tbuckley/cabot-search huggingface dataset:
Abstract IA14: Preclinical models for targeting oncogenic Ras signaling in cancer.
Authors: Kevin Shannon
Journal: Clinical Cancer Research (2015)

Abstract Somatic RAS mutations occur in 30% of human cancers, and are common in both melanoma and hematopoietic cancers. Importantly, whereas KRAS mutations predominate in epithelial cancers, NRAS is mutated much more often in melanoma and hematopoietic cancers. The most obvious therapeutic strategy for cancers with RAS mutations – developing specific inhibitors of the mutant protein – is extremely challenging due to the very high affinity of Ras for GTP, structural considerations of the Ras/GTPase activating protein (Ras/GAP) molecular switch, and the loss of normal enzymatic activity as a consequence of oncogenic RAS mutations. Given these issues, most recent drug discovery efforts have focused on inhibiting downstream biochemical targets of mutant Ras such as Raf, MEK, and Akt with many compounds undergoing clinical evaluation. We have exploited strains of mice that recapitulate endogenous expression of cancer-associated RAS alleles or NF1 inactivation to model human hematologic cancers and to conduct biologic and preclinical studies. In particular, we have deployed the MOL4070LTR retrovirus as an insertional mutagen to generate genetically heterogeneous transplantable myeloid and lymphoid leukemias characterized by hyperactive Ras signaling. We utilize cohorts of mice that are engrafted with the same primary leukemias for preclinical testing. In this presentation, I will focus on three biologic and therapeutic questions related to NRAS in tumorigenesis: (1) loss of the normal NRAS allele in cancers with oncogenic NRAS mutations; (2) responses of primary Nras mutant leukemias to MEK and PI3 kinase inhibitors; and, (3) potential strategies for selectively targeting oncogenic N-Ras in cancer. Note: This abstract was presented as part of the Joint Session: Clinical Science Interactions between Melanoma and Hematologic Malignancies with the AACR Special Conference on Advances in Melanoma: From Biology to Therapy held September 20-23, 2014 in Philadelphia, PA. Citation Format: Kevin Shannon. Preclinical models for targeting oncogenic Ras signaling in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA14.
Phase III multicenter trial of eltrapuldencel-T: Autologous dendritic cells loaded with irradiated autologous tumor cells (DC-TC) in granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with metastatic melanoma (INTUS trial).
Authors: Robert O. Dillman, Michael E. Bayer, James A. Langford, Candace Y. Hseih, Tanya J. Wyatt, Greg Liang, Denysha J. Carbonyell, Andrew N. Cornforth
Journal: Journal of Clinical Oncology (2015)

TPS9082 Background: Melanomas harbor non-synonymous mutations that can result in unique, immunogenic tumor associated antigens (TAA). Recognition of TAA can be induced or enhanced by vaccination. The best source of TAA for this purpose may be proliferating, self-renewing, autologous tumor cells (patient-specific tumor stem cells). Patients with stage IV and recurrent stage III melanoma were treated with repeated s.c. injections of autologous dendritic cells loaded with antigens from irradiated tumor cells derived from autologous melanoma cell lines (DC-TC), and suspended in GM-CSF. In a single arm Phase II trial (n = 54) 5-year survival was 50%. In a randomized Phase II trial (n = 42), 2-year survival was 72% for DC-TC vs. 31% for control patients (HR = 0.27, p = 0.007). Toxicities associated with DC-TC were minimal (n = 72). Improvements in manufacturing have increased the probability of establishing a tumor cell line and decreased the time needed to manufacture DC-TC. Eltrapuldencel-T (DC-TC) was granted special protocol assessment (SPA) and fast track designation by the U.S. Food and Drug Administration in association with approval of this pivotal trial. Methods: INTUS is a Phase III, double-blind, randomized, placebo-controlled trial. Eligible patients have stage IV or recurrent stage III melanoma with at least one lesion amenable to surgical resection. Resected tumor is transferred to a manufacturing facility to grow the cell line. After successful establishment of a cell line and referral for treatment, 250 patients with good performance status (ECOG 0-1) will be stratified by whether they have no evidence of disease, non-measurable disease by RECIST, or measureable disease with elevated LDH or without elevated LDH, then randomized 2:1 to receive either DC-TC or autologous mononuclear cells. Patients undergo leukapheresis to obtain mononuclear cells for each arm. Both products are suspended in 500 micrograms of GM-CSF and injected weekly for 3 weeks, and then monthly for 5 months. The endpoint is overall survival (death from any cause) [NCT01875653]. Clinical trial information: NCT01875653.
Allopurinol in Primary Gout with and after the Administration of Uricosuric Agents
Authors: G. D. Kersley
Journal: Annals of the Rheumatic Diseases (1966)

In four cases allopurinol, oroturic acid, and caparase were compared with regard to their effect on plasma uric acid level, uricosuria, and the urinary excretion of oxypurines.In a 6-day trial with each medication it was found that the lowering of plasma
The Psychiatric Interview in Clinical Practice, Third Editionby Roger A. MacKinnon, M.D., Robert Michels, M.D., and Peter J. Buckley, M.D. Washington, D.C., American Psychiatric Association Publishing, 2016, 704 pp., $79.00 (hardcover).
Authors: Robert Freedman
Journal: American Journal of Psychiatry (2016)

Clinical mental health care providers and trainees will appreciate the up-to-date content and concise writing style.The outstanding organization and concise detail of this book make this a very useful reference for psychiatric providers for test preparation (e.g., for psychiatric residency and board certification exams) and strengthen the clinical foundation for this debilitating but treatable disorder.In addition, therapists, nurses, and interested patients will find this book useful as a broad overview of the disorder.
Long-Term-Cultured Colon Epithelial Cell Lines From Individuals With and Without Colon Cancer Genotypes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: B S Danes
Journal: JNCI Journal of the National Cancer Institute (1985)

In 1982 the characteristics of the first epithelial line established from normal human colon mucosa were reported. The purpose of this report is to describe 5 additional lines established from individuals with and without genotypes associated with genetic predisposition for colon cancer [1 familial polyposis coli (FPC) patient, 1 hereditary nonpolyposis colon cancer (HNPCC) patient, 2 clinically normal individuals (each at risk for one of these autosomal dominant syndromes), and 1 clinically normal individual without any family history of cancer]. The cultured cell lines had the morphologic features associated with epithelium as previously described in the 1982 report. The cell lines derived from genetically (FPC or HNPCC) predisposed individuals had three distinctive characteristics as compared to those derived from individuals without a family history of colon cancer: 1) a higher saturation density (P less than .01); 2) increased in vitro tetraploidy, an in vitro biomarker associated with genetic predisposition for colon cancer; and 3) a higher concentration of carcinoembryonic antigens (CEA) in their conditioned culture medium (P less than .01). Lines derived from normal individuals at risk for the same syndromes were found to have an increased risk status on the first two characteristics. However, the level of CEA did not increase in their culture media, which suggested that the increase in CEA was related to mucosal changes occurring in the preneoplastic sequence in colon cancer.
Risk for developing hyponatraemia in cancer patients treated with targeted therapies: a meta-analysis
Authors: R. Berardi, M. Santoni, S. Rinaldi, E. Nunzi, A. Smerilli, M. Caramanti, F. Morgese, M. Torniai, A. Savini, A. Onofri, M. Pistelli, A. Taccaliti, S. Cascinu
Journal: Annals of Oncology (2015)
Association Between Migraine Headache and Cardiac Syndrome X
Authors: Reza Nemati, Mehran Movahhednia, Somayeh Mehdizadeh, Hooman Salimipour, Darioush Iranpour, Mohammad Reza Pourbehi, Abdolatif Amini, Iraj Nabipour, Mehdi Akbarzadeh, Majid Assadi
Journal: Journal of the American College of Cardiology (2016)
AB0233 RAPID3 Utility in a Spanish Rheumatoid Arthritis Clinic:
Authors: A.D. Gomez-Centeno, E. Graell Martin, H. Costa Ventura, M. Arevalo, M. García Manrique de Lara, M. Larrosa Padro
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> RAPID3 (Routine Assessment of Patient Index Data 3) is an index for rheumatoid arthritis activity evaluation with no formal joint count or analytical parameters. It was developed by T. Pincus and in its English version included in MDHAQ has demonstrated good correlated with composite indices as CDAI or DAS-28 (1). A spanish version of MDHAQ has been made <h3>Objectives</h3> To assess whether the Spanish version of RAPID3 included in the spanish version of MDHAQ is useful to monitoring rheumatoid arthritis (RA) patients in our country <h3>Methods</h3> A questionnaire using only the sections of the Spanish version of MDHAQ included in the calculation of RAPID3 was built. All patients attending to the monographic rheumatoid arthritis clinic completed the questionnaire before entering the office. Once in the office a joints count and physician assessment was performed. Acute phase reactants were and DAS28-ESR, DAS28-CRP, SDAI and CDAI indices were calculated. Results were analyzed using the Spearman correlation coefficient. <h3>Results</h3> 154 patients (78.8% women) mean age (SD) of 59 (14) years and disease duration 11 (10) years were included. All patients were treated with DMARDs. 70% received low-dose corticosteroids. 51% were treated with biologic DMARDs, mostly in combination with methotrexate. 312 questionnaires (2.02 per patient) over6 months were analyzed. Correlation between RAPID3 and other indices was not influenced by sex, treatment, age, disease duration, use of corticoids or biologic DMARDs. The Spearman correlation coefficient between RAPID3 and the different indices were: <h3>Conclusions</h3> RAPID3 may be useful for monitoring RA patients due to its excellent correlation with joint composite indices that use joint counts and acute phase reactants. <h3>References</h3> Pincus T. et al. RAPID3 (Routine Assessment of Patient Index Data 3), a Rheumatoid Arthritis Index Without Formal Joint Counts for Routine Care: Proposed Severity Categories Compared to Disease Activity Score and Clinical Disease Activity Index Categories. The Journal of Rheumatology 2008; 35:11; doi:10.3899/jrheum <h3>Disclosure of Interest</h3> None declared
TCTAP A-013 Long-Term Clinical Impact of Complete Revascularization in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease
Authors: Min Chul Kim, Myung-Ho Jeong, Doo Sun Sim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn
Journal: Journal of the American College of Cardiology (2016)
Potential of PAR1 to be involved in the acquisition of drug resistance in human gastric cancer cell.
Authors: Daisuke Fujimoto, Yuki Ueda, Yasuo Hirono, Takanori Goi, Akio Yamaguchi
Journal: Journal of Clinical Oncology (2015)

94 Background: Side Population (SP) is a FCM term to define cell clusters with strong ability to efflux DNA dye Hoechst 33342 by ABC transporters. In some cases, cancer stem-like cells (CSLCs) were identified using the FCM-based SP technique and SP cells had ability of drug resistance because SP cells were expressed ABC transporter. CSLCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. We had showed PAR1 had an intimate involved in gastric cancer metastasis. And PAR1 contributed to leukemic stem cell maintenance. So we studied PAR1 induced SP cells acquired the ability of drug resistance in gastric cancer. Methods: MKN45 cells stably expressing PAR1 (45-PAR1) were generated in our laboratory. siRNA against PAR1 was synthesized. We studied the change in fraction of SP cell, when PAR1-expressing cell (45-PAR1 and MKN74), PAR1-null expressing cell MKN45 and inhibited PAR1-expressing MKN74 by PAR1 siRNA (74-PAR1siRNA) were treated with PAR1 agonist TFLLR-NH 2 or TFLLR-NH 2 plus PAR1 selective antagonist SCH79797. And, we compared the drug resistance using paclitaxel, cisplatin and 5-FU and researched ABC transporter expression in MKN45, 45-PAR1 and MKN74 with TFLLR-NH 2 or SCH79797 or PAR1 siRNA. Results: We showed the fraction of SP cells in 45-PAR1 and MKN74 achieved dramatic increases by TFLLR-NH 2 . But, the fraction of SP cells in MKN45 and 74-PAR1siRNA remained about the same by TFLLR-NH 2 . When treated with SCH79797, the fraction of SP cells remained about the same, too. As for drug resistance assay, 45-PAR1 and MKN74 achieved the same strong resistance of the SP cells by TFLLR-NH 2 . But, MKN45 and 74-PAR1siRNA were not able to obtain the drug resistance. When treated with TFLLR-NH 2 , 45-PAR1 and MKN74 showed the high expression of ABCG1 and MRP1, that proteins are ABC transporters, compared to MKN45 and 74-PAR1siRNA. These expression levels in 45-PAR1 and MKN74 with TFLLR-NH 2 were equal to the SP cells. Conclusions: PAR1 is closely-involved in that gastric cancer cells achieved the drug resistance and were led to SP enriched in CSLCs.
Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs
Authors: Yohannes T. Ghebre, Ganesh Raghu
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

The prevalence of abnormal acid gastroesophageal reflux (GER) is higher in patients with idiopathic pulmonary fibrosis (IPF) than in matched control subjects. Several studies demonstrated that more than one-third of patients with IPF have abnormal esophageal acid exposures. In addition, many of these studies indicate that the majority of patients with IPF have silent reflux with no symptoms of GER. Findings of abnormal reflux persist in a large proportion of patients with IPF placed on antacid therapy such as proton pump inhibitors (PPIs). This seemingly paradoxical observation suggests that either patients with IPF are somehow resistant to PPI-based intervention or PPIs are inherently unable to suppress acid GER. By contrast, patients with IPF who undergo Nissen fundoplication surgery are effectively relieved from the complications of GER, and retrospective studies suggest improved lung function. Retrospective, anecdotal data suggest a beneficial role of PPIs in IPF including stabilization of lung function, reduction in episodes of acute exacerbation, and enhanced longevity. The recent evidence-based guidelines for treatment of IPF approved conditional recommendation of PPIs for all patients with IPF regardless of their GER status. Recently, we have reported that PPIs possess antiinflammatory and antifibrotic activities by directly suppressing proinflammatory cytokines, profibrotic proteins, and proliferation of lung fibroblasts. Our study provides an alternative explanation for the beneficial effect of PPIs in IPF. In this Perspective, we reviewed emerging progress on antifibrotic effect of PPIs using IPF as a disease model. In addition, we summarized surgical and pharmacological interventions for GER and their downstream effect on lung physiology.
Point: Combination Versus Single-Agent Chemotherapy: The Argument for Sequential Single Agents
Authors: Alison K. Conlin, Andrew D. Seidman
Journal: Journal of the National Comprehensive Cancer Network (2007)

Metastatic breast cancer is a heterogeneous disease, and treatment decisions depend on several individualized patient and tumor characteristics. Although combination therapy often shows improved response rates in metastatic breast cancer, few studies have shown superiority in overall survival. The choice of combination versus sequential single-agent treatment, therefore, must consider many factors, with no one strategy right for all patients. This article reviews several important clinical trials that address this issue, and argues for single-agent sequential therapy for most patients with metastatic breast cancer.
Quality of life (QOL): Use SF-36 or EORTC QLQ-C30 questionnaires in elderly cancer patients?
Authors: C. Terret, D. Pérol, G. Albrand, J. P. Droz
Journal: Journal of Clinical Oncology (2005)

8091 Background: QOL represents a critical issue in geriatric oncology. Cancer in the elderly is often associated with other chronic conditions possibly affecting QOL. Standard QOL tools are not likely to capture the entire impact of all health problems in these patients (pts). Our prospective study aimed to evaluate two QOL questionnaires, EORTC QLQ-C30 and SF-36, in older cancer pts. Methods: Male outpatients over 65 years with genitourinary cancer were asked to fill out a booklet including QLQ-C30 and SF-36 questionnaires, functional assessment scales (ADL, IADL), emotional and pain evaluation (GDS, VAS-pain). Patient performance status was also estimated using the Karnofsky Performance Status scale (KPS). Internal consistency of QOL tools was assessed using Cronbach’s α-coefficient. Correlations between the various tools were analyzed using Spearman’s rank coefficient (r). Results: 72 of 87 men (median age, 76 years [68–86]) completed the questionnaires (83% response rate). Most pts had prostate cancer (74%); half of them had advanced disease. A majority of pts were independent in ADL (67%) and IADL (57% with IADL score >11, because of gender bias). Internal consistency reliability was high (α ≥0.7), except for SF-36 cognitive function (α = 0.62) and QLQ-C30 general health (α =0.57). Moreover, QLQ-C30 subscales showed significant (p <0.001) and substantial (|r| >0.45) correlation with homologous SF-36 scales, except for cognitive function and mental health. Surprisingly, KPS was generally not correlated with both SF-36 and QLC-C30 scales. Moreover, no correlation was found between QOL scales and ADL/IADL functions. Conclusions: QLQ-C30 and SF-36 appear similarly reliable for QOL assessment in this population. However, cognitive function and functional status seem poorly taken into account while they possibly influence the value of QOL self-assessment. We postulate that QOL assessment in elderly cancer pts should be associated with comprehensive geriatric assessment to better meet clinicians’ expectations. No significant financial relationships to disclose.
TCTAP A-104 Predicting Severity of Coronary Lesions Using Framingham Risk Score: Does Gender Difference Matter?
Authors: Johan Senihardja, Agnes Lucia Panda, Janry Anton Pangemanan, Bambang Budiono, Benny Mulyanto Setiadi, Hendro Adi Kuncoro, Yosua Arthur Iskandar, Monique Priscilla Fransiska Rotty, Rizki Francis Pandelaki, Soetandar Widjaja
Journal: Journal of the American College of Cardiology (2016)
ONC201 Exerts p53-Independent Cytotoxicity Through TRAIL and DR5 Induction In Mantle Cell Lymphomas
Authors: Jo Ishizawa, Kensuke Kojima, Archana Dilip, Vivian R Ruvolo, Bing Z Carter, Joshua E Allen, Sattva S. Neelapu, Timothy J. McDonnell, Mala Kiran Talekar, Wafik S. El-Deiry, Larry W. Kwak, Michael Andreeff
Journal: Blood (2013)
Clinical and Genetic Risk Factors for Acute Pancreatitis in Patients With Acute Lymphoblastic Leukemia
Authors: Chengcheng Liu, Wenjian Yang, Meenakshi Devidas, Cheng Cheng, Deqing Pei, Colton Smith, William L. Carroll, Elizabeth A. Raetz, W. Paul Bowman, Eric C. Larsen, Kelly W. Maloney, Paul L. Martin, Leonard A. Mattano, Naomi J. Winick, Elaine R. Mardis, Robert S. Fulton, Deepa Bhojwani, Scott C. Howard, Sima Jeha, Ching-Hon Pui, Stephen P. Hunger, William E. Evans, Mignon L. Loh, Mary V. Relling
Journal: Journal of Clinical Oncology (2016)

Acute pancreatitis is one of the common causes of asparaginase intolerance. The mechanism is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previously identified.To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort of 5,185 children and young adults with acute lymphoblastic leukemia, including 117 (2.3%) who were diagnosed with at least one episode of acute pancreatitis during therapy. A genome-wide association study was performed in the cohort and in an independent case-control group of 213 patients to identify genetic risk factors.Risk factors associated with pancreatitis included genetically defined Native American ancestry (P < .001), older age (P < .001), and higher cumulative dose of asparaginase (P < .001). No common variants reached genome-wide significance in the genome-wide association study, but a rare nonsense variant rs199695765 in CPA2, encoding carboxypeptidase A2, was highly associated with pancreatitis (hazard ratio, 587; 95% CI, 66.8 to 5166; P = 9.0 × 10(-9)). A gene-level analysis showed an excess of additional CPA2 variants in patients who did versus those who did not develop pancreatitis (P = .001). Sixteen CPA2 single-nucleotide polymorphisms were associated (P < .05) with pancreatitis, and 13 of 24 patients who carried at least one of these variants developed pancreatitis. Biologic functions that were overrepresented by common variants modestly associated with pancreatitis included purine metabolism and cytoskeleton regulation.Older age, higher exposure to asparaginase, and higher Native American ancestry were independent risk factors for pancreatitis in patients with acute lymphoblastic leukemia. Those who inherit a nonsense rare variant in the CPA2 gene had a markedly increased risk of asparaginase-induced pancreatitis.