tbuckley/cabot-search huggingface dataset:
Abstract P6-10-05: A pilot study of radiation (RT) and CTLA4-mediated checkpoint blockade with tremelimumab for the treatment of breast cancer brain metastases (BCBM)
Authors: HL McArthur, K Beal, D Halpenny, M Henrich, S Patil, R Young, T Kaley, N Hamilton, C Hudis, J Wolchok, L Norton
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
ABVD Versus VEPEMB in Elderly Hodgkin’s Lymphoma Patients.
Authors: Alessandro Levis, Francesco Merli, Stefania Tamiazzo, Annalisa Arcari, Monica Bellei, Maura Brugiatelli, Massimo Federico, Marina Liberati, Giovanni Partesotti, Patrizia Pregno, Delia Rota Scalabrini, Daniele Sabiu, Flavia Salvi, Caterina Stelitano
Journal: Blood (2007)
Phase II Study of Hyper-CVAD Plus Nelarabine in Previously Untreated Adult T-Cell Acute Lymphoblastic Leukemia and T-Lymphoblastic Lymphoma
Authors: Yasmin Abaza, Hagop M. Kantarjian, Elias J. Jabbour, Deborah A Thomas, Tapan M. Kadia, Gautam Borthakur, Jan Burger, William G. Wierda, Nitin Jain, Stefan Faderl, Susan M. O'Brien, Marina Konopleva, Alessandra Ferrajoli, Steven M Kornblau, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip A Thompson, Mary A. Kelly, Rebecca Garris, Guillermo Garcia-Manero, Jorge E. Cortes, Farhad Ravandi
Journal: Blood (2016)
Depression, Somatic Distress and Anxiety in Adult Long-Term Survivors of Hematopoietic Cell Transplantation (HCT): A Report from the Bone Marrow Transplant Survivor Study.
Authors: Liton Francisco, K. S. Baker, Andrea Carter, Stephen J. Forman, James G. Gurney, Marcia Grant, Leslie L. Robison, Daniel J. Weisdorf, Smita Bhatia
Journal: Blood (2004)
CD11b− Donor Dendritic Cells Enhance Donor T-Cells’ Th1 Polarization and Graft Versus Leukemia Activity in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Jian-Ming Li, Kataryna A. Darlak, Ying Lu, Cynthia Giver, Wayne Harris, David L. Jaye, Edmund Waller
Journal: Blood (2008)
Phase I study of oral gemcitabine prodrug (LY2334737) alone and in combination with erlotinib in patients (pts) with advanced solid tumors
Authors: S. Koolen, P. O. Witteveen, I. Garcia-Ribas, S. Callies, V. Andre, R. H. Kronemeijer, A. Nol, J. H. Beijnen, E. E. Voest, J. H. Schellens
Journal: Journal of Clinical Oncology (2009)

2576 Background: LY2334737 (LY) is an orally available valproic acid prodrug of gemcitabine that was developed to overcome the extensive first-pass metabolism of gemcitabine to 2',2'-difluorodeoxyuridine (dFdU). The objectives of this study were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and pharmacokinetics (PK) of LY as monotherapy and in combination with erlotinib. Methods: Eligible pts had ECOG PS &lt; 2 and adequate hematologic, renal and hepatic function. In Arm A, LY was given daily for 14 days in a 3-week cycle. Pts assigned to Arm B also received erlotinib daily 100 mg continuously. Dose escalation was based on observed toxicity and the modified continual reassessment method (mCRM). The dose was maximally increased by 100% depending on the toxicity observed in the previous cohort. PK of LY, gemcitabine, dFdU and intracellular metabolites were determined. Results: 33 pts (21 m, 12 f, median age 60 yrs (range 24–81)) were treated at 5 different dose-levels (range 5–50 mg/day). Pts received a median of 3 cycles (range 2–17). Three out of 7 pt treated with 50 mg experienced 5 dose limiting toxicities (DLT). DLTs observed at 40 and 50 mg include fatigue (4 pt), thrombocytopenia (1 pt), GGT elevation (1 pt), AST/ALT elevation (1 pt), fever (1 pt), and pulmonary embolism (1 pt). One death was possibly related to LY intake. This pt, treated with 40 mg LY, developed on day 15 dyspnea, hypovolemic shock, and suddenly died. No grade 3 or 4 toxicities were reported at dose-levels &lt; 40 mg. The most common adverse events were fatigue, vomiting, nausea, pyrexia, anorexia, and diarrhea. Two pts with mesothelioma were stable for &gt; 9 months. One pt with refractory prostate cancer presented a PSA CR as assessed by investigator. The PK show dose-proportional increase in exposure of both LY and gemcitabine. Both LY and gemcitabine are rapidly cleared, thus no accumulation occurs. The metabolite dFdU accumulates due to its long half life. Conclusions: LY displays linear PK. The dose level of 50-mg is non-tolerable and 40-mg is being confirmed as the MTD as single agent and in combination with 100 mg erlotinib. Antitumor activity warrants further development. Pt accrual is ongoing. [Table: see text]
Abstract P1-04-08: Non-nuclear SUMO dynamics regulate mammary epithelial cell transformation
Authors: S Karami, F-M Lin, S Kumar, J Ren, S Bahnassy, T Bawa-Khalfe
Journal: Cancer Research (2017)

Abstract Objective: The reversible SUMO-posttranslational modification of protein substrates regulates various cellular processes and consistently is important for normal cell physiology. Disruption of SUMO enzymatic components supports onset of various pathophysiological disorders, including cancer. Our recent study identified a splicing event that differentially modulates expression of 2 SENP7 isoforms. The novel SENP7 variant SENP7S is the predominant SUMO protease in normal mammary epithelia; however onset of precancerous ductal carcinoma in situ (DCIS) reduces SENP7S significantly and stays low in all breast cancer (BCa) subtypes. Inversely, the full-length SENP7L isoform is upregulated in BCa and directly leads to BCa metastasis. Unlike SENP7L, SENP7S isoform contribution to carcinogenesis is unclear. Our objective is to define the biological function of this novel deSUMOylase SENP7S in normal versus cancerous epithelial cells. Results: Consistently with mRNA levels, protein levels of the 2 SENP7 isoforms are also inversely expressed in human BCa versus normal mammary epithelia. SENP7S is localized in the cytosol of MCF10-2A unlike other SUMO proteases including SENP7L that are predominantly nuclear enzymes. Beta-catenin and a component of the Beta-catenin destruction complex, Axin1 are substrates for SENP7S catalytic activity as in the absence of SENP7S, Beta-catenin and Axin 1 are both SUMOylated. Consistently, SENP7S regulates Beta-catenin signaling pathway. SUMOylated Axin1 loses its interaction with Beta-catenin, allowing the Beta-catenin to escape ubiquitylation and further proteasomal degradation. SUMOylated Beta-catenin translocates to the nucleus and activates multiple target genes that potentiate cell proliferation. Increase in cell proliferation and anchorage dependent growth of non-cancerous MCF10-2A cells was observed with inhibition of SENP7S. Additionally, SENP7S depletion potentiates anchorage independent growth of MCF10-2A with significantly greater number and size of spheroids. In comparison to the control. Loss of SENP7S also potentiates the self-renewal properties of the cells, indicative of mammary epithelial cell transformation. Conclusion: SENP7S modulates Beta-catenin stability and signaling and consequently is critical for normal mammary epithelial cell physiology. Loss of SENP7S, as observed in DCIS, initiates mammary epithelial cell transformation. Citation Format: Karami S, Lin F-M, Kumar S, Ren J, Bahnassy S, Bawa-Khalfe T. Non-nuclear SUMO dynamics regulate mammary epithelial cell transformation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-04-08.
Small airway dysfunction in well-treated never-smoking HIV-infected individuals
Authors: Andreas Ronit, Inger Hee Mathiesen, Marco Gelpi, Thomas Benfield, Jan Gerstoft, Tanja Pressler, Anders Christiansen, Jens Lundgren, Jørgen Vestbo, Susanne Dam Nielsen
Journal: European Respiratory Journal (2017)

Global projections from the World Health Organization rank chronic obstructive pulmonary disease (COPD) and HIV as the third and eighth leading causes of death by 2030, respectively [1]. An increasingly large number of individuals will consequently face a double burden of disease. The incidence of COPD is relatively high in the HIV-infected population [2], and HIV has been shown to be an independent risk factor [3, 4]. Well preserved spirometry but evidence of small-airway dysfunction in never-smoking HIV-infected individuals <http://ow.ly/oZCC308iUpo> We thank all the study subjects for their participation. Contributors: A. Ronit and I.H. Mathiesen designed the study. A. Ronit, I.H. Mathiesen, M. Gelpi, and S.D. Nielsen collected the data. A. Ronit was responsible for the statistical analysis. All authors interpreted the data. A. Ronit drafted the manuscript. All authors have critically revised and approved the final version. A. Ronit is the guarantor of the study.
Physical activity during cancer treatment (PACT) study: Short- and long-term effects on fatigue of an 18-week exercise intervention during adjuvant chemotherapy in patients with breast or colon cancer.
Authors: Anne Maria May, Miranda Velthuis, Noemie Travier, Charlotte N Steins Bisschop, Elsken Van Der Wall, Petra Peeters
Journal: Journal of Clinical Oncology (2014)

9535 Background: Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors still report serious fatigue three years post- treatment. Physical exercise during cancer treatment might reduce symptoms of fatigue. The primary aim of the present multicenter randomized controlled trial was to compare the short- and long-term effects on fatigue of an 18-week exercise intervention during adjuvant chemotherapy for breast or colon cancer patients. Methods: 237 patients (204 breast and 33 colon cancer) were randomly assigned to supervised aerobic and resistance exercise (n=119) or usual care (n=118). In addition to the supervised exercise, the intervention group was asked to be physical active for 30 minutes a day on 3 other days. Fatigue was assessed with the validated Multidimensional Fatigue Inventory at baseline (i.e. within 6 or 10 weeks after diagnosis for breast and colon cancer patients, respectively), after 18 weeks and after 9 months. Results: Intention to treat analyses using linear mixed-effects models showed a significant effect over time in favor of the intervention group for general and physical fatigue (p=0.001 and 0.02, respectively). Changes of general and physical fatigue were -0.90 (95% confidence interval: -1.77 to -0.04) and -1.24 (2.17 to -0.32) from baseline to 18 weeks and -1.12 (-2.01 to -0.22) and -0.66 (-1.62 to 0.30) from baseline to 9 months, respectively. Effects for mental fatigue, reduced activity and motivation were not significantly different. Conclusions: The 18-week exercise program during adjuvant treatment for breast or colon cancer showed positive results on general and physical fatigue directly after the intervention and also 4 ½ months later. Hence, exercise might be a beneficial addition to routine cancer care during adjuvant cancer treatment. Clinical trial information: ISRCTN43801571.
Eating and body image: Does food insecurity make us feel thinner?
Authors: Klaudia B Ambroziak, Elena Azañón, Matthew R Longo
Journal: Behavioral and Brain Sciences (2017)

Abstract Body image distortions are common in healthy individuals and a central aspect of serious clinical conditions, such as eating disorders. This commentary explores the potential implications of body image and its distortions for the insurance hypothesis. In particular, we speculate that body image may be an intervening variable mediating the relationship between perceived food scarcity and eating behavior.
Getting Real about Health Care Costs — A Broader Approach to Cost Stewardship in Medical Education
Authors: Ravi B. Parikh, Arnold Milstein, Sachin H. Jain
Journal: New England Journal of Medicine (2017)

Cost stewardship is too often viewed from the perspective of payers and institutions rather than that of patients. Physicians need to be taught to reduce spending across the care continuum, especially for patients who are subject to substantial cost sharing.
Abstract P2-02-03: Optimized prediction of deleterious missense mutations in <i>BRCA1</i> and <i>BRCA2</i> genes
Authors: SN Hart, T Hoskin, H Shimelis, B Feng, NM Lindor, A Monteiro, E Iversen, DE Goldgar, V Suman, FJ Couch
Journal: Cancer Research (2017)

Abstract Approximately 15% of genetic screens for mutations in BRCA1 and BRCA2 identify Variants of Uncertain Significance (VUS). Primarily missense mutations, VUS are often difficult to interpret, leading to either uncertainty in how to properly counsel a patient or an unnecessary prophylactic surgery. Given the paucity of data for which missenses are classified as truly pathogenic, computational deleterious missense prediction (DMP) algorithms are used to predict whether a mutation is likely deleterious or neutral. Accuracy of DMPs can vary considerably and have only been calibrated on a relatively small number of missense mutations of demonstrable effect on protein function. In this study, the performance of 41 different DMPs was compared to functional data from 455 functionally characterized missense variants in BRCA1 and BRCA2. New optimized thresholds for classifying missense mutations as deleterious are presented for several existing models as well as a newly derived naïve voting method (NVM). The areas under the curve estimates for the NVM approach are between 0.889-0.922, much higher than previous methods. We estimate that the overall pathogenic potential of missense variants to be 6.8% for BRCA1 and 3.2% of BRCA2, but can be as high as 50% depending on protein location. Overall these results provide key insights into how to predict deleterious missense mutations in BRCA1 and BRCA2. Citation Format: Hart SN, Hoskin T, Shimelis H, Feng B, Lindor NM, Monteiro A, Iversen E, Goldgar DE, Suman V, Couch FJ. Optimized prediction of deleterious missense mutations in BRCA1 and BRCA2 genes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-03.
Abstract P2-01-24: Evaluating lymph node ratio (LNR) as a prognostic indicator in node-positive breast cancer
Authors: A Kelliher, M Boyce, E Donnellan, D O Connor, C Murphy, B Bird
Journal: Cancer Research (2017)

Abstract Purpose: To determine whether LNR can provide additional prognostic information to pN staging in node-positive breast cancer patients. Methods: We previously reported on the utility of LNR as a prognostic indicator in lymph node-positive early breast cancer. We present an updated analysis with a prolonged median follow-up of 85 months. A retrospective review of original histopathology reports was undertaken in a sample group of 214 patients diagnosed with node-positive breast cancer between January 2000 and January 2011. The LNR was defined as the number of positive lymph nodes divided by the total number of lymph nodes (LNs) removed. LNR cut off points were divided into low (≤0.14), intermediate (0.15-0.39) and high (≥0.40) by trichotomy. Patients were also divided into three groups based on nodal status in accordance with the AJCC staging system. Those with 1-3 positive nodes were classified as pN1, those with 4-9 positive nodes were pN2 and those with 10 or more positive nodes were classified as pN3. Overall survival (OS) and invasive Disease Free Survival (iDFS) were calculated using the Kaplan Meier Method. Results: The mean age at diagnosis was 58 (SD=12) years. The median follow-up time was 85 months. The 5-year OS and iDFS for node-positive patients were 80% and 70%, respectively. The mean number of lymph nodes examined was 15.2 (SD=6.6) and the mean number of positive nodes was 5.3 (SD=6.1). When patients were stratified according to LNR groupings OS was 80% in the low LNR group, decreasing to 67% in the intermediate LNR group and 47% in the high LNR group (p&amp;lt;0.0001). Similarly, iDFS in the low LNR group was 71% decreasing to 57% in the intermediate LNR group and 42% in the high LNR group (p&amp;lt;0.0009). Conclusions: These updated results from a cohort of patients with lymph node-positive early breast cancer at a median follow-up of over 7 years confirms the utility of LNR as a prognostic indicator. Univariate and multivariate analyses to assess the ability of LNR to discriminate risk in addition to AJCC nodal grouping will be presented. Citation Format: Kelliher A, Boyce M, Donnellan E, O Connor D, Murphy C, Bird B. Evaluating lymph node ratio (LNR) as a prognostic indicator in node-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-24.
The Mutational Patterns Associated with Cytogenetic Subsets of De Novo Acute Myeloid Leukemia (AML): A Study of 1603 Adult Patients (Pts)
Authors: Ann-Kathrin Eisfeld, Krzysztof Mrózek, Jessica Kohlschmidt, Deedra Nicolet, Shelley Orwick, Karl Kroll, James S. Blachly, Andrew J. Carroll, Jonathan E. Kolitz, Bayard L Powell, Eunice S. Wang, Richard M. Stone, Albert de la Chapelle, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2016)
Stratification based on acute on chronic liver failure (ACLF) has greater prognostic accuracy than stratification based on creatinine, Acute Kidney Injury (AKI), Encephalopathy or Child-Pugh score. Pognostic relevance of 48 hour post-enrolment ACLF stratification
Authors: Paolo Angeli, Pere Ginès, Fabio Piano, Elisabet Garcia, Filippo Morando, Ezequiel Rodriguez, Ana Ariza, Elsa Solà, A Guevara, Richard Moreau, Rajiv Jalan, Juan Cordoba, Marco Pavesi, François Durand, Thierry Gustot
Journal: Hepatology (2013)
The Clinical Significance of Matching for Alleles at the Low Expression HLA Loci DP, DQ and DRB3/4/5 in Unrelated Hematopoietic Stem Cell Transplantation
Authors: Marcelo Fernandez-Vina, John Klein, Michael D Haagenson, Stephen R Spellman, Stephanie J. Lee, Claudio Anasetti, Lee Ann Baxter-Lowe, Pedro Cano, Neal Flomenberg, Mary M. Horowitz, Carolyn K Hurley, Machteld Oudshoorn, Effie W Petersdorf, Michelle Setterholm, Richard Champlin, Marcos De Lima
Journal: Blood (2008)
AML Patients in Minimal Residual Disease Vaccinated with a Novel Generation of Fast Dendritic Cells Expressing WT-1 and PRAME Mount Specific Immune Responses That Relate to Clinical Outcome
Authors: Iris Bigalke, Yngvar Fløisand, Guri Solum, Kirsti Hønnåshagen, Marianne Lundby, Kristina Anderson, Stein Sæbøe-Larssen, Else-Marit Inderberg, Judith Eckl, Dolores J Schendel, Gunnar Kvalheim
Journal: Blood (2015)
Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia
Authors: Piyanuch Kongtim, Uday R. Popat, Antonio M. Jimenez, Sameh Gabella, Riad O. El Fakih, Gabriela Rondon, Julianne Chen, Carlos E. Bueso-Ramos, Gautam Borthakur, Naveen Pemmaraju, Guillermo Garcia-Manero, Hagop M. Kantarjian, Amin M. Alousi, Chitra M. Hosing, Paolo Anderlini, Issa F. Khouri, Partow Kebriaei, Borje S. Andersson, Betul Oran, Katayoun Rezvani, David Marin, Elizabeth J. Shpall, Richard E. Champlin, Stefan O. Ciurea
Journal: Blood (2015)
Targeted Oral Busulfan (BU)/Cyclophosphamide (CY)/VP-16 and Autologous Stem Cell Transplant (ASCT) for Hodgkin's (HL) and Non-Hodgkin's Lymphoma (NHL) Results in Excellent 5-Year Survival and Low Treatment-Related Mortality: Ten-Year Single Center Experience of 246 Consecutively Treated Patients
Authors: Scott R. Solomon, Sanacore Melissa, Xu Zhang, Katelin Connor, Melhem Solh, Asad Bashey, Lawrence E. Morris, H. Kent Holland
Journal: Blood (2015)
Overall survival (OS) in treatment (tmt) naive patients with unresectable stage III/IV (USIII/IV) melanoma: A systematic literature review and network meta-analysis (NMA).
Authors: Srividya Kotapati, Paul Lorigan, Cora Verduyn, Michael Lees, Kevin M. Chin, Jeroen P. Jansen
Journal: Journal of Clinical Oncology (2012)

e19010 Background: Tmt with ipilimumab (IPI) &amp; dacarbazine (DTIC) resulted in greater OS than DTIC alone (Robert et al., 2011) in tmt naïve patients with USIII/IV melanoma. Direct comparisons vs. other systemic therapies in first line are lacking. The objective was to compare OS of patients receiving systemic therapies, including IPI, for naïve USIII/IV melanoma based on randomized controlled trials (RCTs). Methods: A systematic literature search was performed to identify RCTs. Kaplan-Meier OS curves for each intervention (ITV) were digitized, survival proportions over time were obtained from these images, and data were combined with a NMA using the best fit survival distribution resulting in pooled survival proportions (SPs) and expected OS (mean OS). Results: 16 studies provided OS curves and allowed for a NMA of the ITV groups listed in the table. Populations were comparable across trials other than in the vemurafenib study that selected patients with a BRAF mutation. IPI with DTIC showed greater mean OS than other ITVs (Table). The short follow-up for vemurafenib (median 3.8 months, max 12 months) did not allow for valid comparisons. Conclusions: Results of this NMA suggests that mean OS is expected to be greater with IPI &amp; DTIC than with other ITVs for the management of tmt naïve patients with USIII/IV melanoma. [Table: see text]
Evaluation of efficacy and toxicity of carcinoembryonic antigen related cell adhesion molecule (CEACAM)6 targeted immunotherapy in pancreatic adenocarcinoma
Authors: Laura A. Strickland, Philip Risser, Caroline Verbeke, Paul Polakis, Hartmut Koeppen
Journal: Cancer Research (2005)

4195  Carcinoembryonic Antigen Related Cell Adhesion Molecule (CEACAM)6, a glycosylphosphoinositol (gpI)-linked, cell surface member of the Carcinoembryonic Antigen (CEA) family of molecules, has been suggested as a potential target for immunotherapy in pancreatic adenocarcinoma. However, expression of CEACAM6 on an array of normal tissues, including myeloid cells, suggests the potential for antigen dependent toxicity, which can not be delineated in murine models because CEACAM6 has no murine ortholog. The aims of this study were to further characterize the expression of CEACAM6 in human tissues and on leukocytes of the peripheral blood (PB) and bone marrow (BM), and to determine the efficacy and antigen dependent toxicity of an anti-CEACAM6 directed immunoconjugate in relevant in vivo models. Using a murine monoclonal antibody (MAb) against CEACAM6 (Genentech, Inc.) we have expanded the characterization of CEACAM6 expression in human normal and malignant tissues, and PB and BM leukocytes, by immunohistochemistry (IHC) and fluorescence activated cell sorting analysis (FACS), respectively. Furthermore, we employed the antibody in unconjugated and maytansinoid (DM1)-conjugated forms to assess efficacy in a murine xenograft model and antigen dependent toxicity in non-human primates. CEACAM6 was expressed in 97% (65 of 67 cases) of ductal pancreatic adenocarcinoma by paraffin section IHC. In the PB and BM, CEACAM6 expression was limited to differentiated myeloid cells (CD33+, CD15+, CD13+, CD14+, CD116+). Myeloid lineage progenitor cells (CD34+/CD38+/CD33+) did not express CEACAM6, indicating that the immunoconjugate should not bind this population of regenerating cells. In a murine xenograft model of pancreatic cancer, the DM-1 immunoconjugate, but not the unconjugated anti-CEACAM6 MAb, caused tumor regression in a dose dependent manner. When administered to Cynomolgus macaques (single dose), the DM-1 immunoconjugate, but not the unconjugated antibody, conferred a decrease in absolute neutrophil count 7 days after dosing; staining of bone marrow smears from these animals with myeloperoxidase, a marker for myeloid cells indiscriminant of differentiation, showed that myeloid cells were present. In conclusion, CEACAM6 is expressed in a large proportion of ductal pancreatic adenocarcinomas as well as myeloid cells in PB and BM. CEACAM6 directed immunoconjugate therapy is efficacious in a murine xenograft model but more work is needed to fully characterize the antigen dependent toxicity, before such strategies can move forward.