tbuckley/cabot-search huggingface dataset:
Abstract 932: A plasma microRNAs test predicts prognosis and disease status at follow-up in screening-detected lung cancer patients
Authors: Gabriella Sozzi, Stefano Sestini, Mattia Boeri, Carla Verri, Alfonso Marchiano', Carlotta Galeone, Nicola Sverzellati, Carlo La Vecchia, Ugo Pastorino
Journal: Cancer Research (2015)

Abstract Background: We previously reported that a miRNA signature classifier (MSC) based on 24 plasma circulating microRNAs is a sensitive and early biomarker for lung cancer, able to increase the specificity of low dose computed tomography (LDCT) in screening trials (Boeri et al. PNAS 2011; Sozzi et al. JCO 2014). In the present study, we have investigated the capacity of plasma MSC to predict prognosis and monitor the disease status at follow-up in LDCT screening detected lung cancer patients. Methods: Between 2000 and 2010, 3411 heavy smokers were enrolled in a screening program, with annual (2225) or biennial (1186) LDCT. During the first five years of screening, a total of 77 lung cancer patients underwent plasma MSC analysis, with three levels of risk: High, Intermediate or Low. Median follow-up of the alive patients was 4.5 years (Inter Quartile Range, IQR = 6.5). Changes of MSC risk profile at follow-up was assessed in 33 patients, with longitudinal plasma samples (n = 96) collected before and after surgical resection. Results: Five-year survival was 78% for low- to intermediate risk MSC (median nc), and 35% for High risk MSC (median 2.9 yrs, p&amp;lt;0.01). The prognostic power of MSC persisted when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (5-years survival: 87% vs. 38% respectively, p&amp;lt;0.01). Within stage I, the 5-years survival was 100% in Low to Intermediate risk MSC and 77% in High risk MSC (p = 0.10). Reduction of MSC risk profile after surgery was observed in 73% of the 26 analyzable subjects who remained disease free, at median time of 18 months (IQR = 24). In all relapsing patients the MSC test returned to Intermediate or High risk at the time of second primary or metastatic progression. Conclusions: Plasma MSC predicted lung cancer outcome and tumor recurrence at follow-up, showing potential efficacy in LDCT screening and lung cancer management. Citation Format: Gabriella Sozzi, Stefano Sestini, Mattia Boeri, Carla Verri, Alfonso Marchiano', Carlotta Galeone, Nicola Sverzellati, Carlo La Vecchia, Ugo Pastorino. A plasma microRNAs test predicts prognosis and disease status at follow-up in screening-detected lung cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 932. doi:10.1158/1538-7445.AM2015-932
Interstitial Lung Disease in Patients with Diffuse Large B-Cell Lymphoma Receiving CHOP-Based Chemotherapy Is Associated with the Use of Rituximab.
Authors: Ronald S. Go, Kevin M. Riggle, Sue A. Beier-Hanratty, Jacob D. Gundrum, Jonean E. Schroeder, Linda J. Wright, Brian A. Manske
Journal: Blood (2007)
Intensity of end-of-life cancer care among seniors: Variations by principal health care provider.
Authors: K. Murray, L. Lucas, S. Miesfeldt
Journal: Journal of Clinical Oncology (2011)

9132 Background: Quality end-of-life cancer care involves a shift from aggressive therapy to supportive services.Reasons for variations in intensity of late-life cancer care are incompletely understood. The goal of this work was to examine intensity of care based on principal healthcare provider in the last month of life, comparing primary care providers (PCPs) with oncology specialists. Methods: A retrospective claims-based analysis of hospitalizations, emergency department (ED) visits, intensive care unit admissions in the last 30 days of life; in-hospital deaths; terminal chemotherapy; and under-use/late hospice referrals among a 20% sample (n=235,821) of Medicare beneficiaries dying with poor-prognosis cancers. Logistic regression was used to quantify care variations comparing PCPs with oncology specialists as well as combined care by PCPs and oncology specialists Results: Among the 235,821 individuals studied, mean age at death was 78 years, 51.4% were male, 90.8% were non-black race, 73.5% lived in urban areas, and median income was $46,634. Of these, 74% received care from a PCP and/or an oncology specialist in the last month of life. Data (expressed as %) comparing the full cohort with those principally cared for by PCPs versus by oncology specialists versus combined care by PCPs and oncology specialists follow. Conclusions: Most measures of care intensity fell outside published benchmarks, signifying overly aggressive care. Intensity of late-life care among cancer-affected seniors varies significantly by principal healthcare provider with the most intensive care shown among those receiving combined care from PCPs and oncology specialists. All patients Primary care (PCP) only Oncology specialist only PCP and oncology n= 235,821 100,766 (42.7%) 33,318 (14.1%) 39,554 (16.8%) More than 1 hospitalization 10.2 12.4 8.5 18.3 More than 1 ED visit 10.2 13.5 6.2 17.2 Admitted to ICU 23.7 29.2 18.1 31.3 Died in an acute care facility 28.8 30.3 31.1 37.8 Chemotherapy within 14 days of death 6.0 1.6 16.4 15.9 Chemotherapy within 30 days of death 12.5 3.7 34.2 31.4 No hospice services within 6 months of death 44.8 50.6 43.2 54.6 Admitted to hospice within 3 days of death 15.1 18.3 17.3 27.4
Increased Circulating Plasma Cells Predicts Poor Overall Survival in Symptomatic Plasma Cell Myeloma Patients
Authors: Mi Hyun Bae, Sang Hyuk Park, Chan-Jeoung Park, Bo Hyun Kim, Young-Uk Cho, Seongsoo Jang, Dong-Hyun Lee, Eul-Ju Seo, Jung-Hee Lee, Dok Hyun Yoon, Cheolwon Suh
Journal: Blood (2015)
Association Of Cytogenetic Response (CyR) With RBC Transfusion-Independence (RBC-TI) and AML-Free Survival In Lenalidomide (LEN)-Treated Patients (Pts) With IPSS Low-/Int-1-Risk Myelodysplastic Syndromes (MDS) With Del(5q)
Authors: Mikkael A. Sekeres, Arlene S. Swern, Aristoteles Giagounidis, Alan List, Brigitte Schlegelberger, Pierre Fenaux, Jack Shiansong Li, Mary M. Sugrue
Journal: Blood (2013)
Abstract B48: Pancreatic cancer cells exhibit heterogeneous glucose and glutamine metabolic dependencies
Authors: Kirsten L. Bryant, Anirban Maitra, Channing J. Der
Journal: Cancer Research (2015)

Abstract Pancreatic cancer cells demonstrate altered metabolism that is consistent with amplified aerobic glycolysis, fueled by increased glucose uptake. Concurrently, additional studies have established an enhanced dependence on glutamine to power anabolic processes. Recently, there has been a renewed interest in understanding the altered metabolic requirements of cancer cells with the goal of targeting differential nutrient dependencies for therapeutic gain. We screened a panel of twelve well established and widely studied KRAS mutant pancreatic tumor-derived cell lines, as well as seven low passage KRAS mutant pancreatic patient-derived xenograft (PDX)-established tumor cell lines for the ability to proliferate in growth media deficient in glucose and/or glutamine. While 11 of 12 established cell lines were unable to proliferate in these nutrient-depleted conditions, we identified one (Capan-2) that was capable of proliferation in the complete absence of glucose. By comparison, of the seven PDX-derived cell lines screened, four demonstrated complete glucose or glutamine dependency, whereas one was capable of proliferation in the absence of glutamine and two proliferated in the absence of glucose. Our ongoing studies are focused on elucidating the mechanistic basis for glucose or glutamine independent growth. Defining these mechanisms may identify pharmacologic approaches that target metabolic pathways for the treatment of KRAS mutant pancreatic cancer. Citation Format: Kirsten L. Bryant, Anirban Maitra, Channing J. Der. Pancreatic cancer cells exhibit heterogeneous glucose and glutamine metabolic dependencies. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B48.
Abstract 3620: An oral procaspase activating drug, PAC-1, shows preclinical promise for glioblastoma therapy
Authors: Avadhut D. Joshi, Rachel C. Botham, Howard S. Roth, Timothy M. Fan, Theodore M. Tarasow, Paul J. Hergenrother, Gregory J. Riggins
Journal: Cancer Research (2015)

Abstract PAC-1 is an oral administered procaspase-3 activating drug developed to overcome the malignant cell's barrier to apoptosis. The promising preclinical safety and efficacy of PAC-1 has led to its consideration for a first in human phase 1 clinical trial for recurrent and advanced malignancies. We have found that because PAC-1 is able to reach intracranial brain tumors in effective concentrations, that it is particularly useful for glioblastoma (GBM), an aggressive and invasive malignancy responsible for the most deaths due to brain cancer. In glioblastoma patients a worse prognosis was correlated with high expression of procaspase-3 mRNA, indicating that procaspase-3 activation may be involved in the pathology of the tumor progression. In preclinical testing of PAC-1, it showed significant survival benefit and low systemic toxicity, in orthotopic animal models of glioblastoma. An aqueous suspension of PAC-1 delivered orally to rats with intracranial 9L glioblastoma improved survival compared to untreated controls. Additionally, when PAC-1 was administered as an oral capsule to rats with 9L glioblastoma, median survival increased over three fold. Oral PAC-1 improved survival significantly also in a human xenograft model (p = 0.04) compared to controls. PAC-1 combined effectively with standard of care, and in some animals, either alone or in combination resulted in long term survival. PAC-1 has the ability to penetrate sufficiently within intracranial tumors and its ability to overcome resistance to apoptosis and activate widespread cell death specifically in the malignant cells makes it a promising small molecule for further preclinical and clinical development. Citation Format: Avadhut D. Joshi, Rachel C. Botham, Howard S. Roth, Timothy M. Fan, Theodore M. Tarasow, Paul J. Hergenrother, Gregory J. Riggins. An oral procaspase activating drug, PAC-1, shows preclinical promise for glioblastoma therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3620. doi:10.1158/1538-7445.AM2015-3620
Sabutoclax, a Novel Pan BCL2 Family Inhibitor, Sensitizes Dormant Blast Crisis Chronic Myeloid Leukemia Stem Cells to Dasatinib
Authors: Heather S. Leu, Daniel J Goff, Janine Low-Marchelli, Angela C Court Recart, Kristen M. Smith, Wenxue Ma, Anil Sadarangani, Alice Y. Shih, Jun Wei, Dayong Zhai, Jason Gotlib, Mark D. Minden, Giovanni Martinelli, Marco A. Marra, Kelly A Frazer, Maurizio Pellecchia, John C. Reed, Catriona Jamieson
Journal: Blood (2012)
Distinctions between adult T-cell leukemia-lymphoma (ATLL) secondary to human T-cell lymphotropic virus 1 (HTLV1) and peripheral T-cell lymphoma (TCL).
Authors: G. D. Ayalew, J. Yao, K. A. Killoran, K. Laveaux, C. A. Axiotis, A. S. Braverman
Journal: Journal of Clinical Oncology (2011)

6573 Background: ATLL is a peripheral T cell neoplasm with characteristic clinical and immunopathological features, occurring in some individuals infected with HTLV-1, usually from specific endemic regions. Histopathology does not distinguish ATLL from non-HTLV1-related TCL. HTLV serology (HTLVs) can rule ATLL out, but does not exclude the presence of a non-HTLV-related TCL. Objective:To compare the clinical and immuno-pathological features of ATLL to those of patients with TCL not associated with HTLV1 infection. Methods: The charts of patients presenting to the Kings County Hospital Center and University Hospital of Brooklyn between 1999 and 2010, whose biopsies showed ATLL or TCL, were reviewed for the following: HTLV1 serology (HTLVS), circulating lymphocytes with multi-lobed nuclei (LML), serum calcium (Ca) levels, cutaneous involvement (Cut), survival (OS), CD25 and Foxp3 expression, and phenotypic markers determined by flow cytometry. Results: Of the 59 patients available for study, 24 were men and 35 women, ranging from 33 to 81 years of age (median 54). All but 2 of the 44 ATLL patients were acute or lymphomatous. HTLVs was available in 30 and positive in 28 of the 44 ATLL patients. Data are presented in the table. Only 4 ATLL patients were neither hypercalcemic nor had LML. All Foxp3+ patients were CD25+. Of the 28 patients known to be serologically positive for HTLV1, 25 were CD25+ (89%). On flow cytometry, 12 of 12 ATLL patients were CD25+ but only 6% were CD7+. None of these parameters were determined for TCL patients. Conclusions: ATLL and TCL can usually be diagnosed by clinical and laboratory findings. CD25 and Foxp3 expression may prove helpful in distinguishing between them. No. of patients Cut LML Ca median (range) Ca ↑ CD25+ Foxp3+ CD30+ OS ≥1 yr ATLL 44 (75%) 5% 55% 14 (8.6-28) 73% 89% 44% 33% 16% TCL 15 (25%) 33% 13% 10 (8.6-14) 26% 26% ND 70% 40%
433. Sequence-Optimized Nitroreductase for Retroviral Replicating Vector (RRV) Mediated Prodrug Activator Gene Therapy in Human Glioma Models
Authors: Sara A. Collins, Christopher R. Logg, Akihito Inagaki, Shuichi Kamijima, Panos Lehouritis, Peter F. Searle, Mark Tangney, Noriyuki Kasahara
Journal: Molecular Therapy (2015)

Our studies to date have demonstrated dramatic survival benefit when tumor-selective retroviral replicating vectors (RRV) are employed for prodrug activator gene therapy in a variety of preclinical cancer models. RRV-mediated gene therapy using yeast cytosine deaminase (CD) is under investigation in multi-center ascending dose trials in patients with recurrent high grade glioma in the United States. We have further developed an RRV encoding E.coli nitroreductase (NTR), a prodrug activator enzyme which converts CB1954 to a potent bifunctional alkylating agent. We constructed RRV encoding wild-type E.coli NTR genes (RRV-NfsA, RRV-NfsB) as well as NTR variants extensively modified to optimize human codon usage and vector stability (RRV-NAO, RRV-NBO). NTR transgene insertion did not affect vector replication, which resulted in increasing NTR expression over time in U87 human glioma cultures for all vectors, but sequence optimisation significantly increased genomic stability of the RRV-NAO and RRV-NBO vectors over serial passage. U87 cells fully transduced with the optimized vectors showed higher levels of NTR protein and increased levels of enzymatic activity compared with cells transduced with wild-type vectors. In vitro cytotoxicity was examined by MTS assay after CB1954 treatment of fully transduced U87 cells. Viability was reduced by >80% within 48 hrs in cells transduced with RRV-NAO, which showed the most potent cell killing efficiency and bystander effect among all vectors tested. Significant reduction in luminescence and inhibition of tumor growth was observed in subcutaneous U87-FLuc2 tumors initiated with 2% RRV-NAO transduction followed by intraperitoneal administration of CB1954. In intracerebral U87-FLuc2 orthotopic tumor models, stereotactic intratumoral injection of RRV-NAO and repeated cycles of prodrug treatment also resulted in significant luminescence reduction, and achieved prolonged survival benefit. These data indicate that we have been successful in developing an improved prodrug activator gene with therapeutic efficacy when delivered by RRV in experimental models of human glioma.
Abstract 3349: Optimizing radioimmunotherapy techniques for the alpha-emitter 225Actinium
Authors: Ricklie A. Julian, Chi Soo Kang, Xiang Sun, Hyun A. Song, Ekaterina Revskaya, Hyun-Soon Chong, Ekaterina Dadachova
Journal: Cancer Research (2015)

Abstract Introduction: Radioimmunotherapy (RIT) is a potent therapeutic technique that may be applicable to the treatment of numerous human cancers. Currently available RIT therapies employ beta- and alpha-emitting radionuclides. Alpha-emitters, such as 225Actinium (225Ac), have promising advantages over beta-emitters RIT such high linear energy transfer and independence of the tumor oxygenation status. RIT using 225Ac radionuclide directed by the monoclonal antibodies trastuzumab or panitumumab may provide effective, targeted antineoplastic effects. Methods: Antibodies trastuzumab to HER2/neu and panitumumab to EGFR were conjugated to the bifunctional ligands NETA, DOTA, DECA, DEPA and DETA. The conjugates were labeled with 225Ac at room temperature and 37°C. At selected time points, the mixture was analyzed by instant thin layer chromatography (ITLC). Radiolabeling reaction kinetics and yields were calculated for 225Ac and for its daughter isotopes 221Francium (221Fr) and 213Bismuth (213Bi) using the energy discrimination function of the multichannel analyzer in the gamma counter. Summary of the new data: Radiolabeling with Actinium was effective for several ligand-antibody combinations and completed within 30 min. Radiolabeling yields for 225Ac and it daughters 221Fr and 213Bi were most robust for NETA and DECA conjugates to trastuzumab and panitumumab, labeled at 37°C. Conclusion: Several novel ligands were evaluated for radiolabeling of monocloncal antibodies trastuzumab or panitumumab with 225Ac radionuclide and demonstrated fast kinetics of radiolabeling. Potential for targeted therapeutic applications will be explored in future experiments. Citation Format: Ricklie A. Julian, Chi Soo Kang, Xiang Sun, Hyun A. Song, Ekaterina Revskaya, Hyun-Soon Chong, Ekaterina Dadachova. Optimizing radioimmunotherapy techniques for the alpha-emitter 225Actinium. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3349. doi:10.1158/1538-7445.AM2015-3349
Abstract 3871: Telomere length and cancer mortality and all-cause mortality
Authors: Stig E. Bojesen, Børge G. Nordestgaard, Line Rode
Journal: Cancer Research (2015)

Abstract Introduction: Short telomeres are associated with increased age and age-related diseases. We tested the hypothesis that short telomeres are associated with increased cancer mortality and all-cause mortality. Methods: We studied 64637 individuals recruited from 1991 and onwards from two prospective cohort studies; the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by Q-PCR in DNA from peripheral blood and had the telomere length-associated genotypes of rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. We calculated the sum of telomere length shortening alleles from the three SNPs combined. We conducted Cox regression, and instrumental variable analyses in a mendelian randomization design, using the allele sum as a genetic instrument for telomere length. Results: Telomere length shortened by 17 (P&amp;lt;10E-300) and 69 (P = 110E-104) base pairs per increase of one year of age, and one allele increase of allele sum, respectively. Of the 7607 deaths during up to 22 years of follow-up, 2420 were due to cancer. Shortening of telomeres (200 base pairs) was associated with increasing cancer mortality and all-cause mortality with hazard ratios of 1.02(95% CI;1.01-1.03) and 1.02(95% CI;1.02-1.03) in multifactorially adjusted models. In contrast, in the genetic analyses, the corresponding odds ratios were 0.86(95% CI;0.76-0.96) and 0.98(95% CI;0.91-1.05). Conclusion: In an observational design, short telomeres were associated with increased cancer mortality and all-cause mortality. In contrast and importantly; in a mendelian randomization design, short telomeres were associated with decreased cancer mortality, suggesting that short telomeres are likely causative in protecting against cancer mortality. Citation Format: Stig E. Bojesen, Børge G. Nordestgaard, Line Rode. Telomere length and cancer mortality and all-cause mortality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3871. doi:10.1158/1538-7445.AM2015-3871
189. Airway Pre-Treatment Enhances Mouse Lung Lentiviral Reporter Gene Expression
Authors: Sharnna Devereux, Patricia Cmielewski, Nigel Farrow, David Parsons
Journal: Molecular Therapy (2015)

Cystic fibrosis (CF) is the most common, fatal genetic disease among the Caucasian population. VSV-G pseudotyped lentiviral (LV) gene vectors have the potential to treat CF long-term, however physiological barriers prevent efficient vector access to ciliated and basal (stem) cells residing on the basement membrane. We have previously demonstrated the effectiveness of our lysophosphatidylcholine (LPC) pre-treatment and LV vector dosing technique for producing ciliated and basal cell transduction in mouse nasal airways. The aim of this experiment was to determine if LPC pre-treatment enhances LV reporter gene transduction in mouse lung conducting airways (the primary target of a CF gene therapy). A HIV-1 LV vector carrying the LacZ transgene was instilled directly into the trachea of C57Bl/6 mice (n=10 per group) via orotracheal intubation, 1 hour after a pre-treatment of PBS (control), 0.1% LPC, or 0.3% LPC. LacZ expression was assessed by X-gal staining of the lungs after mice were humanely killed 11 weeks after dosing. Dosing was well tolerated. There was no LacZ transduction in the control group that received the PBS pre-treatment, however there was a consistent pattern of strong LacZ transduction of the conducting airways in both LPC treatment groups. H&E staining of lung sections revealed that 0.3% LPC produced the greatest number of LacZ positive cells. In both LPC treatment groups the majority of cell transduction occurred in ciliated epithelial cells, with some basal cell transduction. LPC pre-treatment prior to LV vector delivery into mouse lungs improves the level of transduction achieved. The LPC pre-treatment groups also showed basal-cell transduction that may indicate effective targeting of resident airway stem cells.