tbuckley/cabot-search huggingface dataset:
Abstract B4: Specificity of ▵Np63α-repressed target genes is determined by changes in p63-interacting proteins
Authors: Matthew R. Ramsey, Benjamin Ory, Lei He, Leif W. Ellisen
Journal: Cancer Research (2009)

Abstract The transcription factor p63 has been reported to have many functions, including regulation of proliferation, suppression of apoptosis, suppressing differentiation, and maintaining stem cell self-renewal. These various functions are carried out by activation or repression of a diverse set of target genes. However, the mechanisms that lead to selective regulation of target genes have remained elusive. In human Squamous Cell Carcinoma (SCC) ▵Np63α is expressed at high levels, and serves to block TAp73-mediated induction of pro-apoptotic target genes such as Puma. Our previous work has shown that ▵Np63α and TAp73 physically associate, and that p63 binds to the promoter of TAp73-activated target genes such as Puma. We have constructed a panel of p63 point and deletion mutants in order to examine the role of different functional domains in p63-mediated repression. Using Luciferase reporter assays and a physiologic reconstitution model with mutant p63 in SCC cells, we have identified mutants defective in suppression of apoptosis and TAp73 target genes. Examination of point mutants defective in DNA binding, but able to bind to TAp73 normally has revealed a requirement for DNA binding in suppression of TAp73 target gene activation and apoptosis, suggesting that ▵Np63α-TAp73 heteromeric complexes on DNA are repressive. We have also performed a si-RNA based screen for regulators of p73 activity, and identified Daxx as a p63-interacting protein involved in the repression of p73 activity in SCC cells. These data demonstrate that ▵Np63α functions as part of a repressive complex to regulate pro-apoptotic target genes in human SCC. Thus, ▵Np63α plays a crucial role in maintaining the survival of SCC cells and promoting tumorigenesis. Citation Information: Cancer Res 2009;69(23 Suppl):B4.
Randomized, placebo-controlled, phase II trial of EGFR and COX-2 inhibition in advanced non-small cell lung cancer.
Authors: K. L. Reckamp, M. Koczywas, M. C. Cristea, J. Dowell, B. Gardner, G. Milne, S. Fouladi Rad, R. A. Figlin, R. Elashoff, S. M. Dubinett
Journal: Journal of Clinical Oncology (2010)

TPS337 Background: Signaling through the cyclooxygenase-2 (COX-2) pathway presents a novel mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC). This resistance is mediated through an EGFR-independent activation of MAPK/Erk by the COX-2 metabolite PGE2 (Krysan et al Cancer Res 2005). Another mechanism of COX-2 mediated resistance to EGFR TKIs relates to PGE2 promotion of epithelial to mesenchymal transition (EMT). Suppression of epithelial markers such as E-cadherin leads to resistance to erlotinib (E), and PGE2 downregulates E-cadherin expression. More effective therapy may require blocking both the EGFR-dependent and EGFR-independent pathways, such as signaling through COX-2/PGE2. Our phase I study of E and celecoxib (C) established the optimal biological dose of C at 600 mg bid, revealed improved clinical responses, and identified potential predictive biomarkers (Reckamp et al. Clin Cancer Res 2006). We hypothesize that EGFR and COX-2 inhibition will augment the efficacy of EGFR TKI therapy in NSCLC by increasing tumor E-cadherin expression and blocking PGE2-mediated resistance to EGFR inhibition. Methods: This is a randomized, placebo-controlled, phase II trial of the combination of E and C vs. placebo enrolling 86 pts with advanced NSCLC. To date, 65 pts have been enrolled. The study evaluates clinical efficacy by time to progression. Secondary endpoints include evaluation of molecular markers to assess the basis for targeting multiple pathways and evaluating EGFR TKI-resistance. All pts have pretreatment tissue available for the measurement of tumor E- cadherin, COX-2, and EGFR by IHC, EGFR amplification by FISH, and EGFR mutation status to correlate with clinical response. A subset of pts will undergo biopsy at week 8 to evaluate change in E-cadherin, COX-2, and EGFR at the time of tumor assessment. Serum will be evaluated for markers of COX-2 signaling, and urine will be assessed for urinary PGE-M. We hypothesize that molecular correlates in tumor, blood, and urine will identify a targeted population who will benefit from combination COX-2 and EGFR inhibition. Supported by NIH 1 P50 CA90388 and K12 CA01727. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Pfizer, Tragara Pharmaceutical, Tragara Pharmaceuticals Genentech Genentech, OSI Pharmaceuticals, Pfizer, Tragara Pharmaceuticals
Coronary Stenting to Treat Dyspnea in a Patient With Severe Lung Disease
Authors: David S. Raymer, David L. Brown
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
P3-081: Erlotinib as monotherapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) and poor performance (PS=2)
Authors: Ramon Garcia, Vicente Alberola, Jose Enrique Ales, Alfredo Carrato, Alfredo Frau, Isidoro Carlos Barneto, Javier Castellanos, Alvaro Montaño, Pilar Regueiro, Luis Paz-Ares
Journal: Journal of Thoracic Oncology (2007)
Abstract A33: The regulation of extracellular acidosis and cell survival by the TIMP-1/CD63 axis in breast carcinoma
Authors: Abdo J. Najy, Young Suk Jung, Hyeong-Reh Choi Kim
Journal: Cancer Research (2016)

Abstract Breast Cancer (BrCa) resistance to conventional therapies often leads to more aggressive and metastatic disease highlighting the importance of understanding the resistance pathway. The Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is among the most reliable prognostic markers for therapy resistance as well as metastasis of breast cancer via promotion of breast cancer cell survival through its unique interaction with the tetraspanin CD63. Recent work has shown that levels of TIMP-1 and the carbonic anhydrase family member CAIX in circulating tumor cells (CTCs) predict BrCa progression-free and overall survival. Since CAIX is known to play a critical role in the regulation of extracellular acidosis that contributes to therapy resistance, we investigated whether TIMP-1/CD63 signaling regulates extracellular acidosis involving CAIX. We utilized the murine 4T1 and human MCF10A progression models of breast cancer and demonstrated increased CAIX and TIMP-1 expression in the more aggressive 4T1 and MCF10CA1h cells. When we monitored pH change using a digital pH reader and the pH sensitive DF fluorescein dye, the more aggressive human MCF10Ca1h cells exhibited marked extracellular acidosis compared to the minimally malignant MCF10A and MCF10AneoT cells. Importantly, downregulation of TIMP-1 or CD63 in MCF10CA1h cells specifically reduced CAIX expression and its associated extracellular acidosis. To determine the functional significance of CAIX in TIMP-1/CD63-mediated extracellular acidosis, we attenuated CAIX expression and demonstrated a significant reduction of the acidosis phenotype observed in MCF10CA1h cells. Importantly, CAIX knockdown drastically reduced BrCa cell survival in a clonogenic cell survival assay. Taken together, we have identified a unique TIMP-1/CD63-mediated signaling pathway, resulting in extracellular acidosis and cell survival of BrCa cells involving CAIX. This study further provides salient information as to TIMP-1-specific function in breast cancer. Citation Format: Abdo J. Najy, Young Suk Jung, Hyeong-Reh Choi Kim. The regulation of extracellular acidosis and cell survival by the TIMP-1/CD63 axis in breast carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A33.
Trichinellose liée à la consommation de viande de cheval : règlementation européenne et gestion de risque
Authors: E Maillot
Journal: Eurosurveillance (1998)

Les epidemies de trichinellose survenues en Italie et en France fin 1975 mettaient en cause une espece animale, le cheval, qui n’etait pas auparavant consideree comme un risque vis-a-vis de cette pathologie. La reglementation europeenne ne concernait alors que le controle de la viande de porc.
CPT-11/5-fluorouracil (5-FU)/leucovorin (FA)/oxaliplatin (L-OHP) (CPT-11-FFL) plus cetuximab (Cmab) in unselected advanced colorectal cancer (ACC) patients.
Authors: C. Garufi, A. Torsello, C. Campanella, G. M. Ettorre, G. Vennarecci, E. Melucci, M. Zeuli, I. Sperduti, A. Gelibter, F. Cognetti
Journal: Journal of Clinical Oncology (2010)

3551 Background: We previously showed in a phase II trial that a triplet combination of chronomodulated CPT-11/5-FU/FA/L-OHP plus Cmab was highly effective in pts with liver metastases from ACC (Garufi, ESMO 2009). Here we reviewed our experience in unselected pts. Methods: Pts received a 6-h infusion (peak 13:00) of CPT-11, 130 mg/m2/d1, and 12-h, days 2-5, infusion of L-OHP 15/mg/m2/d (peak at 16:00), FA 150 mg/m2/d plus 5-FU 550 mg/m2/d (peak at 4:00), q2 weeks + weekly Cmab. Treatment was delivered by a disposable system (CIP). Pts with > grade 2 toxicity had a 20% dose reduction. Only pts treated after October 2008 received Cmab on the basis of K-RAS status. Results: From 07/20/2006 to 06/30/2009 we enrolled 32 pts: M/F 17/15; median age 58 y (29-78). Primary tumor colon/rectum 29/3; primary tumor resected 30 pts (94%), synchronous/metachronous metastases 21/11 pts; number (n.) of metastatic site: a) 1: 26 (81%) (20 liver), b) ≥ 2: 6 (19%); untreated/pretreated pts 13/19; previous chemotherapy lines: a) 1: 4, b) ≥ 2 15 . Median n. of courses (c) per pt was 9 (4-15) in pretreated and 7 (2-14) in untreated pts. We had 1 RC, 13 PR, 8 SD, 8 PD. ORR was 43.8% (CI95% 26.8-60.9) with 66.7% in untreated and 33.3% in pretreated pts (p = 0.056). Complete resection of liver mets was achieved in 5 pretreated pts, while surgery is too early for untreated pts. At multivariate logistic regression analysis for response untreated pts (p = 0.03) and number of metastatic lines (1) (p = 0.056) were significantly found. Major limiting toxicity was G2/3diarrhea: 54.7/74.9%, of pts, only 18.1/8.7% of c, consistently reduced after dose modification. G2/3 neutropenia: 36.5/0% pts, 24.3/0% c. Females experienced more dose-reduction for toxicity 8/15 (53.3%) than males, 5/17 (29.4%). Median follow-up was 10 m (range 2-36), median PFS 13 m (CI95% 5.81-20.18); median OS 24.3 m (CI 16.9-31.74). Conclusions: These results in unselected ACC population confirm: 1) the high activity of triplet combination plus Cmab particularly in untreated pts with only 1 metastatic site; 2) women developped more toxicity than men with diarrhea being relevant; 3) 25% of pretreated pts can be recovered to liver surgery. No significant financial relationships to disclose.
Sugar Industry and Coronary Heart Disease Research
Authors: Cristin E. Kearns, Laura A. Schmidt, Stanton A. Glantz
Journal: JAMA Internal Medicine (2016)

Early warning signals of the coronary heart disease (CHD) risk of sugar (sucrose) emerged in the 1950s. We examined Sugar Research Foundation (SRF) internal documents, historical reports, and statements relevant to early debates about the dietary causes of CHD and assembled findings chronologically into a narrative case study. The SRF sponsored its first CHD research project in 1965, a literature review published in the New England Journal of Medicine, which singled out fat and cholesterol as the dietary causes of CHD and downplayed evidence that sucrose consumption was also a risk factor. The SRF set the review's objective, contributed articles for inclusion, and received drafts. The SRF's funding and role was not disclosed. Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD. Policymaking committees should consider giving less weight to food industry-funded studies and include mechanistic and animal studies as well as studies appraising the effect of added sugars on multiple CHD biomarkers and disease development.
Efficacy of Mitomycin C plus a Fluoropyrimidine in pre-treated patients with metastatic colo-rectal cancer eligible to Regorafenib. Results of a retrospective study
Authors: C. Martines, S. Cordio, H. Soto-Parra, G. Novello, G. Burrafato, F. Martorana, M. Aiello, M. Mattina, M. Uccello, R. Bordonaro, P. Vigneri
Journal: Annals of Oncology (2015)
Panic Disorder Comorbidity with Medical Conditions and Treatment Implications
Authors: Alicia E. Meuret, Juliet Kroll, Thomas Ritz
Journal: Annual Review of Clinical Psychology (2017)

Panic disorder (PD) is unique among the anxiety disorders in that panic symptoms are primarily of a physical nature. Consequently, comorbidity with medical illness is significant. This review examines the association between PD and medical illness. We identify shared pathophysiological and psychological correlates and illustrate how physiological activation in panic sufferers underlies their symptom experience in the context of the fight-or-flight response and beyond a situation-specific response pattern. We then review evidence for bodily symptom perception accuracy in PD. Prevalence of comorbidity for PD and medical illness is presented, with a focus on respiratory and cardiovascular illness, irritable bowel syndrome, and diabetes, followed by an outline for potential pathways of a bidirectional association. We conclude by illustrating commonalities in mediating mechanistic pathways and moderating risk factors across medical illnesses, and we discuss implications for diagnosis and treatment of both types of conditions.
Soluble guanylate cyclase deficiency selectively abolishes NO-mediated pulmonary vasodilation and increases the pulmonary vascular remodeling response to chronic hypoxia
Authors: Pieter Vermeersch, Peter Pokreisz, Glenn Marsboom, ES Buys, Hilde Gillijns, Marijke Pellens, M Swinnen, F Ichinose, Mieke Dewerchin, P Brouckaert, KD Bloch, Stefan Janssens
Journal: Circulation (2005)
Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis
Authors: Ali A. Mokdad, Rebecca M. Minter, Hong Zhu, Mathew M. Augustine, Matthew R. Porembka, Sam C. Wang, Adam C. Yopp, John C. Mansour, Michael A. Choti, Patricio M. Polanco
Journal: Journal of Clinical Oncology (2016)

Purpose To compare overall survival between patients who received neoadjuvant therapy (NAT) followed by resection and those who received upfront resection (UR)-as well as a subgroup of UR patients who also received adjuvant therapy-for early-stage resectable pancreatic adenocarcinoma. Patients and Methods Adult patients with resected, clinical stage I or II adenocarcinoma of the head of the pancreas were identified in the National Cancer Database from 2006 to 2012. Patients who underwent NAT followed by curative-intent resection were matched by propensity score with patients whose tumors were resected upfront. Overall survival was compared by using a Cox proportional hazards regression model. Early postoperative and oncologic outcomes were evaluated. Results We identified 15,237 patients with clinical stage I or II resected pancreatic head adenocarcinoma. From the NAT group, 2,005 patients (95%) were matched with 6,015 patients who underwent UR. The NAT group was associated with improved survival compared with UR (median survival, 26 months v 21 months, respectively; stratified log-rank P < .01; hazard ratio, 0.72; 95% CI, 0.68 to 0.78). Patients in the UR group had higher pathologic T stage (pT3 and T4: 86% v 73%; P < .01), higher positive lymph nodes (73% v 48%; P < .01), and higher positive resection margin (24% v 17%; P < .01). Compared with a subset of UR patients who received adjuvant therapy, NAT patients had a better survival (adjusted hazard ratio, 0.83; 95% CI, 0.73 to 0.89). Conclusion NAT followed by resection has a significant survival benefit compared with UR in early-stage, resected pancreatic head adenocarcinoma. These findings support the use of NAT, particularly as a patient selection tool, in the management of resectable pancreatic adenocarcinoma.
PD1-2-7: Differences in high-resolution computed tomography (HRCT) Findings between mucinous and non-mucinous Bronchioloalveolar Carcinoma (BAC) less than 3cm
Authors: Keisei Tachibana, Kazuo Nakagawa, Masahiro Endo, Yasuhisa Ohde, Takehiro Okumura, Haruhiko Kondo, Ichiro Ito, Toru Kameya
Journal: Journal of Thoracic Oncology (2007)
A phase II open-label prospective study of preoperative chemoradiation with oxaliplatin/5FU in locally advanced rectal cancer followed by total mesorectal excision and adjuvant FOLFOX6.
Authors: K. Siu, R. Young, P. Kozuch, T. Mirzoyev, V. Rosenwald, D. Francois, S. M. Cohen, K. Hu, M. L. Grossbard, S. C. Malamud
Journal: Journal of Clinical Oncology (2010)

e14128 Background: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer. Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant FOLFOX6. Methods: 27 patients with stage II/III rectal cancer were treated with OXA 60 mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8 Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6. Results: 92% and 93% of intended neoadjuvant OXA and 5FU doses were given. First 5 patients enrolled received weekly continuous 5FU d1-7, later subjects received 5FU d1-5 due to toxicity. After nCRT, 10 subjects withdrew from study due to disease progression (n = 3), death (n = 1), and OXA intolerance (n = 6). 23 patients underwent TME, 20 pathologically downstaged and 13% attained pCR. 17 patients initiated adjuvant FOLFOX6 with 87% and 92% of intended doses of OXA and 5FU given. 1 patient withdrew from OXA intolerance and 1 death from cancer. Acute grade 3-4 toxicities occurred in 16 pts, mainly hypersensitivity reactions and OXA associated peripheral neuropathy. At a median follow up of 28 months, overall survival (OS) was 92% and disease-free survival (DFS) was 70%. Local recurrences occurred in the two patients with positive margins. Among 20 downstaged patients, 2 year OS/DFS were 100% and 85%, local and distant control were 95% and 90%. Patients who completed adjuvant FOLFOX had a 2 year OS of 100% and a DFS of 87.5%. Conclusions: The addition of OXA to nCRT and adjuvant therapy demonstrated encouraging downstaging rates and 2 yr OS/DFS in patients who completed therapy. Developing strategies to minimize prohibitive neuropathy and hypersensitivity reactions may allow a greater proportion of patients to benefit from this regimen. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
The BBAP E3 Ligase Monoubiquitylates Histone H4 at Lysine 91 and Selectively Modulates the DNA Damage Response in Chemotherapy-Resistant Lymphomas.
Authors: Qingsheng Yan, Shilpee Dutt, Rong Xu, Katherine Graves, Przemyslaw Juszczynski, John Manis, Margaret A. Shipp
Journal: Blood (2009)
Fatty Acid Metabolism, Bone Morphogenetic Protein Receptor Type 2, and the Right Ventricle
Authors: Brian B. Graham, Jeffrey C. Robinson, Rubin M. Tuder
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

In this issue of the Journal, Hunter and colleagues (pp.739-747) report on the results of a large-scale multicenter study evaluating the relationship between obstructive sleep apnea (OSA) and neurocognitive test results (1).The authors propose a dosedependent causal relationship between OSA and decreased neurocognitive performance and, as such, advocate for early
Novel tumor vaccine gp96-Ig fusion heat shock protein in advanced non-small cell lung cancer (NSCLC) patients who have failed palliative chemotherapy and erlotinib.
Authors: E. Podack, L. E. Raez, E. Fisher, E. Leibovitch, J. E. Gomez, P. Baldie, K. A. Tolba, E. S. Santos, G. Walker
Journal: Journal of Clinical Oncology (2010)

e18042 Background: To determine the safety, immunogenicity, and clinical response to our newly developed allogeneic gp96-Ig tumor vaccine for NSCLC patients (pts) with advanced disease who have failed standard chemotherapy and erlotinib. Methods: Allogeneic, cultured lung adenocarcinoma cells transfected with HLA A1 and gp96-Ig were irradiated and injected intradermally into pts suffering from advanced, relapsed, or metastatic NSCLC in a phase I clinical trial. HLA matching was not required. Three dose-schedule combinations were considered (total of 4.5 × 107 cells administered by 9 biweekly (DS1), 18 weekly (DS2), or 36 twice weekly (DS3) injections). We planned to enroll a maximum of 36 patients. Immune response to vaccination of patients was measured by determining adenocarcinoma-specific CD8 CTL frequencies in ELI-spot assays for interferon-γ (IFN-γ) and by measuring the frequency of FoxP3+ CD4+ Treg. If pts had a clinical response, defined as complete (CR), partial (PR), or stable disease (SD), they continued with the next course of vaccinations for up to 3 courses (9 - 36 vaccinations total). Results: 14 patients were consented, one was never treated due to early progression and another other one was found to be a screen failure. Median age was 65 (38-86), 8/12 were female, most of them Hispanic. Most of the patients had failed at least 2 lines of chemotherapy and erlotinib. 9 patients were treated in DS1 cohort, two in DS2 and one in DS3. None of the patients experienced serious adverse events (SAE) that were related to vaccine. Grade I: rash, skin induration and skin erythema were seen in 5/12/12 patients respectively. Two patients had SD, one for more than 6 months. Four pts (including the 2 pts that had SD) had an immunological response determined by ELI-spot, and in most of the patients the frequency of FoxP3+ CD4+ Treg decreased. Conclusions: Minimal toxicity and immunologic response has been seen so far in this very advanced population of NSCLC pts. No significant financial relationships to disclose.
Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system
Authors: Binlong Chen, Wenbing Dai, Dong Mei, Tongzhou Liu, Suxin Li, Bo He, Bing He, Lan Yuan, Hua Zhang, Xueqing Wang, Qiang Zhang
Journal: Journal of Controlled Release (2016)