tbuckley/cabot-search huggingface dataset:
A combined HER3-EGFR score in triple-negative breast cancer: racial differences.
Authors: Angela Ogden, Shristi Bhattarai, Nikita Wright, Sergey Klimov, Sonal Pattni, Mohammad Aleskandarany, Andrew R. Green, Emad Rakha, Ian O. Ellis, Xiaoxian Li, Ceyda Sonmez Wetherilt, Uma Krishnamurti, Michelle D. Reid, Padmashree C.G. Rida, Ritu Aneja
Journal: Journal of Clinical Oncology (2016)

e12560 Background: HER3 must heterodimerize with EGFR in triple-negative breast cancer (TNBC) to activate the oncogenic PI3K-Akt signaling pathway. PI3K-Akt signaling is often elevated in TNBCs, but compensatory HER3 and EGFR activation limits the efficacy of PI3K-Akt inhibitors. We recently reported that HER3 expression was not associated with survival in TNBC in multivariable (MV) analysis, but a combined HER3-EGFR score was. It is unknown whether the prognostic potential of a HER3-EGFR score varies by race in TNBC. Methods: HER3 and EGFR were immunolabeled and scored as weighted indices (WIs) in formalin-fixed paraffin-embedded TNBC cores from 146 European American (EA) and 39 African American (AA) patients treated with adjuvant chemotherapy at Emory and Nottingham University City Hospitals. The HER3-EGFR score was defined as the sum of the respective WIs. PTEN and phosphoAkt (Ser437) immunolabeling were also performed in EA cases. The impact of HER3-EGFR on overall survival (OS) and distant metastasis-free survival (DMFS) was analyzed by the Kaplan-Meier method and MV Cox regression using backward elimination with bootstrapping of final model covariates for internal validation. Results: The mean rank of HER3-EGFR was higher in EAs than AAs (101 vs. 64, P < 0.001), but no significant differences were found based on tumor size, grade, or lymph node positivity. In MV categorical regression, race was the strongest predictor of HER3-EGFR (P < 0.001, HR = 1.43). In Kaplan-Meier analysis, high HER3-EGFR ( ≥ 125) was associated with worse OS and DMFS in EAs (P = 0.012 and P = 0.049, respectively) but not AAs (P = 0.88 and P = 0.61, respectively). In MV analysis adjusting for tumor size, grade, age at diagnosis, and lymph node positivity, high HER3-EGFR was associated with worse OS and DMFS in EAs (P = 0.014, HR = 2.87 and P = 0.017, HR = 2.82, respectively) but not in AAs, for whom HER3-EGFR did not appear in final models. In EAs, HER3-EGFR predicted phosphoAkt positivity (P = 0.005, HR = 1.49) adjusting for PTEN WI. Conclusions: A combined HER3-EGFR score is a valuable poor prognosis marker in EA TNBC patients who receive adjuvant chemotherapy. It could also potentially identify which of these patients may benefit from targeted HER3 and EGFR inhibition.
Serum androgen profile and physical performance in women Olympic athletes
Authors: Emma Eklund, Bo Berglund, Fernand Labrie, Kjell Carlström, Lena Ekström, Angelica Lindén Hirschberg
Journal: British Journal of Sports Medicine (2017)

Background The role of endogenous androgens for body composition and physical performance in women athletes is still not elucidated. Aim To examine the serum androgen profile in relation to body composition and physical performance in women Olympic athletes and to compare endocrine variables and body composition to controls. Study design Cross-sectional study, conducted between 2011 and 2015 at the Women’s Health Research Unit, Karolinska University Hospital, Stockholm. Methods Swedish women Olympic athletes (n=106) and age-matched and body mass index-matched sedentary controls (n=117) were included in the study. Blood sampling was performed in a rested, fasting state for the measurement of serum androgens and their metabolites by liquid chromatography–tandem mass spectrometry. Body composition was determined by dual-energy X-ray absorptiometry (controls n=100, athletes n=65). The athletes performed standardised performance tests (n=59) (squat jump (SJ) and countermovement jump (CMJ). Results The athletes demonstrated significantly higher levels of the precursor androgens dehydroepiandrosterone (DHEA) and 5-androstene-3β, 17β-diol (5-DIOL) and the metabolite etiocholanolone glucuronide (Etio-G), significantly lower levels of estrone (p&lt;0.05, respectively), higher bone mineral density (p&lt;0.001) and more lean mass (p&lt;0.001) compared with controls. Serum levels of DHEA, 5-DIOL and Etio-G correlated positively to lean mass variables and physical performance in the athletes. DHEA and lean mass legs explained 66% of the variance in SJ, whereas lean mass explained 52% of the variance in CMJ. Conclusions The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes.
<i>Irf4</i>-dependent CD103<sup>+</sup>CD11b<sup>+</sup>dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus
Authors: Judith-Mira Pohl, Sebastian Gutweiler, Stephanie Thiebes, Julia K Volke, Ludger Klein-Hitpass, Denise Zwanziger, Matthias Gunzer, Steffen Jung, William W Agace, Christian Kurts, Daniel Robert Engel
Journal: Gut (2017)

Objective Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. Design POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment. Results We found that Cd11c-Cre + Irf4 flox/flox mice lack CD103 + CD11b + DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C – macrophages and infiltrating chemokine receptor 2-dependent Ly6C + monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C + monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI. Conclusions Our findings reveal that CD103 + CD11b + DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.
Prostate cancer genome-wide association study from 89,000 men using the OncoArray chip to identify novel prostate cancer susceptibility loci.
Authors: Rosalind Eeles
Journal: Journal of Clinical Oncology (2016)

1525 Background: Genome-wide association studies (GWAS) and fine-mapping efforts have identified 112 loci associated with prostate cancer susceptibility to date. Combined multiplicatively, these loci explain 33% of the familial relative risk for prostate cancer among populations of European ancestry. Methods: In order to identify novel prostate cancer susceptibility loci we conducted a GWAS involving 53,000 prostate cancer cases and 36,000 controls using the OncoArray that includes a 260K GWAS backbone and a custom portion of 310K SNPs developed from previous GWAS and fine-mapping studies of multiple cancer types (http://epi.grants.cancer.gov/oncoarray/). Following standard quality control procedures, the prostate cancer OncoArray genotyped data were imputed using the October 2014 release of the 1000 genomes project data as a reference and analysed by participating study for overall and advanced prostate cancer using logistic regression. The study-specific results were combined using inverse variance fixed effect meta-analysis. Regions surrounding previously associated variants (+/- 500kb of the reported index variant) were excluded to identify novel associations. Results: In the OncoArray meta-analysis, we identified more than 30 novel loci significantly associated (P < 5.0x10-8) with overall prostate cancer risk, including loci associated with advanced (Gleason ≥ 8, death from prostate cancer, PSA > 100, or disease stage “Distant – outside the pelvis”), or early-onset ( ≤ 55 years of age) prostate cancer. Conclusions: These results combined with fine mapping analyses will yield a genetic profile of about 150 SNPs for large scale genotyping which will improve the utility of genetic risk scores to identify populations for targeted screening and prostate cancer prevention.
THE USE OF ARSPHENAMIN IN NONSYPHILITIC DISEASES
Authors: Mathew A. Reasoner, Henry J. Nichols
Journal: JAMA (1920)

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 single institution experience with hepatic arterial infusion (HAI) of oxaliplatin followed by L-folinic acid modulated continuous HAI of 5-fluorouracil with or without cetuximab for the treatment of stage IV colorectal cancer limited to the liver
Authors: B Neyns, Yves Van Nieuwenhove, M Aerts, G Delvaux, J De Greve
Journal: Annals of Oncology (2006)
"TALC MEDIATES ANGIOSTASIS IN MALIGNANT PLEURAL EFFUSIONS VIA ENDOSTATIN INDUCTION". N. NASREEN, K.A. MOHAMMED, S. BROWN, Y. SU, P.S. SRIRAM, B. MOUDGIL, R. LODDENKEMPER AND V.B. ANTONY. EUR RESPIR J 2007; 29: 761-769.
Journal: European Respiratory Journal (2007)

Unfortunately, a small section of text in the above paper (in the Discussion, paragraph four) was reported incorrectly.The sentence ''Apart from case B, who was suffering from disseminated M. tuberculosis complex infection, no patients described in the present report were likely to be immunocompromised.''should read ''Apart from case B, who was suffering from disseminated MOTT infection, no patients described in the present report were likely to be immunocompromised.''
CD133 topographic gradient expression within human carcinomas
Authors: Natalia Malara, Paolo Macri, M Renne, D Foca, L Santoro, Giuseppe Viglietto, Rocco Damiano, Rocco Savino
Journal: Clinical Cancer Research (2007)

A45  The CD133+ cells display, due to their stemness characteristics, a preferential tissue localization with specific environmental features (lower growth factor concentration, lower blood afflux, hypoxia and other). In the search for the “ideal” CD133+ habitat, we classified and mapped the tumor area in diverse fragments from the same surgical specimen and measured the CD133+ yield identified through cytometric evaluation. We next set up a system of co-culture of primary stroma and epithelial cells, which enriched the CD133+ compartment. Human tumoral prostatic tissues were obatined, with patients informed consensus, from 8 patients (age range 54-70 years) undergoing radical prostatectomy for prostatic adenocarcinomas. Human non small cell lung cancer specimens were obtained from two patients (age 50-60 years) and breast specimens from two patients affected by intraductal cancer (31-60 years). Using a descriptive map, obtained through a preliminary diagnostic biopsy and identifying the effective tumor localization, we dissected the surgical specimen to obtain several fragments representative of the heterogeneous cancer cellular population. We obtained five fragments or areas that displayed different capacity to generate spheres. In particular, the area correspondent to normal tissue showed a lower spheres forming ability. The area with the highest sphere forming capacity displayed a CD133 positivity up to 40% and higher in the fresh cell population; this percentage increased of 20% in the spheres first generation, obtained from the floating cell population derived from the correspondent primary culture. The correlation between CD133+ cell abundance and the in vitro sphere forming capacity was found in all tumor samples analyzed. In conclusion the topografic gradient found for CD133 cellular positivity population in all surgical specimen analyzed suggests some kind of architecture of the tumoral tissue rather than anarchy that was so far postulated.
Randomized phase II 8-arm factorial study of adjuvant dose-dense (dd) temozolomide (TMZ) with permutations of thalidomide (Thal), isotretinoin (CRA), and/or celecoxib (Cel) for newly diagnosed glioblastoma (GBM).
Authors: Mark R. Gilbert, Kenneth R. Hess, Lore Lagrone, Morris D. Groves, Victor A. Levin, John Frederick De Groot, Monica Elena Loghin, Vinay K. Puduvalli, Michael Fisch, Pierre Giglio, Howard Colman, Charles A. Conrad, Kenneth D. Aldape, W. K. Alfred Yung
Journal: Journal of Clinical Oncology (2012)

2003 Background: Concurrent radiation and TMZ followed by 6-12 months of adjuvant TMZ (d 1-5 of a 28d cycle) is the current standard of care for patients with newly diagnosed GBM. The addition of cytostatic or signal transduction agents may enhance efficacy without a significant increase in toxicity. A phase I trial (Neuro-oncology 2009) established the safety of ddTMZ with 2 or 3 of the cytostatic agents. Methods: This randomized phase II study was conducted by the Brain Tumor Trials Collaborative (BTTC) and the MDACC CCOP. The primary objectives: determine if specific cytostatic agents added to ddTMZ alters outcomes (PFS, OS) and compare triplet with doublet therapy. Eligibility criteria: centrally confirmed newly diagnosed GBM, age ≥18, KPS≥60, stable or improved after chemoradiation (pseudoprogression allowed), adequate hematologic, renal and hepatic function. Pts were randomly assigned to 12 treatment cycles (28 d/cycle) in 8 arms: ddTMZ alone (150 mg/m2/day, 7-d on, 7-d off) or TMZ-containing doublet, triplet and quadruplet combinations with Thal, CRA, or Cel. Results: The study enrolled 155 eligible patients from 11/2005 to 9/2010 to the 8 arms of the factorial design. Median age was 53 (18-84) and median KPS, 90 (60-100). Compared with TMZ alone, the TMZ+CRA doublet had worse PFS (10.5, 6.5 mo; p=0.043) and OS (21.2, 11.7 mo; p=0.037). Trends were also seen for worse outcome (PFS, OS) for CRA-containing regimens, improved OS for Cel containing arms and no impact of Thal. A strong trend for OS improvement was seen for triplet compared with doublet regimens (20.1, 17.0 mo; p=0.15), but no difference for PFS. Treatment was well tolerated with expected high rates of grade 3/4 lymphopenia, and overall a modest toxicity rate. Conclusions: The results indicate that the addition of CRA to ddTMZ may be detrimental in patients with newly diagnosed GBM. This study demonstrated the utility of the factorial design in efficiently testing drug combinations, the impact of individual agents in these combinations as well as doublet vs. triplet regimens and supports its utility in testing combinations of targeted agents.
Bioactuators: Damage, Healing, and Remodeling in Optogenetic Skeletal Muscle Bioactuators (Adv. Healthcare Mater. 12/2017)
Authors: Ritu Raman, Lauren Grant, Yongbeom Seo, Caroline Cvetkovic, Michael Gapinske, Alexandra Palasz, Howard Dabbous, Hyunjoon Kong, Pablo Perez Pinera, Rashid Bashir
Journal: Advanced Healthcare Materials (2017)

Biological materials can adaptively respond to their environment, motivating their use as functional components of engineered machines. In article number 1700030, Rashid Bashir and co-workers present a skeletal muscle-powered bio-hybrid robot (bio-bot) that can adapt to loss-of-function damage stimuli, completely healing and recovering functionality within two days. This presents a significant step forward in developing robust, resilient, and dynamically responsive biohybrid machines.
Outcomes after observation stays among older adult Medicare beneficiaries in the USA: retrospective cohort study
Authors: Kumar Dharmarajan, Li Qin, Maggie Bierlein, Jennie E S Choi, Zhenqiu Lin, Nihar R Desai, Erica S Spatz, Harlan M Krumholz, Arjun K Venkatesh
Journal: BMJ (2017)

Objective To characterize rates and trends over time of emergency department treatment-and-discharge stays, repeat observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from observation stays.Design Retrospective cohort study.Setting 4750 hospitals in the USA.Participants Nationally representative sample of Medicare fee for service beneficiaries aged 65 or over discharged after 363 037 index observation stays, 2 540 000 index emergency department treatment-and-discharge stays, and 2 667 525 index inpatient stays from 2006-11.Main outcome measures Rates of emergency department treatment-and-discharge stays, observation stays, inpatient stays, any hospital revisit, and death within 30 days of discharge from index observation stays. Rates were compared with corresponding outcomes within 30 days of discharge from both index emergency department treatment-and-discharge stays and index inpatient stays.Results Among 363 037 index observation stays resulting in discharge from 2006-11, 30 day rates of emergency department treatment-and-discharge stays were 8.4%, repeat observation stays were 2.9%, inpatient stays were 11.2%, any hospital revisit was 20.1%, and death was 1.8%. Of all revisits, 49.7% were for inpatient stays. Revisit rates for emergency department treatment-and-discharge stays, repeat observation stays, and any hospital revisit increased from 2006-11 (P<0.001 for trend), while 30 day rates of inpatient stays (P=0.054 for trend) and 30 day mortality (P=0.091 for trend) were both unchanged. Averaged over the study period, 30 day rates of any hospital revisit were similar after discharge from index emergency department treatment-and-discharge stays (19.9%) and index observation stays (20.1%), as was 30 day mortality (1.8% for both). Rates of any hospital revisit (21.8%) and death (5.2%) were highest after discharge from index inpatient stays.Conclusions Hospital revisits are common after discharge from observation stays, frequently result in inpatient hospitalizations, and have increased over time among Medicare beneficiaries. As revisit rates are similar after emergency department and observation stays, strategies shown to enhance emergency department transitional care may be reasonable starting points to improve post-observation outcomes.
Use of immunotherapy in recurrent glioblastoma.
Authors: Ashley Love Sumrall, David Lowell Jennings, Daniel Ernest Haggstrom, James Thomas Symanowski
Journal: Journal of Clinical Oncology (2017)

e13523 Background: With the recent explosion of interest in immunotherapy to treat cancer, it has moved into management of glioblastoma (GBM). Several trials are ongoing, investigating use of checkpoint inhibition for newly diagnosed and recurrent GBM. Methods: We reviewed the records of patients with recurrent glioblastoma (including gliosarcoma). Six of the eight patients demonstrated PD-1 positivity via immunohistochemical (IHC) staining. Two patients demonstrated PD-L1 positivity as 2+ staining intensity via IHC. Patients were managed with checkpoint inhibitors for at least four weeks. When feasible, patients had tumor profiling of initial tumor and recurrent tumor. Patients were followed for response, progression, and survival. Results: Eight patients were identified with recurrent GBM who received immunotherapy with checkpoint inhibitors. They ranged from first through fifth recurrence following radiation and temozolomide. Three patients received pembrolizumab. Of those, two were PD-L1 positive. Five patients received nivolumab, and all were PD-1 positive. There were no partial or complete responses. Five of the eight subjects died, and the median survival time among the 8 subjects was 3.6 months. Six of eight subjects progressed on treatment, and the median PFS was 2.2 months. Bevacizumab was given to two patients for suspected “tumor flare” while on nivolumab. Four of the eight patients had tumor profiling completed at initial diagnosis and recurrence. Treatment was well-tolerated with only minimal toxicity observed. Conclusions: Despite increasing interest in utilizing these medications for recurrent glioblastoma, overall survival in our cohort was consistent with historical control (3 to 5 months). Additionally, we did not witness any responses.
Coexistence of driver aberrations in NSCLC patients including ALK/RET/ROS1 rearrangements.
Authors: Gabriel Alejandro Bien-Willner, Dong Yang, Dianren Xia, Jixin Wang, Sandra Indiviglio, Jamie Renard, George Miles, Elizabeth Mambo
Journal: Journal of Clinical Oncology (2016)

e13118 Background: Major driver mutations of lung cancer are largely considered to be mutually exclusive. Although a few exceptions of coexisting driver mutations have been noted, it is thought that the coexistence of ALK, RET, and ROS1 rearrangements with other major driver mutations is also rare. However, NGS has allowed us to revisit this assumption given the amount of clinical data that are generated. We report findings of the frequency of driver mutations and their coexistence in a cohort of 181 lung cancer patients tested in our laboratory. Methods: A comprehensive molecular- and histopathology-based strategy was conducted on FFPE samples of 181 lung cancer patients. NGS molecular profiling was performed using Molecular Health’s Engineus Profile+ 613-targeted gene panel. For patients diagnosed with adenocarcinoma; ALK, RET, and ROS1 rearrangements were evaluated using FISH method (Personalized Dx, CA). Results: Including both NGS and FISH analysis, major driver aberrations were detected as follows: KRAS codon 12/13 (50, 28%), EGFR exon 19/21 (26, 14%), BRAF V600E (7, 4%), BRAF non-V600E (4, 2%), PIK3CA (5, 3%), ERBB2 amplification (4, 2%), MET amplification (4, 2%), ALK rearrangement (7, 4%), RET rearrangement (3, 2%), and ROS1 rearrangement (2, 1%). The majority (101 out of 109, 93%) of these specimens harbored only one major driver mutation. Coexistence of two major drivers were identified in 8 patients (8 out of 109, 7%), including KRAS/PIK3CA (3), KRAS codon 12/13/BRAF non-V600E (1), ALK fusion/KRAS p.G12V (1), ALK fusion/EGFR p.L858R (1), RET fusion/KRAS p.G12C (1), and RET fusion/EGFR exon 19 del (1). Among tumors with ALK, RET or ROS1 rearrangements, 30% (4/12) harbored another driver mutation. Conclusions: Our results illustrate the coexistence of multiple driver mutations in a small but significant number of NSCLC patients, including ALK, RET, or ROS1 rearrangements. Concomitant testing of both ALK, RET, and ROS1 rearrangements and comprehensive molecular profiling of other driver genes may be necessary for better clinical management of NSCLC patients.