tbuckley/cabot-search huggingface dataset:
AhR mediates an anti‐inflammatory feedback mechanism in human Langerhans cells involving Fcε<scp>RI</scp> and <scp>IDO</scp>
Authors: S. Koch, T. J. Stroisch, J. Vorac, N. Herrmann, N. Leib, S. Schnautz, H. Kirins, I. Förster, H. Weighardt, T. Bieber
Journal: Allergy (2017)

Abstract Background Aryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells ( LC ) in the epidermis of patients with atopic dermatitis ( AD ) carry the high‐affinity receptor for IgE, Fcε RI , and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes. Objectives We investigated AhR and AhR repressor (Ah RR ) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro ‐generated LC . Methods Epidermal cells from healthy skin were analyzed for their expression of AhR and Ah RR . LC generated from CD 34 + hematopoietic stem cells ( CD 34 LC ) were treated with the UV photoproduct and AhR ligand 6‐formylindolo[3,2‐b]carbazole ( FICZ ). Cell surface receptors, transcription factors, and the tolerogenic tryptophan‐degrading enzyme indoleamine 2,3‐dioxygenase ( IDO ) were analyzed using flow cytometry and quantitative PCR . Results Epidermal LC and CD 34 LC express AhR and Ah RR . AhR was also found in keratinocytes, which lack Ah RR . AhR activation of LC by FICZ caused downregulation of Fcε RI in CD 34 LC without affecting their maturation. AhR‐mediated regulation of Fcε RI did not involve any known transcription factors related to this receptor. Furthermore, we could show upregulation of IDO mediated by AhR engagement. Conclusions Our study shows that AhR activation by FICZ reduces Fcε RI and upregulates IDO expression in LC . This AhR‐mediated anti‐inflammatory feedback mechanism may dampen the allergen‐induced inflammation in AD .
Nonseminomatous germ cell testicular tumors clinical stage II: Retroperitoneal lymph node dissection, chemotherapy or both?
Authors: T. Sava, S. Pessa, L. Nicoletti, A. Perin, A. P. Fraccon, F. Merlin, A. Rosa-Bian, V. Fosser, G. L. Cetto, T. Franceschi
Journal: Journal of Clinical Oncology (2004)

4746
Abstract 17295: Cardiovascular Biomarkers and Long-term Outcomes in Patients with Type 2 Diabetes Mellitus Treated with Alogiptin vs. Placebo in the EXAMINE Trial
Authors: David A Morrow, Christopher P Cannon, Faiz Zannad, William C Cushman, George L Bakris, Steven E Nissen, Simon R Heller, Richard M Bergenstal, Alfonso T Perez, Penny R Fleck, Cyrus R Mehta, Stuart Kupfer, Hung Lam, Craig Wilson, William B White
Journal: Circulation (2014)

BACKGROUND: Thorough evaluation of the cardiovascular (CV) safety of new drugs for diabetes mellitus (DM) is now mandated by the US FDA. Alogliptin, a dipeptidyl-peptidase 4 inhibitor, is one of a new drug class for treatment of DM. CV biomarkers may provide useful insight with respect to CV safety of new treatments for DM. We evaluated the predictive value of baseline biomarkers for CV outcomes in a high risk population of DM patients (pts) in a large CV safety trial. METHODS: EXAMINE was a randomized, double-blind, placebo-controlled, multinational trial of alogliptin in pts with DM enrolled 15 to 90 days after an acute coronary syndrome (ACS). We measured B-type natriuretic peptide (BNP) and high sensitivity troponin I (hsTnI) at baseline (Abbott ARCHITECT). The primary endpoint was major adverse CV events (MACE) defined as CV death (CVD), myocardial infarction, or stroke. The composite of CV death or heart failure (HF) was also assessed as an exploratory endpoint. RESULTS: A total of 5230 pts with baseline biomarkers were followed for 18 mo (median). Baseline BNP and hsTnI showed a significant graded relationship with CV outcomes at 18 mo (Figure bars). BNP and hsTnI remained strongly and independently related to CV outcomes through the pts’ final visit after adjusting for age, sex, type of qualifying ACS, eGFR, &amp; history of HF (Figure, adjusted HRs). The rates of MACE were similar with alogliptin vs. placebo in the highest risk pts identified by BNP (Group 4: 19.9 vs. 22.2%) or hsTnI (Group 4: 18.3 vs. 20.6%). Similar results were observed for CV death/HF based on BNP (17.5 vs. 19.4%) or hsTnI (14.3 vs. 14.9%). There was no evidence for heterogeneity in the effect of alogliptin on CV death/HF across BNP strata (p-interaction=0.71). CONCLUSIONS: Among pts with DM who were stable after a recent ACS, BNP &amp; hsTnI identified pts at high risk of poor CV outcomes. In this study, the rates of MACE, including CV death or HF, were not increased with alogliptin vs. placebo even in these high risk pts.
Insomnia may raise risk of MI and stroke, review finds
Authors: Susan Mayor
Journal: BMJ (2017)

Insomnia is associated with increased risk of future myocardial infarction (MI) and stroke, a meta-analysis of prospective cohort studies has found.1

Insomnia—characterised by difficulty initiating or maintaining sleep, early morning waking, or non-restorative sleep—is common, as studies show that it affects around one in three adults. Sleep problems have previously been associated with cardiovascular or cerebrovascular events, but results of studies have been inconsistent. …
The EOS® System for the Detection of Bone Lesions in Patients with Multiple Myeloma,
Authors: Bastien Dutouquet, Xavier Leleu, Antoine Moraux, Eileen Boyle, Jordan Gauthier, Houria Debarri, Salomon Manier, Marie Pierre Noel, Thierry Facon, Marie Helene Vieillard, Anne Cotten, Nathalie Boutry
Journal: Blood (2011)
Quantitation of immune responses against the cancer testis antigen NY-ESO-1 following vaccination with protein with and without ISCOMATRIX adjuvant
Authors: J. S. Cebon, I. D. Davis, C. Barrow, H. Jackson, W. Hopkins, L. Miloradovic, P. Parente, S. Green, E. Hoffman, W. Chen
Journal: Journal of Clinical Oncology (2004)

2518 Background: One major challenge for cancer immunology is the measurement of the immune response so that any relationship to clinical outcomes can be evaluated using stringent criteria. Methods: We have applied a novel scoring system in order to better quantitate integrated antibody and cellular immune responses in patients vaccinated with a full-length protein cancer testis antigen, NY-ESO-1. The score accounts for rate of onset, duration and intensity of an immune response (the immune equivalent of AUC). Forty-six patients (pts), 42 with melanoma, all with fully resected disease, were vaccinated IM on three occasions at monthly intervals. NY-ESO-1 protein was administered with or without the ISCOMATRIX adjuvant, which has been shown to induce both antibody and T cell responses. NY-ESO-1 ISCOMATRIX vaccine doses were:10μg (n=3), 30μg (n=3), and 100μg (n=16). 16 pts received 100μg NY-ESO-1 protein alone and 8 pts received placebo. NY-ESO-1 immunity was assessed by Delayed Type Hypersensitivity (DTH) to NY-ESO-1 protein, by ELISA for antibody and by tetramer and ICS for the number of reactive NY-ESO-1 CD8+ & CD4+ T cells. Results: Although low level immune responses were seen against protein alone, the addition of adjuvant greatly increased immune responses in a dose-dependent fashion. In an unplanned analysis, the relapse free survival (RFS) of melanoma pts was assessed. Despite small numbers, patients in cohorts with higher immune response scores appeared to have longer RFS than those from cohorts with low scores. Conclusions: A prospective evaluation of this is required determine whether immune responses to NY-ESO-1 is correlated clinical outcome of pts with tumours which express this antigen. Using a system to quantitate immune responses will also facilitate strategies aimed at optimising vaccine potency. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CSL Ltd. CSL Ltd.
Patterns and correlates of breast reconstruction: results of a population based study
Authors: M. Morrow, P. Lantz, N. Janz, A. Fagerlin, M. Mujahid, S. Katz
Journal: Journal of Clinical Oncology (2004)

557 Background: Little is known about patterns and correlates of breast reconstruction (BR) for patients with breast cancer who undergo mastectomy in the community. Methods: All women with DCIS and a 20% random sample of women with non-metastatic invasive breast cancer aged 79 and younger diagnosed in 2002 and reported to the Detroit and Los Angeles metropolitan SEER registries were identified and surveyed shortly after receipt of surgical treatment. Response rate was 74.3% (N=1489). Results: The mean age was 59.9 years and 28.8% were non-Caucasian. Overall, 35.0% of women received M, of whom 30.8 % received BR. BR was more frequent for those with DCIS (53.8%) than those with Stage 1 (35.9%) or 2 (28.9%) invasive cancer. In multivariate analyses, Caucasian race, earlier stage, younger age, and higher education levels were positively associated with BR. After adjustment for co-variates, 38.7% of Caucasian women had BR compared to 19.0% of African American women, and 20.9% of other races (p=.001). In the subset of M patients who did not receive BR, the desire to avoid more surgery (35.5%), lack of importance of BR (43.7%), and lack of a surgeon recommendation (17.9%) were the most commonly cited reasons. More African American than Caucasian women endorsed lack of knowledge about BR (9.2% vs 1.0%, p=.003) and lack of surgeon recommendation (26.2% vs 15.9%, p=.03) as reasons for not having the procedure. Fewer African Americans than Caucasians reported that their surgeon discussed BR (48.9 vs 69.6%, p=.001). These differences remained significant after controlling for age, marital status and co-morbidity. Conclusions: The majority of women undergoing M do not receive BR. Receipt of BR was highly associated with earlier stage, younger age, higher education, and Caucasian race. Results suggest that patient-provider communication about treatment may contribute to the observed racial differences in receipt of BR. No significant financial relationships to disclose.
Induction of T cell precursors in advanced melanoma treated with autologous tumor lysate loaded dendritic cells
Authors: T. S. Crocenzi, C. G. Tretter, J. Fisher, N. Crosby, D. Truman, M. S. Ernstoff
Journal: Journal of Clinical Oncology (2004)

2623 Background: Immunotherapy in melanoma patients (pts) is limited by tumor-induced effector cell inhibition. Dendritic cells (DC) are powerful initiators of tumor-specific immune responses. We proposed a pilot study that hypothesized that DC matured ex vivofrom the peripheral blood (PB) and pulsed with autologous tumor lysate (TuLy) would stimulate tumor-specific immune activation. Methods: 6 stage III/IV melanoma pts were enrolled and CD14+ precursors were obtained from PB by apheresis and elutriation prior to each treatment. DC were cultured ex vivo for 9 days with IL-4 and GM-CSF, pulsed with autologous TuLy and matured with TNFa. Pts received 3 treatments administered intravenously (IV) over 5–10 minutes at 4 week intervals. Efficiency of DC generation was determined by measuring total DC per apheresis and phenotype. NCI Common Toxicity Criteria v2.0 was used. Tumor-specific immune induction was evaluated using the Dye Dilution Proliferation Assay which measures T cell precursor frequencies (Tp) in response to stimuli; in this case pulsed or unpulsed mature DC. Results: 3 pts each have been treated with 1x106and 5x106DC respectively. Adequate yields of DC were achieved for all treatments. Toxicity was minimal with transient grade 2 ataxia. Mature DC highly expressed MHC class I and II, costimulatory markers (CD80, CD86, CD40) and the maturity marker CD83. We observed a 6-fold increase in CD8+ Tp and 1.5-fold increase in CD4+ Tp after 2 treatments (n=2) as shown in the table. Elevated Tp persisted 30 days following completion of treatment. Conclusions: Ex vivogeneration and IV administration of mature DC is feasible and safe. Preliminary data support induction of tumor-specific T cells evidenced by increased Tp. No significant financial relationships to disclose.
The prognostic importance of the CA19–9 tumour marker and its use as a biochemical indicator of treatment response during (chemo-) radiotherapy of locally advanced pancreatic cancer
Authors: R. Wilkowski, P. Stieber, A. Nolte, E. Duhmke, V. Heinemann
Journal: Journal of Clinical Oncology (2004)

4177 Introduction: CA19–9 has been shown to have prognostic and predictive importance in pancreatic cancer patients undergoing chemoradiotherapy for unresectable locally advanced disease. Patients and Methods: CA19–9 tumour marker kinetics (Roche, Elecsys 2010) were investigated in 171 pancreatic cancer patients immediately before and after radiotherapy as well as 4–8 weeks after end of radiotherapy. Three modalities of treatment were analysed: 37 pts received radiotherapy (RT) alone, 58 pts simultaneous chemoradiotherapy (CRT), and further 76 pts received chemoradiotherapy followed by systemic chemotherapy (CRT-CT). Biochemical response to treatment was determined in accordance to the criteria published by Ishii et al. (Hepatogastroenterology 44: 279–283, 1997), where a >50% decline of CA19–9 from baseline levels was evaluated as a partial response. Pts not expressing elevated CA19–9 levels (cut-off = 37 U/L)were evaluated separately (n=29). Results: Median CA19–9 levels measured immediately before and after radiotherapy as well as 4–8 wks after end of treatment were: 308 U/l, 226 U/l, and 145 U/l, respectively. The analysis of CA19–9 tumour marker kinetics in the treatment groups RT, CRT, and CRT-CT indicated stable disease (SD) in 25%, 35,4%, and 33,4% of pts which was accompanied by an overall remission rate (ORR) of 0%, 31,3 %, and 43,1%, respectively. Interestingly, the biochemical response status had no impact on overall survival (OS). Initial CA19–9 measured before treatment start did not predict response or progression-free survival (PFS). Compared to the group with elevated CA19–9 levels, pts without CA19–9 elevation had a significantly longer PFS (13.1mos vs 8.9 mos, p=0.012) and OS (15.4 mos vs 11.5 mos, p=0.02). Conclusions: Non-pathological CA19–9 levels measured before treatrment start appear to be a favourable prognostic parameter in locally advanced pancreatic cancer treated with (chemo-) radiotherapy. While CRT and CRT-CT was more effective to induce a biochemical response than RT alone, this did not influence survival. No significant financial relationships to disclose.
Size-corrected PET SUV predicts nodal or distant metastases at presentation in NSCLC
Authors: S. Sachs, T. V. Bilfinger
Journal: Journal of Clinical Oncology (2004)

7188 Background: Standardized uptake value (SUV) has been linked to tumor aggressiveness and long-term prognosis. Based on the hypothesis that positron emission tomography (PET) SUV serves as a surrogate for biologic aggression, we set out to establish whether SUV in the primary lesion, when corrected for size, correlates with the presence of nodal or distant metastases at the time of presentation. Methods: We retrospectively reviewed the computed tomography (CT) scan, PET scan, and histologic findings of consecutive patients in our lung cancer referral population evaluated between 12/15/00 and 12/15/03. Only patients with nonsmall cell lung cancer and pathologic confirmation of nodal status or conventionally accepted non-PET related proof of distant metastases were included for analysis. SPSS for Windows 12.0 software (SPSS Inc., Chicago, Illinois) was used for statistical analysis. Results: 125 patients had complete results, including CT, PET, and independent confirmation of nodal or distant disease. The stage distribution was as follows: 22 stage IA, 21 stage IB, 7 stage IIA, 12 stage IIB, 18 stage IIIA, 7 Stage IIIB, and 38 stage IV. Logistic regression analysis demonstrated a highly significant correlation between the SUV of the primary lesion and the presence of nodal or distant metastases at the time of presentation, P = 0.002. This correlation remained significant when controlled for size of the primary lesion, P = 0.032. When calculating odds ratios, a 19% increase in the likelihood of nodal/distant disease was found for every unit increase in SUV; this decreased to 15% when corrected for size. Conclusions: PET SUV corrected for size is a marker of biologic aggressiveness. In addition to its previously established long-term prognostic implication, SUV in the primary can influence up-front management. High SUV in the primary at presentation should prompt high suspicion and an aggressive search for nodal or distant disease. No significant financial relationships to disclose.
The Art of Repeal — Republicans’ Health Care Reform Muddle
Authors: Jonathan Oberlander
Journal: New England Journal of Medicine (2017)

Interview with Dr. Jonathan Oberlander on Republican lawmakers' efforts to pass new health care legislation. (09:29)Download Republicans' failure to advance the American Health Care Act reflects persistent divisions within the party and underscores a crucial reality: 7 years after Obamacare's enactment, the GOP still lacks a viable replacement for it. So what will Republicans do next?
What is the prognosis of patients with operable breast cancer (BC) five years after diagnosis?
Authors: G. N. Hortobagyi, S.-W. Kau, A. U. Buzdar, R. L. Theriault, D. J. Booser, K. Gwyn, V. Valero
Journal: Journal of Clinical Oncology (2004)

585 Background: Recent publications suggested that extended adjuvant systemic therapy (AST) started 5 years after diagnosis following standard adjuvant therapy further reduced risk of recurrence. Residual risk of recurrence 5 years after state-of-the-art adjuvant therapy is not well defined. Methods: We identified all patients (pts) treated on prospective clinical trials of AST at our institution between 4/74 and 7/98 and who remained without recurrence 5 years after diagnosis. All received postoperative anthracycline-based AST and endocrine therapy when indicated. 5 and 10-year relapse-free survival (RFS) rates were calculated. Results: 2246 pts were registered on 6 AST trials. 839 pts were excluded because of relapse during first 5 years, follow-up < 5years or death without recurrence. The 1407 patients relapse-free at 5 years had a median follow-up of 74 months from the 5th anniversary of diagnosis. 101 had stage I BC, 1104 stage II and 202 stage III; 823 were younger than age 50. 407 had ER/PR-negative BC; 706 had ER or PR+ tumors. RFS rates 5 and 10 years after the 5th anniversary (10 and 15 years from diagnosis) are shown on the table: Conclusions: Pts with all Stages of primary BC have substantial residual risk of relapse following completion of AST and would benefit from additional risk reduction. Additional analysis of larger databases of pts with stage Ia and Ib BC would help in calculating benefit from extended AST. No significant financial relationships to disclose.
Medical Marijuana Is Legal in Most States, but Physicians Have Little Evidence to Guide Them
Authors: Rita Rubin
Journal: JAMA (2017)

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Phase I trial of imatinib mesylate (IM), cisplatin (P), and irinotecan (I) in small cell lung cancer (SCLC)
Authors: F. M. Johnson, H. T. Tran, V. G. Prieto, P. Tamboli, B. O. Peeples, B. S. Glisson
Journal: Journal of Clinical Oncology (2004)

7257 Background: SCLC cell lines commonly express c-kit and its ligand, suggesting an autocrine loop promoting cell growth. IM inhibits c-kit kinase activity. SCLC cells treated with IM in vitro undergo cell cycle arrest. In this study we investigated the feasibility of combining IM with cytotoxic chemotherapy for extensive disease SCLC. Methods: Six patients received P (30 mg/m2) and I (65 mg/m2) on days 1 and 8 every 21 days for four cycles. IM (300 mg) was given daily during chemotherapy and then as maintenance until progression of disease. Immunohistochemistry (IHC) for potential IM targets was done on patients' pre-treatment biopsies. Results: The first 3 patients experienced significant neutropenia that required GCSF support. One patient died during treatment from neutropenic fever. GCSF was added prophylactically to the subsequent 3 patients who did not experience significant neutropenia. Five patients had grade 2 diarrhea and one had grade 3 diarrhea. One patient had a deep vein thrombosis. This patient and one additional patient had asymptomatic pulmonary emboli. All 6 patients had marked tumor regression after cycle one. Four patients were evaluable for response after 4 cycles and all had partial responses. Pharmacokinetic studies showed that the addition of IM increased the AUC of I by 67% (±56%) which may explain the high incidence of diarrhea and neutropenia. There was no significant change in the disposition of P. There was marked interpatient variability in the serum concentration of IM with an average value of 2.8 μM (±3.7). IHC was considered positive if >25% cells stained moderately or strongly positive. Conclusions: This regimen was tolerable with G-CSF support. With this schedule of PI, IM at 300 mg/day is the maximal tolerated dose. An extension of this phase I study evaluating a schedule that separates I administration from IM is planned to improve tolerance and increase exposure to IM. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Novartis
US stops funding United Nations Population Fund
Authors: Owen Dyer
Journal: BMJ (2017)

The Trump administration is ending US support of the United Nations Population Fund (UNFPA), having accused the family planning and sexual health organization of cooperating in China with government programs that are implicated in forced abortions and involuntary sterilization.

The fund, which promotes family planning in more than 150 countries, strongly denied the claims.

The move comes after President Donald Trump signed an executive order in January cancelling aid to non-governmental organizations that provide or “promote” abortions, a policy of successive Republican presidents. The Netherlands stepped in to fill …