tbuckley/cabot-search huggingface dataset:
Association of <i>HER2 </i>and <i>ErbB3 </i>molecular alterations with afatinib sensitivity in platinum-refractory metastatic urothelial carcinoma (UC) in a phase II trial.
Authors: Noura Choudhury, Alexa Campanile, James Lloyd Wade, Tatjana Antic, Walter Michael Stadler, Yusuke Nakamura, Peter H. O'Donnell
Journal: Journal of Clinical Oncology (2015)

e15516 Background: Platinum-refractory UC has a dismal prognosis, with no FDA-approved second-line therapies. Somatic mutations and copy number (CN) variation in EGFR (ErbB1), HER2 (ErbB2), and ErbB3 are frequent in UC and may represent viable targets for novel therapies. We aimed to investigate whether afatinib, an oral, irreversible Erb family blocker, has clinical benefit in metastatic UC. Methods: In this single arm, phase II trial, patients (pts) with unresectable platinum-refractory UC who received ≤ 1 chemotherapy in the metastatic setting received afatinib 40 mg/day continuously until disease progression or intolerable toxicity.Primary endpoint was 3-month progression-free survival (PFS3), with drug deemed promising if ≥ 42% pts had PFS3. Pre-specified analysis for EGFR, HER2, ErbB3, and ErbB4 was conducted using targeted next-generation sequencing (Life Technologies) and CN analysis (Taqman). Results: 15 ptshave enrolled: median age 66 (44-78), 11 M/4 F, ECOG PS 0 in 20%, PS 1 in 80%, Hb < 10 g/dl in 20%, liver metastases in 13%, median time from prior chemotherapy = 4.4 mo. Rash (73%), diarrhea (33%), and fatigue (13%) were the most common drug-related toxicities; 1 pt required dose-reduction (grade 3 fatigue). 3/14 pts (21%) had PFS3 (1 partial response (PR), 2 stable disease); 1 pt has not reached 3 mo on therapy. All 3 responders had molecular alterations in Erb genes: 1 pt with 4 copies of HER2 achieved PR and responded for 6.9 mo; 1 pt with Gly284Arg ErbB3 mutation responded for 7 mo; and 1 pt with 73 copies of HER2 and Arg103Gly ErbB3 mutation never progressed on therapy, but discontinued after 10.3 mo due to depressed left ventricular ejection fraction. None of the 10 non-responders had alterations in these four genes. Time to progression/discontinuation was 8.1 mo in pts with molecular alterations vs. 1.8 for pts without alterations (p = 0.02). Conclusions: Afatinib demonstrates activity in platinum-refractory UC, with all responders bearing HER2 and/or ErbB3 alterations. The potential contribution of ErbB3 to afatinib sensitivity is novel. These data support ongoing testing of afatinib as a potential therapy for refractory UC in marker-selected pts. Clinical trial information: NCT02122172.
Expression of the c-met protooncogene in human hepatocellular carcinoma
Authors: K Suzuki
Journal: Hepatology (1994)

The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcin genesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met–positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma. (Hepatology 1994;20:1231–1236).
Philosophy, prescriptions, and politics
Authors: D. R. Bess
Journal: JAMA (1980)

<h3>Philosophy</h3> SINCE the 1960s, the complex topic of so-called "substitution, drug product selection, or generic dispensing"<sup>1</sup>has evoked much<i>stürm und drang</i>("storm and stress") in both lay and professional articles. To the detriment of patient, physician, and pharmacist, the issue of generic substitution has been more obfuscated with rhetoric than enlightened by fact. Even exactly what is debated is often unclear, as "positions have had time to harden into symbolic and rigid polarities: Free Enterprise vs. Government, Big Business vs. Consumer Groups, and—especially today—Quality Assurance vs. Cost Containment."<sup>2</sup> Basic concepts of pharmacokinetics (the study of the absorption, distribution, metabolism, and excretion of a drug) have been reviewed elsewhere<sup>3</sup>and will not be covered in this article. The reader, however, is strongly urged to acquaint himself with the basic concepts of bioavailability—such as disintegration and dissolution rates, single-dose and steady-state study designs, blood concentration-time curves, and the
DDIS-34. HIGH-THROUGHPUT DRUG SCREENING OF FDA-APPROVED ANTINEOPLASTIC DRUGS FOR THE TREATMENT OF AGGRESSIVE MENINGIOMAS
Authors: Gerhard Jungwirth, Tao Yu, Fang Liu, Rolf Warta, Andreas Unterberg, Christel Herold-Mende
Journal: Neuro-Oncology (2019)

Abstract Currently, we are facing several challenges in the treatment of meningiomas: only subtotally removable tumors, high rate of recurrence in higher-grade meningiomas, malignancy, and lack of effective chemotherapeutic agents for aggressive or inoperable tumors. For these reasons, there is an urgent need for more successful treatments for aggressive meningiomas. Therefore, we used 147 FDA-approved antineoplastic drugs on two different meningioma cell lines, including the genetically modified cell line Ben-Men-1 (WHO°I) and the newly established anaplastic meningioma cell line NCH93 (WHO°III). The impact of the drugs on proliferation was assessed in a high-throughput 386-well format with CellTiter-Glo (Promega) and further validation was done by crystal-violet assay. Subsequent screening of 147 FDA-approved drugs resulted in the identification of potential 5 drugs, including Bortezomib, Carfilzomib, Omacetaxine, Paclitaxel, and Ponatinib. Dose-curve analysis revealed IC50 values of these drugs in the Ben-Men-1 and NCH93 cell lines as follows: Bortezomib 16.2 and 5.7 nM, Carfilzomib 4.8 and 2.6 nM, Omacetaxine and 5.0 and 8.9 nM, Paclitaxel 2.6 and 1.9 µM, and Ponatinib 278 and 206 nM. Inhibitor dosage of 10xIC50 values and higher lead to an average inhibition of Ben-Men-1 and NCH93 cells by up to 90% on day 2 (P&lt; .001). The impact of the antineoplastic agents on the cell cycle was analyzed by flow cytometry. Percentages of sub-G1 phase were significantly elevated with increasing drug concentrations of all five tested compounds (P&lt; .001). To assess the effects of the drugs on migration scratch assay was performed. Drug concentrations of 10xIC50 values resulted in an inhibition of migration in Ben-Men-1 cells for Bortezomib, Carfilzomib, and Omacetaxine by 49%, 30%, and 23%, respectively (P&lt; .05). In conclusion, we identified 5 promising drugs for the treatment of aggressive meningiomas by applying a high-throughput drug screening of 147 FDA-approved antineoplastic drugs.
Misrepresentation of Academic Accomplishments by Applicants for Gastroenterology Fellowships
Authors: Hans Richard Barthel
Journal: Annals of Internal Medicine (1996)

Letters15 February 1996Misrepresentation of Academic Accomplishments by Applicants for Gastroenterology FellowshipsHans Richard Barthel, MDHans Richard Barthel, MD61462 Koenigstein, GermanySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-4-199602150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:When studying the curricula vitae of applicants for a gastroenterology fellowship, Sekas and Hutson [1] found that 30.2% of articles cited as “in print” were not finally published. Several points, however, need further discussion. Residents applying for fellowships are often in the midst of their first research activity. Papers representative of their research experience are most likely either in the process of being written or have only recently been submitted. Most articles are rejected or are only accepted if major changes are made, leading to rewriting and resubmission. In addition, many articles may not be under the ...REFERENCE1. Sekas G, Hutson WR. Misrepresentation of academic accomplishments by applicants for gastroenterology fellowships. Ann Intern Med. 1995; 123:38-41. Google Scholar Author, Article, and Disclosure InformationAuthors: Hans Richard Barthel, MDAffiliations: 61462 Koenigstein, Germany PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 February 1996Volume 124, Issue 4Page: 456-457KeywordsFellowshipsForecasting ePublished: 15 August 2000 Issue Published: 15 February 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Readers Respond to 'Dirtball'
Journal: JAMA (1983)

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
Extended pelvic lymphadenectomy in men undergoing radical prostatectomy - an update on &gt; 300 cases
Authors: A. Heidenreich, R. Von Knobloch, Z. Varga, R. Hofmann, U. Engelmann
Journal: Journal of Clinical Oncology (2004)

4612 Background: Lymph node dissection (LND) in PCA is considered as a mere staging procedure and limited to obturator and external iliac nodes. Since the prostate drains into the external iliac, hypogastric, lateral and subaortic sacral nodes, metastases might be missed by the standard approach. We performed a radical pelvic lymphadectomy (RLND) in pts with PCA to assess frequency and location of lymph node metastases and to evaluate the reliability of current prediction models for lymph node involvement. Methods: 311 pts underwent RLND at time of radical retropubic prostatectomy via an extraperitoneal approach. RLND comprised 8 selective fields: external, internal and common iliac nodes, obturator nodes bilaterally. Nodes from each location and side were submitted separately for pathohistologic evaluation. Pathohistology of lymph nodes was compared to serum PSA, preoperative clinical stage and biopsy Gleason sum, pathohistological stage and Gleason sum of the prostatectomy specimen. Reliability of Partin tables, CART analysis and clinical parameters in terms of accurate prediction of lymph nodes metastases was evaluated. Results: Lymph node metastases were diagnosed in 19.8%; mean number of dissected lymph nodes was 28 (21–42). 22% of lymph node metastases were located in the internal and common iliac region only. 23/58 pts had 1 positive lymph node, 18 pts had 2, 7 pts had 3 and 8 pts had > 3 lymph nodes involved. Preoperative PSA serum levels were 26.8 (3.5–133)ng/ml and 16.5 (2.5–125)ng/ml in pts with and without lymph node metastases, resp. (p<0.05). CART nomograms did not accurately predict lymph node metastases with 58% of pN+ having been understaged. 27% and 58% of pN+ pts had serum PSA levels <10ng/ml and a biopsy Gleason sum <7, resp. The Partin tables understaged 33.5% of pts with positive lymph nodes. Conclusions: 47% of pts demonstrate positive lymph nodes around the internal and common iliac artery making this area essential for adequate staging LND. Current clinical staging systems (Partin, CART) miss up to 50% of all pN+ pts. Radical pelvic lymphadenectomy represents the standard lymphadenectomy technique of choice in surgical management of PCA. No significant financial relationships to disclose.
The Laws of Health. Physiology, Hygiene, Stimulants, Narcotics.
Journal: JAMA (1885)

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
THE PSYCHOLOGICAL IMPACT OF ELECTROCARDIOGRAM SCREENING IN NATIONAL COLLEGIATE ATHLETIC ASSOCIATION ATHLETES
Authors: Irfan Asif, Scott Annett, Alex Ewing, Ramy Abdelfattah, Justin Rothmier, Kimberly Harmon, Jonathan Drezner
Journal: British Journal of Sports Medicine (2017)

Background Cardiovascular screening is a means to prevent sudden cardiac death in athletes. The American Heart Association has raised concerns that false-positive electrocardiogram (ECG) screening may cause undue anxiety. Objective Determine the psychological impact of false-positive ECG screening in NCAA athletes and to stratify experiences based on screening outcome, race, gender, sport, and division of play. Design Prospective, multi-site investigation. Setting Seven NCAA institutions. Patients (or Participants) 1192 student-athletes (55.4% male, median age 19 years, 80.4% Caucasian). Assessment of Risk Factors Pre-participation screening with a standardized history, physical examination, and ECG. Main Outcome Measurements Pre- and post-screen validated assessments for health attitudes, anxiety, and impact of screening on sport. Results 96.8% of athletes had a normal cardiovascular screen (96.8%), 2.9% had a false-positive ECG, and 0.3% were diagnosed with a serious cardiac condition. Prior to screening, 4.5% worried about cardiac risk and 70.1% preferred knowing about an underlying condition, rather than play sports without this knowledge. There was no difference in anxiety described by athletes with a normal versus false-positive screen (p=0.369). Reported anxiety levels during screening also did not differ when analyzed by different gender, race, division of play, or sport. Athletes with normal and false-positive screens had similar levels of satisfaction (p=0.714) and would recommend ECG screening to other athletes at similar rates (p=0.322). Compared to athletes with a normal screen, athletes with false-positive results also reported feeling safer during competition (p&gt;0.01). In contrast, athletes with false-positive screens were more concerned about the possibility of sports disqualification (p&lt;0.001) and the potential for developing a future cardiac condition (p&lt;0.001). Conclusions False-positive results from ECG screening do not cause excessive anxiety in NCAA athletes. Further understanding of athlete experiences could better prepare the practicing physician on ways to counsel athletes with an abnormal ECG in order to address additional concerns.
Abstract 3605: O-linked N-acetylglucosamine transferase as a potential therapeutic target for metastatic gastric cancer
Authors: Joon Young Hur, Jeeyun Lee, Kyoung-Mee Kim, Sun-Ju Byeon, Inkyoung Lee, Won Ki Kang
Journal: Cancer Research (2019)

Abstract Introduction Many cancer types display elevated O-GlcNAcylation and aberrant expression of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Here, we describe metabolic reprogramming linked to aberrant increased O-GlcNAcylation, and then inhibition of O-GlcNAcylation as a potential therapeutic target for gastric cancer (GC) treatment. Methods We utilized 17 established GC cell lines including 6 primary cell lines (AGS, OCUM-2M, MKN45, SNU1, SNU484, and SNU719), 4 metastatic cell lines (MKN1, MKN28, MKN74, and SNU216), 6 ascite cell lines (SNU5, SNU19, SNU601, SNU620, SNU638, and SNU668), and 1 pleural effusion cell line (KATO III). We collected 21 matched pairs of primary GC and normal gastric tissues and Patient-derived cells (PDCs) (N = 10) at the Samsung Medical Center. PDCs and all cells were grown in RPMI-1640 medium supplemented with 10% FBS. For immunoprecipitation, cells were transfected with pFlag-OGT or siOGT, washed with cold PBS, and lysed in a buffer. Protein extracts (300-500 μg) were incubated with protein G-agarose beads (sc-2002; Santa Cruz) Results Cell lines of primary, metastasis and ascites showed expression of O-GlcNAc and OGT. OGT expression is increased in tumor cell and ascites and western blot results showed that OGT expression is more increased in ascites than tumor cell. OGT knockdown inhibited MKN1 cell growth and colony formation. To determine the effect of OGT knockdown on tumor growth in vivo, BALB/c nude mice were injected subcutaneously in the bilateral flank with siC and siOGT transfected MKN1 cells (1 x 107 cells). OGT overexpression enhances O-GlcNAcylation of NFκB p65, c-Myc, and K-Ras. NFκB p65, c-Myc, and K-Ras immunoprecipitates obtained from the cellular extracts were analyzed by immunoblotting for O-GlcNAc. OGT knockdown inhibited PDC (collected from malignant ascites) cell growth. OGT knockdown inhibited GC PDC (1 x 104 cells) cell invasion. Targeting OGT with siRNA in xenograft models decreases the growth of tumors. Conclusion Depletion of OGT inhibits cancer cell proliferation and OGT knockdown significantly delays tumor growth in xenograft model. Future work will take advantage of approaches to explain the impact of O-GlcNAc modification on GC. Citation Format: Joon Young Hur, Jeeyun Lee, Kyoung-Mee Kim, Sun-Ju Byeon, Inkyoung Lee, Won Ki Kang. O-linked N-acetylglucosamine transferase as a potential therapeutic target for metastatic gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3605.
Consensus conference. Fresh-frozen plasma. Indications and risks
Journal: JAMA (1985)

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
Institutional countertransference
Authors: M H Gendel, D E Reiser
Journal: American Journal of Psychiatry (1981)

The authors present the case of a patient with an institutional transference and point out the existence of institutional countertransference, which confounded his therapy and obscured his potential for change. Confronted with the patient's tradition in the institution, the new therapist had to overcome feelings of unimportance and therapeutic impotence to focus on the patient as a person in his own right. The authors discuss the signs of institutional countertransference and describe how it can seriously hinder clinical assessment of patients with institutional transferences.
Diagnostic and therapeutic technology assessment. Vasoactive intracavernous pharmacotherapy for impotence: intracavernous injection of prostaglandin E1
Journal: JAMA (1991)

The DATTA panelists consider PGE1 to be a useful addition to the family of vasoactive agents used to treat organic impotence. It is associated with fewer side effects than either papaverine or phentolamine. Although most patients can achieve an erection with PGE1, some will not, and the other vasoactive agents may be of benefit in these cases. Synergy has been demonstrated when papaverine and PGE1 are used together, and a combination of the two in reduced dosages may be effective in producing an erection with a reduction in side effects. Intracavernosal therapy should be prescribed and monitored by a urologist who is experienced in the treatment of impotence and who is able to treat any of the potential side effects. Whether long-term use of local injections will produce additional complications is yet to be determined.