tbuckley/cabot-search huggingface dataset:
Models of molecular diversity to facilitate marker guided therapy
Authors: Joe Gray, Debopriya Das
Journal: Clinical Cancer Research (2008)

KN01   Several hundred drugs targeted against molecular defects in cancer are now being tested clinically. This number will grow substantially as comprehensive analyses of cancer genomes are completed. Early development of biomarkers that predict clinical response will allow these drugs to be tested in tumors most likely to respond. This will increase the probability that drugs effective in tumor subpopulations will not be missed and will decrease the cost of early trials by allowing them to be tested in small numbers of patients whose tumors are most likely to respond. It also will allow predictive biomarkers to be developed in parallel with experimental drugs so that successful drugs enter the clinical market with fully validated predictive biomarkers. We are pursuing the hypothesis that selection of predictive markers for breast cancers can be accomplished by assessing responses to new drugs in an  in vitro  system comprised of 50 breast cancer cell lines and correlating these with genomic, transcriptional and proteomic features measured in order to identify molecular features associated with response. This  in vitro  systems approach is based on our observations that the cell line collection models much of the molecular diversity and recurrent aberrations found in primary tumors and that predictive markers can be developed using information about molecular features associated with response in vitro. In order to test the  in vitro  approach, we have developed novel computational and experimental approaches for identification of non-linear signatures of response and we have applied these in assessing responses to ~40 approved and experimental therapeutic agents. We have tested the clinical utility of one of these-- a 6-gene predictive assay for lapatinib developed using this approach, in two independent clinical trials.
Gene Discovery Provides Clues to Cause of Age-Related Macular Degeneration
Authors: Bridget M. Kuehn
Journal: JAMA (2005)

A trio of studies has identified a gene variant that may be responsible for about half of the 15 million age-related macular degeneration (AMD) cases in the United States. The finding also suggests that inflammation plays an important role in the etiology of the disease.
Diagnosis of prostate cancer using differentially expressed genes in stroma
Authors: Zhenyu Jia, Yipeng Wang, Anne Sawyers, Huazhen Yao, Farahnaz Rahmatpanah, Xiao-Qin Xia, Qiang Xu, Rebecca Pio, Tolga Turan, James A. Koziol, Steve Goodison, Philip Carpenter, Jessica Wang-Rodriguez, Anne Simoneau, Frank Meyskens, Manuel Sutton, Waldemar Lernhardt, Thomas Beach, Michael McClelland, Dan Mercola
Journal: Clinical Cancer Research (2010)

Abstract Over 1 million prostate biopsies are performed in the U.S. every year. A failure to find cancer is not definitive in a significant percentage of patients due to the presence of equivocal structures or continuing clinical suspicion. We have identified gene expression changes in stroma that can detect tumor nearby. We compared gene expression profiles of 13 biopsies containing stroma near tumor and 15 biopsies from volunteers without prostate cancer. More than a thousand significant expression changes were found and thereafter filtered using large numbers of other expression profiles to eliminate possible age-related genes and genes expressed at detectable levels in tumor cells. A stroma-specific classifier was constructed based on 114 candidate genes and tested on 364 independent samples, including 243 tumor-bearing samples and 121 non-tumor samples (normal biopsies, normal autopsies, remote stroma, as well as stroma within a few millimeters of tumor). The classifier predicted the tumor status of patients using tumor-free samples with an average accuracy of 97.2% (sensitivity = 97.9% and specificity = 88.0%) whereas classifiers trained with sets of 100 randomly generated genes had no diagnostic value. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for categorizing the presence of tumor in patients when a prostate sample is derived from near the tumor but does not contain any recognizable tumor.
Adiponectin and Risk of Coronary Heart Disease
Authors: Amnon Schlegel
Journal: JAMA (2004)

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 17020: Molecular Spect Imaging of Early Angioproliferative Group I Pulmonary Arterial Hypertension Using an Adrenomedullin Receptor Ligand
Authors: Nassiba Merabet, Quang Trinh Nguyen, Sophie Marcil, Bernard Meloche, Yan Fen Shi, Jean-Claude Tardif, François Harel, Jocelyn Dupuis
Journal: Circulation (2014)

Introduction: The main limitation in the development of drugs against pulmonary arterial hypertension (PAH) is the absence of a non-invasive and early marker of disease. Adrenomedullin (AM) is a vasodilator peptide predominantly cleared by pulmonary endothelial receptors. Hypothesis: Our lab has developed Pulmobind PB, an AM derivative radiolabeled with 99mTc for SPECT imaging of pulmonary circulation to detect non-invasively the anomalies of pulmonary circulation caused by PAH. Methods: An angioproliferative model of group I PAH was used. After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker Sugen (20 mg/kg), rats were exposed to hypoxia for 3 weeks followed by normoxia for 4 weeks. PAH rats were compared to their littermate controls (normoxia for 7 weeks). After 7 weeks, Right ventricular (RV) structure, function and hypertrophy as well as lung 99mTc-PB uptake kinetics were assessed by echocardiography and SPECT analyses. Results: RV end-diastolic anterior ...
Anatomie humaine: Descriptive et topographique.
Authors: Henri Rouvière
Journal: JAMA (1933)

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
Development of a novel micromachined parylene membrane filter device for capture and characterization of circulating tumor cells from peripheral blood.
Authors: Henry K. Lin, Siyang Zheng, Marija Balic, Yu-Chong Tai, Ram H. Datar, Richard J. Cote
Journal: Cancer Research (2006)

5147   Metastasis is probably the most important event determining clinical outcome in cancer patients. Sensitive detection of earliest metastatic spread of tumor in a minimally invasive and user-friendly manner will revolutionize the clinical management of caner patients. The current methodology for circulating tumor cell (CTC) capture and identification has significant barriers including multiple procedural steps, handling of relatively large volumes of blood, substantial human intervention, extremely high cost and importantly, the lack of reliability and standardization for the detection methods. We report here development, optimization and actual clinical application of a novel parylene membrane filter microdevice for capturing CTC from undiluted human peripheral blood. To our knowledge, this is the first micromachined membrane filter used for rare CTC detection. Even without much optimization, the device already demonstrates greater than 80% recovery with high enrichment factor, which out-performs most current methods used in the field. Moreover, less than 10 minutes are required for each CTC capture operation, compared to current multi-step processing requiring more than an hour. Data will be presented for the application of this tumor cell capture device in both model system using cultured cancer cells admixed in blood and cancer patient blood samples. This novel filter based CTC enrichment device will provide a cost effective method for CTC monitoring with higher recovery rate, faster processing time and more reliable results due to minimal human intervention.
Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor
Authors: Lois E. H. Smith, Wei Shen, Carole Perruzzi, Shay Soker, Fumi Kinose, Xianghong Xu, Gregory Robinson, Sam Driver, Joyce Bischoff, Bei Zhang, James M. Schaeffer, Donald R. Senger
Journal: Nature Medicine (1999)
Upper and lower airway inflammation and bronchial hyperresponsiveness in allergic rhinitis children with or without asthma
Authors: Alla Nakonechna, Yuriy Antipkin, Tatjana Umanets, Vladimir Lapshyn
Journal: European Respiratory Journal (2011)

Background: Although allergic rhinitis and asthma frequently coexist, the nature of this association is still not clearly identified.

Objective: To estimate the upper and lower airway inflammation in allergic rhinitis (AR) children with or without asthma in relation with bronchial responsiveness.

Methods: 145 children aged 7-12 years with AR alone or AR with asthma and 35 age-matched healthy controls were observed.

Lung functions, bronchial hyperreactivity tests (methacholine and exercise) nasal and induced sputum samples were performed in all patients. Total and antigen specific IgE, IL-5, IL-10, γ-IFN levels were assessed by ELISA.

Results: Children with AR alone (39%) but no clinical evidence of asthma showed increased nasal and induced sputum eosinophil counts and bronchial hyperreactivity to methacholine and exercise challenge compared with healthy control. In children with AR and asthma (61%) nasal and induced sputum eosinophilia and bronchial hyperresponsiveness were more significant compared with AR alone (p<0.05).

Remarkable, that blood eosinophil count, nasal and sputum eosinophilia were inversely correlated with bronchial hyperreactivity in all allergic patients. These parameters correlated with increasing production of IL-5, IL-10 and decreased gamma-IFN production and were more significant in AR with asthma children (p<0.05).

Conclusion: In children with AR without asthma subclinical changes in the lower airways and inflammatory mediators were detected. These data support the concept of significant links between upper and lower respiratory tract involvement in AR children with or without asthma and its association with bronchial hyperresponsiveness.
The Treasury of Human Inheritance.
Authors: Karl Pearson, W. Bulloch
Journal: JAMA (1926)

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
Recent Advances in Platinum (IV) Complex‐Based Delivery Systems to Improve Platinum (II) Anticancer Therapy
Authors: Xiaopeng Han, Jin Sun, Yongjun Wang, Zhonggui He
Journal: Medicinal Research Reviews (2015)

Abstract Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose‐ dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous‐to‐oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy.
Effective incorporation of biospecimen collection for translational studies into a phase III trial: The NeoALTTO experience (BIG 01-06).
Authors: Paolo Nuciforo, Jose Jimenez, Claudia Aura, Debora Fumagalli, Marion Maetens, Ludmila Prudkin, Francoise Rothe, Josep Vazquez, Sherene Loi, Holger Eidtmann, Christos Sotiriou, Jose Baselga
Journal: Journal of Clinical Oncology (2013)

3012 Background: Translational research studies in the context of clinical trials using targeted therapies are essential for the identification of biomarkers of response or resistance. However, many challenges (e.g. logistic, technical) can impede proper biological sample collection. The NEOALTTO study provided an excellent opportunity to address these issues. Methods: In this large neoadjuvant phase III multicenter, multinational clinical trial, serial samples (plasma, serum, frozen and FFPE specimens) from patients with breast cancer were collected in 86 sites (23 countries) at several time points (baseline, week 2 and surgery). Standardized operating procedures were made available to sites together with pre-assembled kits for sample collection, processing, storage, and shipment to reduce the variability and increase compliance with the study protocol. All biospecimens were centralized for long term storage. Baseline fresh/frozen samples were processed for downstream analyses according to a pre-defined workflow. Evaluable sample population (ESP) was determined based on the following criteria: tumor cellularity, RNA integrity (RIN), and yield. Results: A total of 12,193 serial samples from 449 of 455 randomized patients was collected. The overall sample missing rate was 9.5% (includes samples not collected by site, withdrawn patients and pCR). Missing rates were 9%, 8%, 13%, and 9% for plasma, serum, frozen and FFPE specimens, respectively. At least 1 frozen tumor tissue was available for 423 (94%), 431 (96%), and 334 (74%) patients at baseline, week 2, and surgery, respectively. After 2 extraction cycles, 629 and 516 baseline frozen samples were processed for RNA and DNA extraction, respectively. The ESP was 71% (58% when RIN considered) and 80% for downstream RNA- and DNA-based analyses, respectively. Incorrect material, inappropriate sample processing and low or absent tumor cellularity were some of the factors affecting the ESP. Conclusions: These results show that careful upfront logistic and technical planning in NEOALTTO had a significant impact on the compliance and the quality of collected material, which may ultimately result in valuable research data. Clinical trial information: NCT00553358.
Partitioning of Pulmonary Vascular Resistance in Primary Pulmonary Hypertension 11This study was supported by Grant 3.4517.95 from the Fonds de la Recherche Scientifique Médicale Belgium and by the Belgian Foundation for Cardiac Surgery, Brussels. Sophia Abdel Kafi was a fellow of the Erasmus Foundation, Brussels.
Authors: Sophia Abdel Kafi, Christian Mélot, Jean-Luc Vachiéry, Serge Brimioulle, Robert Naeije
Journal: Journal of the American College of Cardiology (1998)
OBSERVATIONS OF ATYPICAL PNEUMONIAS OF THE INFLUENZAL VIRUS TYPE
Authors: Edward A. Brethauer, Robert T. Thompson
Journal: Annals of Internal Medicine (1944)

ExcerptDuring the months of December 1942, January and February 1943, a series of cases of atypical pneumonias of the influenzal virus type was observed at the Elizabeth Steel Magee Hospital, Pittsburgh, Pennsylvania. Because of the high mortality rate encountered in this type of pneumonia and because of the unusual termination in fatal cases by the rapid development of generalized pulmonary edema, our interest was awakened by certain clinical observations to be presented. These observations are considered important because they indicate the necessity for revision of certain therapeutic measures, and because they are a definite aid in prognosis.During the autumn...
A memorable afternoon: Fifty five years later
Authors: M. Fairman
Journal: BMJ (2000)

A February afternoon in medical outpatients. Seventeen follow ups and six new patients. And there was a new senior house officer (SHO) to show the ropes to. A German, from Dresden.Very nice chap, unusually curious about war time England. Yes, there had been some excitement in this fenland market town about one particular incident at that time. In fact, one of the clinic patients expected that day had previously told me about it. Billy B had been on antiaircraft duty in Grantham in 1942 defending a tank factory. They had seen almost no action, but one night a stray German bomber on the way home from Coventry had famously been …
283. Adeno-Associated Viral Vector Expression Angiostatin and IL-15 for Brain Cancer Gene Therapy
Authors: Horng Jyh Harn, Kuang Wen Liao, Shinn Zong Lin
Journal: Molecular Therapy (2004)

Malignant brain tumors are extremely aggressive cancers currently lacking effective treatment modalities. Gene therapy represents a promising approach for this disease. Several of effective therapeutic genes for gene-based therapies of brain cancer mainly include prodrug activating enzyme genes, tumor suppressor genes, immune regulatory genes and genes for producing inhibitors of angiogenesis. Gene therapy with immune regulatory gene can elicit the specific remembered immune responses to seek and attack uninfected tumor cells, thus the method may complement and improve the weakness of gene therapy that to efficiently delivery the therapeutic gene into the most tumor cell. To study clinical tumor cases, it was found that more malignant tumor cells lose their surface expression of major histocompatibility complex (MHC) and the loss of MHC expression will lift the MHC-restriction for the cytotoxicity of the NK cells. Thus, the activities of the host cell-mediated cytotoxic immune effectors will be activated to suppress the growth of tumor. IL-15 was indicated that it has several different activities to activate T, B and NK cells. Therefore, IL-15 was utilized to prevent tumor growth and the results showed it could significantly suppress tumor growth. Therefore, we extend the study with several modifications to improve the immunotherapy. First, the separated angiostatin and IL-15 genes were constructed into the plasmid. Second, because the AAV gene delivery system is considered as the safest viral delivery system, the AAV viral vector was utilized to express angiostatin or IL-15 proteins. The AAV viral vectors that encode angiostatin or IL-15 proteins will be used to produce recombinant therapeutic AAV in cGMP laboratory at Tzu-Chi Hospital. The high quality and high titers recombinant AAVs were attempted to co-infect brain tumor cell (RG-2 rat glioma) and the results showed the combination of two genes could suppress the growth of subcutaneous RG-2 tumor.