tbuckley/cabot-search huggingface dataset:
Management of Platinum-Resistant, Relapsed Epithelial Ovarian Cancer and New Drug Perspectives
Authors: Eric Pujade-Lauraine, Susana Banerjee, Sandro Pignata
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.19.00194 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403868 Management of Platinum-Resistant, Relapsed Epithelial Ovarian Cancer and New Drug Perspectives Eric Pujade-Lauraine, MD, PhD1xEric Pujade-LauraineSearch for articles by this author; Susana Banerjee, MA2xSusana BanerjeeSearch for articles by this author; and Sandro Pignata, MD, PhD3xSandro PignataSearch for articles by this author Show More 1ARCAGY-GINECO (Association de Recherche contre les Cancers dont Gynécologiques-Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire, gynécologiques et du sein), Paris, France2The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom3Istituto Nazionale Tumori Fondazione G Pascale, Istituto di Ricovero e Cura a Carattere Scientifico, Napoli, Italy https://doi.org/10.1200/JCO.19.00194 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Pathways of progression of head and neck carcinomas and premalignancies revealed by gene expression profiling.
Authors: Paul R. Harrison, Keith D. Hunter, Janis T. Fleming, Johanna K. Thurlow, Paul J H Drake, Keith J. Vass, Ken E. Parkinson, Gordon D. MacDonald, Des Higham, Gabriela Kalna
Journal: Cancer Research (2005)

217  Immortality is one of the recognised hallmarks of cancer. Head and neck cancers (HNSCCs) may be preceded by recognisable premalignancies, such as leukoplakias and erythroplakias, which have widely different progression rates. However, by current histopathology methods, it is impossible to predict prognosis of dysplasias in individual patients. To investigate the molecular changes associated with HNSCC progression, we have isolated cultures from biopsies of 20 HNSCCs and 20 dysplasias, as well as normal oral mucosa, using the feeder layer method of Rheinwald and colleagues. Although the majority of head and neck cancers (HNSCC) are immortal, a subset has a mortal phenotype in vivo (1-3) and generally these have a better prognosis. A minority of dysplasias are also immortal and this is consistently associated with specific molecular changes, for example loss of p16INK4A and retinoic acid receptor-beta expression, p53 mutations and activation of telomerase (4-6). Thus acquisition of immortality and invasiveness can be acquired independently. By gene expression profiling of HNSCC cultures followed by validation in biopsies by IHC, we have demonstrated that mortal HNSCCs express markers commonly associated with motility and invasion, as well as chemokines, whereas immortal HNSCCs have a greater tendency to recur and show elevated expression of cell cycle markers and loss of differentiation characteristics (recently reviewed in (7)). We have also identified an immortality gene expression signature common to immortal HNSCCs and dysplasias, some of which are p53-target genes. It also appears possible to identify gene expression patterns characteristic of cultured high risk dysplasias that may be precursors to the mortal and immortal HNSCC types. This could potentially be valuable diagnostically, if confirmed in larger in vivo prospective studies. 1. J. E. Burnset al., Br J Cancer 67, 1274 (1993). 2. K. G. Edington, O. P. Loughran, I. J. Berry, E. K. Parkinson, Mol Carcinog 13, 254 (1995). 3. K. E. Gordonet al., Cancer Res 63, 458 ( 2003). 4. F. McGregoret al., Cancer Res 57, 3886 (1997). 5. F. McGregoret al., Cancer Res 62, 4757 ( 2002). 6. A. Muntoniet al., Oncogene 22, 7804 ( 2003). 7. K. D. Hunter, E. K. Parkinson, P. R. Harrison, Nature Reviews Cancer , in press (February 2005).
Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE): a multicentre, randomised, parallel, single-blinded trial
Authors: Laura Koskenvuo, Taru Lehtonen, Selja Koskensalo, Suvi Rasilainen, Kai Klintrup, Anu Ehrlich, Tarja Pinta, Tom Scheinin, Ville Sallinen
Journal: The Lancet (2019)
Characterization of HPV-16 E7-specific cytotoxic T lymphocyte responses in HLA-A*0201 transgenic mice induced by DNA vaccines
Authors: Shiwen Peng, Chien-Fu Hung, Cornelia Trimble, Liangmei He, Ya-Chea Tsai, T.-C. Wu
Journal: Cancer Research (2004)

1286  Objective: Previously we have designed DNA vaccines against HPV-16 E7 using intracellular targeting strategies that enhance MHC class I presentation. These vaccines have demonstrated significantly enhanced potency, generating strong E7-specific CD8+ antitumor immunity. In this study, we attempted to characterize the cytotoxic T lymphocyte (CTL) responses induced by a DNA vaccine encoding calreticulin (CRT) linked to HPV-16 E7 in HLA-A2/AAD transgenic mice. Material and Methods: The HLA-A2/AAD gene was transduced into a HPV-16 E6 and E7-expressing tumor cell line, TC-1, to generate TC-1/AAD. HLA-A2/AAD transgenic mice on C57BL/6 background were immunized with pcDNA3-CRT/E7, pcDNA3-CRT/mtE7 (E7 with aa49-57 deletion), or control DNA via gene gun. Splenocytes from immunized mice were stimulated with E7 peptides to identify E7-specific immune responses using IFN-r intracellular staining. Antitumor effect was tested by TC-1/AAD. Results: The H-2Db-restricted E7 aa49-57 epitope suppressed the presentation of HLA-A2-restricted epitopes, since the CD8+ T cell immune response induced by CRT/E7 in HLA-A2/AAD transgenic mice is E7 aa49-57 dominant. However, only an HLA-A2-restricted E7 aa11-20 dominant immune response was observed when E7 aa49-57 was removed. This HLA-A2-restricted E7 aa11-20 specific immune response prevented TC-1/AAD growth in the HLA-A2/AAD transgenic mice. Conclusions: In this study, an HPV-16 E6 and E7 expressing HLA-A2 mouse tumor model was established to test HPV-16 E7 DNA vaccines. In HLA-A2/AAD transgenic mice, H-2Db-restricted E7 aa49-57 epitope suppressed the presentation of E7 HLA-A2 epitopes. Removal of this H-2Db-restricted epitope generated an HLA-A2-restricted E7 aa11-20 dominant immune response. This immune response was able to prevent E7-expressing HLA-A2 tumor growth. Relevance of this study to the design of HPV-16 E7 vaccine was discussed.
Fabrication Techniques for Vascular and Vascularized Tissue Engineering
Authors: Ziyu Wang, Suzanne M. Mithieux, Anthony S. Weiss
Journal: Advanced Healthcare Materials (2019)

Impaired or damaged blood vessels can occur at all levels in the hierarchy of vascular systems from large vasculatures such as arteries and veins to meso- and microvasculatures such as arterioles, venules, and capillary networks. Vascular tissue engineering has become a promising approach for fabricating small-diameter vascular grafts for occlusive arteries. Vascularized tissue engineering aims to fabricate meso- and microvasculatures for the prevascularization of engineered tissues and organs. The ideal small-diameter vascular graft is biocompatible, bridgeable, and mechanically robust to maintain patency while promoting tissue remodeling. The desirable fabricated meso- and microvasculatures should rapidly integrate with the host blood vessels and allow nutrient and waste exchange throughout the construct after implantation. A number of techniques used, including engineering-based and cell-based approaches, to fabricate these synthetic vasculatures are herein explored, as well as the techniques developed to fabricate hierarchical structures that comprise multiple levels of vasculature.
Perceived Bullying Among Internal Medicine Residents
Authors: Manasa S. Ayyala, Rebeca Rios, Scott M. Wright
Journal: JAMA (2019)

Lindsey M. Zhang, MD, MS; Ryan J. Ellis, MD, MS; Meixi Ma, MD, MS; Elaine O. Cheung, PhD; David B. Hoyt, MD; Karl Y. Bilimoria, MD, MS; Yue-Yung Hu, MD, MPH
An enhanced genetic model of colorectal cancer progression history
Authors: Lixing Yang, Su Wang, Jake June-Koo Lee, Semin Lee, Eunjung Lee, Eve Shinbrot, David A. Wheeler, Raju Kucherlapati, Peter J. Park
Journal: Genome biology (2019)

The classical genetic model of colorectal cancer presents APC mutations as the earliest genomic alterations, followed by KRAS and TP53 mutations. However, the timing and relative order of clonal expansion and other types of genomic alterations, such as genomic rearrangements, are still unclear.Here, we perform comprehensive bioinformatic analysis to dissect the relative timing of somatic genetic alterations in 63 colorectal cancers with whole-genome sequencing data. Utilizing allele fractions of somatic single nucleotide variants as molecular clocks while accounting for the presence of copy number changes and structural alterations, we identify key events in the evolution of colorectal tumors. We find that driver point mutations, gene fusions, and arm-level copy losses typically arise early in tumorigenesis; different mechanisms act on distinct genomic regions to drive DNA copy changes; and chromothripsis-clustered rearrangements previously thought to occur as a single catastrophic event-is frequent and may occur multiple times independently in the same tumor through different mechanisms. Furthermore, our computational approach reveals that, in contrast to recent studies, selection is often present on subclones and that multiple evolutionary models can operate in a single tumor at different stages.Combining these results, we present a refined tumor progression model which significantly expands our understanding of the tumorigenic process of human colorectal cancer.
Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in <i>EGFR</i>-Mutated Lung Cancer
Authors: Vanita Noronha, Vijay Maruti Patil, Amit Joshi, Nandini Menon, Anuradha Chougule, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Rajiv Kumar, Sucheta More, Supriya Goud, Nandkumar Kadam, Nilesh Daware, Atanu Bhattacharjee, Srushti Shah, Akanksha Yadav, Vaishakhi Trivedi, Vichitra Behel, Amit Dutt, Shripad Dinanath Banavali, Kumar Prabhash
Journal: Journal of Clinical Oncology (2019)

Standard first-line therapy for EGFR-mutant advanced non-small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)-directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes.This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity.Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively (P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively (P < .001).Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.
Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis
Authors: Scott J Antonia, Hossein Borghaei, Suresh S Ramalingam, Leora Horn, Javier De Castro Carpeño, Adam Pluzanski, Marco A Burgio, Marina Garassino, Laura Q M Chow, Scott Gettinger, Lucio Crinò, David Planchard, Charles Butts, Alexander Drilon, Joanna Wojcik-Tomaszewska, Gregory A Otterson, Shruti Agrawal, Ang Li, John R Penrod, Julie Brahmer
Journal: The Lancet Oncology (2019)
Hdmx-mediated antagonism of p53-dependent cell death
Authors: Mark Wade, Federico Bernal, EeTsin Wong, Jayne Stommel, Mengjia Tang, Gregory Verdine, Geoffrey Wahl
Journal: Cancer Research (2007)

2533  The tumor suppressor p53 is wild type in many human cancers, providing a putative Achille9s heel upon which to develop new therapeutic drugs. Current models indicate that wild type p53 activity in tumors can be suppressed by overexpression of hdm2, and the closely related hdmx protein. These proteins bind to p53 and control its stability and transcriptional activation function. A prevailing view is that hdm2 mainly controls p53 via its ubiquitin ligase activity, while hdmx, which lacks ubiquitin ligase function limits p53-dependent transactivation. A major research focus directed towards p53 reactivation in cancer has been the development of antagonists of the hdm2/p53 interaction. One such antagonist is the hdm2-binding compound, Nutlin, which stabilizes p53 and unleashes its transcriptional program to induce cell cycle arrest or apoptosis. Despite the homology between hdm2 and hdmx, here we present data demonstrating that Nutlin does not antagonize the hdmx/p53 interaction. We show that Nutlin can also induce degradation of hdmx, although this can be attenuated in some tumor cell lines. We and others have demonstrated that high levels of hdmx are associated with resistance to Nutlin, suggesting that hdmx antagonists may provide an additional chemotherapeutic strategy. Finally, we present data obtained using a novel p53-activating compound that appears to target both the hdm2/p53 and hdmx/p53 interaction.
Investigating the effect of AQP1 on growth and migration of glioblastoma multiforme cell lines
Authors: Ezra Mirvish, Anjan Misra, Janice Nigro, Ivan Smirnov, Leon Kapp, Michael Berens, Burt Feuerstein
Journal: Cancer Research (2007)

1365  Glioblastoma Multiformae (GBM), the highest grade (IV) of astrocytic tumor, is a lethal disease with median survival time of around one year, despite aggressive combinations of tumor resection, radiotherapy, and adjuvant chemotherapy. We used high-throughput DNA and expression microarrays to identify three genetic subgroups - mesenchymal, proliferative, and proneural - that correspond to survival (Phillips H. S., et al. Cancer Cell 9(3): 157-173 (2006); Nigro, J. M., et al. Cancer Res 65(5): 1678-1686 (2005)). The analysis yielded several genes overexpressed in GBM patients with poor survival. The water channel Aquaporin1 (AQP1) is one such gene. AQP1 is believed to increase cellular motility and may contribute to the infiltrativeness of these tumors. To study the biological effects of AQP1 overexpression in GBM, we have developed a stable GBM cell line that constitutively overexpresses AQP1, as verified by Real-Time, Quantitative Reverse Transcriptase PCR (qRT-PCR) and Western blotting. Our experiments suggest that the overexpression does not affect cell growth. We are now characterizing the effect(s) of AQP1 over-expression on cell survival, cell cycle distribution, apoptosis rate, migration and invasion, and genomic instability in this model system.  Supported by the NIH (NS42927 and CA85799), National Brain Tumor Foundation, the Barrow Neurological Foundation, and the Brain Tumor Resource and Information Network
Consultant who oversaw FGM guidelines is struck off for possessing extreme pornography
Authors: Clare Dyer
Journal: BMJ (2019)

A consultant obstetrician who was responsible for guidelines on treating victims of female genital mutilation (FGM) has been struck off the UK medical register over the possession of extreme pornographic images.

Manish Gupta, who was an obstetrician and gynaecologist at Whipps Cross University Hospital in London, was convicted at Snaresbrook Crown Court last October of possessing pornographic images and video that show acts that were “likely to result in serious injury to anus/breasts/genitals.”

He was also found guilty of possessing one image showing an act of “intercourse/oral sex with a dead/live animal” and 14 prohibited images of children. These showed cartoon animated children, a lesser offence than possessing pornographic images of …
Is Fluoride Potentially Neurotoxic?
Authors: David C. Bellinger
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life
Authors: Amy B Wisniewski, Rafael L Batista, Elaine M F Costa, Courtney Finlayson, Maria Helena Palma Sircili, Francisco Tibor Dénes, Sorahia Domenice, Berenice B Mendonca
Journal: Endocrine Reviews (2019)

Abstract Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual’s sex chromosomes, gonads, and/or anatomic sex. Advances in the clinical care of patients and families affected by 46,XY DSD have been achieved since publication of the original Consensus meeting in 2006. The aims of this paper are to review what is known about morbidity and mortality, diagnostic tools and timing, sex of rearing, endocrine and surgical treatment, fertility and sexual function, and quality of life in people with 46,XY DSD. The role for interdisciplinary health care teams, importance of establishing a molecular diagnosis, and need for research collaborations using patient registries to better understand long-term outcomes of specific medical and surgical interventions are acknowledged and accepted. Topics that require further study include prevalence and incidence, understanding morbidity and mortality as these relate to specific etiologies underlying 46,XY DSD, appropriate and optimal options for genitoplasty, long-term quality of life, sexual function, involvement with intimate partners, and optimizing fertility potential.
Pizza Leavening Technique Influences Postprandial Glucose Response: A Randomized Controlled Trial in Patients With Type 1 Diabetes
Authors: Luisa Cavagnuolo, Lutgarda Bozzetto, Luca Franco, Giuseppina Costabile, Gabriele Riccardi, Angela Albarosa Rivellese, Giovanni Annuzzi
Journal: Diabetes Care (2019)

Achieving optimal postprandial glucose control remains a major issue in people with type 1 diabetes (T1D), including those using innovative technologies (1,2). Eating pizza is challenging for patients with T1D (3) because of its high and extremely variable glycemic index (4) and prolonged postprandial hyperglycemia. Bread leavened by sourdough instead of brewer’s yeast may reduce postprandial glucose response (PGR), and duration of sourdough leavening could play a beneficial role (5). Whether this holds true for pizza and in patients with T1D is unknown.

We compared PGR for pizzas differing in type and duration of dough leavening in 16 T1D patients (9 men, 7 women) on an insulin pump. The study was approved by the institutional ethics committee (reg. no. NCT03619031, ClinicalTrials.gov). According to a randomized crossover design, participants consumed—at home, on three nonconsecutive evenings over 3 weeks—a pizza prepared with 1 ) brewer’s yeast and wheat flour, 5-h leavening (usual leavening time) (Brew5); 2 ) sourdough and flour mix, 5-h leavening (Sour5); or 3 ) sourdough and flour mix, 60-h leavening (Sour60). Premeal insulin doses, calculated by the individual insulin–to–glycemic load ratio (2) (the same for each participant on the three occasions, range 6–14 IU) were given as an 80/20% dual-wave bolus extended for 4 h. PGR was evaluated by the real-time continuous glucose monitoring system (Dexcom, Guardian, or Freestyle) used by …