration. We conclude that participation in an introductory lifestyle change program such as the HEAL-1 program has immediate short-term benefits. Long-term benefits will require further investigation. No significant financial relationships to disclose.
Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving anthracycline-cyclophosphamide (AC)-based chemotherapy.
Authors: Daniel Powers, Ian D. Schnadig, Manuel R. Modiano, Sujata Arora, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2015)

208 Background: Rolapitant, a novel NK-1 receptor antagonist, demonstrated efficacy in the prevention of CINV in pts receiving moderately- or highly emetogenic chemotherapy (MEC; HEC). In this post-hoc analysis, we evaluated safety and efficacy outcomes in pts receiving AC-based therapy, now considered HEC. Methods: This double-blind, active-controlled study randomized pts to oral rolapitant 180 mg plus granisetron 2 mg and dexamethasone 20 mg or granisetron/dexamethasone alone (active control). Complete response (CR = no emesis and no use of rescue medication), no emesis, no significant nausea, and time to emesis or rescue medication during overall, acute, and delayed phases and treatment-emergent adverse events (AEs) are presented. Results: 703 pts received AC-based therapy, of which 97% had breast cancer. CR was significantly higher for rolapitant vs. active control for delayed and overall phases in pts receiving AC-based therapy (Table). Time to first emesis or use of rescue medication was significantly longer with rolapitant vs. active control (between-group comparison, p = 0.032); median was not reached in either treatment arm. A significantly greater proportion of pts on rolapitant (73.0%) vs. active control (60.2%) had no emesis during the overall phase (p &lt; 0.001). Rates of no significant nausea were similar for rolapitant (63.7%) and active control (62.4%) in the overall phase (p = 0.728). Treatment-related AEs (TRAEs) during Cycle 1 occurred in 8.7% and 8.8% of pts on rolapitant vs. active control. Most frequent TRAEs were constipation (2.9% vs. 2.7%), fatigue (2.3% vs. 2.2%), and headache (2.3% vs. 3.3%). Conclusions: Rolapitant was superior to active control in preventing CINV during delayed and overall phases after AC-based chemotherapy. The safety profiles of the rolapitant and control arms were similar. These results are consistent with those of the overall pt population in this study. Clinical trial information: NCT01500226. [Table: see text]
Abstract 14024: Results of a Phase I / II Multicenter Investigation of Udenafil in Adolescents After Fontan Palliation
Authors: David J Goldberg, Victor Zak, Bryan H Goldstein, Shan Chen, Michelle S Hamstra, Elizabeth A Radojewski, Eileen Maunsell, Seema Mital, Shaji C Menon, Kurt R Schumacher, R. M Payne, Mario Stylianou, Jonathan R Kaltman, Stephen M Paridon
Journal: Circulation (2015)

Introduction: Many pediatric clinical trials fail due to use of sub-therapeutic dosing. This phase I / II clinical trial was designed to evaluate the short-term safety, pharmacokinetics (PK), and preliminary efficacy of udenafil, a phosphodiesterase type 5 inhibitor, in adolescents following Fontan palliation to inform dose selection for a phase III clinical trial. Methods: This was a dose escalation trial with 5 dosing cohorts of 6 subjects each at 37.5 mg, 87.5 mg, and 125 mg daily, as well as 37.5 mg and 87.5 mg twice daily (bid) for 5 days. Efficacy testing (echocardiography, exercise stress test, endothelial function assessment) was performed at baseline and on day 5. A control cohort of 6 subjects underwent exercise testing without drug administration. Serum samples for PK analysis were collected on days 6-8. Adverse events (AE) were recorded throughout the 8-day study period and for 3 months thereafter. Comparison between baseline and day 5 testing was performed using ANOVA and visual trend lines. PK analysis was performed using a non-linear mixed effects model. Results: The trial enrolled 36 subjects at a mean age of 15.8 years (58.3% male). Subject characteristics were similar between cohorts. No drug-related serious AEs were reported during the study period, while 24 subjects had non-serious AEs possibly or probably related to study drug. Headache was the most common, occurring in 20 of the 30 subjects. Other possibly or probably medication related side effects occurring in more than one subject included: facial flushing (10 subjects), nasal congestion (7), spontaneous penile erection (6), nausea (3), and abdominal discomfort (2). The 87.5 mg bid cohort achieved the highest steady state serum concentration (172 ng/mL, range 117-202), the highest maximal concentration (506 +/- 188 ng/mL), and the greatest area under the curve for 24 hours (6701 +/- 1591 ng*hr/mL). Efficacy test results did not change significantly in any cohort. Conclusion: Udenafil was safe and well tolerated at all dosing levels while the 87.5 mg bid cohort achieved the highest serum drug level. With a 5-day treatment period and small sample size no significant clinical changes were observed. These data suggest that the 87.5 mg bid regimen may be most appropriate for a Phase III clinical trial.
Characteristics of Patients without Bleeding in a Pivotal Trial of Extended Half-Life, Pegylated, Full-length Recombinant Factor VIII (BAX 855) in the Treatment of Hemophilia A
Authors: Alice D. Ma, Robert Klamroth, Marilyn J. Manco-Johnson, Werner Engl, Jacqueline A Dyck-Jones, Brigitt E. Abbuehl
Journal: Blood (2015)
Abstract IA08: p62/SQSTM1 accumulation links chronic tissue damage to malignant progression in liver and pancreas
Authors: Michael Karin
Journal: Cancer Research (2016)

Abstract Despite extensive genomic exploration, the mechanisms that initiate malignancy remain obscure. We addressed this issue by studying how chronic liver diseases progress to hepatocellular carcinoma (HCC). We focused our studies on the role of p62/SQSTM1, whose accumulation is a hallmark of premalignant liver disease. Using mice, we found that hepatocyte-specific p62 ablation inhibits HCC development in four distinct models, with strongest effect exerted in etiologies involving mTORC1 activation. Forced p62 expression in autophagy-competent livers suffices for HCC induction. Amongst p62 activities including aggregate formation, binding ubiquitinated proteins, mTORC1 stimulation and transcription factor activation, most critical is the NRF2 pathway, which is mutationally activated in 14% of human HCCs. We propose that environmentally-induced p62-dependent NRF2 signaling is a key early event inHCC pathogenesis that together with mTORC1 promotes survival and expansion of superoxide-accumulating HCC-initiating cells. Indeed, high p62 expression in preneoplastic human liver predicts rapid HCC recurrence after curative ablation. Citation Format: Michael Karin. p62/SQSTM1 accumulation links chronic tissue damage to malignant progression in liver and pancreas. [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 IA08.
Preliminary Results of a Phase 1/2, Multi-Center, Open-Label Study (CLL- 001) Investigating a Stepwise Dose-Escalation Schedule of Lenalidomide in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Authors: Clemens M Wendtner, Daruka Mahadevan, Stephan Stilgenbauer, Olga Frankfurt, Adrian Bloor, Francesc Bosch, Lutz Uharek, Richard R Furman, Marco Gobbi, John G. Gribben, Eva K. Kimby, Mikkael A. Sekeres, Larry D. Cripe, Elyane Lombardy, Sheetal Shah, Laure A Moutouh-de Parseval, Asher Alban Chanan-Khan, Robert D. Knight
Journal: Blood (2008)
Prognostic Factors and Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Vs. Non-Transplant Chronic Lymphocytic Leukemia (CLL) Patients: A Comparative Analysis with the Leukemia/BMT Program of British Columbia (BC) and the BC Provincial CLL Database
Authors: Sebastian J. Swic, Alexander G. T. MacPhail, Chinmay B. Dalal, Steven J.T. Huang, Alina S. Gerrie, Thomas J. Nevill, Heather J. Sutherland, Raewyn Broady, Stephen H. Nantel, Sujaatha Narayanan, Kevin Song, Yasser R Abou Mourad, Donna E. Hogge, Maryse M. Power, Michael J. Barnett, Donna L. Forrest, Sean S Young, Tanya L. Gillan, Cynthia L. Toze
Journal: Blood (2014)
Serum Heavy-Light Chains (HLC) and Free Light Chains (FLC) As Predictors For Early CR In Newly Diagnosed Myeloma Patients Treated With Carfilzomib, Lenalidomide, and Dexamethasone (CRd)
Authors: Manisha Bhutani, Rene Costello, Neha Korde, Elisabet E. Manasanch, Mary Kwok, Nishant Tageja, Sham Mailankody, Dickran Kazandjian, Peter Wu, Adriana Zingone, Debra Burton, George Carter, Diamond Zuchlinski, Marcia Mulquin, Irina Maric, Katherine R Calvo, Raul C. Braylan, Constance Yuan, Maryalice Stetler-Stevenson, Seth M. Steinberg, Mark Roschewski, Ola Landgren
Journal: Blood (2013)
GW26-e1348 Exendin-4 protects adipose-derived mesenchymal stem cells (ADMSCs) from apoptosis induced by Hydrogen Peroxide through PI3K/Akt-Sfrp2 pathways
Authors: Hao Zhou, Dandan Li, Junjie Yang, Feng Tian, Ying Zhang, Tianwen Han, Shunying Hu, Ying Zhou, Jun Guo, Feng Cao, Yundai Chen
Journal: Journal of the American College of Cardiology (2015)
Panitumumab and pegylated liposomal doxorubicin to platinum-resistant epithelial ovarian cancer with KRAS wild-type: An ongoing, nonrandomized, multicenter, phase II trial.
Authors: K. D. Steffensen, M. Waldstr∅m, B. Lund, K. Bergfeldt, N. Keldsen, C. Marth, I. B. Vergote, A. K. Jakobsen
Journal: Journal of Clinical Oncology (2010)

TPS254 Background: Currently, randomized trials support the use of either pegylated liposomal doxorubicin (PLD) or topotecan as second-line therapy in women with recurrent platinum-resistant ovarian cancer (OC). However, patients with platinum-resistant recurrent OC have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). Results in colorectal cancer have clearly indicated that KRAS mutant tumors do not respond to treatment with EGFR inhibitors. To date, panitumumab has been evaluated in combination with chemotherapy in patients with colorectal, lung, and head and neck cancer. No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. Methods: Eligibility criteria are confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with maximum 2 prior lines of chemotherapy, measurable disease by CA125 criteria and with KRAS wild type are eligible. Patients are treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m2 day 1, every 4 weeks. Tumor assessment is performed at baseline and at every third cycle according to CA-125 criteria. The trial is based on Simon's two-stage minimax design with a division into two steps. 18 patients are included in the first step. If 4 responses or fewer are seen the trial is terminated. Otherwise accrual continues to a total of 33 patients. At present, 15 patients have been enrolled. The primary endpoint is to investigate the response rate in platinum-resistant, KRAS wild- type OC patients treated with PLD supplemented with panitumumab. Translational research is included as a secondary endpoint and tumor tissue/blood samples are collected as part of the trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
Mesenchymal Stem Cells from Patients 1 Year Following Autologous Stem Cell Transplantation Have a Pro-Inflammatory and Senescent Phenotype Compromising the Support of Hematopoietic Stem Cells
Authors: Carin L.E. Hazenberg, Fiona A.J. van den Heuvel, Ben N.G. Giepmans, Jan Jacob Schuringa, Edo Vellenga
Journal: Blood (2014)
Recurrent Mutations of Multiple Components of Cohesin Complex in Myeloid Neoplasms
Authors: Ayana Kon, Lee-Yung Shih, Masashi Minamino, Masashi Sanada, Yuichi Shiraishi, Yasunobu Nagata, Kenichi Yoshida, Yusuke Okuno, Masashige Bando, Shumpei Ishikawa, Aiko Sato-Otsubo, Genta Nagae, Claudia Haferlach, Daniel Nowak, Yusuke Sato, Tamara Alpermann, Masao Nagasaki, Teppei Shimamura, Hiroko Tanaka, Kenichi Chiba, Ryo Yamamoto, Tomoyuki Yamaguchi, Makoto Otsu, Naoshi Obara, Mamiko Sakata-Yanagimoto, Tsuyoshi Nakamaki, Ken Ishiyama, Florian Nolte, Wolf-Karsten Hofmann, Shuichi Miyawaki, Shigeru Chiba, Hiraku Mori, Hiromitsu Nakauchi, H. Phillip Koeffler, Hiroyuki Aburatani, Torsten Haferlach, Katsuhiko Shirahige, Satoru Miyano, Seishi Ogawa
Journal: Blood (2012)
Synthesis, characterization and in vivo evaluation of a magnetic cisplatin delivery nanosystem based on PMAA-graft-PEG copolymers
Authors: Efstathia Voulgari, Aristides Bakandritsos, Sotiris Galtsidis, Vassilis Zoumpourlis, Benjamin P. Burke, Gonçalo S. Clemente, Christopher Cawthorne, Stephen J. Archibald, Jiři Tuček, Radek Zbořil, Vasiliki Kantarelou, Andreas Germanos Karydas, Konstantinos Avgoustakis
Journal: Journal of Controlled Release (2016)
De Novo Purine Biosynthesis in Drug Resistance and Tumor Relapse of Childhood ALL
Authors: Hui Li, Benshang Li, Fan Yang, Caiwen Duan, Yun Bai, Jun J Yang, Jing Chen, Arend von Stackelberg, Hongzhuan Chen, JingYan Tang, Adolfo A. Ferrando, Jinghui Zhang, Shengyue Wang, Renate Kirschner-Schwabe, Bin-Bing S. Zhou
Journal: Blood (2015)
Carfilzomib: High Single Agent Response Rate with Minimal Neuropathy Even In High-Risk Patients
Authors: Ravi Vij, Jonathan L. Kaufman, Andrzej J Jakubowiak, A. Keith Stewart, Sundar Jagannath, Vishal Kukreti, Kevin T. McDonagh, Melissa Alsina, Nizar J Bahlis, Andrew Belch, Frederic J. Reu, Nashat Y Gabrail, Jeffrey Matous, David H. Vesole, Robert Z. Orlowski, Mai H. Le, Peter Lee, Michael Wang, The MMRC
Journal: Blood (2010)
Immune Targeting of the Phosphoproteome in Lymphoma and Leukemia.
Authors: Mark Cobbold, Joy M. Polefrone, Jie Qian, Fiyaz Mohammed, Andrew Norris, Andrea M. De Santis, Angela L. Zarling, Jeffery Shabanowitz, Benjamin E. Willcox, Michael E. Williams, Donald F. Hunt, Victor H. Engelhard
Journal: Blood (2007)
Germline genetic determinants of immunotherapy response in metastatic melanoma.
Authors: Christina Adaniel, Justin Rendleman, David Polsky, Russell S. Berman, Richard L. Shapiro, Yongzhao Shao, Adriana Heguy, Iman Osman, Anna C. Pavlick, Tomas Kirchhoff
Journal: Journal of Clinical Oncology (2014)

3004 Background: Ipilimumab-based immunotherapy has substantially increased survival for patients with advanced melanoma, however, the benefit is observed only in a small portion of treated patients. It is highly plausible, yet completely unexplored, that germline genetic factors modulate immunotherapy outcome. In this study we performed whole-exome sequencing (WES) to discover novel germline determinants of response to ipilimumab. Methods: Blood samples were collected from >60 metastatic melanoma patients treated by ipilimumab at the New York University Langone Medical Center. WES was performed on objective responders (OR) and non-responders (NR), defined by immune-related response criteria, using the Nextera platform (Illumina) at average 30x coverage. We have implemented a novel modified method for testing the association between OR and NR by variant, gene and enrichment of molecular networks. Gene-Set Enrichment Analysis and Pathway Studio were used to test the pathway associations. Results: The preliminary data comparing an initial subset of 30 ORs and 30 NRs identified significant associations with ipilimumab response for several loci including RPS6KB1 (p=0.001) and LNX2 (0.001). In addition, the pathway analysis showed significant associations for SMAD 3 (p=0.04) and interleukin 1 (p=0.04) related pathways. Conclusions: Preliminary findings provide promising evidence supporting the presence of germline genetic factors associated with response to ipilimumab therapy and pointing to immune-related pathways associated with outcomes. As the study is still in progress, the anticipated accrual of a larger sample collection is underway. This will further increase the analytical power of the discovery phase, but will also allow expanded validation of the current findings, suggesting for the first time that germline genetic factors modulate immunotherapy response.
PDK1 Controls the Differentiation of Hematopoietic Stem Cells Via Modulating ROS Levels
Authors: Tianyuan Hu, Cong Li, Le Wang, Yingchi Zhang, Luyun Peng, Weili Wang, Xiaomin Wang, Yajing Chu, Yingdai Gao, Bing Liu, Zhenyu Ju, Tao Cheng, Weiping Yuan
Journal: Blood (2015)
Characteristics of a single-centre series of familial testicular germ cell tumours
Authors: J. Coffey, R. A. Huddart, A. R. Norman, D. Dudakia, M. R. Stratton, E. A. Rapley
Journal: Journal of Clinical Oncology (2006)

10039 Background: Testicular germ cell tumors (TGCTs) account for 1% of all male cancers with increasing incidence rates documented. A family history of TGCT occurs in 2% of patients, conferring relative risks of 8–10 for brothers and 4–6 for fathers or sons of patients. These risks are high in comparison to other solid cancers and suggest that the risk of developing TGCT may be, at least in part, inherited rather than acquired. Methods: Pedigrees with &gt;1 male family member with TGCT were identified from a tumor database and systematically collected from 1992. Patients donated samples and medical details with full informed consent and under ethical review board approval. Pedigree and medical data were obtained by interview, mail and telephone contact. Results: This series examines 78 pedigrees, containing 160 cases and 170 TGCTs. In the period 1994–2003 6% of all cases had a family history of TGCT. It includes 35 sib-pairs, 12 father-son pairs, 11 uncle-nephew pairs, 10 cousin pairs and 4 pedigrees with ≥ 3 cases of TGCT. The dataset contains 66 seminomas, 56 non-seminomas, 17 mixed histology, 1 CIS and 30 tumors of unconfirmed histology. The median age at diagnosis was 33 (range 17 to 87). The median difference in age at diagnosis between the cases in each pedigree was 6 years (0–58). Histology was concordant between family members in 22 of the 53 (41.5%) 2-case pedigrees. 11 pedigrees contained a case with bilateral TGCTs (6.9% of all cases, compared to 1.1% in the sporadic patient population, p&lt;0.001) with 50% histological concordance. The median age at diagnosis of bilateral tumors was 32 (21–42) for the first tumor and 35 (26–49) for second tumors. 24 TGCT cases (15%, compared to an expected rate of 10%, p=0.045) reported a history of UDT. 9/162 (5.5%) of TGCT cases also developed non-TGCT cancers, including penile, bladder, colorectal, hepatic and pancreatic tumors. Conclusions: When systematic collection is undertaken the incidence of familial TGCT may be higher than previously reported. Familial cases have a higher incidence of UDT and bilateral disease. The majority of this set has been used in an international genome-wide linkage analysis to identify TGCT susceptibility genes. No significant financial relationships to disclose.