tbuckley/cabot-search huggingface dataset:
Abstract P3-06-31: Patient-derived xenografts accurately predict patient response in breast cancer patients
Authors: Lisa Stow, Amanda Katz, Hanna Irie, Elisa Port, Justin Stebbing, Daniel Ciznadija, Angela Davies, Keren Paz
Journal: Cancer Research (2015)

Abstract PURPOSE/OBJECTIVES: A growing body of evidence demonstrates that patient-derived xenografts (PDXs) represent living tumor models that accurately reflect the biology of the primary patient tumor. More importantly, we have previously shown that PDX models show responses to therapeutic agents that are concordant with patient clinical response and can be used to direct personalized cancer treatments (Stebbing, 2014). Here we report the ability of PDX models to predict for patient response to drug treatment in a cohort of breast cancer patients. MATERIALS/METHODS: Tumors were resected from patients with either primary or metastatic breast cancer and implanted into immunodeficient mice to establish PDX models. Successfully engrafted PDX models were expanded and randomized for drug sensitivity testing. Tumor growth inhibition and tumor regression were captured and results were correlated with a patient’s clinical response. In some cases, PDX results were used to personalize cancer treatment and some patients used PDX-directed treatments over multiple lines of therapy. RESULTS: A total of 42 tumors from 40 patients were implanted resulting in 21 successfully engrafted PDX models (50% engraftment rate). Notably, engraftment rates were much higher for patients with triple negative breast cancer (TNBC) and resulted in 7 successful PDX models from 8 TNBC patients (87.5% engraftment rate). Drug sensitivity testing was offered to patients with established PDX models. Drugs and drug combinations tested included standard and nonstandard chemotherapy as well as biologics. At that time of this publication, 4 patients (3 TNBC and 1 HER2+) with completed drug sensitivity tests also had clinical data available resulting in 7 clinical correlations; 4 retrospective and 3 prospective. In all 7 cases, the PDX model accurately predicted patient clinical response demonstrating an accuracy of 100%. Five of the drug tests predicted drug sensitivity and 2 tests predicted resistance, indicating the potential of the PDX platform to predict for both sensitivity and resistance to therapy. The 3 prospective correlations resulted in concordant clinical benefit in 2 patients for duration greater than 6 months each. CONCLUSIONS: These data support the use of the personalized PDX model as a platform for therapeutic decision making that can guide treatment for patients with breast cancer. A prospective clinical trial in TNBC is currently underway. Citation Format: Lisa Stow, Amanda Katz, Hanna Irie, Elisa Port, Justin Stebbing, Daniel Ciznadija, Angela Davies, Keren Paz. Patient-derived xenografts accurately predict patient response in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-31.
Fetal Environment May Have Profound Long-term Consequences for Health
Authors: Tracy Hampton
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
Sildenafil for "blue babies"
Authors: J. Oliver
Journal: BMJ (2002)

Editor—We were disappointed to hear that a doctor in India has been criticised for treating pulmonary hypertension in three neonates (so called blue babies) with the phosphodiesterase type 5 inhibitor sildenafil (Viagra), a drug not licensed for this purpose.1

Many drugs are widely and appropriately used outside their product licence.2 Such prescribing practice is common in adult medicine, but is particularly prevalent in paediatrics because companies rarely undertake the work necessary to gain a licence for children. The decision to prescribe outwith a drug's licence should be supported by evidence of safety and potential benefit and, when possible, by a reasonable body of supporting professional opinion.

Of course, controlled clinical trials should be performed when possible to evaluate new treatments for specific indications. But these data are not always available, and then clinicians must make difficult decisions as to whether other information, such as efficacy and safety in other groups of patients, justifies unlicensed drug use. Subsequently, case reports should be published, facilitating scientific debate and informing the design of clinical trials.

Evidence is growing that sildenafil acts as a vasodilator in the pulmonary circulation and is effective in lowering pulmonary artery pressure in pulmonary arterial hypertension. This effect has been shown in adults with pulmonary hypertension and healthy volunteers with pulmonary hypertension induced by hypoxia.3,4 Intravenous sildenafil also normalised pulmonary artery pressure in an animal model of neonatal pulmonary hypertension.5

The evidence currently available is not sufficient generally to recommend the use of sildenafil in neonates with pulmonary hypertension. Assuming, however, that sildenafil was used as a last resort, after standard treatment, we believe that there are sufficient data to support the actions of this doctor. Perhaps the publicity that has arisen about this action will encourage further clinical research into the potential of inhibiting phosphodiesterase type 5 as a treatment for neonatal pulmonary hypertension, which may ultimately result in wider benefit to patients.
Multicentre, open-label study using imiquimod 5% cream in one or two 4-week courses of treatment for multiple actinic keratoses on the head
Authors: E. Stockfleth, W. Sterry, M. Carey-Yard, J. Bichel
Journal: British Journal of Dermatology (2007)

Journal Article Multicentre, open‐label study using imiquimod 5% cream in one or two 4‐week courses of treatment for multiple actinic keratoses on the head Get access E. Stockfleth, E. Stockfleth Haut Tumor Centrum Charité/Skin Cancer Center Charié, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, D‐10117 Berlin, Germany *3M Medica, Neuss, Germany Correspondence: Eggert Stockfleth. E‐mail: eggert.stockfleth@charite.de Search for other works by this author on: Oxford Academic Google Scholar W. Sterry, W. Sterry Haut Tumor Centrum Charité/Skin Cancer Center Charié, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, D‐10117 Berlin, Germany *3M Medica, Neuss, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Carey‐Yard, M. Carey‐Yard Haut Tumor Centrum Charité/Skin Cancer Center Charié, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, D‐10117 Berlin, Germany *3M Medica, Neuss, Germany Search for other works by this author on: Oxford Academic Google Scholar J. Bichel J. Bichel Haut Tumor Centrum Charité/Skin Cancer Center Charié, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, D‐10117 Berlin, Germany *3M Medica, Neuss, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue s2, 1 December 2007, Pages 41–46, https://doi.org/10.1111/j.1365-2133.2007.08272.x Published: 01 December 2007
Review: Perioperative β-blockade reduces nonfatal MI but increases mortality in noncardiac surgery
Authors: David L. Brown
Journal: Annals of Internal Medicine (2015)

Source Citation Wijeysundera DN, Duncan D, Nkonde-Price C, et al. Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64:2406-25. 25091545*
The active compound of garlic to treat non-small cell lung cancer: in vitro studies
Authors: Yehuda Schwarz, Limor Kindil, Amir Bar-Shai, Aharon Rabinkov, Alex Star
Journal: European Respiratory Journal (2013)

Background : Lung cancer is one of the most lethal malignancies in the Western world. The research goal of this study is to examine the capacity of a novel compound, allylmercapto-S-thiol (AMST), the derivate of Allicin (an organic sulphur compound derived from garlic) to treat the Non Small Cell Lung Cancer (NSCLC) cells.   Materials and methods : Human and murine NSCLC cell lines, H1299 and 3LL, respectively, were used in the study. XTT proliferative assay was used to analyze the anti-proliferative property of AMST. In order to detect AMST influence on apoptosis, FACS analysis using Annexin V-FITC/propodium iodide was performed. Cell motility was measured by migration to artificial wound and Transwell assays. Adhesion properties were evaluated by cell attachment to glass and plastic substrates and homotypic aggregation assays. Western blot analysis was used to study the biochemical mechanisms of AMST-induced apoptosis.   Results:  Our results demonstrate that AMST inhibits significantly in vitro proliferation of two NSCLC cell lines and also induces apoptosis in H1299 cells. It also inhibits lung cancer cell properties consistent with in vitro metastatic phenotype including cell motility, adhesion and aggregation. Western blot analysis demonstrated correlation between AMST-induced apoptosis and inhibition of BCL-2 antiapoptotic protein in NSCLC cells.   Conclusions : Our results indicate possible antitumorigenic and antimetastatic properties of novel garlic compound AMST in NSCLC cells and justifies further in vivo studies.
Abstract 3708: microRNAs involved in BRAF inhibitor resistance
Authors: Lisa Koetz, Elena Sokolova, Brian D. Brown, Eva Hernando
Journal: Cancer Research (2014)

Abstract BRAF inhibitors (BRAFi) have shown remarkable clinical activity in advanced metastatic melanomas with mutant BRAF(V600E). However, there is considerable variability in both the extent and the duration of patient responses, and acquired resistance invariably emerges. To date, a number of mechanisms underlying acquired resistance to BRAF inhibitors have been identified, most of which reactivate ERK signaling while simultaneously engaging parallel survival pathways. However, these mechanisms account for only a fraction of progressed melanoma and do not explain the large variability of initial response rates and time to progression of melanoma patients subjected to these therapies. We hypothesize that in addition to genetic events, non-genetic alterations such as microRNA changes are critical in mediating time to progression in melanoma tumors treated with BRAF inhibitors. In order to identify microRNAs involved in BRAF inhibitor resistance we performed a functional screen approach utilizing a novel lentiviral-based library of microRNA ‘decoys’. These constructs are better able to stably suppress endogenous microRNA activity than the hairpin RNAs traditionally used. This pooled parallel loss-of-microRNA function analysis in BRAF(V600E) mutant melanoma cells showed enrichment and loss of specific decoys after drug treatment, corresponding to microRNAs that may enhance or compromise the response, respectively. MicroRNA decoys that are positively or negatively selected during drug treatment are being validated using single decoy constructs for their ability to modulate BRAFi response. MicroRNA target genes will be determined by a combination of microarray analysis, in silico predictive algorithms, and 3′UTR-luciferase reporter assay. MicroRNAs and target genes are being validated on human samples from treated patients. Those potentially involved in processes/pathways known to influence drug resistance (i.e. survival genes) will be examined for their ability to mimic or counteract microRNA effects in BRAFi resistance when silenced or overexpressed, respectively. Identification of novel modulators of drug resistance provides the opportunity to design rational combinatorial approaches that will enhance and prolong the effect of these therapies, with the ultimate goal of achieving cures. Citation Format: Lisa Koetz, Elena Sokolova, Brian D. Brown, Eva Hernando. microRNAs involved in BRAF inhibitor resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3708. doi:10.1158/1538-7445.AM2014-3708
Expanded Screening of Newborns for Genetic Disorders—Reply
Authors: Neil A. Holtzman
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
A patient who changed my practice: How we improved our treatment of hypertension
Authors: A. Williams
Journal: BMJ (2000)

In my early years of general practice I was enthusiastic about controlling blood pressure. One particular patient, a retired civil servant, presented with a sore throat, and an incidental finding showed a blood pressure of 200/130.

I was not sure how much of this was caused by meeting a new doctor so I took his blood pressure several times and it continued to be high. A general physical examination was unremarkable apart from a soft ejection systolic murmur at the left sternal edge. In particular, he had no protein in his urine and his fundi showed only grade 1 retinopathy. Baseline investigation showed his renal function was normal, mid—stream urine specimen was negative, and serum urate was normal. I initially started him on bendrofluazide at a dose of 5 mg a day, which was …
Bone-Density Testing Interval and Transition to Osteoporosis
Authors: Angela M Cheung, Alexandra Papaioannou
Journal: New England Journal of Medicine (2012)

To the Editor: There has been a disconnect between osteoporosis and its consequence, the increased risk of fractures.1 The article by Gourlay et al. (Jan. 19 issue)2 focuses physicians and the general public again on bone mineral density (BMD) testing alone for fracture risk assessment, a concept that many international groups have worked hard to change. The terms “mild, moderate, and advanced” osteopenia do not convey fracture risk information. A 50-year-old postmenopausal woman who has been deemed to have osteoporosis on the basis of BMD testing (T score, −2.5) has a lower 10-year fracture risk than a 75-year-old woman with “mild osteopenia.” In 2005, we published charts showing 10-year fracture risks according the Canadian Association of Radiologists and Osteoporosis Canada.3 We then updated the charts in the 2010 guidelines4 and recommended the assessment of clinical risk factors for fractures when considering BMD testing. It is time for us (the international osteoporosis community) to change the testing algorithm to one that is based on overall fracture risk or transition of fracture risk categories (e.g., from moderate to high 10-year fracture risk) and examine the cost-effectiveness of different intervals for clinical screening and BMD testing for preventing fractures. Angela M. Cheung, M.D., Ph.D.
Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis
Authors: J.-H. Lee, J.-W. Choi, Y.-S. Kim
Journal: British Journal of Dermatology (2010)

Journal Article Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta‐analysis Get access J.‐H. Lee, J.‐H. Lee Department of Pathology, Korea University Ansan Hospital, 516, Gojan‐1 Dong, Danwon‐Gu, Ansan‐Si, Gyeonggi‐Do 425‐707, Korea Search for other works by this author on: Oxford Academic Google Scholar J.‐W. Choi, J.‐W. Choi Department of Pathology, Korea University Ansan Hospital, 516, Gojan‐1 Dong, Danwon‐Gu, Ansan‐Si, Gyeonggi‐Do 425‐707, Korea Search for other works by this author on: Oxford Academic Google Scholar Y.‐S. Kim Y.‐S. Kim Department of Pathology, Korea University Ansan Hospital, 516, Gojan‐1 Dong, Danwon‐Gu, Ansan‐Si, Gyeonggi‐Do 425‐707, Korea Young‐Sik Kim. E‐mail: apysk@korea.ac.kr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 4, 1 April 2011, Pages 776–784, https://doi.org/10.1111/j.1365-2133.2010.10185.x Published: 01 April 2011
Primary upper-limb lymphoedema
Authors: S. Vignes, M. Arrault, A. Yannoutsos, M. Blanchard
Journal: British Journal of Dermatology (2012)

Journal Article Primary upper‐limb lymphoedema Get access S. Vignes, S. Vignes Department of Lymphology, Centre National de Référence des Maladies Vasculaires Rares (lymphœdèmes primaires), Hôpital Cognacq‐Jay, 75015 Paris, France Stéphane Vignes. Email: stephane.vignes@cognacq-jay.fr Search for other works by this author on: Oxford Academic Google Scholar M. Arrault, M. Arrault Department of Lymphology, Centre National de Référence des Maladies Vasculaires Rares (lymphœdèmes primaires), Hôpital Cognacq‐Jay, 75015 Paris, France Search for other works by this author on: Oxford Academic Google Scholar A. Yannoutsos, A. Yannoutsos Department of Lymphology, Centre National de Référence des Maladies Vasculaires Rares (lymphœdèmes primaires), Hôpital Cognacq‐Jay, 75015 Paris, France Search for other works by this author on: Oxford Academic Google Scholar M. Blanchard M. Blanchard Department of Lymphology, Centre National de Référence des Maladies Vasculaires Rares (lymphœdèmes primaires), Hôpital Cognacq‐Jay, 75015 Paris, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 2, 1 February 2013, Pages 272–276, https://doi.org/10.1111/bjd.12024 Published: 01 February 2013 Article history Accepted: 23 August 2012 Published: 01 February 2013
Abstract 4400: The <i>let-7</i> microRNA binding site variant in the <i>KRAS</i> 3′-UTR is not associated with the risk of head and neck cancer
Authors: Nejat Dalay, Semra Demokan, Yusufhan Suoglu, Rasim Yilmazer, Murat Ulusan
Journal: Cancer Research (2014)

Abstract The KRAS gene is activated by somatic mutations in many cancer types. However, KRAS mutations are relatively rare in squamous cell carcinomas. In squamous cell cancers of the head and neck (HNSCC) amplification of the KRAS gene has been shown to promote tumor growth. miRNAs are short non-coding RNAs which play an important role as regulators of gene expression. They bind to the 3′-untranslated regions (UTRs) of the mRNAs and prevent translation of their target genes. SNPs in the miRNA binding sites are associated with disease risk and prognosis. The let-7 family of miRNAs regulate multiple oncogenes including the KRAS gene and have been shown to play a critical role in different cancer types. A functional polymorphism in the KRAS gene, not included in the GWAS platforms has been identified by candidate gene approach and was found to be a genetic marker of cancer risk and increased susceptibility to the carcinogenic effects of tobacco smoke. The polymorphism is referred to as the LCS6 (let-7 complementary site 6) variant and disrupts the let-7 binding site leading to higher KRAS expression. Such an increase in KRAS expression associated with the variant allele may represent an alternative form of KRAS activation in HNSCC and could lead to impairment of the EGFR signaling. In this study we evaluated the frequency of the KRAS variant in 216 patients with head and neck cancer and 85 healthy individuals. DNA was extracted from whole blood prior to chemotherapy or radiotherapy. The variant allele was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype and allele frequencies were evaluated using the De-Finetti case control program. 13 % of the patients were heterozygous and 3 patients (1.5 %) were homozygous for the variant allele. The polymorphism was present in heterozygous form in 12 % of the controls. No homozygous individual was detected in the control group. The frequencies of the variant allele were 92 % and 94 % in the patients and controls, respectively. Our data indicate that the KRAS let-7 LCS6 variant allele is not associated with an increased risk of HNSCC. Citation Format: Nejat Dalay, Semra Demokan, Yusufhan Suoglu, Rasim Yilmazer, Murat Ulusan. The let-7 microRNA binding site variant in the KRAS 3′-UTR is not associated with the risk of head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4400. doi:10.1158/1538-7445.AM2014-4400
Abstract 15640: Risk Stratification at Admission to Identify ST-Segment Elevation Myocardial Infarction Patients Receiving Fibrinolysis Who May Benefit from Early Angioplasty: Insights from the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)
Authors: Andrew T Yan, Warren J Cantor, Raymond T Yan, Bjug Borgundvaag, Eric A Cohen, Vlad Dzavik, John Ducas, Mary Tan, Amparo Casanova, Shaun G Goodman
Journal: Circulation (2010)