tbuckley/cabot-search huggingface dataset:
The anticancer drug development pipeline of the pharmaceutical (P) and biotech (B) industries
Authors: F. P. Thomas
Journal: Journal of Clinical Oncology (2009)

e14589 Background: The rapidly growing market for anticancer drugs has attracted numerous companies, and this therapeutic area represents more that a third of all drug development candidates. We studied the pipeline of Pharma (P) and Biotech (B) companies to look at possible differences and 2008 changes in composition. Methods: The anticancer drug pipeline including candidates in Phase I to III and marketed products still actively developed in new indications was reviewed by systematically searching the websites of 41 P and 269 B active in oncology. Results: B, defined as entrepreneurial R&amp;D-focused companies had 463 molecules including 160 in Phase I, 202 in Phase II, 73 in Phase III, and 28 marketed. P develop 219 molecules including 78 in Phase I, 61 in Phase II, 38 in Phase III, and 42 marketed. The number of candidates decreased by 10 in B and increased by 15 in P pipelines during H2, 2008, translating difficult economic conditions for B (with few candidates entering Phase I) and an increased focus of P on oncology (internal R&amp;D efforts and B acquisition that accounts for 39 of its 219 molecules). B licensed out 119 of its candidates to P or other B. The portfolio of B and P analyzed by mechanism of action significantly differs. Symptomatic/adjuvant treatments represent 7.1 vs 5.5%, targeted small molecules 28.7 vs 42.9%, cytotoxics including reformulations 20.5 vs 22.4%, cell/gene therapies, oncolytic viruses, and oligonucleotides 7.3 vs 0%, antibodies and related proteins 19% vs 17.8%; immunotherapy 13.1% vs 5%, photodynamic and radio- therapy 2.8% vs 0.5% for B vs P, respectively. The number of antibodies and targeted small molecules increased during H1, 2008 by 2.1 and 4.4%, respectively. P recently enriched its antibody portfolio through B acquisition, but completely moved out of cytotoxics, except mid-size European and Japanese P. An update as of May,1st 2009 with a trend analysis including the potential impact of the financial crisis on B portfolio will be presented. Conclusions: The oncology pipelines of P and B are broad, different for B and P, and rapidly changing in composition. No significant financial relationships to disclose.
Normal Blood Pressure and Hypertension: New Definitions.
Authors: Arthur Morris Master, Charles I. Garfield, Max B. Walters
Journal: JAMA (1952)

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
Abstract 17035: Myocardial Ischemia or Degree of Coronary Artery Stenosis as Predictors of Events in Renal Transplant Candidates
Authors: Luis Henrique W Gowdak, Flavio J de Paula, Luiz Antonio M Cesar, Eduardo M Krieger, Jose Jayme G de Lima
Journal: Circulation (2010)

Background: Patients (pt) with chronic kidney disease (CKD) stage V are at greater risk for major adverse cardiovascular events (MACE), mostly due to coronary artery disease (CAD). Objective: To de...
Clinical and molecular evaluation of patients with esophageal adenocarcinoma from the United States and Japan
Authors: M. Gibson, H. Orita, M. Brock, L. Xu, S. Yang, R. Heitmiller, J. Herman, E. Gabrielson, A. Forastiere
Journal: Journal of Clinical Oncology (2006)

4087 Background: Esophageal adenocarcinoma (EAC) is more common than squamous cancer (ESC) in the US versus Japan (J); however, EAC in J is now more frequently recognized. We assessed features of EAC in J and US patients to determine if the cohort of EAC in Japan is similar to the US. Methods: Patients with EAC who underwent primary curative surgery were identified by reviewing all surgical cases from 1998 to the present at Johns Hopkins Hospital (n = 57) and Juntendo University Hospital (n = 20). Clinical variables included: gender, age, pathologic stage, date of surgery and of death. Methylation of APC, E-cadherin, MGMT, ER, p16, DAP-kinase and TIMP3 was determined with methylation specific-PCR for each J patient and compared to historical control US EAC patients. Logistic regression and survival analysis were used to evaluate the relationship between clinical variables and methylation status to outcome in these two patient groups. Results: Age and gender were similar in each cohort. Gender (50M/6F in US; 16M4F p = 0.29). Median age (65.5 in US; 64 in J). Path stage was lower in US patients but not significant compared to J patients. Stage distribution US: stage I (n = 30), IIA (n = 2), stage IIB (n = 6), stage III (n = 9) and stage IV (n = 4). Stage distribution in J: stage I (n = 6), IIA (n = 5), stage IIB (n = 5), stage III (n = 3) and stage IV (n = 3). Path stage unavailable in 5 US patients. Overall median survival was 4.2 years. Median survival for US was 2.9 years but not reached for J (note 15/20 J patients outcome not known). For the combined cohort, age and path stage (adjusted for clinical co-variates) correlated with worse survival. Age HR 1.05; 95% CI 1.01–1.09. Pathologic Stage HR 1.4; 95% CI 1.19–1.65. These were also predictive within each subgroup. The fraction of patients with methylation is available for three genes: APC (66% US; 70% J). p16 (39% US; 20% J). MGMT (63% US; 75% J). Conclusions: Clinical data are similar for US and J patients with EAC. Early stage in US patients may by due to induction chemoRT in the US. Predictors of survival (age and pathologic stage) are also similar. This suggests that EAC is similar in US and J patients, perhaps reflecting similar environmental and molecular causes. Methylation data for all 7 genes and their correlation with outcome will be presented at the meeting. No significant financial relationships to disclose.
Abstract 12834: Cardiac Catheterization Lab Activations for ST-Segment Elevation Myocardial Infarction (STEMI) are Frequently Cancelled at a Major Los Angeles County STEMI-Receiving Center
Authors: David Lange, Stanley Conte, Effie Pappas-Block, Mamoo Nakamura, Hasan Jilaihawi, Raj Makkar, Saibal Kar, Timothy Henry
Journal: Circulation (2014)

Introduction:  Los Angeles County (LAC) has developed ST-elevation myocardial infarction (STEMI)-receiving centers (SRC) which integrate pre-hospital electrocardiograms (PHECG) into a cardiac catheterization laboratory (CCL) activation algorithm as a strategy to reduce door-to-balloon (DTB) times. While DTB times have improved, CCL cancellations have become a challenging problem. We report the frequency and reasons for cancellation at a major LAC SRC.   Methods:  We reviewed 1275 consecutive PHECG STEMI-activations between 1/1/2007 and 12/31/2012.   Results:  Of the 1275 patients, 392 (31%) PHECG-activations were taken emergently to the CCL while 883 (69%) were cancelled. Reasons for cancellation (Figure 1) included poor-quality PHECG (n = 293, 23%), non-STEMI ST-segment abnormality (n = 123, 9.6%), dysrhythmia (n = 105, 8.2%), bundle-branch block (n = 96, 7.5%), early repolarization abnormality (n = 57, 4.5%), medical condition other than STEMI (n = 31, 2.4%), paced rhythm (n = 27, 2.1%), patient preference or goals of care (n = 22, 1.7%), and pericarditis (n = 14, 1.1%).   Conclusion:  PHECG STEMI-activations were frequently cancelled at this Los Angeles SRC. This was most commonly attributable to a poor-quality PHECG. Further investigation is warranted to determine the clinical characteristics of patients who are taken to the CCL and those who are cancelled, as well as to determine the clinical outcomes for the various groups.
Chemokine CXCL13 is overexpressed in the tumor tissue and in the peripheral blood of breast cancer patients
Authors: D. Atanackovic, Y. Hildebrandt, A. Marx, Y. Cao, C. Bokemeyer, S. Hegewisch-Becker, J. Panse
Journal: Journal of Clinical Oncology (2008)

22029 Background: The unique abilities of chemokines in regulating cellular migration are utilized by a variety of (patho-)biological networks including developing malignancies. However, little is known about the relation between chemokine expression and the development and progression of solid tumors like breast cancer. Methods and Results: We applied pathway-focused and real-time PCR-based microarrays to malignant and normal breast tissue samples from patients with breast cancer (n=10) in order to investigate their chemokine expression profiles. We found that chemokine CXCL13 was consistently overexpressed in tumor samples showing a 18-fold higher expression than autologous normal breast tissue. This finding was confirmed by gene-specific real-time PCR in a larger set of breast cancer samples (n=34) and was further validated on the protein level performing Western blot and ELISA-based analyses. Immunohistochemistry performed on breast cancer tissues verified cytoplasmatic overexpression of CXCL13 in epithelial tumor cells. RNA and protein levels of CXCR5, the only known receptor for CXCL13, were relatively low in both malignant and normal breast tissue and CXCR5 expression was not detected on the surface of breast cancer cell lines in vitro. However, we observed a strong and significant (p = 0.0004) correlation between copy numbers of CXCL13 and CXCR5 expressed in breast cancer tissues indicating a biologically relevant role of CXCR5 as a receptor for CXCL13 in vivo. Finally, we observed significantly elevated serum concentrations of soluble CXCL13 protein in patients with metastatic disease (n=54) compared to normal controls (n=44) and to breast cancer patients without evidence of disease (n=48). Conclusions: Taken together, our findings show, that CXCL13, a chemokine hitherto only known to be involved in homing and trafficking of lymphocytes, is overexpressed within breast cancer tissues at the mRNA and protein levels and that increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a possible role of CXCL13 within the development and progression of breast cancer and suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in breast cancer. No significant financial relationships to disclose.
Strangers bearing gifts: a retrospective look at the early years of community mental health center consultation
Authors: J F Borus
Journal: American Journal of Psychiatry (1984)

Many early community mental health center (CMHC) consultations floundered when consultants attempted to apply Gerald Caplan 's community consultation theory, which the author describes as based on a private consultation paradigm, to the very different realities of government-mandated public paradigm consultation by CMHCs to public agencies. CMHC consultants were often perceived by consultees as "strangers bearing gifts" due to the lack of clarity concerning the rationale, contracts, roles, responsibilities, evaluation, and consultant- consultee exchanges of their public paradigm consultations. The otherwise disastrous recent losses of financial support for CMHCs are beneficially forcing them to shift their community consultation practices toward the private paradigm.
Circulating Levels of Troponin Measured by a Highly Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention
Authors: D. Leistner, J. Klotsche, L. Pieper, G. K. Stalla, H. Lehnert, S. Silber, W. Afarz, H. U. Wittchen, A. M. Zeiher
Journal: Circulation (2011)
Feeding Our Old Fashioned Children: A Background for Modern Mealtimes
Authors: C. Anderson Aldrich, Mary M. Aldrich
Journal: JAMA (1941)

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
Epidemiology in Relation to Air Travel
Authors: Arthur Massey
Journal: JAMA (1935)

This is a very interesting book, especially for the scientist, in which Clark sets forth the fallacies incurred in applying mathematical reasoning to pharmacological processes.He points out what type of reasoning is justified, and its limits.While valuable to the scientist, it would be of little value to the ordinary practitioner.Epidemiology.in Relation to Air Travel.
Abstract 14614: Deleterious Effect of Interleukin-23/Interleukin-17 Axis and γδT Cells in Left Ventricular Remodeling After Myocardial Infarction
Authors: Xiaoxiang Yan, Motoaki Sano, Takashi Shichita, Tomohiro Matsuhashi, Yoshinori Katsumata, Akihiko Yoshimura, Keiichi Fukuda
Journal: Circulation (2011)

[Background] Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause of heart failure. Myocardial necrosis releases or exposes normally sequestered antigenic cons...
Carotinoids and Related Pigments, the Chromolipoids.
Authors: Leroy Sheldon Palmer
Journal: JAMA (1923)

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
Suicide Risk: Sunshine or Temperature Increase?
Authors: Jui-Feng Tsai
Journal: JAMA Psychiatry (2015)

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 Psychiatry 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 Psychiatry journal
<i>Ex vivo</i> generation and expansion of autologous anti-tumor CTL lines for adoptive cell therapy in patients with solid tumors
Authors: P. Pedrazzoli, I. Tunin, C. Tullio, E. Montini, R. Schiavo, M. La Grotteria, F. Locatelli, R. Maccario, S. Siena, D. Montagna
Journal: Journal of Clinical Oncology (2006)

12516 Background: Ex-vivo generation of cytotoxic T cell (CTL) lines able to selectively kill autologous tumor cells (TC) is crucial for adoptive cell therapy of cancer. We have described the ex vivo generation of anti-tumor HLA-restricted CTL using CD8-enriched blood mononuclear cells (PBMC) and dendritic cells, pulsed with apoptotic TC as source of tumor antigens (Montagna, Int J Cancer 2004). These cells possess a marked cytotoxicity against TC but very low levels of cytotoxicity against autologous non-malignant controls, suggesting their safe in vivo use. Aim of this study was to evaluate the possibility of generating a large number of anti-tumor CTL lines, in compliance with good manufacture procedure (GMP), to be utilized for adoptive cell therapy. Methods: Four patients with advanced, pretreated solid tumors have been evaluated: 2 sarcoma, 1 renal carcinoma and 1 ovarian carcinoma. Tumor sample was obtained during surgical procedures planned for therapeutic purposes, while PBMC were obtained by a single apheresis. All reagents employed for cultures were produced under GMP. Based on our reported method, the current protocol included two or three rounds of tumor-specific stimulation, followed by two rounds of antigen-independent expansion. Results: We have obtained, after the first round of expansion and in total, a range of 0.5–2×10 9 and 5–20×10 9 CTL, respectively. Such large amounts of anti-tumor CTL were generated even if a low number of viable TC was available. In 3 out of 4 anti-tumor CTL lines, &gt;85% of effector cells were CD3+/CD8+. Conclusions: We demonstrated the feasibility of obtaining, in GMP conditions, large quantities of anti-tumor specific CTL suitable for in vivo use. A phase I protocol of lymphoablative therapy followed by CTL transfer in vivo has been designed and submitted for approval to the competent regulatory agency. No significant financial relationships to disclose.
Abstract 4912: Thin Fibrous Caps with Excessive Macrophage Infiltration in Culprit Lesions of Patients with Acute Coronary Syndromes are Associated with Increased Local Temperature
Authors: Maria Riga, Konstantinos Toutouzas, Eleftherios Tsiamis, Antonios Karanasos, Costas Tsioufis, Elli Stefanadi, John Karabelas, Athanasios Trikas, Dimitrios Tousoulis, Christodoulos Stefanadis
Journal: Circulation (2008)

Background: Optical coherence tomography (OCT) provides detailed analysis of the morphological characteristics of the culprit lesion (CL) and determines macrophage density within fibrous caps. Intracoronary thermography (ICT) detects the local inflammatory activation of the CL. We investigated the correlation between morphological and functional characteristics of the CL as analysed by OCT and ICT in patients with acute coronary syndromes (ACS). Methods: We studied 31 CL of 31 pts (mean age 61±14 years) with ACS. We measured by ICT the temperature difference between the lesion and the healthy proximal vessel wall (ΔT). Thereafter, we measured the minimal thickness of the fibrous cap (mTFC) at CL by OCT. CL with mTFC ≤65 μm were characterized as thin cap plaques and CL with mTFC &gt;65 μm as thick cap plaques. By OCT, macrophage density in the fibrous cap of the CL was also determined from optical signals. Results: Nineteen CL (61.29%) had increased plaque temperature (ΔT≥0.05°C) and 12 CP (38.7%) had low ΔT (ΔT&lt;0.05°C). All CL (100%, p&lt;0.01) with low ΔT had thick cap (mTFC=98±22 μm). Three CL (15.78%) with high ΔT had thick cap (mTFC=78±9μm, p=0.02), whereas 16 CL with high ΔT (84.2%) had thin cap plaques (mTFC=49±12μm, p=0.02) (Figure ). Among CL with high ΔT, 18 CL (94.7%) had excessive macrophage infiltration in OCT analysis. Only 1 CL with low ΔT(8.3%) had macrophage infiltration of its fibrous cap (p&lt;0.01). Conclusions: CL with thin fibrous cap have increased inflammatory activation. Morphological and functional characteristics of the CL of pts with ACS, evaluated by OCT and ICT, are correlated. Thus, the use of OCT and ICT can provide more information regarding the high-risk plaques.
Cancer of the Larynx
Authors: C. C. Wang, A. R. O'Donnell
Journal: New England Journal of Medicine (1955)

SINCE Coutard1 described a group of patients with inoperable cancer of the larynx successfully treated by radiation in the early 1930's, radiotherapy as well as surgery has been accepted as a useful means of dealing with this disease. Numerous valuable contributions have subsequently appeared in the literature. The present report deals mainly with the evaluation of therapeutic results in a group of 253 patients in whom the cancer arose on the vocal cords or had extended to involve the immediately adjacent structures — that is, endolaryngeal tumors. All cases were histologically proved. The group included patients who were registered in . . .
Indikationen für die operative Behandlung der Frauenkrankheiten.
Authors: Walther Benthin
Journal: JAMA (1927)

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