tbuckley/cabot-search huggingface dataset:
Modulation of angiogenic biomarkers in patients receiving high-dose TRC105.
Authors: Yingmiao Liu, Mark Starr, John C Brady, Herbert Pang, Andrew Dellinger, Bryan R. Leigh, Charles P. Theuer, Herbert Hurwitz, Andrew B. Nixon
Journal: Journal of Clinical Oncology (2012)

e21038 Background: TRC105, an anti-CD105 monoclonal antibody, has completed phase 1 testing and is being studied in multiple phase 2 trials. We previously reported that low dose TRC105 (0.01-1.0 mg/kg) modulated the expression of soluble angiogenic biomarkers in patients [J Clin Oncol 29: 2011 (suppl; abstr 10565)]. In this report, we evaluated angiogenic biomarkers in patients receiving higher doses of TRC105 including the recommended phase 2 dose. Methods: Patients with advanced refractory solid tumors were treated with escalating doses of TRC105 until disease progression. Serial plasma samples were analyzed via an optimized multiplex ELISA platform. 36 biomarkers related to tumor growth, angiogenesis, and inflammation were assayed at baseline (BL), after 1 month (C2D1), concurrent with radiological restaging near the end of cycle 2 (C2D22), and at end of study (EOS). Results: 32 patients treated with TRC105 at doses of 0.3 to 15 mg/kg were evaluated for biomarker expression. Wilcoxon signed rank tests indicated that the following analytes were significantly different at C2D1 when compared with baseline (p&lt;0.05): Ang-2, IGFBP-3, total PAI-1, PDGF-AA, PDGF-BB, TSP-1, VEGF-D were all down-regulated; and E-Cadherin, soluble CD105, E-Selectin, IL-6, OPN, TSP-2, vWF were all up-regulated. At EOS, significant increases from C2D1 were observed for the following analytes: Ang-2, CRP, ICAM-1, IGFBP-1, IL-6, TSP-2, and VCAM-1 (p&lt;0.05). Additionally, dose-dependent increases in soluble CD105 at C2D1 were observed (p&lt;0.0001, r=0.9), suggesting direct target modulation by TRC105. Conclusions: TRC105 therapy is associated with early down-regulation of certain key angiogenic biomarkers and a dose-dependent increase in sCD105. Increases in many initially down-regulated angiogenic factors were observed at the time of progression, suggesting possible mechanisms for acquired resistance to TRC105. Further analysis of TRC105 in specified patient populations is underway and may provide more insight into the biological effects of this drug.
Resistance to cisplatin-induced apoptosis is partly due to nuclear localization of phospho-ERK2 in cisplatin resistant ovarian cancer cells
Authors: Sooyong Lee, Dong-Hyun Kim
Journal: Cancer Research (2005)

1486   Extracellular signal-regulated kinase 1/2 (ERK1/2) is known to have bi-functional role in cell death and survival. Cisplatin activates ERK pathway but the exact role of ERK signaling in cisplatin-induced apoptotic cell death is still controversial. We studied the role of nuclear localization of phospho-ERK in cisplatin-induced apoptosis using sensitive OVCAR-3 cells and resistant OVCAR-3/CDDP cells. Western blot analysis showed that considerable amount of phospho-ERK2 existed in the nuclei of OVCAR-3/CDDP cells in the absence of cisplatin whereas it was not detected in OVCAR-3 cells. Nuclear levels of phospho-ERK2 showed biphasic pattern when treated with cisplatin. The levels in OVCAR-3/CDDP cells were increased up to 3 hr, decreased thereafter and then increased again after 24 hr. Similar pattern was observed in OVCAR-3 cells but the levels was significantly lower compared to those in OVCAR-3/CDDP cells. Pre-localization of phospho-ERK2 in nuclei of OVCAR-3/CDDP cells was observed when cisplatin was treated after serum starvation. Treatment of PD98059 and U0126 sensitized OVCAR-3 cells to cisplatin but it did not affect the sensitivity of OVCAR-3/CDDP cells to cisplatin, suggesting that pre-existed phospho-ERK2 in the nuclei is involved in cisplatin resistance. To further demonstrate the role of nuclear localization of phospho- ERK2, cisplatin-induced apoptosis was examined after pretreatment of OVCAR-3 cells with PMA (phorbol 12-myristate 13-actate). Pretreatment of PMA resulted in decrease of cisplatin-induced apoptosis in OVCAR-3 cells. These results collectively suggest that pre-localized phospho-ERK2 in the nuclei inhibits the initiation of cisplatin-induced apoptosis in OVCAR-3/CDDP cells.
O041 : Increasing association of non-alcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma in the United States: Data from surveillance, epidemiology and end results (SEER)-Medicare registries (2004–2009)
Authors: Z. Younossi, M. Otgonsuren, L. Henry, C. Venkatesan, A. Mishra, M. Erario, S. Hunt
Journal: Journal of Hepatology (2015)
A retrospective multicenter study of MSKCC poor-prognosis patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib
Authors: D. Y. Heng, P. Elson, A. R. Golshayan, M. A. Warren, C. Kollmannsberger, K. N. Chi, T. Cheng, S. A. North, J. A. Garcia, R. M. Bukowski, B. I. Rini
Journal: Journal of Clinical Oncology (2008)

16057 Background: Sunitinib is currently a standard of care for the treatment of mRCC. Due to the inclusion criteria and selection bias inherent to clinical trials, only 6% of patients enrolled in the pivotal phase III sunitinib vs interferon trial had poor-prognosis MSKCC criteria and thus further investigation of the effect of sunitinib in this population is required. Methods: Provincial registries and/or clinical databases were used to identify all patients with mRCC treated with sunitinib in British Columbia, Calgary, Edmonton, and the Cleveland Clinic. Medical records were searched to identify only those patients with MSKCC poor prognosis criteria (3 or more of the following criteria: Karnofsky Performance Status (KPS) <80, diagnosis to treatment interval <1 year, LDH >1.5 times upper limit of normal (ULN), serum corrected calcium >10mg/dL, and hemoglobin below the lower limit of normal (LLN)). Baseline characteristics, overall survival (OS) and progression-free survival (PFS) were collected. Results: 61 poor-prognosis patients met inclusion criteria and were treated with sunitinib (50 mg/d 4/2 wks). Median age of these patients was 60 years (range 23–83) and 43% had prior treatment. 79%, 18% and 3% had 3, 4, and 5 adverse prognosis factors, respectively. 41% had prior nephrectomy, 75% had diagnosis to treatment intervals <1 year, 91% had KPS scores of <80, 70% had >1 metastatic site, 90% had hemoglobin<LLN, 44% had elevated serum corrected calcium, and 26% had LDH elevated 1.5 times ULN. The estimated median PFS and OS of this cohort were 3.9 months and 6.4 months, respectively. There was no difference in outcome according to having prior treatment (PFS p=0.58, OS p=0.72) or prior nephrectomy (PFS p=0.60, OS p=0.91). A KPS score of ≤60 and 70 was associated with a median PFS of 2.9 and 5.1 months, respectively while the median PFS for patients with KPS ≥80 has not been reached (trend test p=0.04). Conclusion: Patients with poor-prognosis MSKCC criteria treated with sunitinib have a PFS that is comparable to clinical trial subsets of similar patients. This remains true despite many of these patients having prior treatment and many being treated outside the context of a clinical trial. The post-progression overall survival of these patients is short. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech™ BioOncology, Novartis, Pfizer Oncology, Wyeth Bayer, Celgene, Genentech™ BioOncology, Novartis, Pfizer Oncology, Wyeth Bayer, Bristol-Myers Squibb, Celgene, Genentech™ BioOncology, Novartis, Pfizer Oncology, Wyeth
Organ transplantation may link to deaths from cancer, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Patients who receive kidney, liver, heart, or lung transplants are at higher risk of dying from cancer than the general population, research published in JAMA Oncology has found.1

Canadian researchers carried out a population based cohort study of patients who underwent solid organ transplantation in Ontario from 1991 to 2010, with 85 557 person years of follow-up until 31 December 2011. Using data from the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the …
TCT-78 Long-Term (4-Year) Clinical Outcomes of Total Occlusions and Completeness of Revascularisation in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Trial
Authors: Vasim Farooq, Patrick Serruys, Hector M. Garcia-Garcia, Yaojun Zhang, Christos Bourantas, Roberto Diletti, Michail Papafaklis, David Holmes, Michael Mack, Ted Feldman, Marie-Claude Morice, Elisabeth Ståhle, Stefan James, Antonio Colombo, Ton de Vries, Marie Angèle Morel, Gerrit Anne Van Es, Friedrich Mohr, Keith Dawkins, A. Pieter Kappetein, Georgios Sianos
Journal: Journal of the American College of Cardiology (2012)
Cish actively silences tcr signaling in CD8+ T cells to maintain tumor tolerance
Authors: Douglas Palmer, Geoff Guittard, Zulmarie Franco, Shashank Patel, Christopher A Klebanoff, Madhusudhanan Sukumar, Robert L Eil, David Clever, Lakshmi Balagopalan, Rahul Roychoudhuri, Larry Samelson, Nicholas Restifo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Improving the functional avidity of effector T cells is critical in overcoming inhibitory factors within the tumor microenvironment and eliciting tumor regression. We have found that Cish, a member of the Suppressor of Cytokine Signaling (SOCS) family, is induced by TCR
Trends in Short- and Long-Term Outcomes for Takotsubo Cardiomyopathy Among Medicare Fee-for-Service Beneficiaries, 2007 to 2012
Authors: Karthik Murugiah, Yun Wang, Nihar R Desai, Erica S Spatz, Sudhakar V Nuti, Rachel P Dreyer, Harlan M Krumholz
Journal: JACC Heart Failure (2015)
Autologous PBMCs pulsed with HPV16 E6 as an immunotherapeutic agent for patients with advanced cervical cancer
Authors: R. A. Ibrahim, M. S. Achtar, V. E. Herrin, B. Gause, S. Bernstein, F. Grollman, D. Contoise, S. Steinberg, J. A. Berzofsky, S. N. Khleif
Journal: Journal of Clinical Oncology (2005)

2508 Background: Cervical cancer is the second leading cause of cancer deaths amongst women. Despite the success of early discovery, some patients still present with metastatic disease. More than 90% of human cervical carcinoma harbor high risk HPV DNA most of which are HPV16 and 18. Persistent expression of the early proteins E6-E7 is mandatory for the malignant transformation and maintenance of the disease, which makes them good targets for vaccine therapy. Methods: Nineteen patients with advanced cervical cancer (HPV16–18 positive) were enrolled in our phase II/pilot study. PBMCs pulsed with the E6 peptide was administered intra-venously at least one hour after testing for both type I and type IV immune response. The pulsed Pre-immature dendritic cells (PIDC) were administered 3 weeks apart between the first and the second vaccine and then monthly for a total of 15 cycles or until disease progression. Results: Using Cr release assay we were able to detect E6 specific CTLs in 11/17 patients (64.70%) post vaccination. ELISPOT assay confirmed the above Results: Interestingly, a significant increase in the number of IFN-γ secreting cells was seen not only against the E6 peptide but also against the E7 peptide and not two irrelevant peptides. The median survival and the median progression free survival for all patients was (9.3 and 3.8 months), for the patients with immunological response (10.5 and 6.0 months) and for patients with no immunological response (5.0 and 1.6 months). No grade IV toxicity was seen. Six patients had grade III toxicity (mainly anemia), which most likely is due to the disease Conclusions: Despite the poor immunological status of the patients, our vaccine has been shown to be safe and induced vaccine antigen specific cell mediated immunity. With the potential association of immunological response and clinical outcome, this vaccine strategy warrants further study. No significant financial relationships to disclose.
Gastrointestinal stromal tumor associated with other primaries: A study of 154 patients
Authors: R. K. Pandurengan, S. S. Strom, J. Trent
Journal: Journal of Clinical Oncology (2009)

10567 Background: The objective of this study is to investigate the characteristics and survival rate of patients with Gastrointestinal Stromal Tumor (GIST) associated with other primary malignancies. Methods: 783 patients with GIST were treated at M. D. Anderson Cancer Center from 1995 to 2007. Multiple primaries included tumors that were not considered to be a metastasis, invasion or recurrence of GIST excluding non-melanoma skin cancer. Data on gender, age at diagnosis of cancer, follow-up time after diagnosis, and death rate were collected. Results: Of the 783 patients, 154 (20%) were identified with at least one other primary other than GIST (GIST+). The ratio of men and women was 1.5 and 1.3 in patients with GIST+ compared to those with GIST only, respectively. Median age at diagnosis of GIST was 57 for patients with GIST only whereas it was 68 in patients with GIST+. The stomach was the frequent site of occurrence in GIST only and GIST+. The total numbers of other primaries developed before the diagnosis of GIST was higher (134) than the primaries developed after the diagnosis of GIST (53). The most frequent primaries observed before the diagnosis of GIST were prostate (25), breast (12), esophagus (9), kidney (7) and melanoma (6). Lung (5) and kidney (5) were the most frequent type of primaries that developed after the diagnosis of GIST. The 5-yr survival was 68% for patients with GIST+ when the other primary occurred before GIST, 61% for patients with GIST+ when the other primary occurred after the diagnosis of GIST, 58% for patients with GIST only, and 49% for GIST++ patients with two or more other primaries (p=0.002). Conclusions: Superior survival in GIST+ patients may be due to the bias of early detection. The etiology and clinical implications of the association of other primaries in GIST patients should be further investigated. No significant financial relationships to disclose.
Transforming activity of the MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation
Authors: Lizi Wu, Jingxuan Liu, Ping Gao, Makoto Nakamura, James D. Griffin
Journal: Cancer Research (2005)

2596   Salivary gland tumors, a group of histologically diverse benign and malignant neoplasms, represent a challenging problem for diagnosis and treatment. A specific recurring chromosome translocation, t(11;19)(q21;p13), is associated with two types of salivary gland tumors, mucoepidermoid carcinomas and Warthin’s tumors. This translocation generates a fusion protein comprised of the N terminal CREB-binding domain of the CREB regulator MECT1 and the C terminal transcriptional activation domain of the Notch co-activator Mastermind-Like 2 (MAML2). Here we demonstrate that the MECT1-MAML2 fusion protein induces expression of multiple genes known to be CREB-mediated transcriptional targets. MECT1-MAML2 was found to bind to CREB, recruit p300/CBP into the CREB complex through a binding domain on MAML2, and constitutively activate CREB-dependent transcription. The transforming activity of MECT1-MAML2 was blocked by interfering with CREB DNA binding. Thus, this fusion oncogene functions to constitutively activate the cAMP signaling pathway. This study has identified a novel, critical mechanism of transformation for an oncogene associated very specifically with salivary gland tumors, and identified potential targets for the development of novel therapies.
Bone Marrow Stroma-Derived Prolactin Is Involved in Basal and Platelet-Activating Factor–Stimulated In Vitro Erythropoiesis
Authors: Graziella Bellone, Paola Astarita, Elisa Artusio, Stefania Silvestri, Katia Mareschi, Anna Turletti, Stefano Buttiglieri, Giorgio Emanuelli, Lina Matera
Journal: Blood (1997)
Clinical introtumoral chemoimmunotherapy for late stages of lung cancer.
Authors: B. Yu, Z. Ma, C. Guan, G. Liu, H. Ding, Y. Yin, W. Han
Journal: Journal of Clinical Oncology (2011)

e21001 Background: Currently cancer therapy is not satisfied with the effectiveness of available treatment. In addition to surgery, radiotherapy interventional treatment and chemotherapy, engaging the power of immune system of individual patient has been considered as a highly attractive way for cancer treatment. Provenge is an autologous cellular vaccine and represents a significant milestone for cancer immunotherapy. ChemoVac is similarly with Provenge function and plays in kill tumor cells meanwhile induces body own immunological effect against tumors. Methods: Methods: Introtumoral injection of ChemoVac into tumor of NSCLC (39 patients), which is a proprietary therapeutic regimen and composed of three components, i.e. an slow releasing agent, a cytotoxic drug and a hapten. Results: Results: CT guided intratumoral injection into mass of NSCLC, the drug-release controlling agent to effectively coagulate tumor mass for sustained drug release, which improves drug utilization by extending duration of drug in the tumor and reducing dosing frequency. While the injected chemotherapeutic drug kills tumor cells, autologous tumor antigens released from the dead tumor cells by the drug then trigger immune response as a self-vaccination. Meanwhile, a small molecule hapten binds to these antigens and other large carriers to further boost systemic humoral and cellular immunity for suppression and eradication of tumor recurrence and metastasis. Therefore, it resulted in one year survial rate is 36%(treated) compared 14%(control) with P<0.05.in addition to the innovation for sustained drug release, more importantly, ChemoVac provides a new option for cancer treatment by integrating local chemotherapeutic effect with systemic anti-tumor immunity; cell death induced by chemotherapeutic drugs is a priming event and allows the injected tumor act as its own vaccine. Conclusions: Introtumoral injection of ChemoVac is a safe, aggressive (higher drug concentration in the tumor) and cost-effective clinical treatment for solid tumors like NSCLC. ChemoVac displays the following advantages: clinically effective for NSCLC and can repeats introtumoral injections; minimal side effects and better quality of life.
Structural, infrastructural and procedural barriers to oncology clinical trials
Authors: D. M. Dilts, A. Sandler, S. Moore, D. Browning, A. Johnson, A. Pardeshi, D. Rouch, B. Xie
Journal: Journal of Clinical Oncology (2004)

6010 Background: While barriers to clinical trials are well known, there is a paucity of literature concerning the structural, infrastructural, and procedural barriers that take place outside the realm of the patient-physician interaction. For example, the time required prior to opening a trial can span from 8 to 16 months, which detracts from the time available to enroll patients. Our study assesses the impact of these barriers in such areas as time to institutional review board acceptance, number of committees requiring approval prior to opening a study, and the number of signatures required. Methods: The setting is the Vanderbilt-Ingram Cancer Center (VICC), a NCI designated Comprehensive Cancer Center. Using process design methodologies, we completed interviews with all major stakeholder groups and developed comprehensive process flow map and four sub-maps for: Institutional Review Board, Scientific Review Board, Clinical Trials Office, and General Clinical Research Center. Results: Over 80 major steps required to begin a clinical trial were documented. Each of these steps may require repetition, as initiation of any trial is a negotiated process among the investigator, the sponsor, and the internal system. We discovered that over 27 different groups or individuals are involved in the approval process and, before any trial can be opened, from 16 to 27 signatures are required. Conclusions: We have completed this analysis at one comprehensive cancer center and have plans of extending the methodology to document process flows at the VICC Affiliate Network and selected Affiliate sites that include community hospitals and private oncology practices. Future direction for this research is to utilize process redesign techniques to streamline the process. Support for the research was provided by the Vanderbilt Discovery Grants Program. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vanderbilt Discovery Grant
A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer
Authors: Folefac Aminkeng, Amit P Bhavsar, Henk Visscher, Shahrad R Rassekh, Yuling Li, Jong W Lee, Liam R Brunham, Huib N Caron, Elvira C van Dalen, Leontien C Kremer, Helena J van der Pal, Ursula Amstutz, Michael J Rieder, Daniel Bernstein, Bruce C Carleton, Michael R Hayden, Colin J D Ross, Michael R Hayden, Bruce C Carleton, Colin J D Ross, Stuart MacLeod, Anne Smith, Claudette Hildebrand, Reza Ghannadan, Shahrad R Rassekh, Henk Visscher, Folefac Aminkeng, Fudan Miao, Michelle Higginson, Nasim Massah, Adrienne Borrie, Ursula Amstutz, Shevaun Hughes, Kaitlyn Shaw, Satvir Dhoot, Amit P Bhavsar, Yuling Li, Jong W Lee, Kaarina Kowalec, Jessica Stortz, Tessa Bendyshe-Walton, Duncan Waltrip, Rachel Bader, Cheri Nijssen-Jordan, David Johnson, Linda Verbeek, Rick Kaczowka, Patti Stevenson, Carnation Zhuwaki, Paul Grundy, Kent Stobart, Bev Wilson, Sunil Desai, Maria Spavor, Linda Churcher, Terence Chow, Kevin Hall, Nick Honcharik, Sara Israels, Shanna Chan, Byron Garnham, Michelle Staub, Geert 't Jong, Michael J Rieder, Becky Malkin, Carol Portwine, Amy Cranston, Gideon Koren, Shinya Ito, Paul Nathan, Mark Greenberg, Facundo Garcia Bournissen, Miho Inoue, Sachi Sakaguchi, Toshihiro Tanaka, Hisaki Fujii, Mina Ogawa, Ryoko Ingram, Taro Kamiya, Smita Karande, Sholeh Ghayoori, Mariana Silva, Stephanie Willing, Régis Vaillancourt, Donna Johnston, Herpreet Mankoo, Elaine Wong, Brenda Wilson, Lauren O'Connor, Caleb Hui, Cindy Yuen, Jean-Francois Bussières, Denis Lebel, Pierre Barret, Aurélie Clauson, Eve Courbon, Léna Cerruti, Nada Jabado, Anelise Espirito Santo, Martine Nagy, Margaret Murray, Darlene Boliver, Marilyn Tiller, Carol-anne Osborne, Lisa Goodyear, Lynette Bowes, Norma Kean, Jack Hand
Journal: Nature Genetics (2015)