tbuckley/cabot-search huggingface dataset:
Results of a phase I study to evaluate the feasibility, safety, and biological effects of intravenous administration of wild-type reovirus with docetaxel to patients with advanced malignancies
Authors: S. M. Rudman, C. Comins, D. Mukherji, M. Coffey, K. Mettinger, A. Protheroe, K. J. Harrington, H. Pandha, J. F. Spicer
Journal: Journal of Clinical Oncology (2009)

e13524 Background: Reovirus has minimal pathogenicity in humans but selectively replicates in cells with activated Ras. Wild- type reovirus serotype 3 Dearing strain (Reolysin) has selective antitumor activity in vitro, in murine models, and after systemic delivery in humans in phase 1 trials. Synergistic tumour kill has been observed combining reovirus with taxanes in a range of cancer cell lines and in vivo. Methods: Patients were treated in an open-label, dose-escalating, phase I trial and received 3- weekly 75mg/m2 docetaxel i.v. and reovirus i.v. (day 1–5 of first week inclusive). Reovirus was administered at a starting dose of 3x10 9 tissue culture infectious dose (TCID50) and then increased to 1 x 10 10 and 3 x 10 10 TCID50. Primary endpoints were to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and to recommend a dose and schedule for future investigation. Secondary endpoints were to evaluate pharmacokinetics, neutralizing antibody development, cell- mediated immune response and anti-tumour activity. Results: 17 patients were treated (15 males, median age 60 years). No MTD has been reached. DLT's observed were G4 neutropenia (and a recurrent perianal abcess) and G3 rise in AST. Other toxicities observed were fatigue, hypotension and neutropenic sepsis. At present, 5 patients remain on treatment. We have observed 2 partial responses (breast and gastric carcinoma) and 10 patients had stable disease as best response. Conclusions: Reovirus is well tolerated when administered in combination with intravenous docetaxel, with predictable toxicity observed. The recommended dose has been defined at 3x10 10 TCID50 and phase II studies are planned. Objective radiological evidence of anticancer activity for this combination has been observed. [Table: see text]
Abstract A27: Addiction to the NF-κB–triggered IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells
Authors: Kana Tominaga, Noriko Gotoh
Journal: Clinical Cancer Research (2016)

Abstract An inflammatory microenvironment contributes to tumorigenesis. The pro-inflammatory transcription factor nuclear factor-kappa B (NF-kappa B) is known to play important roles, but how it regulates cancer stem cells (CSCs) remains largely unclear. We comprehensively analyzed which targets of NF-kappa B are activated by heregulin (HRG), a tumor sphere-forming ligand, in breast cancer cells. We identified many cytokines downstream of HRG-phosphatidyl inositol 3 kinase (PI3K)-NF-kappa B signaling. Insulin-like growth factor 2 (IGF2) was identified as a key downstream target; IGF2 treatment induced tumor spheres in most samples of patient-derived primary breast cancer cells, and anti-IGF2 antibody treatment greatly reduced HRG-induced tumor sphere formation, even though many other cytokines were simultaneously produced. The IGF2 receptor, IGF-1R, was specifically expressed at high levels in CSC-enriched populations in freshly obtained primary breast cancer cells. Moreover, IGF2-PI3K signaling induced expression of a stemness transcription factor, ID1, and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft (PDX) model. Thus, NF-kappa B may trigger IGF2-ID1-IGF2 positive feedback circuits and PI3K-mediated feed-forward circuits that allow cancer stem-like cells to appear; it may then stabilize the feedback circuits, to which the cancer stem-like cells become addicted. Because the stemness circuits may be the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs. Citation Format: Kana Tominaga, Noriko Gotoh. Addiction to the NF-κB–triggered IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A27.
Analysis of Outcomes In Adolescents and Young Adults (AYA) with Chronic Myeloid Leukemia (CML) Treated with Upfront Tyrosine Kinase Inhibitors (TKI)
Authors: Naveen Pemmaraju, Hagop Kantarjian, Jianqin Shan, Elias Jabbour, Alfonso Quintas-Cardama, Srdan Verstovsek, Farhad Ravandi, William G. Wierda, Susan O'Brien, Jorge E. Cortes
Journal: Blood (2010)
Abstract P6-05-04: Relationship between obesity and breast tumor pathology in a contemporary set of patients
Authors: RE Ellsworth, L Lovejoy, N Costantino, CD Sheiver
Journal: Cancer Research (2017)

Abstract Background: Obesity is a risk factor for breast cancer in postmenopausal women, and is associated with decreased survival regardless of menopausal status. This outcome disparity has been attributed to clinical factors such as delayed diagnosis, inadequate dosing with chemotherapeutic agents, and co-morbid conditions. Here, we evaluated the association between pathological characteristics and BMI in a cohort of patients enrolled in the Clinical Breast Care Project (CBCP) 2001-2013. Methods: All female patients with invasive breast cancer who had height and weight recorded at the time of diagnosis were identified from the CBCP database. BMI was calculated and patients categorized as normal/lean (&amp;lt;24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (&amp;gt;30.0 kg/m2). Chi-square univariate analysis was performed to determine statistical significance followed by multivariate logistic regression. Statistical significance was defined as p &amp;lt;0.05. Survival analysis was done using Cox proportional hazard regression models. Results: Of the 1,705 patients, 32.4% were normal/lean, 31.6% were overweight and 36.0% were obese. Univariate analysis revealed that obese women were significantly more likely to be older at age at diagnosis, African American, menopausal and treated at Joyce Murtha Breast Care Center, a rural civilian hospital in western-central PA. These factors were thus include in multivariate analysis which showed that obese patients were at an increased risk relative to normal/lean patients of having a higher tumor stage (OR = 1.32, 95% CI [1.043-1.681], p = 0.021), size (OR = 1.42, 95% CI [1.091-1.857], p = 0.009), and grade (OR = 1.37, 95% CI [1.085-1.718], p = 0.008) but at decreased risk of PR- tumors (OR=0.57, 95% CI [0.394-0.837], p = 0.004). Overweight patients did not differ significantly from either normal weight or obese patients. Neither breast cancer-specific nor overall survival differed significantly between groups. Discussion: Higher tumor stage and size may reflect delayed detection in obese women. In contrast, tumor grade and PR status likely reflect underlying biological differences driven by increased adiposity in the breasts of obese women. Despite these differences in pathology, survival did not differ by BMI status, suggesting that factors such as suboptimal dosing may not be relevant in current patient care. Citation Format: Ellsworth RE, Lovejoy L, Costantino N, Sheiver CD. Relationship between obesity and breast tumor pathology in a contemporary set of patients [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 P6-05-04.
Phase II Study of Intrathecal Long Acting Liposomal Cytarabine (Depocyte®) In the Prophylaxis of Lymphomatous Meningitis In HIV-Related Non-Hodgkin's Lymphoma
Authors: Michele Spina, Ferdinando Martellotta, Massimiliano Berretta, Ernesto Zanet, Arben Lleshi, Vincenzo Canzonieri, Pietro Bulian, Michele Bibas, Andrea Antinori, Umberto Tirelli
Journal: Blood (2010)
Development and validation of the CLIF-AD score for the prognosis of patients with acute decompensation of cirrhosis not fulfilling criteria for acute-on-chronic liver failure (ACLF)
Authors: Rajiv Jalan, Marco Pavesi, Faouzi Saliba, Alex Amoros, Javier Fernandez, Peter Holland-Fischer, Rohit Sawhney, Rajeshwar Mookerjee, Paolo Caraceni, Tania Tm Welzel, Richard Moreau, Pere Ginès, François Durand, Paolo Angeli, Carlo Alessandria, Wim Laleman, Jonel Trebicka, Didier Samuel, Stefan Zeuzem, Thierry Gustot
Journal: Hepatology (2014)
The Human Severe Congenital Neutropenia-Associated Gfi1N382S Mutant Critically Requires Deregulated Expression of CSF1 To Block Granulopoiesis.
Authors: Chinavenmeni S. Velu, Avinash M. Baktula, Tristan Bourdeau, Shane R. Horman, H. Leighton Grimes
Journal: Blood (2007)
Transient Ex Vivo Inhibition of Heme Oxygenase 1 (HO-1) in Hematopoietic Stem/Progenitor Cells (HSPCs) By Small-Molecule Inhibitors Enhances Their Migratory Responsiveness to Bone Marrow (BM)-Secreted Chemoattractants a Novel and Simple Strategy to Improve Homing of HSPCs
Authors: Mateusz Adamiak, Joseph B Moore IV, John Zhao, Ahmed Abdelbaset-Ismail, Marcin Wysoczynski, Mariusz Z Ratajczak
Journal: Blood (2015)
Abstract MP080: Contributions of Social, Behavioral, and Biological Factors to Racial Disparities in Incident Obesity: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Kiarri N Kershaw, Gareth Dutton, David C Goff, Penny Gordon-Larsen, David Jacobs, Catarina Kiefe, Cora E Lewis, Donald M Lloyd-Jones, Hongyan Ning, James Shikany, Stephen Sidney, Kara Whitaker
Journal: Circulation (2017)

Background: A combination of social, behavioral, and biological factors are hypothesized to account in large part for racial disparities in obesity, but few studies have shown this empirically. Thus, the goal of this study was to determine the extent to which these factors accounted for racial differences in the development of obesity in men and women over a 30-year period (mean follow-up 21.7 years). Methods: This study includes the 1,617 Black (743 men and 874 women) and 1,950 White (928 men and 1,022 women) CARDIA participants with complete data on all baseline covariates who were not obese at baseline (1985-1986; ages 18-30). A series of gender-stratified Cox proportional hazards models were run adjusting separately for socioeconomic, psychosocial, neighborhood, lifestyle, and physiological factors to determine the extent to which they explained race differences in incident obesity. Results: Among men, 36.9% of Whites and 43.7% of Blacks became obese over follow-up. In women, 33.7% of Whites and 60.3% of Blacks became obese. After adjusting for age and baseline BMI, Black men were 1.39 (95% confidence interval (CI): 1.19, 1.62) times more likely to become obese than White men (Table). Covariate adjustment reduced race differences by 34%; neighborhood factors were the strongest contributors. Black women were 1.63 (95% CI: 1.42, 1.88) times more likely to become obese than White women in the base model. This association was reduced by 57% in fully adjusted models. Lifestyle factors explained the largest proportion of the race difference, followed by individual-level socioeconomic factors and neighborhood conditions. Conclusions: Racial disparities in incident obesity, and the extent to which these disparities were explained by baseline covariates, differ for men and women. Whereas substantial attenuation occurred after adjustment for a wide variety of baseline covariates, race differences in obesity incidence remained significant.
Abstract P3-04-03: S100β as a predictive biomarker and monitoring tool in endocrine resistant breast cancer
Authors: S Charmsaz, É Hughes, C Byrne, F Bane, P Tibbitts, M McIlroy, AD Hill, LS Young
Journal: Cancer Research (2017)

Abstract In estrogen receptor positive breast cancer, endocrine therapy is the standard line of treatment and even though it results in reduced recurrence and mortality, a significant number of patients will eventually relapse. Early detection of metastatic disease would significantly enhance management of endocrine resistant breast cancer. Here we investigate the potential of the calcium-binding protein S100β as a predictive biomarker and monitoring tool in endocrine treated patients. Furthermore, the efficacy of S100β inhibition as therapy in patients that fail first line endocrine therapy was examined. Primary tumor tissue expression of S100β protein was assessed in a retrospective cohort of endocrine treated breast cancer patients. Expression of S100β indicated a significant reduction in time to disease recurrence (n=509, Wilcoxon p&amp;lt;0.0001, hazard ratio 2.43, 95% C.I. is 1.607 to 3.69, p&amp;lt;0.0001, Cox proportional hazard model). S100β protein is also detectable in serum of breast cancer patients and elevated levels of serum S100β prior to removal of primary tumor is associated with poor disease free survival in endocrine treated patients (n=190, Wilcoxon p=0.0367, hazard ratio 2.68, 95% C.I. is 1.12 to 6.41, p=0.026, Cox proportional hazard model). Serum levels of S100β are significantly reduced after primary tumor resection (n=19, p=0.0003). In serial samples taken during the treatment period, elevated levels of S100β significantly associated with disease progression and with the emergence of metastatic disease (p=0.0031). In an in-vivo model of endocrine resistant breast cancer, raised levels of S100β marked the emergence of disease progression. The oncogene steroid receptor co-activator 1 (SRC1) and its interaction with homeobox protein (HOXC11) regulates S100β production in a src-kinase dependent manner. Here, src-kinase inhibition reduced tumor burden with a concomitant reduction in serum S100β. We also observed a marked reduction in expression of proliferative marker Ki67 and S100β protein following the treatment of endocrine resistant patient tumor explants with src-kinase inhibitor. Associations between elevated levels of serum S100β and subsequent disease progression in endocrine treated patients, suggests S100β as a monitoring tool for early detection of disease progression. Additionally high level of S100β can be used as a potential companion diagnostic tool for stratifying patients on endocrine therapy suitable for treatment with small molecule src-kinase inhibitor. Citation Format: Charmsaz S, Hughes É, Byrne C, Bane F, Tibbitts P, McIlroy M, Hill AD, Young LS. S100β as a predictive biomarker and monitoring tool in endocrine resistant 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 P3-04-03.
The CD45−LIN− Adult Marrow-Derived CXCR4+ SSEA-1+ Oct-4+ Very Small Embryonic-Like (VSEL) Stem Cells Form In Vitro Spheres Which May Differentiate into CD45+ Hematopoietic Cells.
Authors: Janina Ratajczak, Magda Kucia, Ewa Zuba-Surma, Ryan Reca, Mariusz Z. Ratajczak
Journal: Blood (2006)
HLA-E up-Regulation on IFN-γ Activated AML Blasts Impaired CD94/ NKG2A-Dependent NK Cytolysis Following Haplo-Mismatched Haematopoietic Stem-Cell Transplantation
Authors: Stéphanie Nguyen, Vivien Beziat, Nathalie Dhedin, Mathieu Kuentz, Madalina Uzunov, Jean-Paul Vernant, Patrice Debre, Vincent Vieillard
Journal: Blood (2008)
Dasatinib Is Well-Tolerated and Efficacious in Imatinib-Intolerant Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML).
Authors: Hanna Jean Khoury, Michael J. Mauro, Yousif Matloub, Tai-Tsang Chen, Erkut Bahceci, Michael Deininger
Journal: Blood (2009)
Plasma B-Cell Maturation Antigen Levels Are Elevated and Correlate with Disease Activity in Patients with Chronic Lymphocytic Leukemia
Authors: Kyle A Udd, Laura Z. Rassenti, Michael E David, James Wang, Suzie Vardanyan, Julia Linesch, Mingjie Li, Eric Sanchez, Haiming Chen, Tanya M. Spektor, Thomas J. Kipps, James Berenson
Journal: Blood (2015)
A comparison of prognostic systems in hepatocellular carcinoma treated with sorafenib.
Authors: Elizabeth Marie Bagnall, Gillian Gresham, Piotr Czaykowski, Kelvin K. Chan, Jennifer Fung, Susan Cuvelier, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2015)

e17696 Background: Prognostic systems remain important tools in clinical oncology to relay information to patients (pts) and to aid in therapeutic decision-making, but many were developed before the introduction of biologics. For hepatocellular carcinoma (HCC), it is unclear which of the available prognostic systems is most appropriate in an era where sorafenib has become the standard of care in advanced disease. We aimed to 1) evaluate the utility of four different prognostic scores (Okuda, BCLC, CLIP and French) and 2) identify additional independent predictors of overall survival (OS) in the setting of HCC pts treated with sorafenib. Methods: We included 339 pts with HCC treated with sorafenib from 2007 to 2014 across 3 Canadian provinces. Pt demographics, laboratory values, radiology reports, additional treatments received, performance status, and Child-Pugh scores were collected. The four existing prognostic systems were evaluated by Kaplan-Meier curves and c-statistics were ascribed to each. Independent parameters predictive of OS were identified first by univariable analyses and further validated by multivariable analyses. Results: The pt cohort was predominantly male (81%) with representation from both early (T1, 28%) and late (M1, 25%) stages of disease at presentation. Primary etiologies of liver cirrhosis included HBV (38%), HCV (26%) and EtOH (18%). Pts received a median number of three cycles of sorafenib. The median OS from the initiation of sorafenib was 7.3 months. Comparison of the four prognostic systems revealed that the French and CLIP scoring systems performed the strongest (c-indices 0.73 and 0.68, respectively), while BCLC and Okuda performed the worst (c-indices 0.64 and 0.52, respectively). Multivariable analyses confirmed that portal vein invasion, AFP > 400 and WHO performance status > 0 were significantly and independently predictive of OS. Conclusions: The French prognostic score may be better suited for pts receiving sorafenib compared to other prognostic scales, but modern prognostication of HCC may be further enhanced by a novel system that considers all of the predictive variables. This study highlights a need to revisit the utility of prognostic scores developed prior to the era of biologics.
Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk
Authors: Celia Byrne, Giske Ursin, Christopher F. Martin, Jennifer D. Peck, Elodia B. Cole, Donglin Zeng, Eunhee Kim, Martin D. Yaffe, Norman F. Boyd, Gerardo Heiss, Anne McTiernan, Rowan T. Chlebowski, Dorothy S. Lane, JoAnn E. Manson, Jean Wactawski-Wende, Etta D. Pisano
Journal: JNCI Journal of the National Cancer Institute (2017)

Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown. We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate. Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51). We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications.
Preclinical Efficacy Testing of Baxter's Recombinant ADAMTS13 in a Mouse Model of TTP.
Authors: Alexandra Schiviz, Marlene Resch, Elisa Farnleitner, Hanspeter Rottensteiner, Friedrich Scheiflinger, Hans Peter Schwarz, Werner Hoellriegl, Eva-Maria Muchitsch
Journal: Blood (2012)
Lenalidomide Plus Dexamethasone (Rev/Dex) in Newly Diagnosed Myeloma: Response to Therapy, Time to Progression, and Survival.
Authors: Martha Lacy, Morie Gertz, Angela Dispenzieri, Suzanne Hayman, Susan Geyer, Steven Zeldenrust, Shaji Kumar, Philip Greipp, Rafael Fonseca, John Lust, Stephen Russell, Robert Kyle, Thomas Witzig, Leif Bergsagel, S. Vincent Rajkumar
Journal: Blood (2006)
Cytoplasmic Immunoglobulin Fluorescence In Situ Hybridization (cIg FISH) Enhances the Quantitative Detection of Chromosome Abnormalities In Plasma Cell Neoplasms Compared to Conventional FISH
Authors: Hai-Su Yang, Josephine Montella, Laura Holt, Christine Stephenson, Pauline Brenholz, Guoxian Sun, Carol Berger, Thomas Scholl, Ajai Chari, Amitabha Mazumder, Sundar Jagannath, Henry Y. Dong
Journal: Blood (2010)