tbuckley/cabot-search huggingface dataset:
Pilot trial of CRLX101 in patients (pts) with advanced, chemotherapy-refractory gastroesophageal cancer (GEC).
Authors: Joseph Chao, James Lin, Paul Henry Frankel, Andrew J. Clark, Devin T. Wiley, Edward Graeme Garmey, Marwan Fakih, Dean Lim, Vincent M. Chung, Eloise Luevanos, Scott Eliasof, Mark E. Davis, Yun Yen
Journal: Journal of Clinical Oncology (2016)

44 Background: Camptothecin (CPT) derivatives such as irinotecan have activity in 2 nd -line therapy in advanced GEC with reported response rates of 0-15%. CRLX101 is an investigational nanoparticle-drug conjugate (NDC) with a CPT payload. Preclinical evidence indicates preferential uptake in tumors, and animal GEC xenograft models demonstrate superiority of CRLX101 over irinotecan. A pilot trial was conducted at recommended phase 2 dosing (RP2D) to assess preferential uptake of CRLX101 in tumor vs. adjacent normal tissue in endoscopically accessible tumors in patients with chemotherapy-refractory GEC. Data demonstrating preferential tumor uptake of CRLX101 has been presented separately and here we report on the clinical outcomes of patients enrolled. Methods: All pts initiated CRLX101 dosed intravenously at RP2D (15 mg/m 2 ) on days 1 and 15 of a 28-day cycle until disease progression or intolerant toxicity. While detection of preferential CRLX101 tumor uptake was the primary endpoint, with 10 pts enrolled a secondary analysis could be performed with the study having 90% power to detect ≥ 1 responder if the true response rate is ≥ 21%. Responses were assessed using RECIST 1.1. Results: Between Dec. 2012 and Dec. 2014, 10 patients with chemotherapy-refractory (median 2 prior lines of therapy, range 1-4) GEC and adenocarcinoma histology were enrolled and evaluable for response and toxicity. The median time-to-progression was 1.9 mo (range 0.6-8.7 mo). Best response was seen in 1 pt with stable disease (SD) for 8 cycles. Only ≥ grade 3 toxicities related to CRLX101 occurred in a single patient with grade 3 anemia and chest pain who was able to resume therapy without any further toxicity after CRLX101 was reduced to 12 mg/m 2 . Conclusions: CRLX101 demonstrated minimal activity with SD as best response in this heavily pretreated population. Future efforts with CRLX101 in advanced GEC should focus on combination strategies. Its favorable toxicity profile and evidence of preferential tumor uptake support further clinical research of combining CRLX101 with other targeted therapies such as anti-angiogenesis (ramucirumab) and/or immune checkpoint inhibitors. Clinical trial information: NCT01612546 Clinical trial information: NCT01612546.
Abstract 4570: Decreased interleukin-17RA expression inhibits the tumorigenesis and independently predicts good prognosis of colorectal cancer patients
Authors: CHIH-YUNG YANG, Jeng-Kai Jiang
Journal: Cancer Research (2016)

Abstract Background: Interleukin-17 receptor type A (IL-17RA) plays critical role in promoting early colorectal tumor development and affects immune response in tumorigenesis. Our previous study have reported interleukin-17A modulated tumorigenesis and affected metastasis in colorectal cancers, but the roles of its receptor (IL-17R) in colorectal cancers remain unknown. This study explores potential role and function of IL-17RA in colorectal cancers. Materials and Methods The expression of IL-17RA was determined in colorectal cancer tissues and adjacent normal tissues using quantitative real-time PCR and immunohistochemistry. The IL-17RA expression level and clinical parameters were then analyzed. To investigate the functional significance of IL-17RA, IL-17RA knockdown cells were analyzed using transwell assay in vitro and implanted subcutaneously in mice, and monitored for primary tumor growth and angiogenesis. Results IL-17RA was overexpression in colorectal cancer tissues compared with adjacent normal tissues (P&amp;lt;0.05).The elevated expression level of IL-17RA was associated with poor survival (P&amp;lt;0.001). In vitro, the IL17RA knockdown cells reduced migration and invasion. In mice, the decreased IL-17RA inhibited tumor growth and angiogenesis. Conclusions These results demonstrated that IL-17RA plays a critical role in growth, angiogenesis and prognosis of colorectal cancer. Citation Format: CHIH-YUNG YANG, Jeng-Kai Jiang. Decreased interleukin-17RA expression inhibits the tumorigenesis and independently predicts good prognosis of colorectal cancer patients. [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 4570.
Abstract LB-203: Development of a nonclinical model for the assessment of oncology therapy-induced cardiomyopathy
Authors: Michelle Hemkens, Samantha Cardenas, Jessica Frey, Brad Hirakawa, Petra Koza-Taylor, Jianying Wang, Paul Butler
Journal: Cancer Research (2016)

Abstract With the increasing number of people surviving cancer, patients and doctors are becoming equally focused on the quality of life in survivorship as they are on fighting cancer. Consequently, cardio-oncology has emerged as a new clinical discipline with focus on both the stratification of patients at risk and therapies that pose a cardiovascular risk, eg molecularly targeted therapies including tyrosine kinase inhibitors (TKI). Therefore, nonclinical research should strive not only to detect preclinical drug-induced changes in cardiac structure or function, but also to understand the relevance of these cardiotoxic effects to humans. As is typical for new disciplines, there is an unmet need for early and predictive tools to identify both of these factors. Currently, preclinical assessment of cardiovascular toxicity consists of repeat-dose in vivo toxicity studies focused primarily on histopathological endpoints; additional measures, such as cardiac function and biomarkers of cardiac injury, are not routinely assessed in these studies. Furthermore, analysis of these studies suggests that using young and healthy, drug-naïve animals do not adequately translate the TKI-induced cardiomyopathy phenotype; therefore, new nonclinical models are needed to address this gap. The developed model would ideally be used to assess the preclinical cardiotoxicity of proposed oncology therapies, but may also have utility in assessing cardioprotective therapies for use in cardio-oncology. This poster will propose a new model for studying cardio-oncology nonclinically that includes myocardial transcriptional signatures, strain echocardiography imaging, and pharmacologic (dobutamine) stress challenge. In general, rats with radiotelemetry were treated with vehicle or low dose doxorubicin (2 mg/kg/week IP) for 1 month. Cardiac structure and function at rest and during stress were assessed using strain echocardiography in concert with a weekly dobutamine infusion. Circulating blood biomarkers of cardiac toxicity (eg, NTproBNP, NTproANP, cTropin, and miR-208) were collected weekly and at necropsy. At the end of the study, samples of cardiac tissue were taken from the ventricular apex and were submitted for transcriptional profiling along with standard histopathology. These data as well as recent publications give high confidence in developing a rodent model predictive of drug-induced cardiomyopathy. Citation Format: Michelle Hemkens, Samantha Cardenas, Jessica Frey, Brad Hirakawa, Petra Koza-Taylor, Jianying Wang, Paul Butler. Development of a nonclinical model for the assessment of oncology therapy-induced cardiomyopathy. [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 LB-203.
Abstract 546: Impact of therapeutic EGFR inhibition on immune checkpoint blockade in head and neck squamous cell carcinoma
Authors: Laura M. Rogers, Madelyn M. Espinosa-Cotton, Andrean L. Simons, George J. Weiner
Journal: Cancer Research (2016)

Abstract Patients with advanced recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) have few effective treatment options and a poor median survival of 6-8 months. Limited improvement in overall survival has been observed in HNSCC patients treated with EGFR inhibitors despite high expression of epidermal growth factor receptor (EGFR) in these tumors. Remarkable clinical results are emerging from immunotherapy targeting programmed death-1 (PD1) and its ligand programmed death ligand-1 (PDL1). Blockade of the PD1/PDL1 interaction is believed to enhance endogenous anti-tumor immunity by restoring T cell cytotoxic action. PDL1 is highly expressed in primary, recurrent, and metastatic HNSCC and phase 1 clinical trials are ongoing for monoclonal antibodies targeting the PD1/PDL1 axis in HNSCC. We found that activation of EGFR in HNSCC cells by epidermal growth factor (EGF) significantly increases PDL1 expression in a dose dependent manner. EGFR inhibition using tyrosine kinase inhibitors (TKI) or cetuximab suppresses this EGF-induced PDL1 expression in cells with both wild type and constitutively active EGFR. This is consistent with published data that constitutively active EGFR in lung cancer cells correlates with higher PDL1 expression, and this can be reversed by EGFR inhibition. These results suggest there may be interactions between EGFR-targeted therapy and immunotherapy involving the PD1/PDL1 axis. To evaluate potential therapeutic interactions, we used an immunocompetent, syngeneic mouse model of human EGFR-expressing TUBO cancer cells on a BALB/c background. The murine TUBO-EGFR cells are sensitive to human EGFR inhibitors both in vitro and in vivo. Initial studies show that treatment of tumors with EGFR inhibitor (erlotinib) results in increased intratumoral CD8+ T cell infiltration and tumor regression, suggesting that EGFR inhibition can impact the anti-tumor T cell response. We are currently evaluating the effects of EGFR inhibition on PDL1 expression and tumor response to PD1/PDL1 blockade using this model. Further, a clinical trial investigating the impact of cetuximab treatment on intratumoral expression of PDL1 in HNSCC patients is planned to open shortly. We conclude that signaling mediated by EGFR can impact expression of PDL1 by HNSCC. Understanding the interactions between EGFR inhibitors and immune checkpoint blockade could lead to new approaches to combining TKI and cancer immunotherapy. Citation Format: Laura M. Rogers, Madelyn M. Espinosa-Cotton, Andrean L. Simons, George J. Weiner. Impact of therapeutic EGFR inhibition on immune checkpoint blockade in head and neck squamous cell carcinoma. [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 546.
Abstract 3544: Determining autophagic activity following cannabidiol treatment of melanoma: a potential new and novel treatment
Authors: Erika L. Simmerman, Xu Qin, Kouros Motamed, Jack C. Yu, Babak Baban
Journal: Cancer Research (2016)

Abstract Introduction: Autophagy is a catabolic pathway utilized for energy metabolism in nutrient-depleted tumors. Recent studies have reported autophagy to be a survival mechanism found in cancer during stress secondary to cancer progression or treatment. In this study we tested for autophagic activity in malignant melanoma tumors via detection of LC3 antibody following treatment with Cannabidiol (CBD) and cisplatin. The objective of this study was to investigate the effect of treatment with a cannabinoid derivative on autophagic activity in malignant melanoma. Materials and Methods: Murine B16F10 melanoma tumors were established subcutaneously in C57BL/6 mice. These mice were then subjected to treatment with local vehicle (PBS) injection (control - group 1, n = 5), systemic Cisplatin injection (group 2; n = 5), and local cannabidiol injection (group 3; n = 5). Tumor cells were subsequently submitted to immunohistochemistry, Brightfield microscopy, and quantitative analysis (Bioquant) for LC3 expression. Results: The expression level of LC3 was significantly reduced in groups 2 and 3 when compared to the control group 1. Quantitative measurement of the slides using Bioquant software confirmed our immunohistochemistry and microscopic results. Conclusions: If CBD does indeed decrease autophagic activity, it may represent a new and novel therapeutic target in the treatment of malignant melanoma. Additional studies to clarify the specific relationship between CBD and autophagy are in progress and will be reported upon completion. Citation Format: Erika L. Simmerman, Xu Qin, Kouros Motamed, Jack C. Yu, Babak Baban. Determining autophagic activity following cannabidiol treatment of melanoma: a potential new and novel treatment. [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 3544.
Abstract 823: Prevention of pancreatic cancer by cAMP control
Authors: Jheelam Banerjee, Arokya M. Papu John, Mohammed H. Al-Wadei, Hildegard M. Schuller
Journal: Cancer Research (2016)

Abstract Smoking and alcoholism are risk factors for the development of pancreatitis-associated pancreatic ductal adenocarcinoma (PDAC). Using a hamster model of pancreatitis-associated PDAC induced by treatment with ethanol in the drinking water and the nicotine-derived nitrosamine 4-methylnitrosamino-(3-pyridyl)-1-butanone (NNK) by subcutaneous injection as well as immunohistochemistry of human PDAC tissue microarrays, we have previously shown that these cancers overexpressed stress neurotransmitters and cAMP while the inhibitory neurotransmitter ã-aminobutyric acid (GABA) was suppressed. Using our hamster model, the current study has tested the hypothesis that cAMP control by GABA supplementation in the drinking water prevents the development of pancreatitis-associated PDAC. Our data reveal strong preventive effects of GABA supplementation on the development of PDAC and pancreatic intraductal neoplasia (PanIN). ELISA assays and immunohistochemistry revealed significant decreases in the levels of cyclic adenosine monophosphate (cAMP) and interleukin 6 accompanied by reductions in the expression of several cancer stem cell markers, phosphorylated signaling proteins associated with cell proliferation and migration in pancreatic exocrine cells of GABA treated animals. We conclude that cAMP control by GABA supplementation inhibits multiple cancer supporting pathways at the level of cancer stem cells, differentiated cancer cells and the immune system, identifying this approach as promising novel tool for the prevention of PDAC in individuals with a history of smoking and alcoholism. Citation Format: Jheelam Banerjee, Arokya M. Papu John, Mohammed H. Al-Wadei, Hildegard M. Schuller. Prevention of pancreatic cancer by cAMP control. [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 823.
Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline
Authors: Alexi A. Wright, Kari Bohlke, Deborah K. Armstrong, Michael A. Bookman, William A. Cliby, Robert L. Coleman, Don S. Dizon, Joseph J. Kash, Larissa A. Meyer, Kathleen N. Moore, Alexander B. Olawaiye, Jessica Oldham, Ritu Salani, Dee Sparacio, William P. Tew, Ignace Vergote, Mitchell I. Edelson
Journal: Journal of Clinical Oncology (2016)

To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer.
Sulindac and Erlotinib for Familial Adenomatous Polyposis
Authors: Claude Matuchansky
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Hypnose und Schmerz. Die hypnosuggestive Analgesie
Authors: R. Hassler, F. Duensing, H. Sommer, G.S. Barolin, R. Alnaes, G. Kienle, A.W. von Eiff, H. Roemer, A. Mellgren, H.J. Prill, E. Schaetzing, W. Dogs, J. Lassner, R. Frey, K. Schürmann, I. Horvai, W.P.J. Vië;tor, J.M. Zwart, D. Langen, D. Langen, E. Svalland
Journal: Psychotherapy and Psychosomatics (1966)
iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes
Authors: Lorena Simón-Gracia, Hedi Hunt, Pablo Scodeller, Jens Gaitzsch, Venkata Ramana Kotamraju, Kazuki N. Sugahara, Olav Tammik, Erkki Ruoslahti, Giuseppe Battaglia, Tambet Teesalu
Journal: Biomaterials (2016)
Abstract 3802: Evaluation of microfilament-directed cytochalasins as novel antineoplastic agents
Authors: Matthew Trendowski, Timothy D. Christen, Christopher Acquafondata, Thomas P. Fondy
Journal: Cancer Research (2016)

Abstract Despite inherent differences between the cytoskeletal networks of malignant and normal cells, and the clinical antineoplastic activity of microtubule-directed agents, there has yet to be a microfilament-directed agent approved for clinical use. Cytochalasins are mycotoxins known to potently inhibit the polymerization of filamentous (F)-actin, and have long been used in vitro to examine the importance of microfilaments in fundamental cellular processes. It has previously been demonstrated that cytochalasins preferentially multinucleate malignant cells, suggesting that the congeners may exert novel antineoplastic activity. We have taken these findings, and further expanded upon their potential importance. We have shown in vitro efficacy with multiple congeners, including cytochalasin B, which potentiates substantial sensitivity to clinically approved antineoplastic agents, X-radiation, and low frequency ultrasound. Further, we have shown that cytochalasin B is more cytotoxic against neoplastic cells selected for high metastatic propensity than are their less invasive counterparts. Interestingly, we have also demonstrated that nine cytochalasin congeners may be substantially less affected by drug efflux due to overexpression of ATP-binding cassette (ABC) transporters than are doxorubicin, paclitaxel, or vinblastine, as demonstrated with SK human ovarian carcinoma cell lines of varying levels of drug resistance. Finally, we have shown that cytochalasins B and D elicit substantial antitumor and antimetastatic activity in numerous preclinical mammalian models of malignancy, suggesting that the novel mechanisms by which these congeners exert antineoplastic activity is worth further examination. Citation Format: Matthew Trendowski, Timothy D. Christen, Christopher Acquafondata, Thomas P. Fondy. Evaluation of microfilament-directed cytochalasins as novel antineoplastic agents. [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 3802.
The Hunger Games
Authors: Rebecca E. MacDonell-Yilmaz
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal