tbuckley/cabot-search huggingface dataset:
Post-progression survival after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations.
Authors: Yoshihito Kogure, Chiyoe Kitagawa, Masahide Oki, Hideo Saka
Journal: Journal of Clinical Oncology (2013)

e19005 Background: Non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) mutation show a survival benefit on treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI); however, few studies report on post-progression tumor behavior after treatment with EGFR-TKI. Methods: We retrospectively reviewed clinical data of stage IV or recurrent NSCLC patients harboring the EGFR mutation, who received EGFR-TKI as first-line treatment in our institute from 2009 to 2011. Results: Thirty-six patients received EGFR-TKI as first-line therapy. Thirty of these patients with recurrent NSCLC were enrolled in this study. The median age of the patients was76 years (range, 38–97), and the male/female ratio was 4/26. The median progression-free survival (PFS) after EGFR-TKI treatment was 8.2 months. Sites of relapse in patients with progressive disease (PD) were the brain, pleural effusion, bone, and lung (n=5, 13, 6, and 8, respectively). Twenty-one patients received sequential therapy: 11 patients received continued EGFR-TKI treatment beyond PD and 10 patients received second-line therapy. Second-line therapies were platinum-based doublet therapy, monotherapy, and another cycle of EGFR-TKI (n = 6, 2, and 2 patients, respectively). Post-progression survival (PPS) of all the patients after treatment with EGFR-TKI was 9.2 months, whereas that of patients who received EGFR-TKI as second-line chemotherapy was 14 months. Subgroup analysis according to the site of relapse showed that after first-line EGFR-TKI treatment, PFS tended to be higher for patients with a relapse in the brain (11.6 months) than for patients with sites of relapse other than the brain (8.2 months). Conclusions: PPS after EGFR-TKI therapy in patients treated with second-line chemotherapy was similar to the OS of NSCLC patients without an EGFR mutation. Subgroup analysis showed that patients with a relapse in the brain might survive longer.
LONG-TERM BIOCOMPATIBILITY AND MECHANICAL PERFORMANCE OF A NEW BALLOON EXPANDABLE TRANSCATHETER BIOLOGICAL AORTIC VALVE SYSTEM ASSESSED BASED ON NOVEL OVINE AORTIC BANDING MODEL
Authors: Piotr P. Buszman, Carlos Fernandez, Mateusz Kachel, Maciej Pruski, Adam Janas, Magdalena Michalak, Krzysztof Milewski, Andrzej Bochenek, Pawel Buszman
Journal: Journal of the American College of Cardiology (2020)
Combinatorial epigenetic treatment approach for hepatocellular carcinoma
Authors: M. Bitzer, S. Venturelli, S. Armeanu, T. S. Weiss, M. Gregor, U. M. Lauer
Journal: Journal of Clinical Oncology (2006)

10066 Hepatocellular carcinoma (HCC) displays a striking resistance to chemotherapeutic drugs. Alternative approaches comprise employment of epigenetic compounds such as histone deacetylase inhibitors (HDAC-I) or demethylating agents (DA). Since we could recently demonstrate that HDAC-I exhibit inherent in vitro therapeutic activities against HCC cells, we now explored the potential of a HDAC-I / DA combined epigenetic treatment approach for the highly chemotherapy resistant tumor entity HCC. Methods: HCC cell lines (HepG2, Hep3B, HuH7) and primary human hepatocytes (PHH) were treated with a HDAC-I compound (Suberoylanilide hydroxamic acid - SAHA) together with or without a DA (5-aza-2dC) and examined for cellular damage (enzyme release), proliferation inhibition (SRB), apoptotic cells (FACS), histone acetylation pattern (Western blot) and methylation status (methylation specific PCR). The in vivo activity of our approach was investigated in a HuH7 xenograft mouse hepatoma model. Results: Both SAHA and 5-aza-2dC were found to induce substantial antiproliferative effects and apoptotic cell death in HCC cells; interestingly, combinatorial treatment (SAHA plus 5-aza-2dC) resulted in strongly enhanced anti-HCC effects. Interferences between DA and HDAC-I activities could be excluded by determining both (i) the methylation status of two model genes (p16, SOCS-1; known to be abberantly methylated in HCC) as well as (ii) patterns of histone acetylation. Most importantly, non-malignant primary human hepatocytes (5 different donors) did not exhibit any relevant cellular damage even when high doses of SAHA plus 5-aza-2dC were applied. Finally, in vivo testing of our combinatorial regimen (SAHA plus 5-aza-2dC) was found to be superior in suppression of tumor cell growth when compared to the application of single substances (SAHA or 5-aza-2dC) or placebo. Conclusion: Our combined epigenetic approach in chemotherapy resistant HCC not only has been found to be a highly active treatment option with profound anti-tumor effects both in vitro and in a small animal model in vivo, but did not impair primary human hepatocytes. Thus, this combination therapy now is considered for further investigation in clinical trials. No significant financial relationships to disclose.
Residency Education on Sexual and Gender Minority Health
Authors: Kara Sternhell-Blackwell, Matthew Mansh, J. Klint Peebles
Journal: JAMA Dermatology (2020)

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 Dermatology 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 Dermatology journal
LONG-TERM IMPLICATIONS OF LEFT ATRIAL APPENDAGE THROMBUS IDENTIFIED INCIDENTALLY BY PREPROCEDURAL CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY IN PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Yishay Szekely, Haim Shmilovich, Eihab Ghantous, Aviram Hochstadt, Yan Topilsky, Galit Aviram, Yaron Arbel, Maayan Konigstein, Shmuel Banai, Ariel Finkelstein, Amir Halkin
Journal: Journal of the American College of Cardiology (2020)
Primary care networks: LMC leaders vote to reject revised agreement on directed enhanced services
Authors: Abi Rimmer
Journal: BMJ (2020)

GP leaders have rejected the primary care networks directed enhanced service (DES) that was agreed as part of the 2020-21 GP contract in England.

Delegates at a special conference of local medical committees in England, held in London on 11 March, voted in favour of a motion calling on the profession to reject the DES as it is currently written.

The motion also called for the BMA’s general practitioners committee (GPC) to …
CORONARY ARTERY CALCIUM PROGRESSION AND CVD RISK AMONG THOSE ON STATIN THERAPY
Authors: Kashif Shaikh, Robyn McClelland, Venkata Mahesh Alla, Shone Almeida, Fayez Siddiqui, Khurram Nasir, Rine Nakanishi, Moyses Szklo, Nathan D. Wong, Richard Kronmal, Aiden Abidov, Prakrity Urja, Dixitha Anugula, Sajad Hamal, Matthew J. Budoff
Journal: Journal of the American College of Cardiology (2020)
Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial
Authors: Milagritos D Tapia, Samba O Sow, Birahim P Ndiaye, Khardiata D Mbaye, Aliou Thiongane, Cheikh T Ndour, Souleymane Mboup, Julie A Ake, Babajide Keshinro, Gideon A Akintunde, Thompson N Kinge, Guy Vernet, Jean Joel Bigna, Stephen Oguche, Kwadwo A Koram, Kwaku P Asante, Wayne R Hogrefe, Stephan Günther, Abdi Naficy, Iris De Ryck, Muriel Debois, Patricia Bourguignon, Erik Jongert, William R Ballou, Marguerite Koutsoukos, François Roman, Senate Amusu, Leo Ayuk, Catherine Bilong, Owusu Boahen, Makhtar Camara, Fadima Cheick Haidara, Daouda Coly, Siry Dièye, David Dosoo, Melanie Ekedi, Irma Eneida Almeida Dos Santos, Seyram Kaali, Afoke Kokogho, Myron Levine, Nick Opoku, Seth Owusu-Agyei, Simon Pitmang, Fatima Sall, Moussa Seydi, Marcelo Sztein, Mathurin Tejiokem, Awa Traore, Marie-Astrid Vernet, Abena Kunadu Yawson
Journal: The Lancet Infectious Diseases (2020)
ALCOHOL SEPTAL ABLATION FOR TREATING LEFT VENTRICULAR OUTFLOW TRACT OBSTRUCTION WITH SEVERE MITRAL REGURGITATION DUE TO FROZEN MITRAL LEAFLET
Authors: Amr Idris, Adam Shpigel, Jared Christensen, Mohanad Hamandi, Chadi Dib, Sameh Sayfo, Srinivasa Potluri, Zuyue Wang, Molly Szerlip, Karim Al-Azizi
Journal: Journal of the American College of Cardiology (2020)
THE ASSOCIATION BETWEEN SEVERE OBSTRUCTIVE SLEEP APNEA (OSA) PATIENTS WITH NORMAL EGFR AND LATENT KIDNEY DISEASE
Authors: Masahide Tokue, Nobutaka Ikeda, Raisuke Iijima, Hidehiko Hara, Masanori Shiba, Masato Nakamura
Journal: Journal of the American College of Cardiology (2020)
Previously documented mutations in the epidermal growth factor receptor (EGFR) gene in a non-small cell lung cancer (NSCLC) population treated with gefitinib are not associated with response
Authors: D. G. Bebb, T. Pugh, M. Sutcliffe, L. Barclay, J. Fee, R. O’Connor, J. Vielkind, N. Murray, J. J. Laskin, M. Marra
Journal: Journal of Clinical Oncology (2006)

7163 Background: Mutations in the tyrosine kinase domain of EGFR that may correlate with clinical features and response of NSCLC to EGFR tyrosine kinase inhibitors have been described. But, varying methodologies have contributed to an uncertain relationship between EGFR mutational status and response. This study sought to characterize EGFR mutations in microdissected tumour tissue from pts with advanced NSCLC treated with gefitinib and correlate their clinical data. Methods: Biopsy material from pts treated with gefitinib for advanced NSCLC at the British Columbia Cancer Agency was analyzed. Malignant cells (cytology specimens) or tissue (paraffin embedded biopsies) was reviewed and tumour cells isolated by laser- capture microdissection or manual scrape. Genomic DNA was extracted and exons coding for the EGFR tyrosine kinase domain (18 - 24) were amplified by PCR and sequenced. When insufficient, the priority was 18, 19, 21, followed by 20, 23, 22, and 24. EGFR mutational analyses were correlated with response to gefitinib and clinical features. Results: 61 pts were identified, 14 (23%) radiological responders (CR, PR): 10 Asian, 10 female, 8 non-smokers, 8 adenocarcinoma, 2 BAC. Of 51 tumour samples available, 39 had adequate tissue for sequencing analysis. EGFR copy number by FISH is pending. Laser-capture microdissection allowed for high quality DNA to be extracted almost exclusively from tumour. Exons 18, 19, 20, 21, 22, 23 and 24 have been sequenced in 37, 34, 30, 33, 12, 10, and 13 patients, respectively. 4 mutations were identified: 2 in 2 non-smoking Asian pts (exon 19; deletion or substitution of L747-T751) and 2 in Caucasians (exon 20 point mutation resulting in a L798F substitution). None of these pts had a response to gefitinib. Conclusions: As with other series, most responders were female, non-smokers of Asian origin. Our results support the relationship between Asian ethnicity and EGFR mutations but question the role of EGFR mutational status in predicting response. Prospective studies will need to focus the detection of additional genetic features using accurate and reproducible techniques before recommendations for selecting populations to be treated can be made. No significant financial relationships to disclose.
PERCUTANEOUS RETRIEVAL OF AN EMBOLIZED VEGETATION FROM PULMONARY ARTERY AFTER ICD LEAD EXTRACTION
Authors: Hardik M. Bhansali, Antonio Lewis Camargo, Nicholas Ghiloni, Nader Hanna, Luis Alonso Hernandez Mejia, Kevin Leung, Diana Miranda Ruiz, Jose Sleiman, Eduardo Perez, Armin Shivazad, Kevin Stadtlander, Roberto J. Cubeddu, Elsy Navas, Marcelo Helguera, Jose L. Baez-Escudero, Sergio Pinski
Journal: Journal of the American College of Cardiology (2020)
ApoStream, an antibody-independent platform, compared to CellSearch for enumeration of circulating tumor cells (CTCs) in patients with metastatic prostate cancer.
Authors: Andrew Stewart Poklepovic, Wen Wan, Weiguo Wu, Jacky Woo, Vladislava Melnikova, Elena Jouravleva, Kenna Lynn Anderes, Darren Davis
Journal: Journal of Clinical Oncology (2012)

e21058 Background: Development of CTC detection platforms is a rapidly advancing field. The CellSearch technique relies on cell surface expression of EpCAM to select for rare tumor cells in whole blood specimens. Consequently, the use of EpCAM-based enrichment platforms to recover CTCs is limited to EpCAM expressing cells and is poorly suited for recovery of EpCAM negative cells like those having undergone epithelial mesenchymal transition (EMT). ApoStream is an antibody independent enrichment platform which utilizes the principle of continuous flow dielectrophoresis field-flow fractionation (DEP-FFF) to isolate and enrich for CTCs. A head to head comparison of CellSearch to ApoStream for recovery of CTCs in patients with metastatic prostate cancer was performed. Methods: Two 7.5 mL bloodsamples were collected at a single time point for each patient with stage IV prostate cancer. One sample was analyzed by CellSearch CTC enumeration kit, and one sample was analyzed by ApoStream. CTCs recovered by both devices were immunophenotyped using antibodies against cytokeratin (CK), CD45 and DAPI. CTCs were defined as CK+/CD45-/DAPI+ intact cells. CTCs recovered by ApoStream were further analyzed by quantitative laser scanning cytometry (LSC). A paired t-test was used to compare the cell counts in the two devices. Results: The ApoStream CTC enrichment platform isolated a greater number of CTCs from blood of eight patients compared to CellSearch (p= 0.0027). All cell counts obtained by the ApoStream technique were higher than CellSearch, and all patients had detectable CTCs by ApoStream, while only 75% of patients had detectable CTCs with CellSearch. Conclusions: The ApoStream platform is differentiated from EpCAM dependent platforms and is well suited for detection and recovery of CTCs in advanced stage disease where tumor cell heterogeneity is common and expression of EpCAM may be low or lost. [Table: see text]
Changing TACTICS in intermediate HCC: TACE plus sorafenib
Authors: Pompilia Radu, Jean-François Dufour
Journal: Gut (2020)

Hepatocellular carcinoma (HCC) represents a serious health problem, mainly due to the high cancer-related mortality. Transarterial chemoembolisation (TACE) is currently used as the first-line treatment for intermediate-stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage B), despite the fact that this stage comprises patients with a wide range of liver function, variable tumour number and size.1–4 In clinical practice, only 50%–60% of patients with BCLC stage B benefit from TACE, so TACE is usually repeated to achieve maximum tumour recession. The main factors that impact the effectiveness of TACE include the worsening of both the liver function and recurrence rate. The latter is the result of the angiogenic response triggered by TACE-induced hypoxia, which stimulates residual tumour growth.5 This has led to the concept that combining TACE with an antiangiogenic treatment such as sorafenib will offer better tumour control.6 During the last decade, this hypothesis was tested in several trials, but the results were inconsistent.7–10 According to a recent meta-analysis the combination of TACE plus sorafenib for unresectable HCC was superior in terms of time to progression but not in overall survival (OS).11 

In Gut, a new trial combining TACE with sorafenib, the TACTICS trial, is published.12 The authors report that in patients with BCLC stage B, the progression-free survival (PFS), which was 13 months with TACE alone, reached 25 months with the addition of sorafenib to TACE. Similarly, the time to untreatable (unTACEable) progression increased significantly from 21 …
Survival (S) of ovarian cancer (OC) patients (pts) treated on SWOG9701/GOG178: 12 versus (v) 3 cycles (C) of monthly single-agent paclitaxel (PAC) following attainment of a clinically-defined complete response (CR) to platinum (PLAT)/PAC
Authors: M. Markman, P. Liu, S. Wilczynski, B. Monk, L. Copeland, D. Alberts
Journal: Journal of Clinical Oncology (2006)

5005 Background: This phase 3 trial was closed by the SWOG Data Safety and Monitoring Committee (DSMC) when a prospectively-defined interim analysis revealed a highly statistically significant difference in progression-free S (PFS) (28 v 21 months [M]; p = 0.0023; hazard ratio [HR] 2.31) (JCO 2003; 21:2460). At study closure, there were insufficient deaths to describe the impact of 12-C of PAC on overall S (OS). Methods: Eligibility included OC or primary peritoneal cancer, attainment of a CR to PLAT/PAC, and ≤ grade 1 neuropathy. Pts entered into the trial (n = 296) received either 12-C or 3-C of PAC (175 mg/m 2 q-28 days), and were then observed until progression. Results: Of the 146 pts on the 3-C arm, 9 (6%) actually received prolonged PAC (&gt; 3-C) following closure of the study by the DSMC. Median (12-C v 3-C; intention-to-treat analysis): updated PFS (all pts) 22 v 14 M, p = 0.01; OS (all pts) 53 v 46 M, p = 0.27. Exploratory analysis (Cox models adjusting for stratification factors): 12-C v 3-C HR 0.59 (p = 0.03) if baseline CA-125 ≤ 10 (n = 175), and 1.25 (p = 0.34) for baseline CA-125 &gt;10 (n = 121). The treatment v baseline CA-125 interaction was statistically significant (Cox model p = 0.03). Conclusion: OS was not significantly different between 12-C v. 3-C of PAC, either because (a) treatment at relapse equalized OS; (b) the sample size was insufficient to reveal a difference; (c) the crossover of pts from 3-C to longer treatment masked a potential difference; or (d) treatment was possibly prematurely discontinued at 12-C in pts who had not progressed (suggested by a previously reported exploratory analysis -JCO 2003; 21:2460). Of interest, an exploratory analysis strongly suggested an improvement in S for pts receiving 12-C of PAC if the baseline CA-125 level was ≤10, those individuals likely to have the smallest volume of clinically-undetectable residual OC when single-agent “maintenance” PAC was initiated. No significant financial relationships to disclose.
Prognostic effect of EIF4EBP1 on ovarian cancer: A single gene biomarker for overall survival and platinum response.
Authors: Victor Manuel Villalobos, Yan Wang, Scooter Willis, Brian Leyland-Jones, Branimir I. Sikic
Journal: Journal of Clinical Oncology (2013)

5565 Background: Using a novel computational approach, Gene Set Outcome Analysis (GSOA), we were able to identify an area of amplification on chromosome 8p12 that leads to worse prognosis in high grade/high stage ovarian cancer. Located within this amplicon is EIF4EBP1, an effector of DNA translation that is activated by mTOR. Methods: We utilized the MSKCC CBIO cancer genetics portal and the ovarian TCGA clinical dataset, to detect variation in mRNA expression (EXP), (z-scores thresholds ± 2) and copy number variation (CNV), determined using GISTIC 2.0, that are associated with significant differences in PFS and overall survival in grade 3 and stage III/IV ovarian cancer. Results: 6.7% of tumors exhibited upregulation of EIF4EBP1 (CNV amplified and mRNA z &gt; 2) and poorer prognosis with OS of 30.2 vs. 43.8 months (p = 0.0007, n = 445) in tumors not upregulated. Patients with upregulated vs. normal expression showed inferior PFS with first line, platinum based therapy, 10.0 vs. 15.2 months (p = 0.0406, n = 400), respectively. An additional 4.9% of cases had downregulation of EIF4EBP1, with homozygous deletion or mRNA expression z-scores &lt; -2. Downregulation vs. normal expression also showed worse OS of 27.0 vs. 42.1 months (p = 0.0178) and PFS of 11.0 vs. 15.0 months (p = 0.028), respectively. As these groups are mutually exclusive and show a similar trend towards poor prognosis, when combined to compare aberrant vs. normal mRNA expression and copy number, we found an OS of 28.2 vs. 44.6 months (p = &lt;0.0001) and PFS for first line platinum therapy of 10.2 vs. 15.3 months (p = 0.0024), respectively. Conclusions: In this dataset of 445 high-risk ovarian cancer patients, 11.8% exhibited aberrant expression of EIF4EBP1. While amplification of this region showed highly significant changes in OS and PFS, inclusion of both increased and decreased EIF4EBP1 mRNA expression achieved high statistical significance, demonstrating a “Goldilocks effect”, wherein normal expression leads to better outcomes. The potential relationship of gene expression levels of EIF4EBP1 to responsiveness to mTOR inhibitors should be explored in ovarian carcinomas.
COMORBIDITIES AMONG YOUNG ADULTS WITH CONGENITAL HEART DEFECTS: RESULTS FROM THE CONGENITAL HEART SURVEY TO RECOGNIZE OUTCOMES, NEEDS, AND WELL-BEING (CH STRONG), 2016-2019
Authors: Matthew Oster, Aspen Riser, Jennifer Andrews, Elijah Bolin, Maureen Galindo, Wendy Nembhard, Sherry Farr
Journal: Journal of the American College of Cardiology (2020)