tbuckley/cabot-search huggingface dataset:
Determinants of non-adherence to adjuvant endocrine treatment in early stage breast cancer patients: A Swedish population-based registry linkage study.
Authors: Wahyu Wulaningsih, Hans Garmo, Johan Ahlgren, Mieke Van Hemelrijck, Mats Lambe
Journal: Journal of Clinical Oncology (2016)

535 Background: Non-adherence to adjuvant endocrine treatment (ET) among breast cancer patients has been associated with worse prognosis. We sought to identify factors affecting non-adherence to ET, taking into account determinants at baseline and follow-up. Methods: From linkage between Swedish national registers, we identified all women diagnosed with stage I-III, ER-positive breast cancer in Stockholm-Gotland, Uppsala-Örebro and Northern Sweden between 2006 and 2009. A total of 4,413 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up were included in the analysis. A medical possession ratio (MPR) of < 80% was used to define non-adherents. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence to ET. Results: During follow-up, 1,131 (25.6%) women became non-adherents. The following determinants of non-adherence were identified: age, marital status, region of diagnosis, private hospital, tumour size, lymph node metastasis, tumour grade, HER2 status, type of surgery, adjuvant chemotherapy, type of ET, pre-diagnostic hormone replacement therapy, the use of symptom-relieving drugs at baseline and during follow-up, baseline scores and any increase in Charlson co-morbidity index (CCI). In multivariable analysis, non-adherence was only associated with younger age (OR: 0.67; 95%CI: 0.50-0.90 and 0.66; 0.48-0.92 for age 50-65 and 65+ compared to < 50, respectively), marital status (OR: 1.40; 95%CI: 1.23-1.60 for single/divorced/widowed compared to married women), socioeconomic status (OR: 1.17; 95%CI: 1.00-1.37 and 1.60; 1.16-2.21 for white collar and being unemployed compared to blue collar workers, respectively), and pre-diagnostic use of hormone replacement therapy (OR: 1.57; 95%CI: 1.28-1.93). Conclusions: Our study identifies socioeconomic subgroups with increased risk of non-adherence that may be of use when measures for improving adherence are tested. Women with pre-diagnostic use of HRT may represent a biological subset with a disposition for side effects from ET.
In vitro organotypic co-culture model for the study of bronchial epithelial clonal outgrowth during multistep lung tumorigenesis.
Authors: Keith Knutson, Jason Lukas, Bond Almand, Yushe Dang, Mary L. Disis
Journal: Cancer Research (2004)

2359   Chromosome in situ hybridization and molecular genetic analyses of bronchial biopsies of current and former smokers have demonstrated ongoing genetic instability and the presence of clonal and subclonal bronchial cell outgrowths. To better understand the cellular and molecular bases of genetic progression and preferential outgrowth by more advanced clonal epithelial populations, an organotypic co-culture model was established whereby normal human bronchial epithelial cells (NHBE) were allowed to compete for the growth surface with either premalignant, Ad12/SV40-immortalized bronchial epithelial cells (BEAS 2B) or tumorigenic 1170I cells (derived from BEAS 2B cells). To distinguish the competing cell populations, stable fluorescent populations of BEAS 2B and 1170I cells were established by transfection with GFP or YFP vectors. NHBE cells were first plated onto Transwell-clear culture filter inserts, allowed to reach confluence, and an air-liquid interface created. The center of the filter was then scraped free of NHBE cells, BEAS 2B or 1170I cells were plated onto the center, and the competing populations were monitored over time for their ability to proliferate and spatially expand. Proliferative patterns in the interacting populations were quantified spatially using BrdU, Ki67, phospho-Histone H3, and DNA staining followed by laser scanning cytometry, computer-assisted fluorescence microscopy/image analysis, and laser scanning confocal microscopy. When wounded and cultured alone, NHBE cells rapidly migrated, proliferated, filled the wound, and resumed a basal proliferation status. When NHBE and 1170I cells were co-cultured, both populations expanded rapidly and proliferated to fill the wound space. At contact, the NHBE population ceased proliferation (labeling indices of 2-5%), and the 1170I cells migrated around the interface boundary and continued to proliferate (labeling indices of 30-50%). Confocal laser microscopy demonstrated that proliferation occurred only at the basal layer in the multiplayer NHBE populations whereas proliferation occurred throughout the multilayers of the BEAS 2B and 1170I cell populations (accompanied by apoptosis). Over 20% of the anaphase cells of the BEAS 2B and 1170I cell populations showed evidence of ongoing genetic instability in the form of lagging chromosomes and chromosome bridges at anaphase whereas such events were rare (0.7%) in the co-cultured NHBE cells. These studies suggest that NHBE, immortalized, and tumorigenic bronchial epithelial cells retain distinct growth patterns in organotypic co-culture that mimic patterns observed in bronchial biopsies of current and former smokers. This model should prove useful for examining the molecular basis for genetic instability and preferential clonal outgrowth in the bronchial epithelium. Supported in part by DAMD17-02-1-0706, CA-68437, and CA70907.
Place de l'exérèse transanale par microchirurgie endoscopique (tem) dans le traitement des tumeurs du rectum. A propos de 200 Patients
Authors: F Bretagnol, A Merrie, I Lindsey, B George, B Warren, N Mortensen
Journal: Endoscopy (2006)

L'exérèse transanale par microchirurgie endoscopique (TEM) permet l'excision locale complète et monobloc des tumeurs du moyen et haut rectum. Elle a été proposée comme une alternative à l'exérèse locale conventionnelle ou à la résection antérieure pour les tumeurs bénignes mais sa place dans le traitement à visée curative des lésions malignes reste controversée. Le but était d'évaluer la morbidité et les résultats à long terme de la TEM pour le traitement des lésions bénignes et malignes du rectum.
Elevation of TP53 Autoantibody Before CA125 in Preclinical Invasive Epithelial Ovarian Cancer
Authors: Wei-Lei Yang, Aleksandra Gentry-Maharaj, Archana Simmons, Andy Ryan, Evangelia Ourania Fourkala, Zhen Lu, Keith A. Baggerly, Yang Zhao, Karen H. Lu, David Bowtell, Ian Jacobs, Steven J. Skates, Wei-Wu He, Usha Menon, Robert C. Bast
Journal: Clinical Cancer Research (2017)

Purpose: The TP53 tumor-suppressor gene is mutated in >95% of high-grade serous ovarian cancers. Detecting an autologous antibody response to TP53 that might improve early detection.Experimental Design: An immunoassay was developed to measure TP53 autoantibody in sera from 378 cases of invasive epithelial ovarian cancer and 944 age-matched healthy controls from the United States, Australia, and the United Kingdom. Serial preclinical samples from cases and controls were also assayed from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).Results: Using a cutoff value of 78 U/mL to achieve a specificity of 97.4%, TP53 autoantibody was elevated in 30% of 50 cases from MD Anderson, 21.3% of 108 cases from the Australian Ovarian Cancer Study, and 21% of 220 cases from the UKCTOCS. Among 164 cases with rising CA125 detected with the UKCTOCS risk of ovarian cancer algorithm (ROCA), 20.7% had elevated TP53 autoantibody. In cases missed by the ROCA, 16% of cases had elevated TP53 autoantibody. Of the 34 ovarian cancer cases detected with the ROCA, TP53 autoantibody titers were elevated 11.0 months before CA125. In the 9 cases missed by the ROCA, TP53 autoantibody was elevated 22.9 months before cancer diagnosis. Similar sensitivity was obtained using assays with specific mutant and wild-type TP53.Conclusions: TP53 autoantibody levels provide a biomarker with clinically significant lead time over elevation of CA125 or an elevated ROCA value. Quantitative assessment of autoantibodies in combination with CA125 holds promise for earlier detection of invasive epithelial ovarian cancer. Clin Cancer Res; 23(19); 5912-22. ©2017 AACR.
Monitoring Medical Devices
Authors: Andrew M. Ibrahim, Justin B. Dimick
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Next generation sequencing in community oncology practice: Beneficial or economical burden?
Authors: Natraj Reddy Ammakkanavar, Pablo M. Bedano, Anuj Krishna Agarwala, Janvi Bhatia, Arya Bolla, Priti Poojary, Bilal Karim Siddiqui, Shiroo Parshad, Radhika Walling, Gregory William Smith, Mary Louise Mayer, Sumeet Bhatia
Journal: Journal of Clinical Oncology (2017)

102 Background: Precision genomics medicine is a fast growing in cancer care. Targeted therapy has yielded substantial benefit when appropriately used. With next generation sequencing (NSG) use increasing in non-academic setting outside clinical trial, we need to consider benefits and economical burden of this. Methods: Retrospective chart analysis of cancer patients (pts) treated at a large community practice was undertaken. With IRB approval, demographic, clinical and NSG data were collected for 209 pts who had NSG in 2015 and 2016. Pts were placed in 1 of 4 categories based on NSG results with available drug for specific mutation and change in management (CIM): a) CIM for current, b) Potential to CIM with subsequent therapy, c) No CIM due to poor performance status, d) No CIM due to lack of new target and/or drug. Alternate economical standard test for the mutation noted. Statistical analysis was done using chi-square and fisher’s exact test. Results: Median age was 64yr. Most common tumor types tested where as listed in table 96% had stage 4 disease. 82% had ≥1 prior systemic therapy. Pts were assigned to categories as per table below. When RAS mutation status where accounted by standard testing, none of the colon cancer pts benefited from NSG test. 6 of 54 pts who had CIM had alternate test option. Financial responsibility for these tests is approximately $1.21 million. 18 pts in 2015 and 17 pts in 2016 where billed for test after exhausting insurance and support option. More financial data may be available at time of presentation. Conclusions: NGS tumor test might benefit small group of selective pts at time of testing. It is likely not prime time to use for colon cancer. Benefits with later therapy are difficult to predict. NSG should be used more judiciously due to financial implications. [Table: see text]
Genetic ancestry in normal breast tissue donors from the Susan G. Komen tissue bank at the IU Simon Cancer Center (KTB).
Authors: Natascia Marino, Julia McCarty, Guanglong Jiang, Mariah L Johnson, Teresa Mahin, Nicholas Scherer, Anna Maria Storniolo
Journal: Journal of Clinical Oncology (2017)

e13065 Background: When studying complex diseases with a heritable component, such as breast cancer, chances of finding disease susceptibility genes can be increased by accounting for genetic ancestry within the population investigated. The limitation in using self-reported race to reveal population genetic substructure has been extensively reported. Therefore, we employed a panel of genetic polymorphisms, or Ancestry Informative Markers (AIMs), to genetically determine the racial and ethnic background of the tissue donors in the KTB, the only existing biobank of breast tissue cores taken from healthy women. Methods: 4112 women donated breast tissue between 2006 and 2016, and also provided race and ethnicity information. We used a panel of 41 AIMs to estimate genetic ancestry and to maximize the difference between European/ Middle East (Caucasian, C), East Asia and Central/South Asia (Asian), African, and Hispanic populations. We employed the Bayesian Markov chain Monte Carlo (MCMC) method implemented in the program STRUCTURE 2.2. A reference set was obtained from the Human Genome Diversity Project. Results: In women self-identified as Black/African American (AA),White and Asian, the assigned genetic ancestry proportions were 93.8% African, 95% C and 96.6% Asian respectively, while the racial composition among the 318 self-identified Hispanics (of which only 178 were confirmed by the genetic ancestry) was 45.3% C, 5.3% African, and 14.7% Asian. Interestingly, 46.9% of the Asian population failed to report the racial background. This percentage was lower for C (1.3% ) and AA (0.5%). Women with African ancestry were younger (≤35 yrs) at the time of donation (24%), as compared to the C (32%) and Asian (33.7%) donors. The obesity rate (BMI &gt; 30) is higher in the AA (60.6%) and C (36.6%), as compared to the Asian population (26.6%). Conclusions: A well-characterized genetic background of the normal breast tissue donors in the KTB will allow a more accurate examination of the association of the genetic ancestry with breast cancer events or risk factors with the ultimate goal of more fully understanding breast cancer racial disparities and their possible role in the risks for and outcomes of breast cancer.
Neurolinguistic and machine-learning perspectives on direct speech BCIs for restoration of naturalistic communication
Authors: Olga Iljina, Johanna Derix, Robin Tibor Schirrmeister, Andreas Schulze-Bonhage, Peter Auer, Ad Aertsen, Tonio Ball
Journal: Brain-Computer Interfaces (2017)

The ultimate goal of brain-computer-interface (BCI) research on speech restoration is to develop devices which will be able to reconstruct spontaneous, naturally spoken language from the underlying neuronal signals. From this it follows that thorough understanding of brain activity and its functional dynamics during real-world speech will be required. Here, we review current developments in intracranial neurolinguistic and BCI research on speech production under increasingly naturalistic conditions. With an example of neurolinguistic data from our ongoing research, we illustrate the plausibility of neurolinguistic investigations in non-experimental, out-of-the-lab conditions of speech production. We argue that interdisciplinary endeavors at the interface of neuroscience and linguistics can provide valuable insight into the functional significance of speech-related neuronal data. Finally, we anticipate that work with neurolinguistic corpora composed of real-world language samples and simultaneous neuronal recordings, together with machine-learning methodology accounting for the specifics of the neurolinguistic material, will improve the functionality of speech BCIs.
Overall survival of patients with HER2-negative metastatic breast cancer treated with a first-line paclitaxel with or without bevacizumab in real-life setting: Results of a multicenter national observational study.
Authors: Suzette Delaloge, David Pérol, Etienne Brain, Bernard Asselain, Thomas Denis Bachelot, Marc Debled, Veronique Dieras, Mario Campone, Christelle Levy, William Jacot, Veronique Lorgis, Corinne Veyret, Florence Dalenc, Jean-Marc Ferrero, Lionel Uwer, Anthony Goncalves, Irwin Piot, Gaetane Simon, Mathieu Robain, Christian Cailliot
Journal: Journal of Clinical Oncology (2016)

1013 Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data in oncology. Metastatic breast cancer (mBC) was first selected to address the value of bevacizumab (B) added to paclitaxel (P) as first-line chemotherapy (CT) for HER2-negative tumours, while randomized trials have led to mixed results on outcome. Methods: The ESME-mBC database was built from information systems, treatment databases and patients' electronic files including quality control processes. All patients who started a first-line anti-cancer treatment for mBC between 01-Jan-2008 and 31-Dec-2013 were selected. The primary objective of the present study was to assess overall survival (OS) in patients with HER2-mBC treated with a first-line P-based CT ± B. Cox regression with adjustment for the main prognostic covariates was used to estimate the hazard ratio (HR) for OS and progression-free survival (PFS). To adjust for confounders, advanced methodological methods including propensity score, matching factor for nested case-control analyses and sensitivity analyses were performed. Results: Among 14,014 patients recorded in the ESME-mBC database, 10,605 had HER2-negative tumors. Of these, 2,127 and 1,299 received P+B and P respectively as first-line CT. OS was significantly higher in the P+B group compared with P alone (HR = 0.672 [95%CI, 0.601;0.752]; median survival time, 27.7 versus 19.8 months). Results were consistent across all supportive and sensitivity analyses, including in triple-negative and estrogen receptor-positive tumors subgroups. PFS was also higher for those receiving P+B versus P (HR = 0.739 [0.672; 0.813]; 8.1 versus 6.4 months). Conclusions: In this large-scale real-life setting database, patients with HER2-negative mBC who received P+B had a significantly better OS and PFS than those receiving P alone. Despite robust methodology, real-world data should be interpreted with caution. However, these data shed light on the potential interest of real-life data in oncology.
Vitamin K epoxide reductase complex subunit 1 (VKORC1): A pharmacogenomic predictor of response and survival in patients (pts) on triplet hepatic artery infusion (HAI) and intravenous cetuximab (IV-Cet) for initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU trial OPTILIV).
Authors: Francis Levi, Raphael Saffroy, Abdoulaye Karaboue, Christophe Desterke, Valerie Boige, Mohamed Hebbar, Denis Michel Smith, Mohamed Bouchahda, Pasquale Innominato, Julien Taieb, Carlos Carvalho, Rosine Guimbaud, C. N. J. Focan, Michel Ducreux, Rene Adam, Antoinette Lemoine
Journal: Journal of Clinical Oncology (2017)

2569 Background: The HAI of Irinotecan-Oxaliplatin-5-Fluorouracil (IFO) with IV-Cet achieved 29.7% complete uLM-CRC resections (R0+R1) and an overall median survival (OS) of 25.7 months in previously treated pts (Lévi, Ann Oncol 2016). Methods: To identify pharmacogenomic predictors of outcomes, 207 single nucleotide polymorphisms (SNPs) from 34 pharmacology genes were analysed in blood mononuclear cells (ADME PGx, MassArray platform, Sequenom, USA). Relations between SNPs and tumor response, R0+R1, survival, and toxicities were tested using adjusted Mann Whitney, Fisher Exact, Log Rank tests and Hardy-Weinberg Equilibrium. Results: Pts (16F;36M; 33-76 yo; WHO performance status 0-1) received protocol treatment as 2 nd (21 pts) or 3-4 th line (31 pts). VKORC1 SNPs in promoter (rs9923231) and intron (rs9934438) were consistently associated with early and objective responses, and overall survival. For rs9923231, T/T (N = 8) as compared to C/T (N = 21) had greatest chance of achieving early response (50% vs 5%, p = 0.029) or 4-y survival (46% vs 0%, p = 0.006). VKORC1 SNPs also related to HA thrombosis (rs992331, T/T, 77% vs C/C, 30%, p = 0.04). In contrast, NAT2 SNPs (rs1041983 and rs1801280) were associated with up to 5-fold differences in R0-R1 resection rate. Statistically significant associations (p &lt; 0.05) of SNPs with clinical outcomes were found for oxydo-reduction (CYP2E1 and HA thrombosis; CYP2C9 and diarrhea; CYP2C19 and diarrhea, fatigue, and early response), conjugation (UGT1A1 and diarrhea; NAT2 and fatigue); and transport (ABCB1 or SLC0B3 and neutropenia; SLC22A1 and diarrhea; SLC 15A2 and early response). Conclusions: VKORC1 was highlighted for the first time, as a pharmacogenomic predictor of HAI efficacy for LM-CRC. Conversion-to-resection was associated with NAT2 polymorphism. VKORC1 γ-carboxylates vitamin K-dependent proteins. Its polymorphism guides personalized warfarin dosing. VKORC1 SNPs determination could help identify the uLM-CRC pts who best benefit from intensive HAI therapy. Clinical trial information: NCT00852228.
Obesity and Risk of Nonalcoholic Fatty Liver Disease: A Comparison of Bioelectrical Impedance Analysis and Conventionally-Derived Anthropometric Measures
Authors: Maya Balakrishnan, Hashem B. El-Serag, Theresa Nguyen, Jonathan Hilal, Fasiha Kanwal, Aaron P. Thrift
Journal: Clinical Gastroenterology and Hepatology (2017)
Abstract P231: Dispensability of Dmitofusin in Calcium Signaling in Intact Drosophila Heart Tubes
Authors: Casey C Jowdy
Journal: Circulation Research (2011)

Sarcoplasmic Reticulum (SR) drives cardiomyocyte excitation-contraction coupling through the release and storage of Ca2+. Phasic fluctuations of Ca2+ require ATP. Mitochondria occupy ∼30% of the volume of cardiomyocytes and provide cardiomyocytes with ATP. Perturbations of mitochondria therefore have a detrimental effect on the heart. Mitochondrial homeostasis in mammals is regulated in part through fusion and fission by outer mitochondrial membrane proteins mitofusin 1 and 2 (Mfn1 and Mfn2) and in Drosophila by the homolog dMfn. Mutations in Mfn2 show impaired contractile function in humans (hMfn), mice (mMfn) and RNAi suppression in Drosophila (dMfn). Additionally Mfn2, independently of Mfn1, tethers the SR to mitochondria allowing for efficient transfer of Ca2+ between the organelles. It is currently not known whether mitochondria-SR tethering is required for proper Ca2+ cycling in cardiomyocytes. We monitored calcium transients in heart tubes of live flies, using the genetically encoded calcium indicator (GECI) GCaMP3.0 to study dynamic Ca2+ oscillations. Intensity signals from GCaMP3.0 in fly heart tubes are comparable to isolated cardiomyocytes in their rate cycling amplitude, and their response to L-type calcium channel antagonist, nifedipine. Additionally, non-calcium responsive GFP does not produce a signal that mimics the Ca2+ oscillations observed with GCaMP3.0. Comparisons between Wt Drosophila hearts and cardiomyopathic RNAi dMfn hearts expressing GCaMP3.0 have normal amplitude and time to decay constant Ca2+ signals. This study shows that suppression of dMfn with RNAi in the fly heart tube leads to cardiomyopathy. Monitoring intercellular Ca2+ levels with the (GECI) GCaMP3.0 demonstrates that Ca2+ signaling is not affected when mitochondria-SR tethering is disrupted.