tbuckley/cabot-search huggingface dataset:
ZD1839 Modulates Paclitaxel Response in Renal Cancer by Blocking Paclitaxel-Induced Activation of the Epidermal Growth Factor Receptor–Extracellular Signal-Regulated Kinase Pathway
Authors: Makoto Sumitomo, Tomohiko Asano, Junichi Asakuma, Takako Asano, Akio Horiguchi, Masamichi Hayakawa
Journal: Clinical Cancer Research (2004)

We evaluated the antitumor activity of ZD1839, a selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, in combination with paclitaxel in human renal cell carcinomas (RCCs).Eight human RCC lines and the surgical specimens obtained from 10 RCC patients were used. The protein expression was detected by Western blotting, immunohistochemistry and/or flow cytometry. Apoptosis was evaluated by flow cytometry and fragmented DNA ELISA. SKRC-49 tumor xenografts in athymic nude mice were treated with ZD1839 and/or paclitaxel, and tumor volume was determinedEGFR protein was expressed and phosphorylated in eight RCC lines and EGFR expression was markedly increased in RCC specimens compared with adjacent normal renal tissues. Treatment of SKRC-49 with 1 micro M ZD1839 resulted in a marked decrease in the phosphorylation of EGFR but not of HER-2. Treatment of SKRC-49 with ZD1839 in combination with 5 nM paclitaxel resulted in a significant increase in apoptotic cell number compared with paclitaxel alone, whereas ZD1839 alone failed to induce apoptosis. Although administration of ZD1839 or paclitaxel resulted in a transient growth inhibition in SKRC-49 xenografts, significant tumor regrowth delay was observed when paclitaxel was combined with ZD1839. Paclitaxel phosphorylated extracellular signal-regulated kinase through EGFR activation predominantly in cancer cells. ZD1839 promoted paclitaxel-induced Bcl-2 down-regulation resulting in promoting apoptosis by blocking paclitaxel-induced activation of the EGFR-extracellular signal-regulated kinase antiapoptotic pathway independent of Akt activity in SKRC-49.Our findings support the idea that the significant clinical benefit is obtained from ZD1839 in combination with paclitaxel for the treatment of RCC.
Mirror-Image Lymph Node in FDG PET/CT and SPECT/CT for Sentinel Node Detection
Authors: Beatriz Domenech, Pilar Paredes, Sebastià Rubí, Jaume Pahisa, Sergi Vidal-Sicart, Francesca Pons
Journal: Clinical Nuclear Medicine (2014)

We report a case of a patient with presumed stage IB1 squamous cell carcinoma of the cervix in which FDG PET/CT scan revealed 1 hypermetabolic left iliac node suggestive to be malignant. Lymphoscintigraphy and SPECT/CT studies previous to sentinel node (SLN) biopsy revealed unilateral drainage in the right pelvis. Intraoperative pathological assessment of the SLN showed no tumoral involvement, and the hypermetabolic node revealed macrometastasis. Tumor node invasion can lead to a lymphatic blockage and become false-negative for SLN technique. Although FDG PET/CT has lower sensitivity than surgical staging, this case shows its value as a preoperative imaging technique.
The Cost-Effectiveness of Sildenafil
Authors: Kenneth J. Smith, Mark S. Roberts
Journal: Annals of Internal Medicine (2000)

Coverage of sildenafil by health insurance plans is a contentious issue.To evaluate the cost-effectiveness of sildenafil treatment for erectile dysfunction.A Markov decision model to estimate the incremental cost-effectiveness of sildenafil compared with no drug therapy.Values for the efficacy and safety of sildenafil and quality-of-life utilities were obtained from the published medical literature. Base-case values were chosen to bias against sildenafil use.Men 60 years of age with erectile dysfunction.Lifetime.Societal and third-party payer.Sildenafil or no treatment in identical hypothetical cohorts.Cost per quality-adjusted life-year (QALY) gained.The cost per QALY gained for sildenafil treatment compared with no therapy was $11,290 from the societal perspective and $11,230 from the third-party payer perspective.From the societal perspective, the cost per QALY gained associated with sildenafil was less than $50,000 if treatment-related morbidity was less than 0.8% per year, mortality was less than 0.55% per year, treatment was successful in more than 40.2% of patients, or sildenafil cost less than $244 per month. The results were sensitive to variation of erectile dysfunction utilities, but cost per QALY gained was less than $50,000 if successful treatment increased utility values by 0.05 or more on a scale of 0 (death) to 1 (perfect health).In an analysis biased against use of sildenafil, the cost-effectiveness of sildenafil treatment compared favorably with that of accepted therapies for other medical conditions.
740. A Novel Hybrid System Efficiently Expands AAV Packaging Capacity
Authors: Arka Ghosh, Yongping Yue, Dongsheng Duan
Journal: Molecular Therapy (2006)

The small packaging capacity is a long-standing hurdle limiting broad application of adeno-associated virus (AAV) in gene therapy. The trans-splicing and overlapping methods were developed recently to overcome this barrier. However, the trans-splicing method is highly dependent on the existence of an optimal gene splitting site and the overlapping method only works in genes that carry a highly recombinogenic domain in the middle of the gene. To overcome these limitations, we developed a novel trans-splicing/overlapping hybrid vector system that can efficiently reconstitute any large gene. In the hybrid system, we engineered a 0.8kb highly recombinogenic alkaline phosphatase (AP) gene fragment at the end of the splice donor and beginning of the splice acceptor sequences in the trans-splicing vectors. We hypothesize that the addition of the AP gene fragment will facilitate homologous recombination in the trans-splicing vectors and increase the chance of transgene reconstitution. To test this hypothesis, we compared transduction efficiency of the intact gene, trans-splicing, overlapping and hybrid LacZ vectors, all delivered in AAV-6 capsids. In MO59K cells at a moi of 10,000 expression cassettes/cell, |[beta]|-galactosidase activity in the intact gene infected cells was 1086 |[plusmn]| 88 unit/mg protein at 45 hrs post-infection. Activity from overlapping and trans-splicing vectors reached only 20% (238 |[plusmn]| 21 unit/mg protein) and 60% (654 |[plusmn]| 40 unit/mg protein) of that from the intact gene vector, respectively. Surprisingly, activity in hybrid vector infected cells (1137 |[plusmn]| 82 unit/ mg protein) was identical to that of intact LacZ infected cells. To determine the molecular pathways of the transgene reconstitution in hybrid vectors, we performed Southern blot. Consistent with our initial hypothesis, vector genomes formed both ITR-mediated (trans- splicing pathway) and AP-mediated (overlapping pathway) concatamers in hybrid vector co-infected cells. We next examined in vivo efficiency of the hybrid vectors in the tibialis anterior muscles of 6-week-old C57Bl10 mice (10e10 particles of each vector). LacZ expression was determined six weeks post-infection. Amazingly, exactly the same expression profile as we saw in MO59K cells was reproduced in muscle. The levels of |[beta]|-galactosidase activity were 1948 |[plusmn]| 137, 1288 |[plusmn]| 40, 556 |[plusmn]| 76, and 1674 |[plusmn]| 86 unit/mg protein for the intact gene, trans-splicing, overlapping and hybrid vector infected muscles, respectively. In summary, we have developed a generic dual vector approach that can be used to efficiently express any large therapeutic gene.
GW25-e1669 Apelin Treatment Enhances ACE2 expression and Attenuates Angiotensin II-Mediated Aortic Fibrosis in Apolipoprotein E-Deficient Mice
Authors: Zhen-Zhou Zhang, Lai-Jiang Chen, Bei Song, Ying-Le Xu, Dong-Rui Chen, Ding-Liang Zhu, Ping-Jin Gao, Gavin Y. Oudit, Jiu-Chang Zhong
Journal: Journal of the American College of Cardiology (2014)
Outpatient Management of HIV-Related Pneumonia
Authors: Henry Masur
Journal: Annals of Internal Medicine (1996)

Letters1 December 1996Outpatient Management of HIV-Related PneumoniaHenry Masur, MD and James H. Shelhamer, MDHenry Masur, MDNational Institutes of Health, Bethesda, MD 20892.Search for more papers by this author and James H. Shelhamer, MDNational Institutes of Health, Bethesda, MD 20892.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-11-199612010-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Becker raises two issues that were not explicitly addressed in our editorial. First, if the result of an induced-sputum examination is negative for P. carinii, what diagnosis is likely? Second, if the result of an induced-sputum examination is negative for P. carinii, what diagnostic procedures should be used?Regarding the first issue, we believe that at many institutions, induced sputum examination has a high sensitivity for P. carinii pneumonia in patients who are and are not receiving prophylaxis for P. carinii pneumonia (sensitivity, >60% and >90%, respectively) [1]. However, we do not agree that a negative result ...References1. Gill V, Quinn T, Crawford S, Kovacs J, Masur H, Ognibene F, et al. Diagnosis of pulmonary opportunistic infections. Ann Intern Med. 1996; 124:585-99. Google Scholar2. Huang L, Hecht F, Stansell J, Montanti R, Hadley W, Hopewell P. Suspected Pneumocystis carinii pneumonia with a negative induced sputum examination. Am J Respir Crit Care Med. 1995; 151:1866-71. Google Scholar3. Barnes P, Steele M, Young S, Vachon L. Tuberculosis in patients with human immunodeficiency virus infection. Chest. 1992; 102:428-32. Google Scholar4. Kennedy D, Lewis W, Barnes P. Yield of bronchoscopy for the diagnosis of tuberculosis in patients with human immunodeficiency virus infection. Chest. 1992; 102:1040-4. Google Scholar Author, Article, and Disclosure InformationAffiliations: National Institutes of Health, Bethesda, MD 20892. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1996Volume 125, Issue 11Page: 938-939KeywordsBiopsyBronchoalveolar lavageBronchoscopyLung and intrathoracic tumorsPneumoniaProphylaxisPulmonary diseasesResearch laboratoriesSputumTuberculosis Issue Published: 1 December 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract P6-15-20: Development of PEA-15-Based Therapy in Breast Cancer in a Preclinical Study
Authors: X Xie, C Bartholomeusz, DS Maxwell, Z Peng, A Kazansky, WG Bornmann, NT. Ueno
Journal: Cancer Research (2010)

Abstract Background: PEA-15 (phosphoprotein enriched in astrocytes, 15 kDa) has tumor suppressor properties in both breast and ovarian cancer cells. Overexpression of PEA-15 in MDA-MB-468 triple-negative breast cancer cells using adenoviral vector (Ad.PEA-15) inhibited cell growth by inducing apoptosis. Treatment with Ad.PEA-15 led to significant regression of tumors in mice, indicating that PEA-15 could have therapeutic potential in breast cancer. PEA-15 exerts its antitumor activity by binding to ERK in the cytoplasm and preventing its translocation into the nucleus, thereby inhibiting ERK-dependent transcription and cell proliferation. Because ERK inhibitors have been shown to be toxic, in this study, we developed PEA-15 mimetic peptides as a therapeutic agent in breast cancer. These peptides, which are expected to be less toxic because of their ability to mimic PEA-15, are proposed to inhibit cell proliferation by sequestering ERK in the cytoplasm. Material and Methods: PEA-15 mimetic peptides were designed and synthesized based on structural analysis of linear segments from the C-terminal end of PEA-15, which is one of the two regions that are presumably critical for ERK binding, using nuclear magnetic resonance spectroscopy. These synthetic peptides were labeled with FAM to enable determination of their subcellular localization. The PULSin reagent was used as a delivery reagent for peptide penetration into cancer cells. The penetration ability of these peptides into HeLa and MDA-MB-468 cells was analyzed by fluorescence microscope and fluorescence-activated cell sorting. Their effect on ERK subcellular localization was examined by cell-fractionation analysis. Their impact on cell survival was determined by trypan blue viability assay and propidium iodide staining. Results: Ten peptides were designed and synthesized based on the C-terminal segments of PEA-15. Three of these FAM-labeled synthetic peptides delivered with the PULSin reagent were able to penetrate HeLa and MDA-MB-468 cells with 80-90% and 30-40% efficiency, respectively. Further, these peptides redirected ERK into the cytoplasm from the nucleus in MDA-MB-468 cells and caused 31% reduction in viability of HeLa cells as compared to the untreated control. Ongoing studies are evaluating PEA-15 peptides for their ability to interact with ERK using ELISA. In the future, we will also test their therapeutic efficacy and safety using a xenograft breast cancer model. Discussion: Previous studies revealed that PEA-15 has antitumor activity against breast and ovarian cancer cells by sequestering ERK in the cytoplasm. Due to the toxicity of ERK enzymatic inhibitors, we developed PEA-15 mimetic peptides and demonstrated their therapeutic potential for breast cancer, which may provide opportunities for breast cancer patients who currently have limited treatment options. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-20.
Grading quality of evidence and strength of recommendations in clinical practice guidelines
Authors: J. L. Brożek, E. A. Akl, P. Alonso‐Coello, D. Lang, R. Jaeschke, J. W. Williams, B. Phillips, M. Lelgemann, A. Lethaby, J. Bousquet, G. H. Guyatt, H. J. Schünemann
Journal: Allergy (2009)

The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health care. The GRADE system's conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three-part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel's confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.
A piece of my mind. A little night poetry
Authors: W. Schmidt
Journal: JAMA (1988)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Integration of Internship and Residency
Authors: Harold M. Schoolman
Journal: JAMA (1971)

Abroad educational base is a critical requirement in the preparation of a physician for a lifetime of training without much excellence—even competence—swiftly vanishes. The thesis is simple, and as far as I am aware, noncontroversial. The Advisory Committee on Graduate Medical Education has been struggling with the problems of supporting this thesis in the implementation of new trends in graduate education. I say struggling because the implementation was considerably simpler when medical school curricula were essentially uniform—when students' attitudes, aspirations, backgrounds, and educational accomplishments were relatively homogeneous and when the free-standing internship demarcated a single starting point in time for practically all specialty training. The individualization of medical training is a salutary development— one which has by no means reached its full potentiality. It does, however, make it difficult, if not impossible, to formulate regulations or requirements that have broad, if not universal, applicability. The former very high correlation between
Randomized Clinical Trial to Assess the Effectiveness of Breast Irradiation Following Lumpectomy and Axillary Disection for Node-Negative Breast Cancer
Authors: R. M. Clark, P. B. McCulloch, M. N. Levine, M. Lipa, R.H Wilkinson, L. J. Mahoney, V. R. Basrur, B. D. Nair, R. S. McDermot, C. S. Wong, P. J. Corbett
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Randomized Clinical Trial to Assess the Effectiveness of Breast Irradiation Following Lumpectomy and Axillary Disection for Node-Negative Breast Cancer Get access R. M. Clark, R. M. Clark * Ontario Cancer Institute/Princess Margaret HospitalToronto, Ontario, Canada *Correspondence to R. M. Clark, M.D., Princess Margaret Hospital, 500 Sherbourne St., Toronto, ON, M4X 1K9, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar P. B. McCulloch, P. B. McCulloch Ontario Cancer FoundationHamilton, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar M. N. Levine, M. N. Levine Ontario Cancer FoundationHamilton, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Lipa, M. Lipa Toronto HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar R.H Wilkinson, R.H Wilkinson North York General HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Mahoney, L. J. Mahoney St. Michael's HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar V. R. Basrur, V. R. Basrur Ontario Cancer FoundationHamilton, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar B. D. Nair, B. D. Nair Ontario Cancer FoundationOttawa, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar R. S. McDermot, R. S. McDermot Ontario Cancer FoundationOttawa, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar C. S. Wong, C. S. Wong Ontario Cancer Institute/Princess Margaret HospitalToronto, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more P. J. Corbett P. J. Corbett Ontario Cancer FoundationLondon, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 9, 6 May 1992, Pages 683–689, https://doi.org/10.1093/jnci/84.9.683 Published: 06 May 1992 Article history Received: 26 July 1991 Revision received: 14 November 1991 Accepted: 06 January 1992 Published: 06 May 1992
Use of Peer Ratings to Evaluate Physician Performance
Authors: Paul G. Ramsey, Marjorie D. Wenrich, Jan D. Carline, Thomas S. Inui, Eric B. Larson, James P. LoGerfo
Journal: JAMA (1993)

To assess the feasibility and measurement characteristics of ratings completed by professional associates to evaluate the performance of practicing physicians.The clinical performance of physicians was evaluated using written questionnaires mailed to professional associates (physicians and nurses). Physician-associates were randomly selected from lists provided by both the subjects and medical supervisors, and detailed information was collected concerning the professional and social relationships between the associate and the subject. Responses were analyzed to determine factors that affect ratings and measurement characteristics of peer ratings.Physician-subjects were selected from among practicing internists in New York, New Jersey, and Pennsylvania who received American Board of Internal Medicine certification 5 to 15 years previously.Physician performance as assessed by peers.Peer ratings are not biased substantially by the method of selection of the peers or the relationship between the rater and the subject. Factor analyses suggest a two-dimensional conceptualization of clinical skills: one factor represents cognitive and clinical management skills and the other factor represents humanistic qualities and management of psychosocial aspects of illness. Ratings from 11 peer physicians are needed to provide a reliable assessment in these two areas.These findings suggest that it is feasible to obtain assessments from professional associates of practicing physicians in areas such as clinical skills, humanistic qualities, and communication skills. Using a shorter version of the questionnaire used in this study, peer ratings provide a practical method to assess clinical performance in areas such as humanistic qualities and communication skills that are difficult to assess with other measures.
REPORT OF TEN CASES OF MORPHINISM.
Authors: A. J. PRESSEY
Journal: JAMA (1904)

The cases here reported have been selected from among many others which perhaps might be in themselves more interesting; but it has been my aim to select only such as would demonstrate the fact that many of the cases which appear to be the most hopeless will, when properly treated, become good and respectable citizens. A certain percentage of these patients may be restored to perfect health, physically, mentally and morally, and will remain so, regardless of the quantity taken, the length of time used, the manner of administration or the age. Just what that percentage is I do not know. It is with me an utter impossibility to even venture a guess as to who will remain free from the addiction and who will, as soon as the opportunity presents itself, relapse into the former condition. Being unable to distinguish between them, there remains only to do as we