tbuckley/cabot-search huggingface dataset:
Rare pituitary Perivascular Epithelioid Cell tumour (PEComa)
Authors: Khaled Badran, Olimpia Curran, Colin Smith, Avinash Kanodia, Jonathon Berg, Hannah Lord, Graham Leese, Kismet Hossain-Ibrahim
Journal: Neuro-Oncology (2018)

A 63 year old lady presented with general weakness and 4 months progressive visual disturbance. She has a family history of Birt-Hogg-Dube syndrome. Examination revealed bi-temporal hemianopia. MRI imaging showed a pituitary lesion with suprasellar extension causing optic chiasm compression. She underwent transnasal endoscopic debulking of pituitary lesion, with subsequent improvement in vision. Weakness improved with thyroxine. Histopathology showed adenoma-like tumour with evidence of melanin production. Birt Hogg Dubé produces skin papules and renal carcinoma; skin biopsy of two pigmented skin lesions and CT chest / abdo / pelvis was negative. Macroscopically the lesion was fibrous and vascular with similar structure to brain, resulting in residual tumour. She presented 8 months later with sudden headache and worsening visual acuity. MRI brain revealed significant pituitary tumour enlargement with a small haemorrhagic element within. She underwent urgent re-do endoscopic debulking, with slight improvement of vision. Histopathology: positive Melan A labelling of tumour cells and patchy expression of S100 antibody. TFE3 immunohistochemistry was positive but negative with FISH (i.e. not renal carcinoma or alveolar soft part sarcoma), giving a diagnosis of sella turcica perivascular epithelioid cell tumour (PEComa). The patient completed radiotherapy treatment (55Gy33F) and her vision is now normal with subsequent reduction in tumour size. This is the second case reported of primary CNS PEComa tumour – and the first in a patient with Birt Hogg Dubé syndrome. WHO defines PEComas as mesenchymal tumours composed of histologically and immunohistochemically distinctive perivascular epithelioid cells.PEComas-NOS have been reported in gastrointestinal, gynaecological, genitourinary, extremities and the skin (single reports in the heart, breast, oral cavity, orbit, and skull base).Because of the difficulty in achieving complete excision, regrowth and need for radiotherapy, we think that PEComa should be considered in cases of tumours for melanoma markers, especially if they recur.
Companion Diagnostic <sup>64</sup>Cu-Liposome Positron Emission Tomography Enables Characterization of Drug Delivery to Tumors and Predicts Response to Cancer Nanomedicines
Authors: Helen Lee, Daniel Gaddy, Manuela Ventura, Nicholas Bernards, Raquel de Souza, Dmitri Kirpotin, Thomas Wickham, Jonathan Fitzgerald, Jinzi Zheng, Bart S. Hendriks
Journal: Theranostics (2018)

Deposition of liposomal drugs into solid tumors is a potentially rate-limiting step for drug delivery and has substantial variability that may influence probability of response.Tumor deposition is a shared mechanism for liposomal therapeutics such that a single companion diagnostic agent may have utility in predicting response to multiple nanomedicines.Methods: We describe the development, characterization and preclinical proof-of-concept of the positron emission tomography (PET) agent, MM-DX-929, a drug-free untargeted 100 nm PEGylated liposome stably entrapping a chelated complex of 4-DEAP-ATSC and 64 Cu (copper-64).MM-DX-929 is designed to mimic the biodistribution of similarly sized therapeutic agents and enable quantification of deposition in solid tumors.Results: MM-DX-929 demonstrated sufficient in vitro and in vivo stability with PET images accurately reflecting the disposition of liposome nanoparticles over the time scale of imaging.MM-DX-929 is also representative of the tumor deposition and intratumoral distribution of three different liposomal drugs, including targeted liposomes and those with different degrees of PEGylation.Furthermore, stratification using a single pre-treatment MM-DX-929 PET assessment of tumor deposition demonstrated that tumors with high MM-DX-929 deposition predicted significantly greater anti-tumor activity after multi-cycle treatments with different liposomal drugs.In contrast, MM-DX-929 tumor deposition was not prognostic in untreated tumor-bearing xenografts, nor predictive in animals treated with small molecule chemotherapeutics.Conclusions: These data illustrate the potential of MM-DX-929 PET as a companion diagnostic strategy to prospectively select patients likely to respond to liposomal drugs or nanomedicines of similar molecular size.
False Information About Breast Cancer Screening—Reply
Authors: Rita F. Redberg, Deborah Grady
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
EDITOR'S CHOICE: Chasing dreams
Authors: Sabina Dosani
Journal: BMJ (2007)

“Don't write about sitting on a beach drinking New World wines,” warned Jackie Connor, director of BMJ Careers . I've been in New Zealand for five months. Regular readers know I left a consultant post in a London teaching hospital to chase a dream. I'd fantasised about working abroad but am not altruistic enough for Medecins Sans Frontieres or Voluntary Service Overseas. London was a terrific place to train, then exams, a house, a great job, and my husband's career meant it was never a good time to go. The decision was made impulsively. A fortnight after dreaming it might be possible, I was interviewed, a day after that, I …
COMBINED PATTERNS OF OBESITY AND SMOKING STATUS FOR PREDICTION OF CORONARY ARTERY DISEASE: A FOLLOW-UP STUDY ON TREATED HYPERTENSIVE PATIENTS
Authors: Konstantinos P. Tsioufis, Alexandros Kasiakogias, Dimitris Konstantinidis, Theodoros Kalos, Christos Mallios, Ioannis Andrikou, Evaggelia Koutra, Konstantinos Thomopoulos, Kyriakos Dimitriadis, Ioannis Kallikazaros, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
Abstract P4-01-02: Choosing wisely: Radiographic surveillance after breast conservation therapy in HER2+ breast cancer
Authors: A Everett, AS Wallace, JF De Los Santos, GB Rocgue, CS Parker, KS Keene
Journal: Cancer Research (2018)

Abstract Purpose/Objective(s): ASTRO Choosing Wisely campaign recommends no more than annual mammography after breast conservation therapy (BCT). HER2+ disease portends increased risk of locoregional recurrence in comparison to Luminal A disease. Our previous institutional practice included surveillance imaging every 6 months for the first 2-3 years after BCT. The purpose of this study is to evaluate surveillance imaging intervals as a means of detecting early locoregional recurrence at one institution. Materials/Methods: Women with HER2+ locoregionally confined invasive breast cancer treated with lumpectomy and radiation as part of breast conservation therapy at one institution were retrospectively identified after IRB approval. Patient demographics, treatment, surveillance, and outcomes data were captured. BRCA+ patients or those without available surveillance follow-up at our institution were excluded. Surveillance period started after the last fraction of radiation was completed. Results: In 86 women treated from 2008-2016, median age at diagnosis was 57, and 69% were Caucasian. Most patients were treated for Stage I-II invasive ductal carcinoma. All but one were treated with chemotherapy, with similar distribution between adjuvant and neoadjuvant regimens. Receptor status was as follows: ER+ 66%, PR+ 59%, ER+/PR+/HER2+ in 58%, ER-/PR-/HER2+ in 33%. Mammography +/- ultrasound was utilized, with infrequent use of magnetic resonance imaging. Median time from end of radiation to first surveillance imaging was 4 months. All women had 1 post-BCT imaging, with 2nd, 3rd, and 4th available in 91%, 85%, 73% respectively. Interval frequency between first 4 images was 6 months. No patients had expired at the time of analysis. Recurrence were identified in 2 women: 1 identified clinically after negative mammography, and 1 identified on mammography at 27 months. Conclusion: While overall events are small, discordant biannual mammography did not identify locoregional recurrences in this biologically higher risk group in the first two years post-treatment. This data supports current guideline recommendations limiting surveillance breast imaging in patients undergoing breast conservation to an annual frequency. Citation Format: Everett A, Wallace AS, De Los Santos JF, Rocgue GB, Parker CS, Keene KS. Choosing wisely: Radiographic surveillance after breast conservation therapy in HER2+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-01-02.
Overcoming Resistance to DNA-Targeted Agents by Epigenetic Activation of Schlafen 11 (<i>SLFN11)</i> Expression with Class I Histone Deacetylase Inhibitors
Authors: Sai-Wen Tang, Anish Thomas, Junko Murai, Jane B. Trepel, Susan E. Bates, Vinodh N. Rajapakse, Yves Pommier
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Schlafen 11 (SLFN11), a putative DNA/RNA helicase is a dominant genomic determinant of response to DNA-damaging agents and is frequently not expressed in cancer cells. Whether histone deacetylase (HDAC) inhibitors can be used to release SLFN11 and sensitize SLFN11-inactivated cancers to DNA-targeted agents is tested here. Experimental Design: SLFN11 expression was examined in The Cancer Genome Atlas (TCGA), in cancer cell line databases and in patients treated with romidepsin. Isogenic cells overexpressing or genetically inactivated for SLFN11 were used to investigate the effect of HDAC inhibitors on SLFN11 expression and sensitivity to DNA-damaging agents. Results: SLFN11 expression is suppressed in a broad fraction of common cancers and cancer cell lines. In cancer cells not expressing SLFN11, transfection of SLFN11 sensitized the cells to camptothecin, topotecan, hydroxyurea, and cisplatin but not to paclitaxel. SLFN11 mRNA and protein levels were strongly induced by class I (romidepsin, entinostat), but not class II (roclinostat) HDAC inhibitors in a broad panel of cancer cells. SLFN11 expression was also enhanced in peripheral blood mononuclear cells of patients with circulating cutaneous T-cell lymphoma treated with romidepsin. Consistent with the epigenetic regulation of SLFN11, camptothecin and class I HDAC inhibitors were synergistic in many of the cell lines tested. Conclusions: This study reports the prevalent epigenetic regulation of SLFN11 and the dominant stimulatory effect of HDAC inhibitors on SLFN11 expression. Our results provide a rationale for combining class I HDAC inhibitors and DNA-damaging agents to overcome epigenetic inactivation of SLFN11-mediated resistance to DNA-targeted agents. Clin Cancer Res; 24(8); 1944–53. ©2018 AACR.
Major Adverse Limb Events and Mortality in Patients With Peripheral Artery Disease
Authors: Sonia S. Anand, Francois Caron, John W. Eikelboom, Jackie Bosch, Leanne Dyal, Victor Aboyans, Maria Teresa Abola, Kelley R.H. Branch, Katalin Keltai, Deepak L. Bhatt, Peter Verhamme, Keith A.A. Fox, Nancy Cook-Bruns, Vivian Lanius, Stuart J. Connolly, Salim Yusuf
Journal: Journal of the American College of Cardiology (2018)
RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia
Authors: S. Rudat, A. Pfaus, Y. Y. Cheng, J. Holtmann, J. M. Ellegast, C. Bühler, D. Di Marcantonio, E. Martinez, S. Göllner, C. Wickenhauser, C. Müller-Tidow, C. Lutz, L. Bullinger, M. D. Milsom, S. M. Sykes, S. Fröhling, C. Scholl
Journal: Leukemia (2018)
Predicting AID off-targets: A step forward
Authors: Claude-Agnès Reynaud, Jean-Claude Weill
Journal: The Journal of Experimental Medicine (2018)

In this issue of JEM, Álvarez-Prado et al. (https://doi.org/10.1084/jem.20171738) designed a DNA capture library allowing them to identify 275 genes targeted by AID in mouse germinal center B cells. Using the molecular features of these genes to feed a machine-learning algorithm, they determined that high-density RNA PolII and Spt5 binding—found in 2.3% of the genes—are the best predictors of AID specificity.
One of the authors of the <i>Oxford Handbook of Clinical Medicine</i>
Authors: Krishna Chinthapalli
Journal: BMJ (2006)

Murray Longmore is a doctor with two careers. The first, of which few doctors are aware, is general practice in the village of Ferring, Sussex. The second, of which few patients are aware, is as one of the authors of the <i>Oxford Handbook of Clinical Medicine</i>. As it approaches its 21st birthday, the Cheese and Onion (as it has been nicknamed) has now sold three copies for every doctor and medical student in the United Kingdom.
When is “enough” enough?
Authors: Yasmin Akram
Journal: BMJ (2012)

Hindsight can be a wonderful thing, but sometimes even with its glorious benefits you cannot be sure whether a decision was the right one. We all have patients whom we will likely never forget. I have quite a quirky collection—one in particular comes to mind. Mrs A reminded me of my grandmother. They may not have spoken the same language or been the same colour or had the same belief system, but it wasn’t just metastatic cancer that they had in common. Their emotions, resilience, and smiles were much the same.

Mrs A was already on the ward when I started the rotation. The problem was that we did not know where her primary was. So on the consultant’s instructions we scanned her, and when that flagged up something unrelated we investigated …
A cult pop doc
Authors: John Bonner
Journal: BMJ (2005)

Adam Kay is one half of the comedy duo Amateur Transplants. Both he and his performing partner Suman Biswas are pre-registration house officers whose showbiz careers began writing sketches for medical school revues. Their CD <i>Fitness to Practice</i> contains the infamous London Underground song (a meditation on the pleasures of public transport), which has enjoyed notable cult success. Its lyrics lean more heavily towards the profane than the sacred but it has raised thousands of pounds for Macmillan Cancer Relief
From doctor to “hybrid” health professional
Authors: Tom Moberly
Journal: BMJ (2014)

Over the coming decades, doctors’ training and practice will have to undergo substantial change to meet the needs of an ageing and increasingly unwell patient population. Some of those changes will mean shifting the traditional boundaries between different sectors of the health service, and this week Daniel Eckford describes his experience of undertaking foundation training in community geriatrics (http://careers.bmj.com/careers/advice/view-article.html?id=20018142). The project …
Targeting intracellular oncoproteins with single domain antibody for cell therapy of esophageal cancer.
Authors: Bin Gao, Lihui Lv, Zhenkun Xia, Mingzhu Gu, Ying Liu, Zhixia Guo, Meng Liang, Yunchang Yuan
Journal: Journal of Clinical Oncology (2018)

56 Background: Intracellular oncoproteins such as NY-ESO-1 and WT1 are widely distributed in different cancers and ranked as number 1 and 10 prioritized cancer antigen by international experts. It is difficult to target these antigens due to the intracellular nature by conventional antibodies. Methods: Here we reported the development of antibodies to target intracellular antigens, the same way as TCR does, recognizing MHC complex with peptides derived from intracellular oncoproteins. Phage display libraries were screened out against HLA-A2 assembled with different peptides from both WT1 and NY-ESO-1. Antibodies were tested to bind to corresponding HLA-A2/peptides complex on ELISA and FACS and finally the ability to bind to paraffin samples derived from malignancy cancer patients were confirmed. Results: We have identified several antibodies that specifically recognize the corresponding HLA-A2/peptide. Particularly, 2F4 and 1H1 could bind to RMFPNAPYL of WT1 HLA-A2 monomer on ELASA assay, by contrast the antibody did not bind to 5 other non-related HLA-A2 monomers. Furthermore, on FACS assay, both antibodies bound to WT1 peptide loaded T2 cells that express empty HLA-A2 complex on the surface. 2F4 could be routinely expressed as Fc fusion protein and maintained TCR-like feature and could recognize tumor cell lines expressing both HLA-A2 and WT1 antigen on FACS analysis. Both antibodies bind to HLA-A2/ WT1 with the affinity ranging between 10-8 and 10-9 M by Biacore analysis. Finally, paraffin sections from esophageal cancer patients were stained with antibody specific to HLA-A2/RMF and about 30% of samples shown strong reactions and The antibody to HLA-A2/SLL ( NY-ESO-1) shown a similar results although weaker stains due to the lower affinity of the antibody. Conclusions: Intracellular oncoproteins could be targeted by antibodies recognizing HLA associated with the onco-peptide processed. These antibodies have potential applications on CAR-T cell therapy or the development of bi-specific therapeutics for a number of malignancy tumors.
THE PROGNOSTIC VALUE OF RIGHT VENTRICULAR FREE WALL STRAIN AFTER LUNG TRANSPLANTATION IN PATIENTS WITH SCLERODERMA
Authors: Yuko Soyama, Marc Simon, Masataka Sugahara, Akiko Goda, Nobuyuki Kagiyama, Tetsuari Onishi, Norihisa Shigemura, John Gorcsan
Journal: Journal of the American College of Cardiology (2018)
Assessment and prognostic impact of a new classification using HER2 and HER3 status in resected gastric cancer in a european cohort.
Authors: Nieves Martinez Lago, Ihab Abdulkader, Dora Insua Santamaria, Patricia Viaño Nuñez, Juan Jose Carrera, Jose Ramón Antunez Lopez, Maria Elena Padin Iruegas, Rafael López López
Journal: Journal of Clinical Oncology (2018)

65 Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic gastric adenocarcinomas. However, relatively little is known about the role of HER2 and HER3 in the non-metastatic disease in European population. Methods: Immunohistochemical expression of HER2 was analyzed using DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both was scored according to published reports. HER3 expressión was analyzed using HER3 clon DAK-H3-ICHER3 and scored as follows: 0 = no staining, 1+ = light staining, 2+ = moderate staining, and 3+ = strong staining. Slides with score 0 or 1+ were classified as low expression or negative and slides with score 2-3+, as high expression or positive. According HER2 and HER3 status patients were classified into six subtypes: HER2-HER3 negative, HER2 equivocal expression HER3 negative, HER2 positive – HER3 negative, HER2 negative – HER3 positive, HER2 equivocal expression – HER3 positive and HER2-HER3 positive. The relationship between this classification and the clinicopathological characteristics and survival was analyzed retrospectively. Results: We included 106 patients between January 2007 and June 2014. The HER2 positivity was 13.2% and HER3 high expression was identified in 27.4% of patients. HER2 status was significantly associated with HER3 status (p = 0.018). HER2 equivocal or positive subtypes were associated with intestinal subtype (0.020) and HER2 or HER3 positive subtypes were associated with low histological grade (0.050). Our classification have demonstrated prognostic impact (p = 0.032) with a specific mortality rate due to gastric cancer of 45-50% for patients with equivocal or positive HER2 subtypes with HER3 low expression, 30% for patients with HER3 high expression independently of HER2 status, and 18% for patients HER2-HER3 negative. Conclusions: Our classification, using HER2 and HER3 status, stratifies patients into 6 subtypes with differentiated clinical and pathological characteristics and prognostic impact.
I am working as a locum doctor. Can I attend courses such as ALS, MRCS part 1, or ATLS before entering a rotation or a six months post? Where can I find details?
Authors: Montio Morgan
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Is chronic exposure to air pollutants a risk factor for the development of idiopathic pulmonary fibrosis?
Authors: Valérie Siroux, Bruno Crestani
Journal: European Respiratory Journal (2018)

The recent Lancet Commission on Pollution and Health emphasises the considerable health burden attributable to environmental pollution, including air, water, soil, heavy metal and chemical pollution, and occupational exposure [1]. All forms of pollution were responsible for an estimated 9 million deaths in 2015, and air pollution, including both household and ambient air pollution, was responsible for the largest part, with an estimate of 6.5 million deaths [1, 2]. In 2016, air pollution was among the first five risk factors in terms of attributable disability-adjusted life-years at the global level [3]. Noteworthy, these estimates are probably underestimates as they account for the well-established associations between air pollution and disease and do not include unknown or emerging, but still unquantified, health effects of air pollutants. For the first time, a role of air pollution in the development of idiopathic pulmonary fibrosis is suggested <http://ow.ly/EH2V30hBapf>