tbuckley/cabot-search huggingface dataset:
Abstract 1466: Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through the incorporation of murine stromal elements
Authors: Daniel Delitto, Kien Pham, Adrian C. Vlada, George A. Sarosi, Ryan M. Thomas, Kevin E. Behrns, Chen Liu, Steven J. Hughes, Shannon M. Wallet, Jose G. Trevino
Journal: Cancer Research (2015)

Abstract Direct implantation of viable surgical specimens provides a representative preclinical platform in pancreatic adenocarcinoma (PC). Patient-derived xenografts consistently demonstrate retained tumor morphology and genetic stability. However, the evolution of the tumor microenvironment over time remains poorly characterized in these models. This work specifically addresses the recruitment and incorporation of murine stromal elements into expanding patient-derived PC xenografts, establishing the rapidity by which murine cells are integrated into networks of invading cancer cells. In addition, we provide methodology and observations in the establishment and maintenance of a patient-derived PC xenograft model. A total of 25 histologically confirmed pancreatic adenocarcinoma specimens were implanted subcutaneously into NOD-SCID mice. Patient demographics, staging, pathologic analysis and outcomes were analyzed. After successful engraftment of tumors, histologic and immunofluorescent analyses were performed on explanted tumors. PC specimens were successfully engrafted in 15 of 25 (60%) of attempts. Successful engraftment does not appear to correlate with clinicopathologic factors or patient survival. Tumor morphology is conserved through multiple passages and tumors retain metastatic potential. Interestingly, despite morphologic similarity between passages, human stromal elements do not appear to expand with invading cancer cells. Rather, desmoplastic murine stroma dominates the xenograft microenvironment after the initial implantation. Recruitment of stromal elements in this manner to support and maintain tumor growth represents a novel avenue for investigation into tumor-stromal interactions. Citation Format: Daniel Delitto, Kien Pham, Adrian C. Vlada, George A. Sarosi, Ryan M. Thomas, Kevin E. Behrns, Chen Liu, Steven J. Hughes, Shannon M. Wallet, Jose G. Trevino. Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through the incorporation of murine stromal elements. [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 1466. doi:10.1158/1538-7445.AM2015-1466
ACRIN 6690: Can contemporary imaging reduce false-positive rate in liver transplant (LT) allocation? A multicenter comparison of CT and MRI for diagnosis of hepatocellular carcinoma (HCC).
Authors: C. Wald, M. Nalesnik, E. A. Pomfret, M. Russo, M. A. Rosen, D. M. Hartfeil, P. Fox, M. L. Heckel, C. Gatsonis
Journal: Journal of Clinical Oncology (2011)

TPS177 Background: New imaging criteria suggested by Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) for computed tomography (CT) and magnetic resonance imaging (MRI) may accurately diagnose and stage HCC in patients with end-stage disease listed for LT. A large-scale clinical trial is needed to examine the utility of new liver imaging policy guidelines for deceased donor (DD) liver allocation. Data suggest current CT/MRI imaging criteria are inadequate, since 20% of LT recipients diagnosed with HCC by current criteria did not have HCC on explant (Freeman et al. Liver Transpl. 2006:1504-11). This trial compares the accuracy of radiologic staging of HCC by CT and MRI with the reference standard of explant pathology and compares the sensitivity and accuracy of CT and MRI to each other in diagnosing HCC in patients with cirrhosis. Optimally, the new policy will reduce false positive rate of imaging diagnosis of HCC and guide appropriate DD liver allocation. Methods: The trial cohort will comprise 440 participants from 30 ACRIN-qualified transplant centers in the 11 U.S. OPTN transplant regions. Eligible patients are diagnosed with HCC and initially listed for LT with priority HCC-exception MELD (Model for End-Stage Liver Disease) points within 30 days of trial enrollment. Participants will undergo CT and MRI every 90 days. The serial imaging series immediately prior to LT will be read using the new OPTN/UNOS policy and then compared with explant pathology. The primary aim will compare the sensitivity of CT to that of MRI for diagnosing HCC, at lesion and patient levels, in patients with cirrhosis awaiting LT. Additional aims will compare: positive predictive value of CT and MRI in diagnosing HCC, interpretations by radiologists at participating centers, and sensitivity and specificity of CT versus MRI for diagnosing residual or recurrent HCC after local ablative therapy. Exploratory analysis will examine the affects of AFP level on other trial analyses.
Kinetics of Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients May Predict Persistent Polymerase Chain Reaction Negativity after Imatinib Discontinuation.
Authors: Giovanna Rege-Cambrin, Stefano Ulisciani, Giovanna Mattioli, Carmen Fava, Emilia Giugliano, Vanessa Brunetto, Enrico Gottardi, Milena Fava, Giuseppe Saglio
Journal: Blood (2007)
Aberrant spontaneous low-frequency brain activity in amnestic mild cognitive impairment: A meta-analysis of resting-state fMRI studies
Authors: PingLei Pan, Lin Zhu, TingTing Yu, HaiCun Shi, Bing Zhang, Ruomeng Qin, Xiaolei Zhu, Lai Qian, Hui Zhao, Hong Zhou, Yun Xu
Journal: Ageing Research Reviews (2016)
Leukemogenic Transformation of Hematopoietic Cells by Constitutive Activation of Canonical Wnt Signaling in Osteoblast Precursors
Authors: Aruna Kode, Sanil Manavalan, Ioanna Mossialou, Govind Bhagat, Murty Vundavalli, Ronald DePinho, Julie Teruya-Feldstein, Ellin Berman, Stavroula Kousteni
Journal: Blood (2012)
Abstract 1927: Evolutionary novel genes expressed in fish tumors determine progressive evolutionary characters
Authors: Ekaterina Matyunina, Alexander Emelyanov, Andrei Kozlov
Journal: Cancer Research (2015)

Abstract The origin of evolutionary novel genes is connected with the origin and evolution of the novel organismal functions and the increase in morphological complexity of multicellular organisms. Novel gene acquire new or altered functions. Here we describe that evolutionary novel genes, expressed predominantly in transgenic fish tumors after their induced regression, determine progressive evolutionary characters and are conserved in human. We used a sample of genes, which were activated in inducible krasV12 transgenic zebrafish tumors according to the results of RNASeq data. Genes from our sample were expressed after HCC regression upon kras inactivation. The search of orthologs by different tools, such as blastx and psiblast, with e-value cut off not less than 10-3 and query coverage more than 50%, discovered that considerable proportion of tumor-specifically expressed genes are evolutionary novel, i.e. their orthologs are not found in Lamprey. 63 of these novel genes have orthologs in humans. Gene ontology (GO) data were used to analyze their functions. According to the results of GO some of the genes have functions not characteristic to fish. Among known functions of the human orthologues of evolutionary novel genes of zebrafish (vs. Lamprey) there are some important morphogenetic functions. For example, genes ccdc40, lmx1ba and lepa acquired functions in lung, embryonic utera and placenta, i.e. organs originated in taxa higher than fish. A large proportion of genes from our sample are connected with retina type eye, heart and brain development. Citation Format: Ekaterina Matyunina, Alexander Emelyanov, Andrei Kozlov. Evolutionary novel genes expressed in fish tumors determine progressive evolutionary characters. [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 1927. doi:10.1158/1538-7445.AM2015-1927
Cost-effectiveness of systemic therapies for metastatic pancreatic cancer.
Authors: V. C. Tam, Y. Ko, N. Mittmann, K. Kumar, S. Hassan, M. C. Cheung, K. K. Chan
Journal: Journal of Clinical Oncology (2011)

6114 Background: Metastatic pancreatic cancer (MPC) is an aggressive disease with a median survival of 6 months when treated with gemcitabine (G). Gemcitabine + capecitabine (G+C), gemcitabine + erlotinib (G+E), and FOLFIRINOX (FFX) are emerging as new treatment options. However, these new treatment options are costly and it is unclear which is the most cost-effective. Methods: A Markov model was constructed for a hypothetical cohort of patients with MPC to examine the costs and outcomes of 4 treatment options (G, G+C, G+E, FFX) over a time horizon of 2 years. Primary outcome was the incremental cost-effectiveness ratio measured in dollars per quality adjusted life-year ($/QALY). The analysis was conducted from the perspective of the Canadian public healthcare system. Efficacy data of the treatments were obtained from phase III clinical trial literature. Resource utilization data were derived from reviewing charts of consecutive patients (n=42) treated at Princess Margaret Hospital from 2008 to 2009 and supplemented with resource utilization data from the literature. Unit costs were obtained from the Ontario Ministry of Health and Long-Term Care, Sunnybrook Health Sciences Centre and the literature. Utilities were obtained by surveying academic medical oncologists (n=25) across Canada using EQ-5D. Costs were calculated in 2010 Canadian dollars (CAD$). Both cost and effectiveness were discounted at 3%. Results: See table below for costs and outcomes. The incremental cost-effectiveness ratios of G+C, G+E and FFX when compared to G were $82,982/QALY, $204,952/QALY and $154,323/QALY, respectively. The model is mostly driven by the acquisition cost of drugs, and may be sensitive to the relative efficacy of treatments. FFX may be cost-effective at a willingness-to-pay (WTP) threshold of $100,000/QALY if the acquisition costs of the chemotherapy drugs are reduced by 40%. Conclusions: G+C is cost-effective when compared to G if WTP is at $100,000/QALY. Price negotiation between the payer and manufacturer may be important to allow for clinically effective treatment options to be funded cost-effectively. G G+C G+E FFX Cost (CAD$) 29,658 34,139 46,874 65,924 Life expectancy (years) 0.677 0.762 0.790 1.005 QALY 0.529 0.583 0.613 0.764
Folate Pathway Gene Expression Differs in Genetic Subtypes of Acute Lymphoblastic Leukemia and Influences Methotrexate Pharmacodynamics.
Authors: Leo Kager, Meyling H. Cheok, Wenjian Yang, Gianluigi Zaza, Ching-Hon Pui, James R. Downing, Mary V. Relling, William E. Evans
Journal: Blood (2004)
TOR-mediated autophagy regulates cell death in<i>Drosophila</i>neurodegenerative disease
Authors: Tao Wang, Uyen Lao, Bruce A. Edgar
Journal: The Journal of Experimental Medicine (2009)

Objective To study the changes of intramucosal pH(pHi) and serum protein levels after early enteral nutrition in patients with severe craniocerebral injury.Methods According to the vital signs and intestinal sounds,enteral nutrition(EN) and parenteral nutrition(PN) were respectively given to the patients 12 to 72 h after operation.The value of pHi was monitored continuously in the following 5 days.Results The value of pHi and serum protein levels increased in both groups on the 5th day after operation(P0.05).Moreover,the value of pHi and serum protein levels of EN group increased more than that of PN group(P0.05).The restoration of anal exhaust time of EN group shortened significantly than that of PN group(P0.05).Conclusion The use of early enteral nutrition can improve the blood perfusion and oxygenation of gastrointestinal mucosae as well as the nutritional status in severe craniocerebral injury patients.
Umbilical Cord Blood (UCB) Graft T-Cells Correlate with Myeloid Recovery in Adults with Hematologic Malignancies Treated with Reduced Intensity Conditioning (RIC) and Single Unit Infusion.
Authors: Y. Hegerfeldt, L.R. Fanning, P. Fu, H.M. Lazarus, B. Cooper, W. Tse, H. Meyerson, S.L. Gerson, J. Jaroscak, R. Fox, R. Creger, J. Maciejewski, M. Tary-Lehmann, M. Ratajczak, C. Stevens, P. Rubinstein, M.A. Hoffman, Mary J. Laughlin
Journal: Blood (2006)
Differential Plasma Cytokine Levels in Patients with and without Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Caron A. Jacobson, Joshua Geary, Haesook T Kim, Sean McDonough, Carol G Reynolds, Maria I. Herrera, John Koreth, Corey Cutler, Vincent T Ho, Edwin P Alyea, Philippe Armand, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz
Journal: Blood (2012)
t(12;21)/ETV6 -RUNX1 Confers a Specific Pattern of In Vivo Sensitivity to Treatments in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL): Results of the Randomized Trials 58881 and 58951 of the EORTC Children Leukemia Group
Authors: Caroline Piette, Stefan Suciu, Emmanuelle Clappier, Yves Bertrand, Genevieve Plat, Christophe Chantrain, Vitor Costa, Nicole Dastugue, Alina Ferster, Caroline Gilotay, Sandrine Girard, Nathalie Grardel, Patrick Lutz, Francoise Mazingue, Odile Minckes, Martine Munzer, Emmanuel Plouvier, Nicolas Sirvent, Anne Uyttebroeck, Nadine van Roy, Karima Yakouben, Yves Benoit, Hélène Cavé
Journal: Blood (2015)
Differential Protein Expression of Zinc Finger Proteins and Cell Cycle Regulators between Lipopolysaccharide (LPS)-Activated Cord Blood (CB) and Adult Peripheral Blood (APB) Dendritic Cells (DC) Derived from Monocytes: Implication of CB Versus APB DC Differential Innate and Adaptive Immunity.
Authors: H. Jiang, M. S. Lim, K.S.J. Elenitoba-Johnson, C. Wade-Harris, L. Baxi, M. S. Cairo
Journal: Blood (2005)
Phase II/III Randomized Study Comparing Two Different Tacrolimus Blood Levels for the Prevention of Graft-Versus-Host Disease (GVHD).
Authors: Daniel R. Couriel, Peter Thall, Kerry Mickler, Marcos De Lima, Sergio Giralt, Muzaffar H. Qazilbash, Chitra Hosing, Issa Khouri, Partow Kebriaei, Yvonne Hsu, Rima Saliba, Cindy Ippoliti, Richard Champlin
Journal: Blood (2005)
Addressing Unmet Basic Resource Needs as Part of Chronic Cardiometabolic Disease Management
Authors: Seth A. Berkowitz, Amy Catherine Hulberg, Sara Standish, Gally Reznor, Steven J. Atlas
Journal: JAMA Internal Medicine (2016)

It is unclear if helping patients meet resource needs, such as difficulty affording food, housing, or medications, improves clinical outcomes.To determine the effectiveness of the Health Leads program on improvement in systolic and diastolic blood pressure (SBP and DBP, respectively), low-density lipoprotein cholesterol (LDL-C) level, and hemoglobin A1c (HbA1c) level.A difference-in-difference evaluation of the Health Leads program was conducted from October 1, 2012, through September 30, 2015, at 3 academic primary care practices. Health Leads consists of screening for unmet needs at clinic visits, and offering those who screen positive to meet with an advocate to help obtain resources, or receive brief information provision.Changes in SBP, DBP, LDL-C level, and HbA1c level. We compared those who screened positive for unmet basic needs (Health Leads group) with those who screened negative, using intention-to-treat, and, secondarily, between those who did and did not enroll in Health Leads, using linear mixed modeling, examining the period before and after screening.A total of 5125 people were screened, using a standardized form, for unmet basic resource needs; 3351 screened negative and 1774 screened positive. For those who screened positive, the mean age was 57.6 years and 1811 (56%) were women. For those who screened negative, the mean age was 56.7 years and 909 (57%) were women. Of 5125 people screened, 1774 (35%) reported at least 1 unmet need, and 1021 (58%) of those enrolled in Health Leads. Median follow-up for those who screened positive and negative was 34 and 32 months, respectively. In unadjusted intention-to-treat analyses of 1998 participants with hypertension, the Health Leads group experienced greater reduction in SBP (differential change, -1.2; 95% CI, -2.1 to -0.4) and DBP (differential change, -1.0; 95% CI, -1.5 to -0.5). For 2281 individuals with an indication for LDL-C level lowering, results also favored the Health Leads group (differential change, -3.7; 95% CI -6.7 to -0.6). For 774 individuals with diabetes, the Health Leads group did not show HbA1c level improvement (differential change, -0.04%; 95% CI, -0.17% to 0.10%). Results adjusted for baseline demographic and clinical differences were not qualitatively different. Among those who enrolled in Health Leads program, there were greater BP and LDL-C level improvements than for those who declined (SBP differential change -2.6; 95% CI,-3.5 to -1.7; SBP differential change, -1.4; 95% CI, -1.9 to -0.9; LDL-C level differential change, -6.3; 95% CI, -9.7 to -2.8).Screening for and attempting to address unmet basic resource needs in primary care was associated with modest improvements in blood pressure and lipid, but not blood glucose, levels.
Abstract 1283: In situ activity of tumor specific CTL is a prognostic factor in colorectal cancer
Authors: Slava Stamova, Christoph Reissfelder, Christina Gossmann, Marion Braun, Andreas Bonertz, Ute Walliczek, Moritz Koch, Axel Benner, Dirk Jäger, Niels Halama, Khashayarsha Khazaie, Jürgen Weitz, Philipp Beckhove
Journal: Cancer Research (2015)

Abstract The extent of T cell infiltrates in the primary tumor is one of the most important prognostic factors in colorectal cancer (CRC). Still, a putative causal role of T cell infiltrates for prolonged patient survival remains unclear. To answer this question, we studied the presence and functional activity of tumor infiltrating lymphocytes (TIL) together with their specificity in CRC patients and correlated the obtained results to long term survival. We have utilized intracytoplasmic cytokine staining, conjointly with human leukocyte antigen (HLA)- multimers loaded with peptides derived from tumor antigen (TA), as well as antigen specific cytokine secretion assays, to demonstrate that tumor necrosis factor alpha (TNFα) expression characterizes a population of TA specific, in situ active cytotoxic T cells. TNFα was increased in CRC tumors only when patients develop spontaneous systemic T cell responses, as elucidated by IFN-γ Elispot, and this increase correlated with the number of TNFα expressing tumor infiltrating T cells. Based on these observations we concluded that intratumoral TNFα can be a direct indicator of the in situ functionality of tumor specific effector T cells in CRC. In accordance, intratumoral TNFα concentration was an independent long term prognostic factor in a retrospective multivariate analysis of a cohort of 102 CRC patients involving various other immune parameters, such as CD4+, CD8+ T cell infiltration, presence of regulatory T cells or mast cells. In conclusion, our findings provide evidence for a causal relationship between T cell infiltrates and improved survival in CRC patients as the prognostic impact of T cell infiltrates depends on small subpopulations of in situ active TA specific T cells. Furthermore TNFα, as an indicator for the functionality of TIL, might be better and more accurate prognostic parameter in CRC than mere T cell infiltration. Citation Format: Slava Stamova, Christoph Reissfelder, Christina Gossmann, Marion Braun, Andreas Bonertz, Ute Walliczek, Moritz Koch, Axel Benner, Dirk Jäger, Niels Halama, Khashayarsha Khazaie, Jürgen Weitz, Philipp Beckhove. In situ activity of tumor specific CTL is a prognostic factor in colorectal cancer. [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 1283. doi:10.1158/1538-7445.AM2015-1283
Cetuximab-based or bevacizumab-based first-line treatment in patients with <i>KRAS</i> p.G13D mutated metastatic colorectal cancer (mCRC)? A meta-analysis of 54 cases.
Authors: Volker Heinemann, Anke Reinacher-Schick, Sebastian Stintzing, Clemens Albrecht Giessen, Andrea Tannapfel, Ruediger P. Laubender, Thomas Brodowicz, Regina Knittelfelder, Damir Vrbanec, Wolff Schmiegel, Dominik Paul Modest, Christoph Zielinski
Journal: Journal of Clinical Oncology (2012)

511 Background: KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified to represent a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question whether first-line treatment of p.G13D mCRCs should contain cetuximab or bevacizumab. Methods: Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic 1 st -line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. Results: Overall response rate was comparable between cetuximab- and bevacizumab-based regimens (58% vs 57%). Progression-free survival was comparable (8.0 months-cetuximab-group vs 8.7 months bevacizumab-group). Overall survival (OS) was longer in patients treated with cetuximab as first-line therapy (20.1 months vs 14.9 months). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate significantly with poor outcome (p=0.03). Moreover, a strong trend in favour of capecitabine compared to infusional 5-FU (p=0.06) was seen.. Responders among our cohort showed a benefit concerning PFS and OS undergoing cetuximab- but not bevacizumab-based regimen. Conclusions: This retrospective pooled analysis suggests that cetuximab-based first-line therapy in p.G13D mutant mCRC shows similar activity compared to bevacizumab-containing regimen. Infusional 5-FU and oxaliplatin may represent inferior options compared to capecitabine and irinotecan in p.G13D mutant mCRC 1 st -line treatment.
The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients
Authors: B. Lian, C.L. Cui, L. Zhou, X. Song, X.S. Zhang, D. Wu, L. Si, Z.H. Chi, X.N. Sheng, L.L. Mao, X. Wang, B.X. Tang, X.Q. Yan, Y. Kong, J. Dai, S.M. Li, X. Bai, N. Zheng, C.M. Balch, J. Guo
Journal: Annals of Oncology (2016)