tbuckley/cabot-search huggingface dataset:
Cetuximab ameliorates suppressive phenotypes of myeloid antigen presenting cells in head and neck cancer patients
Authors: Jing Li, Raghvendra M. Srivastava, Abhinav Ettyreddy, Robert L. Ferris
Journal: Journal for ImmunoTherapy of Cancer (2015)

<h3>Background</h3> Myeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity. <h3>Methods</h3> Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) on the UPCI 08–013 NCT01218048 trial were treated with single-agent cetuximab before surgery. Blood were collected pre- and post-cetuximab treatment to analyze frequency of monocytic MDSC (CD11b<sup>+</sup>CD14<sup>+</sup>HLA-DR<sup>lo/-</sup>), granulocytic MDSC (LIN<sup>−</sup>CD11b<sup>+</sup>CD15<sup>+</sup>) and CD11b<sup>+</sup>CD14<sup>+</sup>HLA-DR<sup>hi</sup> monocytes by flow cytometry. Besides, CD11b<sup>+</sup>CD14<sup>+</sup>HLA-DR<sup>hi</sup> monocytes were sorted for qPCR analysis of IL-10 and IL-12B transcripts. MDSC were generated in vitro with or without coated hIgG1 and tested for suppressive activity in mixed leukocyte reaction (MLR). Naïve monocytes from HNSCC patients co-cultured with tumor cell lines in the presence of cetuximab or hIgG1 were analyzed for M1/2 surface markers and cytokines. <h3>Results</h3> We observed significantly increased monocytic MDSC in non-responders and decreased granulocytic MDSC in responders after cetuximab treatment. In addition, circulating CD11b<sup>+</sup>CD14<sup>+</sup>HLA-DR<sup>hi</sup> monocytes of cetuximab responders displayed attenuated M2 polarization, with decreased CD163<sup>+</sup> expression and IL-10 transcripts after cetuximab treatment. This beneficial effect appeared to be FcγR dependent, since CD16 ligation reproduced the reversal of suppressive activity of MDSC <i>in vitro</i>. CD14<sup>+</sup> naïve monocytes from the co-cultures of tumor cells, cetuximab and HNSCC patient PBMC or purified monocytes were skewed to an M1-like phenotype, with increased expression of HLA-DR, CD86 and production of IL-12 p70. Likewise, reduced M2 features (expression of CD163 and production of IL-10) were found after crosslinking CD16 on the surface of monocytes to cetuximab-coated tumor cells. <h3>Conclusion</h3> Our studies demonstrate a novel function of cetuximab in ameliorating suppressive phenotypes of FcγR bearing myeloid cells in cancer patients, which is associated with better clinical outcome of cetuximab-treated patients. <h3>Clinical trial registry</h3> #NCT01218048. Registered 7 October 2010.
Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: Letter 4
Authors: Katia Tonkin
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2579 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331344 Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: Letter 4 Katia TonkinxKatia TonkinSearch for articles by this author Show More University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada https://doi.org/10.1200/JCO.2001.19.9.2579 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Idarucizumab, a Specific Dabigatran Reversal Agent, Reduces Blood Loss in a Porcine Model of Trauma With Dabigatran Anticoagulation
Authors: Oliver Grottke, Markus Honickel, Joanne van Ryn, Hugo ten Cate, Rolf Rossaint, Henri M. Spronk
Journal: Journal of the American College of Cardiology (2015)
Abstract #12: Inhibition of benzo[a]pyrene-induced DNA adducts by green tea catechins and hydrolysable tannins and structure activity relationship
Authors: Pengxiao Cao, Jian Cai, Ramesh Gupta
Journal: Cancer Research (2009)

Green tea catechins and hydrolysable tannins are gaining increasing attention as chemopreventive agents. However, the mechanism of action is poorly understood. We investigated the effects of four green tea catechins (epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate) and two hydrolysable tannins (tannic acid, pentagalloglucose) on microsomal benzo[ a ]pyrene (BP)-DNA adducts and the possible structure activity relationship. BP (1 µM) was incubated with rat liver microsomes and DNA in the presence (1-200 µM) of test compound or vehicle alone. Analysis of the purified DNA by  32 P-postlabeling showed two major adducts. These adducts were characterized as dG derivative of  anti -BPDE and epoxide of 9-OH-BP. No qualitative difference was observed in the adduct profile in the absence or presence of test phenolic compounds. However, all test phenolics inhibited the adduct formation. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC 50  = 16 µM) > epicatechin gallate (24 µM) > epigallocatechin (146 µM), epicatechin (462 µM). A strong correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies was found. Tannic acid (IC 50  = 4 µM) and pentagalloglucose (26 µM) elicited as much adduct inhibition activity as the catechins or in fact higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of the catechins and hydrolysable tannins was at least in part due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP produced by microsomal activation, DNA was incubated with  anti -BPDE (0.5 µM) in the presence of test compounds (200 µM) or vehicle. Significant inhibition of adduct formation was found upon  32 P-postlabeling analysis of the purified DNA (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by ESI-MS-MS analysis of the reaction products of  anti -BPDE with the catechins and pentagalloglucose, all of which showed clear peaks with expected mass for the complex formed. In conclusion, our data demonstrate that green tea catechins and the hydrolysable tannins are highly effective in inhibiting BP-DNA adduct formation at least in part due to direct interaction of adjacent hydroxyl groups in their structures, and that the activity is higher with increasing number of functional hydroxyl groups.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 12.
Incidence of Metabolic Risk Factors Among Healthy Obese Adults
Authors: Joshua A. Bell, Mark Hamer, G. David Batty, Archana Singh-Manoux, Séverine Sabia, Mika Kivimäki
Journal: Journal of the American College of Cardiology (2015)

Incidence of Metabolic Risk Factors Among Healthy Obese Adults 20-Year Follow-UpThere is growing evidence that obese adults without metabolic risk factor clustering (the so-called "healthy obese") progress to unhealthy obesity over time (1).However, the pathophysiological changes underlying the long-term transition into an unhealthy obese state have not been well characterized.To inform clinical management of healthy obesity, we aimed to identify the metabolic risk factors responsible for this transition, as well as the timing of their onset.Repeat clinical data were drawn from the Whitehall II cohort study of British adults.We grouped participants as normal-weight (body mass index [BMI] 18.5 to 24.9 kg/m 2 ), overweight (BMI 25 to 29 kg/m 2 ), or obese (BMI $30 kg/m 2 ), and as healthy (2) if they were free of any the following characteristics: high-density lipoprotein cholesterol <1.03 mmol/l (men) and <1.29 mmol/l (women); blood pressure $130/85 mm Hg or antihypertension medication use; fasting plasma glucose $5.6 mmol/l or diabetic medication use; triglycerides $1.7 mmol/l; and homeostatic modelassessed insulin resistance >2.83 (baseline 90th percentile value).Participants provided written FI GURE 1 Incidence of Metabolic Risk Factors Among Initially Healthy Obese Compared With Initially Healthy Normal-Weight Adults Over 20 Years (n ¼ 1,120)Results are incidence ratios and 95% confidence intervals (CI) for having each metabolic risk factor at follow-up, on the basis of Poisson regression models with robust error variances.Models are adjusted for age, sex, and ethnicity.Little difference in high-density lipoprotein cholesterol or triglycerides was observed between groups.Baseline healthy status is defined as having none of 5 metabolic risk factors (hypertension, low high-density lipoprotein cholesterol, high triglycerides, insulin resistance, and high blood glucose).
CRTAM determines the CD4+ cytotoxic T lymphocyte lineage
Authors: Arata Takeuchi, Mohamed El Sherif Gadelhaq Badr, Kosuke Miyauchi, Chitose Ishihara, Reiko Onishi, Zijin Guo, Yoshiteru Sasaki, Hiroshi Ike, Akiko Takumi, Noriko M. Tsuji, Yoshinori Murakami, Tomoya Katakai, Masato Kubo, Takashi Saito
Journal: The Journal of Experimental Medicine (2015)

Naive T cells differentiate into various effector T cells, including CD4+ helper T cell subsets and CD8+ cytotoxic T cells (CTL). Although cytotoxic CD4+ T cells (CD4+CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4+ T cells that express class I–restricted T cell–associated molecule (CRTAM) upon activation possesses the characteristics of both CD4+ and CD8+ T cells. CRTAM+ CD4+ T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM+ T cells are the precursor of CD4+CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4+CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM+ T cells traffic to mucosal tissues and inflammatory sites and developed into CD4+CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4+CTL through the induction of Eomes and CTL-related gene.
Private practice should mirror the NHS
Authors: R E Atkinson, D. G Machin
Journal: BMJ (1998)

Editor—I agree with Machin’s statement that “It is a point of principle that private practice should mirror the NHS.”1 Equality between consultants has been recognised with identical status and remuneration since the inception of the NHS. The advent of day surgery has resulted in the duties of consultant surgeons and anaesthetists becoming identical with regard to preoperative assessment, intraoperative management, and postoperative care; if anything, the anaesthetist has greater involvement on the day, as the surgeon has already seen the patient in the outpatient clinic. In private practice the surgeon charges a fee for this consultation. 

Many anaesthetists believe that the time has come for a radical overhaul of the fee structure in private practice, so that it rewards appropriately the professional skills of anaesthetists rather than reflecting values of a bygone age. Can Machin give an assurance that the BMA’s private practice committee supports the basic principle of private practice mirroring the NHS throughout all private practice? Can he explain why this principle of equality should not apply to remuneration for similar commitment in the independent sector?
Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer.
Authors: M. Cukier, H. Soliman, A. Smith, S. Wong
Journal: Journal of Clinical Oncology (2011)

3544 Background: Complete resection of colorectal cancer improves survival and reduces locoregional recurrence. Although there is an extensive body of literature on the role of neoadjuvant chemoradiotherapy (CRT) in the management of rectal cancer, its role in primary locally advanced adherent colon cancer (LAACC) is unclear. We analyzed the outcome of neoadjuvant CRT and multivisceral resection for LAACC. Methods: We retrospectively reviewed our institutional Colorectal Carcinoma Data Base (January 2000 to July 2010) for 33 patients with potentially resectable, non-metastatic primary LAACC adenocarcinoma who received neoadjuvant CRT followed by multivisceral resection. Patients with a primary within 15 cm from the anal verge were excluded. CRT consisted of radiation (45-50 Gy in 25 daily fractions) and concurrent 5FU infusion (225 mg/m2/day) for the duration of radiation. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier methodology. Results: The median age was 64 (range 31-83) with 21 male patients (63%). The median follow-up was 31 months. The most common site of the primary was in the sigmoid (63%) followed by the cecum (18%), ascending colon (6%), splenic flexure (6%) and transverse colon (6%). Excluding the involved colon, the number of abdominal structures resected ranged from 2 to 6. Postoperative complications developed in 36% of patients but no 30-day mortality was seen. All 33 patients had microscopically clear resection margins (R0). Complete pathologic response was documented in 1 patient (3%) and 66% had ypT4b disease. Seven patients (21%) had ypN0 disease. The median number of lymph nodes retrieved was 18 (0-56). Fourteen patients (42%) received post-operative adjuvant chemotherapy. The 3-year OS and 3-year DFS were 87.6% and 63.7% respectively. At last follow-up, six patients had distant metastases and two developed local recurrence. Conclusions: A multimodality treatment approach to patients with LAACC using neoadjuvant CRT and en-bloc multivisceral resection results in high rates of R0 resection and excellent local control with acceptable morbidity and mortality.
New Stent Implantation for Recurrences After Stenting for In-Stent Restenosis
Authors: Fernando Alfonso, Javier García, Maria-José Pérez-Vizcayno, Lorenzo Hernando, Rosana Hernandez, Javier Escaned, Pilar Jiménez-Quevedo, Camino Bañuelos, Carlos Macaya
Journal: Journal of the American College of Cardiology (2009)
EGFR compound mutants and survival on erlotinib in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study.
Authors: Rafael Rosell, Miguel Angel Molina-Vila, Miquel Taron, Jordi Bertran-Alamillo, Clara Mayo, Alain Vergnenegre, Filippo De Marinis, Bartomeu Massuti, Javier De Castro, Radj Gervais, Enric Carcereny, Cristina Buges, Teresa Moran, Mariacarmela Santarpia, Enriqueta Felip, Margarita Majem, Joaquim Bosch, Felipe Cardenal, Ana Drozdowskyj, Trever Grant Bivona
Journal: Journal of Clinical Oncology (2012)

7522 Background: When EGFR compound mutants (exon 19 deletions or L858R plusT790M) are present at the time of clinical resistance to erlotinib, patients attain longer overall survival (OS) (Oxnard et al. CCR 2011). The H1975 cell line, harboring L858R plus T790M prior to treatment, is sensitive to gefitinib (Sordella et al. Science 2004; Faber et al. Cancer Discovery 2011), though the compound mutant may become dominant after multiple passages in vitro, leading to resistance (Pao et al. PLoS Med 2005). Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P&lt;0.0001). No differences in OS were observed.123 p with remaining available pre-treatment tumor tissue were re-analyzed for the concomitant presence of the T790M mutation with an allelic discrimination Taqman assay in the presence of a PNA clamp designed to inhibit the amplification of the exon 20 wild-type (wt) allele. This assay is capable of detecting the T790M allele at a ratio of 1:5000 wt alleles. Results: The T790M mutation was detected in 21/64 (32.8%) p in the erlotinib arm and 26/59 (44.1%) in the chemotherapy arm. PFS was 12.1 m for p with mutant T790M in the erlotinib arm, 8.8 m for p with wt T790M in the erlotinib arm, 6.3 m for p with mutant T790M in the chemotherapy arm, and 4.5 m for p with wt T790M in the chemotherapy arm (P&lt;0.0001). OS was not reached for p with mutant T790M in the erlotinib arm, 16.1 m for p with wt T790M in the erlotinib arm, 22.6 m for p with mutant T790M in the chemotherapy arm, and 18.4 m for p with wt T790M in the chemotherapy arm (P=0.04). Conclusions: Our unexpected finding that p with EGFR compound mutants attain the maximum benefit from erlotinib suggests a need for more sensitive assays to detect EGFR compound mutants and for studies of inhibitors targeting the EGFR T790M mutation. Whole genome sequencing may provide greater understanding of the genetic factors involved in the differences in OS.
Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy
Authors: K.A. Ahmed, D.G. Stallworth, Y. Kim, P.A.S. Johnstone, L.B. Harrison, J.J. Caudell, H.H.M. Yu, A.B. Etame, J.S. Weber, G.T. Gibney
Journal: Annals of Oncology (2015)
Treatment of Pneumonia in Children
Authors: L. S. Taitz, D. Slone
Journal: BMJ (1960)

The use of oral preparations of penicillin in the successful treatment of pneumonia in adults and children has been reported (British Medical Journal, 1956;Austrian and Winstone, 1956;McWhorter et al., 1957).Because of the shortage of hospital beds, some cases of pneumonia in children have to be treated as out-patients.This necessitates daily attendance for procaine-penicillin injections.A study was undertaken to determine the efficacy of oral penicillin in the out- patient treatment of pneumonia in non-white (Coloured and African) children attending the Paediatric Depart- ment at Coronation Hospital, Johannesburg. Material and MethodsSelection of Cases.-Cases were included in the study if they manifested dyspnoea in the presence of radio- graphic evidence of pneumonia.Sixteen cases showed lobar consolidation, eleven patchy consolidation, and six moderate but unequivocal loss of translucency in one or more lobes.Dyspnoea was evidenced by mobile ala nasi, tachypnoea, and subcostal recession.Most of the cases also had other signs of pneumonia, including pyrexia, dullness to percussion, and bronchial breathing, Summary of ResultsNo. of No.0of
Measuring Quality in Oncology: Challenges and Opportunities
Authors: Jessica K. DeMartino
Journal: Journal of the National Comprehensive Cancer Network (2013)

Variations in the quality of cancer care are well documented. A key element of quality monitoring is standardized measures of care. Quality measures may include both process measures and outcome measures. Process measurement is only one aspect of assessing the quality of cancer care; measuring outcomes and providing the appropriate structure for care are also important. A variety of stakeholders, including professional oncology organizations and public and private payors, have developed programs and quality measures to address variations in the delivery of cancer care. To fulfill the current need to explore and discuss how quality is measured in oncology care, NCCN convened the NCCN Oncology Policy Summit: Measuring Quality in Oncology - Challenges and Opportunities. The summit was a forum to discuss current efforts to use quality measures, the value of quality measures, and patient and caretaker perspectives on quality.
The FDA and the Vaginal Mesh Controversy—Further Impetus to Change the 510(k) Pathway for Medical Device Approval
Authors: Vanessa L. Jacoby, Leslee Subak, L. Elaine Waetjen
Journal: JAMA Internal Medicine (2015)

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Organizing Pneumonia Induced by Nivolumab in a Patient with Metastatic Melanoma
Authors: Kazuhisa Nakashima, Tateaki Naito, Shota Omori, Shusuke Yoshikawa, Masahiro Endo, Yoshio Kiyohara, Toshiaki Takahashi
Journal: Journal of Thoracic Oncology (2015)