tbuckley/cabot-search huggingface dataset:
Abstract 4595: Development and validation of a novel EGF receptor-neutralizing monoclonal antibody
Authors: Krystyna Zuberek Hincman, Christopher A. Manning, Michael R. Nelson, Michael Lewis, Roy Scialdone, Jaime Darce, Stephen R. Lutz, Evans Burford, Herbert Haack, Matthew R. Silver
Journal: Cancer Research (2016)

Abstract The epidermal growth factor receptor (EGFR) is a cell-surface receptor for members of the epidermal growth factor family (EGF-family). EGFR dimerizes upon ligand binding, which leads to autophosphorylation, downstream signaling and ultimately internalization. In cancer, EGFR mutations and amplification have been linked to cell proliferation and survival. Two EGFR neutralizing monoclonal antibodies are currently FDA approved, which includes Cetuximab (Erbitux, BMS; mouse/human chimeric) and Panitumumab (ABX-EGF, Amgen; fully humanized). However, these antibodies are often unavailable to researchers studying this important pathway. Here we describe the development and validation of a new rabbit monoclonal EGFR neutralizing antibody (clone D1D4J). D1D4J was validated using cell-based models and immunofluorescence imaging. D1D4J binds EGFR and neutralizes EGF-induced activation and internalization. Compared to other Research Use Only (RUO) neutralizing antibodies on the market, D1D4J shows superior performance and is a useful research tool in the EGFR signaling space. Citation Format: Krystyna Zuberek Hincman, Christopher A. Manning, Michael R. Nelson, Michael Lewis, Roy Scialdone, Jaime Darce, Stephen R. Lutz, Evans Burford, Herbert Haack, Matthew R. Silver. Development and validation of a novel EGF receptor-neutralizing monoclonal antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4595.
A patient-centered approach to a cancer care delivery innovation for low income patients: Medical-legal partnership with patient navigation.
Authors: Naomi Ko, Sharon Bak, Kerrie Nelson, Ann Han, Emily Bergling, Maria Castano, Vanesa Noel, Na Wang, Christine M Gunn, Kate Festa, Johanna Flacks, Samantha Morton, Tracy Ann Battaglia
Journal: Journal of Clinical Oncology (2015)

e17603 Background: Disparities in cancer outcomes for low income, racial/ethnic minority patients are worsening, partly due to delays in care delivery. Patient-centered innovations in care delivery that address these barriers are necessary to improve care for vulnerable populations. Methods: We used a community-engaged approach to implement a randomized controlled trial for at-risk cancer patients with delays in care. We conducted focus groups with the target population and created a Patient Advisory Group and Community Advisory Board to ensure stakeholder input. With these advisory groups and a Scientific Advisory Board, we designed a collaboration between patient navigation and legal aid from Medical-Legal Partnership Boston (MLP). Each intervention patient is discussed with MLP lawyers to identify level of legal need, and to support role-appropriate advocacy by the patient navigator. Control subjects receive standard navigation. Eligible subjects include patients at an urban academic safety net hospital diagnosed with cancer within 30 days and who speak English, Spanish and Haitian-Creole. Results: To date, we enrolled 76 breast cancer patients (78% non-White, 68% public insurance) of our target enrollment of 374 patients. Research assistants survey patients at baseline, 0, 3, 6 and 12 months to capture patient-centered outcomes, including: a) a recently validated 15 item survey captures socio-legal barriers: I-HELP (Income, Housing, Employment, Legal Status and Personal Stability) b) the CaNDI (Cancer Needs Distress Inventory), c) Distress Thermometer, d) CASE (Communication and Attitudinal Self-Efficacy) survey and e) PSN-1 (Patient Satisfaction with Interpersonal Relations with Navigator). Clinical outcomes including time to first treatment and receipt of quality treatment are extracted from medical records at 6 and 12 months. Conclusions: We demonstrate how a diverse group of stakeholders engage in patient-centered cancer care delivery research. Our study will test if legally-enhanced patient navigation improves delivery of cancer care with patient-centered and clinical outcomes. Clinical trial information: NCT02232074.
A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients
Authors: L.M. Biehl, A. Huth, J. Panse, C. Krämer, M. Hentrich, M. Engelhardt, K. Schäfer-Eckart, G. Kofla, M. Kiehl, C.-M. Wendtner, M. Karthaus, A.J. Ullmann, M. Hellmich, H. Christ, M.J.G.T. Vehreschild
Journal: Annals of Oncology (2016)
Survival outcomes of nivolumab (NIVO) given sequentially with ipilimumab (IPI) in patients with advanced melanoma (CheckMate 064).
Authors: Jeffrey S. Weber, Geoffrey Thomas Gibney, Ryan J. Sullivan, Jeffrey Alan Sosman, Craig L. Slingluff, Donald P. Lawrence, Theodore F. Logan, Lynn Mara Schuchter, Suresh Nair, Elizabeth Iannotti Buchbinder, Elmer Berghorn, Joel Jiang, Christine E. Horak, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2016)

9517 Background: Combining or sequencing immune checkpoint inhibitors that target distinct pathways has the potential to improve survival outcomes compared to either agent alone. This randomized phase II trial (CheckMate 064) previously demonstrated improved response rates with NIVO followed by IPI vs. IPI followed by NIVO in patients (pts) with advanced melanoma. Here, we report the first overall survival (OS) data from this study. Methods: Pts (N = 140) were randomized 1:1 to receive sequential induction treatment with NIVO 3 mg/kg Q2W x 6 doses followed by IPI 3 mg/kg Q3W x 4 doses (cohort A; N = 68 treated) or IPI 3 mg/kg Q3W x 4 doses followed by NIVO 3 mg/kg Q2W x 6 doses (cohort B; N = 70 treated). Following induction, both cohorts received NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. The primary endpoint was to evaluate treatment-related grade 3–5 adverse events (AEs) during the induction periods until week 25. Secondary and exploratory endpoints included objective response rate (ORR) by modified RECIST v1.1, progression-free survival rate, and OS. Results: As previously reported, baseline patient characteristics were mostly balanced between cohorts, although a higher percentage of pts in cohort A had an ECOG performance status of 0, PD-L1 tumor expression ≥ 5%, and brain metastases. Similar rates of treatment-related grade 3/4 AEs occurred during both induction periods to week 25 in cohort A (50%) and cohort B (43%). In the updated analysis (minimum follow-up of 14 months), grade 3/4 AEs were 63% in cohort A and 50% in cohort B across all study periods, which led to discontinuation in 25% and 27% of pts, respectively. ORR was higher in cohort A than in cohort B (54% vs. 31%), with more complete responses (11% vs. 6%). A significant difference in OS was observed between cohorts A and B (hazard ratio: 0.48; 95% CI: 0.29, 0.80; P = 0.0041), with the median not reached vs. 16.9 months, and 1-year OS rates of 76% and 54%, respectively. Conclusions: NIVO followed by IPI continues to show improved efficacy outcomes vs. IPI followed by NIVO, with longer OS. A higher frequency of AEs was observed in cohort A, with the types and rates of AEs similar to that reported for NIVO given concurrently with IPI. Clinical trial information: NCT01783938.
An Important Cause of Child and Youth Homelessness
Authors: Victor Kieu, Shadi Rezai, Cassandra E. Henderson
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Cancer Associated Fibroblasts in Multiple Myeloma: The Urokinase Receptor System in Tumor Growth Regulation
Authors: Simona Serratì, Carla Minoia, Anastasia Chilla, Anna Laurenzana, Francesca Margheri, Maria Antonia Frassanito, Nicola Sgherza, Giacoma De Tullio, Angelo Vacca, Pasquale Iacopino, Mario Del Rosso, Gabriella Fibbi, Attilio Guarini
Journal: Blood (2014)
Analysis of FoxM1 Expression and Regulation of Cell Cycle, and Anti-Leukemic Effectss by FoxM1 Knockdown on Leukemia Cells Transfected with siRNA FoxM1.
Authors: Satoki Nakamura, Takaaki Ono, Yuya Sugimoto, Miki Kobayashi, Naohi Sahara, Kazuyuki Shigeno, Kaori Shinjo, Shinya Fujisawa, Kazunori Ohnishi
Journal: Blood (2006)
Abstract 523: Activating mutations in EGFR abrogate hypoxia-associated radiation resistance in non-small cell lung cancer
Authors: Mohammad Saki, Haruhiko Makino, Nozomi Tomimatsu, Lianghao Ding, Michael D. Story, Sandeep Burma, Chaitanya Nirodi
Journal: Cancer Research (2016)

Abstract Hypoxic tumors tend to be 3-5 times more resistant to ionizing radiation relative to well-oxygenated tumors in part because oxygen is required to stabilize radiation-induced DNA damage. Tumor-adaptive responses also contribute to hypoxia-associated radioresistance but the precise mechanisms are not fully understood. Here we test our evidence-based hypothesis that the epidermal growth factor receptor (EGFR), which is frequently over-expressed in non-small cell lung carcinomas (NSCLCs), has critical roles in a tumor adaptive DNA damage response (DDR) pathway in hypoxic tumors. We find that, despite elevated EGFR activity and pro-survival signaling, hypoxia-associated radioresistance is dramatically reduced in a biologically distinct class of NSCLCs harboring activating mutations, L858R and ΔE746-E750 in EGFR. Hypoxic NSCLCs with EGFR mutations exhibit a unique spectrum of basal and hypoxia-induced DSBs not found in hypoxic wild type EGFR-expressing NSCLCs. These lesions dominate the S-phase of the cell cycle and are linked to collapsed replication forks in hypoxic cells. Replication fork-associated DSBs are repaired in wild type, but not in mutant, EGFR expressing NSCLCs. Microarray gene expression analysis revealed that mutant, but not wild type, EGFR expression results in an altered DDR characterized by dramatic down-regulation of several key components of the HR pathway within 24 hours of exposure to 0.1% oxygen. Our model predicts that NHEJ, not HR, dominates an altered DDR in hypoxic tumors. Elevated EGFR signaling may contribute to this altered DDR state where the EGFR-NHEJ axis becomes critical for hypoxia associated radioresistance and could be a potential target for hypoxic tumor radiosensitization. Citation Format: Mohammad Saki, Haruhiko Makino, Nozomi Tomimatsu, Lianghao Ding, Michael D. Story, Sandeep Burma, Chaitanya Nirodi. Activating mutations in EGFR abrogate hypoxia-associated radiation resistance in non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 523.
The Pathogenesis of Ebola Virus Disease
Authors: Laura Baseler, Daniel S. Chertow, Karl M. Johnson, Heinz Feldmann, David M. Morens
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.
Abstract CT152: Food effect on the pharmacokinetics of 200-mg abemaciclib in healthy subject
Authors: Kellie Turner, Jill Chappell, Palaniappan Kulanthaivel, Wee Teck Ng, Jane Royalty
Journal: Cancer Research (2016)

Abstract Abemaciclib is an oral, selective, and potent small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) being investigated for the treatment of patients with refractory hormone-receptor positive (HR+) advanced or metastatic breast cancer. The absolute bioavailability and effect of food on pharmacokinetics (PK) following a single 200-mg oral dose of abemaciclib in healthy subjects were evaluated in three studies (Table 1). Abemaciclib plasma concentrations were measured serially pre-dose through 192 hours post-dose. Non-compartmental analysis was used to calculate PK parameters, and a mixed-effects model was used for statistical inference. In Study 1 the absolute bioavailability of a 200-mg dose of abemaciclib was 45% (90% CI: 40%, 51%). In Study 2 the ratios of AUC0-? after a high-fat or standard meal compared to fasting showed no effect (90% CIs within 0.80, 1.25). However, Cmax increased by 24% and 25% following high-fat and standard meals, respectively, compared to fasting (upper 90% CIs &amp;gt;1.25). No differences were found in the AUC0-? and Cmax of abemaciclib following a high-fat meal compared to a standard meal (90% CI within 0.80, 1.25). The median tmax was delayed by 2 hours following a high-fat meal compared to fasting (p = 0006). However, there was no difference in median tmax between the standard meal and fasting (p = .7197). Abemaciclib terminal half-life was similar across fed and fasted conditions. The late-breaking Study-3 results will be presented. In conclusion, abemaciclib oral bioavailability is sufficient to achieve therapeutic exposure. Food with abemaciclib does not reduce or increase the inter-individual PK variability and does not have a clinically-relevant impact on the PK of abemaciclib. Therefore, abemaciclib may be administered without regard to food. Table 1Designs for three open-label clinical studies of abemaciclib as a single 200-mg oral dose administered to healthy subjectsStudy ParametersNCT02327143a (Study 1)I3Y-MC-JPBSNCT02059148a (Study 2)I3Y-MC-JPBGNCT02482935a (Study 3)I3Y-MC-JPBUCompleted subjects (N)82329Overall designs and formulationsAbsolute bioavailability, 4 x 50-mg (25% w/w) capsules and tracer IVbPilot food effect, randomized crossover 3 period, 6 sequence 4 x 50-mg (50% w/w) capsulesPivotal food effect, randomized crossover 2 period, 2 sequence 2 x 100-mg (25% w/w) capsulesMeal conditionFastedFastedStandard mealHigh-fat, high-calorie mealFastedHigh-fat, high-calorie meal Citation Format: Kellie Turner, Jill Chappell, Palaniappan Kulanthaivel, Wee Teck Ng, Jane Royalty. Food effect on the pharmacokinetics of 200-mg abemaciclib in healthy subject. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT152.
Insertion and Deletions Mutations of the CEBPA Gene Affecting the bZIP Region Are Strong Predictors for Achieving Complete Remission and Improved Overall Survival in Adult Patients with AML - An Analysis in 1536 Patients Treated in the AML96 Protocol of the DSIL.
Authors: Christian Thiede, Franziska Taube, Thomas Illmer, Markus Schaich, Gerhard Ehninger
Journal: Blood (2007)
Abstract 2713: Combination of PLK1 and PI3K inhibitors shows strong synergy in anaplastic thyroid cancer
Authors: Emrullah Yilmaz, Arturo Orlacchio, Antonio Di Cristofano
Journal: Cancer Research (2016)

Abstract Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer with median of 6 months of survival from diagnosis. Molecular alterations are well defined recently. p53 mutations, and activation of PI3K, RAS and BRAF are among the most common alterations. PLK1 overexpression has also been identified in ATC. We have previously shown that PLK1 inhibitors are effective in ATC cell lines. However PLK1 inhibition in cell lines with PI3K activation resulted in escaping growth arrest and subsequent mitotic catastrophe through mitotic slippage. Since the PI3K activation is common in ATC, there is risk of generating polyploid, genetically unstable cell populations by targeting these tumors with a PLK1 inhibitor. So we tested the effect of combining PLK1 and PI3K inhibitors in ATC cell lines. We combined PLK1 inhibitor BI6727 and PI3K inhibitor BKM120 and measured the cell viability using Alamar Blue. Combination of these two drugs resulted in significant synergy in mouse derived PTEN deleted ATC cell lines. We observed the same synergy in the human ATC cell lines with PIK3CA mutations. BI6727 showed significant G2/M arrest in the cell lines. The combination two drugs enhanced the G2/M arrest. In a low dose that the single drugs showed no inhibition in cell cycle, combination resulted in G2/M arrest. We treated the cells with a dual PI3K and PLK1 inhibitor Rigosertib. Although we have seen some sensitivity of the cells with PIK3CA mutation, the cell lines with PTEN were strongly resistant to Rigosertib. Our results show that combination of PLK1 and PI3K inhibitors is an effective treatment for ATC cells with PI3K activation. This combination results in cell cycle arrest suggesting the role of using combination therapies in this aggressive cancer. Citation Format: Emrullah Yilmaz, Arturo Orlacchio, Antonio Di Cristofano. Combination of PLK1 and PI3K inhibitors shows strong synergy in anaplastic thyroid cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2713.
Tandem Duplication PCR (TD-PCR) Is a Novel Method of Detecting Minimal Residual Disease in FLT3/ITD AML and Is Highly Predictive of Relapse Risk Following Allogeneic Transplant.
Authors: Michael R. Grunwald, Ming-Tseh Lin, Keith W. Pratz, Christopher D. Gocke, Mark J. Levis
Journal: Blood (2012)
Abstract 5095: Hic-5 modulation of the stromal matrix is required for mammary tumor progression
Authors: Gregory J. Goreczny, Jessica Ouderkirk, Eric Olson, Mira Krendel, Christopher Turner
Journal: Cancer Research (2016)

Abstract Primary tumors grow and invade into surrounding tissues/stroma, frequently resulting in metastasis to distant organs. Tumor cell-stroma crosstalk plays a crucial, but incompletely understood role during tumor progression and metastasis. For example, increased stromal matrix density and/or rigidity correlates with poor prognosis in human breast cancer patients. Previous studies have implicated Hic-5, a focal adhesion scaffold protein, in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in mammary tumor progression, Hic-5 -/- mice were generated and crossed with mice expressing Polyoma Middle T Antigen (PyMT) driven by the MMTV promoter. The PyMT mouse is a well-established model for human breast cancer progression. Tumors from the Hic-5 -/- PyMT mice demonstrated an increased latency and had reduced growth as compared to Hic-5 +/- PyMT controls. The absence of Hic-5 did not affect the progression of the tumor to a carcinoma stage, but there was a decrease in metastasis to the lungs. Immunohistochemical analysis showed that Hic-5 is primarily expressed in the cancer associated fibroblasts (CAFs) and the Hic-5 -/- PyMT tumor stroma exhibits reduced extracellular matrix (ECM) deposition. Furthermore, 3D cell-derived matrices (CDM) generated in vitro using isolated CAFs, confirmed that Hic-5 -/- PyMT CAFs do not efficiently deposit and organize ECM. The organization of the stromal matrix has been shown previously to increase the rigidity of the tumor, which in turn promotes FAK Y397 phosphorylation in the tumor cells to promote cell invasion and proliferation. Accordingly, the Hic-5 -/- PyMT tumors exhibited a reduction in FAK phospho-Y397 staining and attenuation of downstream ERK activation, suggesting that their stromal matrix is not optimally organized for tumor cell signaling. Taken together, these data demonstrate that Hic-5 expression in CAFs is important for stromal matrix organization/remodeling during tumor progression and that the loss of the organization of the ECM in the Hic-5 -/- tumor stroma may contribute to the reduced tumor growth and metastasis observed in these animals. Supported by NIH CA163296 to CET, NS066071 to EO and Carol M. Baldwin Breast Cancer Fund to CET. Citation Format: Gregory J. Goreczny, Jessica Ouderkirk, Eric Olson, Mira Krendel, Christopher Turner. Hic-5 modulation of the stromal matrix is required for mammary tumor progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5095.