tbuckley/cabot-search huggingface dataset:
PP83. AN INVESTIGATION INTO THE EVOLUTION OF RACIALLY BIASED DISEASES- GLIOMA, USING A DROSOPHILA MODEL
Authors: Mr Ben Treadwell, Mr Peter Abel, Prof Jaipaul Singh
Journal: Neuro-Oncology (2017)

Glioma is a major form of brain cancer throughout the world and studies have shown that the cases and survival rates of brain cancer differ depending on a person’s race. The only major genetic difference between races is a small amount of DNA bases; single nucleotide polymorphisms (SNP). This is due to little within-species genomic diversity. A predisposition to glioma is neurofibromatosis type 2 (NF2) shown as tumour growth along the spine and brain stem. NF2 encodes one protein, merlin. Merlin has many roles within the cell at both the membrane and nucleus. At the membrane merlin traffics molecules into and out of the cell and regulates many downstream pathways that are associated with cancer development. In the membrane: merlin stabilises the genome, has an impact in cell-cycle regulation and has an influence. Therefore a change in merlin’s function alters the cell, producing many hallmarks of cancer. Glioma and NF2 are both familial, inherited diseases that can pass down and be passed down from parent to offspring. Much research on merlin studies the mutations and potential epigenetic causes of merlin deregulation. Despite this, no study has focused on the inheritance of merlin in relation to its inheritance pattern i.e. Mendelian inheritance. By studying merlin, one can better understand cancer development. Thus by studying the inheritance pattern on merlin, one can deduce the inheritance of familial cancer and the racial bias of brain cancer, confirming merlin’s genetic or epigenetic origin. NF2 is an autosomal-dominant condition, however the inheritance pattern of brain tumour may not correlate to this. So by studying the inheritance pattern of merlin in a human model and studying the DNA methylation of the gene NF2; this could answer the current argument of whether mutant merlin or merlin’s expression patterns cause the phenotype of NF2 and glioma, evidence is available for both. Recent publications have shown that merlin may be a useful biomarker in glioma therapeutics. The aim of this research is to study the inheritance pattern of merlin in human races using a Drosophila model. Firstly, the aim is to examine the inheritance pattern of merlin in Drosophila. Secondly, to examine the inheritance pattern to deduce whether the inheritance/gene mutation is responsible for NF2 or whether epigenetics is the main cause. Studying the inheritance pattern would aid a conclusion of whether mutations of merlin or epigenetic changes to merlin lead to the phenotype of NF2 and glioma.
Abstract B26: A novel applicator for endoscopic gene electrotransfer
Authors: Arya J. Bahrami, Richard J. Connolly, Jean S. Campbell, Robert H. Pierce
Journal: Cancer Research (2017)

Abstract Intratumoral gene delivery is a novel immunotherapy showing promise in cutaneous cancers such as melanoma. However, the broad application of this technology is limited by delivery efficiency and tumor accessibility. Efficient gene delivery requires intimate association of DNA and cells and a coincident electric field. Due to the low diffusion of plasmid DNA combined with the single bolus injection provided by a standard syringe, conventional electrogene transfer yields a small volume of transfected tissue. Our novel use of a corkscrew delivery needle provides the dual benefit of increased DNA-tissue interface and anchoring of the device necessary for endoscopic use. This device has yielded efficient and repeatable delivery of cytokine-encoding plasmid DNA and reporter genes in several tumor models including spontaneous mammary carcinomas (MMTV-PyVT) as well as syngeneic tumor models. Anchoring associated with the action of corkscrew deployment ensures co-localization of the electric field with the injected tissue volume. The small form factor of this device makes it compatible with standard medical devices, including trocars, endoscopes and other catheter based devices, enabling intratumoral gene immunotherapy of previously inaccessible cancers, including breast cancer, lung cancer, and hepatocellular carcinoma. Citation Format: Arya J. Bahrami, Richard J. Connolly, Jean S. Campbell, Robert H. Pierce. A novel applicator for endoscopic gene electrotransfer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B26.
CD4+ Regulatory T Cells Specific for the WT1 Antigen Are Present in Acute Myeloid Leukemia Patients: Implication for Immunotherapy.
Authors: Said Dermime, Cynthia Lehe, Hazem Ghebeh, Abdullah Al-Sulaiman, Ghofran Al Qudaihi, Khaled Al-Hussein, Fahad Almohareb, Naeem A. Chaudhri, Fahad Z. Alsharif, Hazza Al-Zahrani, Said Y Mohamed, Abdelghani Tbakhi, Mahmoud Aljurf
Journal: Blood (2008)
Hospitals and medical staff are targeted in Syria, as UN report blames regime forces
Authors: Owen Dyer
Journal: BMJ (2017)

In a damning report of the war in Syria, UN investigators have accused Syrian regime forces of systematically destroying hospitals and of deliberately targeting a UN and Red Crescent convoy that was bombed from the air last September, killing at least 14 aid workers and sparking international outrage.

“For months, the Syrian and Russian air forces relentlessly bombarded eastern Aleppo city as part of a strategy to force surrender,” said the UN commission’s chairman, Paulo Pinheiro, announcing its findings on Wednesday. “The deliberate targeting of civilians has resulted in the immense loss of human life, including hundreds of children.”

During the city’s recapture, Syrian government forces arrested doctors and aid workers and committed reprisal executions, the investigators found.

The Independent International Commission of Inquiry on the Syrian Arab Republic also accused Syrian forces of systematically destroying hospitals.1 Russian aircraft, too, had repeatedly targeted hospitals, water distribution stations, markets, and bakeries with indiscriminate weapons, completely obliterating …
Abstract P6-09-49: Three-gene signature predictive of high residual risk of recurrence after adjuvant chemotherapy in ER-positive HER2-negative breast cancer
Authors: B Györffy, A Ocana, P Herman, C Hatzis, A Pandiella, L Pusztai
Journal: Cancer Research (2017)

Abstract Background: A proportion of ER-positive, HER2-negative patients treated with both adjuvant endocrine and chemotherapy continue to remain high risk for recurrence. These individuals are the ideal patient population for future adjuvant trials. Methods: We used gene expression data from ER+/HER2- patients who received adjuvant endocrine and chemotherapy. We utilized a training cohort of multiple gene expression datasets (N=131; GSE16391, GSE21653, GSE17907, GSE19615, GSE16716, GSE45255) and a validation cohort (N=277; GSE25066) from similarly treated ER+ patients. All data sets were generated with Affymetrix HGU133 arrays. Cox proportional hazards regression was performed across all genes using all possible cutoff values between the lower and upper quartile. Genes were ranked according to the estimated hazard rates for relapse. The top three genes were combined into a final signature that used the mean expression of these genes as the predictive score. Statistical analyses were performed in the R environment. Results: The final signature capable to predict survival consisted of three genes, MX1, MBD4, and ZWINT. Each of these genes achieved high significance in a univariate analysis: MX1 HR=5.7 (p=1.8E-04) and HR=4.7 (p=1.3E-03), MBD4 HR=3.4 (p=2.8E-04) and HR=4.3 (p=4.4E-04), and ZWINT HR=4.4 (p=1E-03) and HR=3.7 (p=8.5E-03) in the training and validation cohorts, respectively. Using the mean expression of the three genes, the estimated hazard rates for survival were 20.5 (p=2.5E-05) and 17.5 (p=1E-04) in the two cohorts, respectively. Only one patient relapsed in each cohort. In a multivariate analysis including grade and lymph node status as covariates (size was not available), the three-gene signature retained significance (HR=13.2, p=0.011; and HR=13.9, p=0.01 in the two cohorts, respectively), while only lymph node status (HR=3.6, p=0.007) was significant in the validation cohort and no clinical variable was significant in the training cohort. Conclusions: High expression of a 3-gene signature can identify ER+ patients who remain at very high risk for recurrence despite current adjuvant endocrine and chemotherapy. Citation Format: Györffy B, Ocana A, Herman P, Hatzis C, Pandiella A, Pusztai L. Three-gene signature predictive of high residual risk of recurrence after adjuvant chemotherapy in ER-positive HER2-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-49.
New concepts in the management of restless legs syndrome
Authors: Diego Garcia-Borreguero, Irene Cano-Pumarega
Journal: BMJ (2017)

Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED) is a neurological condition with an overall prevalence in adults of 5-10% in Europe and North America. It is characterised by strong feelings of restlessness and distressing paraesthesia-like sensations in the lower legs, particularly when at rest. The symptoms vary considerably in severity and frequency. RLS/WED has a variable clinical expression influenced by genetic, environmental, and medical factors. Research into the pathophysiology of RLS/WED has found that various genetic markers and existing dysfunctions in dopaminergic mechanisms and iron mechanisms play a central role. Until recently, the first line treatment of RLS/WED was with low dose dopamine agonists, with three drugs having been approved by the US Food and Drug Administration and the European Medicines Agency. However, the occurrence of dopaminergic augmentation and an overall increase in severity of symptoms during long term treatment with dopamine agonists is leading to a shift towards non-dopaminergic alternatives as initial treatments, and particularly to α<sub>2</sub>δ ligands. Recent international guidelines recommend, whenever possible, to start treatment with these drugs (α<sub>2</sub>δ ligands) to avoid augmentation from the start. Other (eg, glutamatergic or adenosine) neurotransmitters might also play an important role in causing RLS/WED and might thus lead to new treatments.
Dietary guidelines should encourage a healthy planet
Authors: Anne Gulland
Journal: BMJ (2017)

Government guidelines on healthy eating should recommend a plant based diet to reduce the impact of food production on the planet as well as improve health, campaigners have urged.

In a joint briefing paper the global health charity Medact and civil society alliance Eating Better called on policy makers and health professionals to recommend diets that underline the importance of reducing consumption of meat and dairy.1

The briefing emphasised the large contribution that food production makes to climate change through greenhouse gas emissions and its impact …
Comparison of Male vs Female Resident Milestone Evaluations by Faculty During Emergency Medicine Residency Training
Authors: Arjun Dayal, Daniel M. O’Connor, Usama Qadri, Vineet M. Arora
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> Although implicit bias in medical training has long been suspected, it has been difficult to study using objective measures, and the influence of sex and gender in the evaluation of medical trainees is unknown. The emergency medicine (EM) milestones provide a standardized framework for longitudinal resident assessment, allowing for analysis of resident performance across all years and programs at a scope and level of detail never previously possible. <h3>Objective</h3> To compare faculty-observed training milestone attainment of male vs female residency training <h3>Design, Setting, and Participants</h3> This multicenter, longitudinal, retrospective cohort study took place at 8 community and academic EM training programs across the United States from July 1, 2013, to July 1, 2015, using a real-time, mobile-based, direct-observation evaluation tool. The study examined 33 456 direct-observation subcompetency evaluations of 359 EM residents by 285 faculty members. <h3>Main Outcomes and Measures</h3> Milestone attainment for male and female EM residents as observed by male and female faculty throughout residency and analyzed using multilevel mixed-effects linear regression modeling. <h3>Results</h3> A total of 33 456 direct-observation evaluations were collected from 359 EM residents (237 men [66.0%] and 122 women [34.0%]) by 285 faculty members (194 men [68.1%] and 91 women [31.9%]) during the study period. Female and male residents achieved similar milestone levels during the first year of residency. However, the rate of milestone attainment was 12.7% (0.07 levels per year) higher for male residents through all of residency (95% CI, 0.04-0.09). By graduation, men scored approximately 0.15 milestone levels higher than women, which is equivalent to 3 to 4 months of additional training, given that the average resident gains approximately 0.52 levels per year using our model (95% CI, 0.49-0.54). No statistically significant differences in scores were found based on faculty evaluator gender (effect size difference, 0.02 milestone levels; 95% CI for males, −0.09 to 0.11) or evaluator-evaluatee gender pairing (effect size difference, −0.02 milestone levels; 95% CI for interaction, −0.05 to 0.01). <h3>Conclusions and Relevance</h3> Although male and female residents receive similar evaluations at the beginning of residency, the rate of milestone attainment throughout training was higher for male than female residents across all EM subcompetencies, leading to a gender gap in evaluations that continues until graduation. Faculty should be cognizant of possible gender bias when evaluating medical trainees.
Abstract P3-13-21: Primary surgery in inflammatory breast cancer
Authors: M Muzaffar, N Vohra, J Wong
Journal: Cancer Research (2017)

Abstract Background: Inflammatory Breast Cancer (IBC) is a rare but very aggressive variant of breast cancer accounting for around 1-5% of all breast cancer cases. Current standard of care is multimodality therapy with preoperative chemotherapy followed by modified radical mastectomy and adjuvant radiotherapy. Method and Material: We searched the Surveillance Epidemiology and End results Registry to identify female patients diagnosed with Stage III IBC between 1988-2013.We performed descriptive and univariate analyses of the patients with IBC. Variables assessed included patient age, race/ethnicity, histologic subtype, tumor grade, hormone receptor status, surgery type. Results: We identified 11604 women with IBC from SEER database diagnosed between 1988-2013.The median age was 57 yrs., 80 % ( 9273) of patients were white,14.4 % ( 1667) blacks, and around 73% had nodal involvement. 32.4 % (3756) patients were diagnosed with IBC between 1988-2000, while 67.6 % ( 7848) between 2001-2013.We excluded patients with missing primary surgery information with 7586 patients remaining for analysis. The median age in this final cohort was 56yrs, 80.4 % ( 6097) patients were white, and 13.7 % (1044) were black. The predominant tumor type was invasive ductal carcinoma, majority of the patients had grade 3 tumor 59.4 % ( 4504), grade2 in 23.2 % ( 1757),47.1% were estrogen receptor (ER)positive,43% were ER negative,53% were progesterone receptor negative, and 7% had HER 2 positive tumor. In this cohort 6.4 % (487) patients underwent partial mastectomy and 93.6 % (7099) underwent mastectomy. In the cohort undergoing breast conservation, 15% were during 1988-2000 and 84.4% during years 2001-2013 (p value=0.06). Surgery in non-metastatic inflammatory Breast CancerType of Surgery1988-20002001-2013p-valuePartial Mastectomy76 (6.7%)1140(93.3%)0.06Mastectomy411 (6.9%)5959(93.1%) The median survival was 46 months among patients diagnosed between 1988-2000 and 61 months for 2001-2013 time period(p&amp;lt;0.0001).The median survival in patients undergoing partial mastectomy was 42 months versus 48 months among patients undergoing mastectomy (p=0.0001). Discussion: IBC continues to be an aggressive breast cancer subtype, but survival has improved over last decade. The utility of partial mastectomy has increased in the last decade compared to 1988-2000. Mastectomy still remains the standard surgical option, but with more effective systemic therapeutic agents, better tumor responses are noted especially in Her 2 positive and triple negative IBC. Partial Mastectomy may be a viable option for patients achieving complete clinical response. Citation Format: Muzaffar M, Vohra N, Wong J. Primary surgery in inflammatory breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-21.
Impact of aggressive combined-modality primary therapy in anaplastic thyroid carcinoma (ATC): An updated single-institution experience.
Authors: Naiyarat Prasongsook, Robert Leonard Foote, Julian R. Molina, Jan C. Kasperbauer, Yolanda I. Garces, Daniel Ma, Joseph Rubin, Ronald L. Richardson, Ian D. Hay, Vahab Fatourechi, Bryan McIver, John C. Morris, Geoffrey B. Thompson, Clive S. Grant, Melanie L. Richards, Vera J. Suman, Keith Christopher Bible
Journal: Journal of Clinical Oncology (2014)

e17042 Background: Historical outcomes in ATC have been highly discouraging. However, in response to aggressive first-line therapy combining intensity modulated radiation therapy (IMRT) and multiagent chemotherapy, we had previously observed apparently improved outcomes; we now update our experience. Methods: From January 1, 2003 to January 31, 2013 all newly diagnosed ATC patients seen at Mayo Clinic Rochester were offered aggressive therapy, individualized based upon patient conditions and preferences. Of 40 treated patients, 9 (22.5%), 20 (50%), and 11 (27.5%) had stage IVA, IVB, or IVC ATC respectively. Mean age was 66 years (range, 37-89); half were women. Twenty three patients underwent primary surgery [8 IVA (88.8%), 14 IVB (70%) and 1 IVC (9%)]. Complete (R0) resection was achieved in only 2 IVA (22.2%) and 3 IVB (15%) patients. Twenty-six patients (65%) received definitive intention chemo-radiation therapy: 8 IVA, 17 IVB, and 1 IVC, most receiving doxorubicin + docetaxel + IMRT. Results: Kaplan-Meier median and 1-year overall survival (OS) for the 40 patients combined were 10.1 months (95% CI: 3.9-55) and 48% - compared to 3 months and 20% observed among 134 analogous patients treated at our center over a preceding 50 year period. Median survival for stages IVA, IVB and IVC patients were 61.5 (95% CI: 55-67.9), 5.1 (95% CI: 3.5-22.1), and 2.8 months (95% CI: 0.8-29.6) respectively (p<0.001). One year OS was 100, 33 and 34% for stage IVA, IVB and IVC patients respectively. For IVA patients, Kaplan-Meier survival was 100% at 4 years. There were no treatment-related deaths. Stage at diagnosis, total doses and number of fractions of radiation therapy administered, and response to treatment were each significantly positively associated with OS by univariate analysis. Conclusions: Concordant with a practice change offering more aggressive combined-modality therapy, we observed improved outcomes in ATC. Further multi-center, randomized controlled trials are needed to define optimal treatments for this rare cancer, but continued efforts to pursue aggressive primary combined-modality therapeutic approaches in ATC appear justified.
Abstract P1-01-17: Establishment and preliminary clinical application of breast cancer CTC detection kit based on immune magnetic lipid microsphere/human breast mammaglobin
Authors: B Yang, J Wu, X Liang, S Mei, B Zhou
Journal: Cancer Research (2017)

Abstract Objective To explore the effect of breast cancer CTC detection kit based on immune magnetic lipid microsphere (IML) separation and human breast mammaglobin (hMAN) identification, we combined epithelial cell adhesion molecule (EpCAM) IML enrichment and immune fluorescence staining of CK/hMAN (IML/hM-BCD) method. Methods 74 patients with metastatic breast cancer (MBC) were selected to validate the performance of our integrated CTC capture platform by carrying out side-by-side comparisons with the Cellsearch assay using the same sample. In each study, 15 mL blood was divided equally to identify CTC numbers by employing either Cellsearch and our platform. Results In MBC patients, the rates of diagnostic positive detection of Cellsearch and IML/hM-BCD method were 50% and 83.4%, respectively. The IML/hM-BCD method presented a greater ability to capture CTCs from MBC patients. A significant difference in the number (1~5) of CTCs captured by IMLM was observed in the images (2-fold more for IMLM vs CellsearchTM, P&amp;lt;0.001). Furthermore, the morphology and footprint sizes of the cells detected by IML/hM-BCD method offer another approach to validating these observations from the perspectives of cell pathology and cytology. The combined information was utilized to delineate CTCs (DAPI+/CK+/CD45-, cell size &amp;gt; 5 µm) from WBCs (DAPI+/CK-/CD45+, cell size &amp;lt; 15 µm) and cellular debris. Our immunomagnetic lipid microsphere captured significantly different CTC numbers that corresponded to the patients' clinical data. Conclusions The panel of IML separation and combined CK/hMAN identification may serve as representative enrichment and biomarkers for CTCs, thus it presents potentially significant valve for monitoring early metastasis, therapeutic efficacy and prognosis for the patients with breast cancer. Citation Format: Yang B, Wu J, Liang X, Mei S, Zhou B. Establishment and preliminary clinical application of breast cancer CTC detection kit based on immune magnetic lipid microsphere/human breast mammaglobin [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-17.
Abstract P5-16-01: A randomised phase III trial comparing two dose-dense, dose-intensified approaches (ETC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto)
Authors: A Schneeweiss, V Möbus, H Tesch, C Hanusch, C Denkert, K Lübbe, J Huober, P Klare, S Kümmel, M Untch, K Kast, C Jackisch, B Ingold-Heppner, J Thomalla, J-U Blohmer, M Rezai, V Nekljudova, G von Minckwitz, S Loibl
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.