tbuckley/cabot-search huggingface dataset:
Abstract P115: Effect of an Environmental Intervention on the Nutrient Content of Food Served at Psychiatric Rehabilitation Centers: Results From the ACHIEVE Trial
Authors: Tiffany F Ho, Joseph V Gennusa, Cheryl Anderson, Arlene Dalcin, Lawrence J Appel, Stacy Goldsholl, Gerald Jerome, Faith Dickerson, Deborah Young, Nae-Yuh Wang, Courtney Cook, Gail L Daumit
Journal: Circulation (2015)

Introduction: Institutions that serve on-site meals provide an unrealized opportunity to improve health on a broad scale, especially for underserved populations. Psychiatric rehabilitation programs commonly serve meals to adults with serious mental illness (SMI; schizophrenia and bipolar disorder), a population with a markedly increased prevalence of obesity and high risk of cardiovascular disease mortality. In the context of a behavioral weight-loss trial incorporating weight management counseling for persons with SMI, we delivered an environmental-level intervention, focused on the food environment. Hypothesis: We hypothesized the environmental intervention would reduce the overall calories served at the psychiatric rehabilitation program study sites. Methods: We partnered with kitchen supervisors to reduce calories and improve the nutritional quality of meals served at psychiatric rehabilitation programs. Intervention staff met with kitchen staff at the beginning and followed up quarterly to assess progress and to reinforce key nutritional messages. Environmental interventions included decreasing sugar sweetened beverages, increasing whole grains, and reducing saturated fat in meals. Breakfast and lunch menus were collected at baseline and 18 months after intervention. We calculated mean (SD) total energy and nutrient content of each meal. Results: Ten psychiatric rehabilitation programs participated. Eight sites served breakfast and all sites served lunch. Compared to baseline, average breakfast calories decreased significantly after 18-months from 568.4 to 457.1 (p=0.0048) and average lunch calories decreased from 729.4 to 623.8 (p&lt;0.0001). Saturated fat in breakfast decreased by 1.9g (p=0.015) and 1.8g for lunch (p=0.0061). Total sugars at breakfast decreased from 53.3g to 40.1g (p=0.0008) and at lunch from 38.9g to 33.7g (p=0.004). Sodium was not significantly changed for breakfast (713.5mg to 557.3mg, p=0.148) but decreased by 412.4mg (1527.4mg to 1115.1mg, p=0.0008) for lunch. Conclusions: The environmental intervention implemented at psychiatric rehabilitation programs successfully reduced the amount of calories, saturated fat, sugars, and sodium served. This study suggests that modifying the food environment at psychiatric rehabilitation programs is feasible. Such programs can likely be applied to other institutions that serve on-site meals, and may be especially important in preventing cardiovascular disease in other underserved populations.
Ecteinascidin-743 is a potent inhibitor of P450 3A4 enzyme and accumulates cytoplasmic PXR to inhibit transcription of P450 3A4 and MDR1: Implications for the enhancement of cytotoxicity to chemotherapeutic agents in osteosarcoma
Authors: E. Mensah-Osman, H.-L. Lin, D. Reinke, P. Hollenberg, L. Baker
Journal: Journal of Clinical Oncology (2005)

9026 Background: Ecteinascidin 743 (ET-743) is a marine product that has been suggested to inhibit pregnane xenobiotic receptor (PXR) transcriptional activity based on its ability to down-regulate cytochrome P450 3A4 (P450 3A4) and MDR1. In this study we investigated the effect of ET-743 on the activity of P450 3A4 and determined the mechanism of PXR antagonism in osteosarcoma. Methods: Testosterone 6β-hydroxylation was used to measure the effect of ET-743 on the activity of purified, recombinant P450 3A4. Confocal microscopy was used to determine the cellular localization of PXR in cells exposed to ET-743. P450 3A4 and MDR1 proteins were measured using western blot, and the catalytic activity of P450 3A4 in whole cell lysate was measured using 7-benzyl-4(trifluoromethyl) coumarin as a probe substrate. Cytotoxicity was determined using the trypan blue exclusion method. Results: Addition of ET-743 to incubation mixtures containing P450 3A4 in the reconstituted system resulted in a concentration-dependent decrease in testosterone 6β-hydroxylation with an IC50 value of 10 μM. Dose-dependent accumulation of PXR in the cytoplasm that correlated with decreased expressions of both P450 3A4 and MDR1 proteins was observed when cells were exposed to ET-743. This effect was partially rescued when cells were pre-treated with rifampin, for 24hrs. We tested the hypothesis that interactions of ET-743 with other drugs may occur due to its effect on the pharmacokinetics of agents that are metabolized by P450 3A4 and/or transported by MDR1 protein. Cytotoxicity was enhanced in the osteosarcoma cell line following the initial exposure of cells to ET-743 prior to doxorubicin and ifosfamide. We determined that increases in sensitivity correlated best with the dose-dependent accumulation of PXR in the cytoplasm leading to the down-regulation of P450 3A4 and MDR1. Conclusion: Our data suggest that ET-743 is a potent inhibitor of P450 3A4 transcription and enzymatic activity. ET-743 also dramatically inhibits the synthesis of MDR1 in osteosarcoma cell lines due to the accumulation of PXR in the cytoplasm. No significant financial relationships to disclose.
Letrozole or anastrozole for the prevention of early recurrences in postmenopausal women with early stage breast cancer: Using number needed to treat (NNT) to compare benefit
Authors: M. Rourke, G. Dranitsaris, S. Kaura, H. S. Rugo
Journal: Journal of Clinical Oncology (2008)

17547 Background: The ATAC and BIG 1–98 clinical trials demonstrated that anastrozole (ANA) and letrozole (LET) were more effective than tamoxifen (TAM) in preventing disease relapse in postmenopausal women with early stage breast cancer. However, recent secondary analyses of these trials suggest important differences between LET and ANA in the prevention of early distant recurrences; early being defined as less than three years following the initiation of treatment.NNT represents the number of patients that need to be treated with a new intervention in order to avoid one additional event. In this analysis, the NNT approach was used to compare LET and ANA in preventing early recurrences in this patient population. Methods: The early recurrence data from the pivotal trials for LET and ANA were reviewed (Mauriac, 2007, Houghton, 2006).The time points for evaluating early recurrences for ANA and LET were at 2.5 and 2 years respectively. Patients remaining disease free beyond these time points were censored. NNT, which is the reciprocal of the percent difference in efficacy relative to tamoxifen was calculated for each agent with respect to all recurrences; local-regional, distant recurrences and contralateral breast cancer. Results: For all recurrences, LET and ANA had a comparable NNT of 75 (95%CI: 46 - 200) and 77 (95%CI: 39 - 2349) patients to avoid one recurrence.However, a 3-fold difference in NNT was noted for distant recurrences in favor of LET; 100 (95%CI: 58 - 371) patients would have to be treated with LET to avoid one such event compared to 300 (95%CI: 74 - 8) with ANA. Conclusions: In situations of multiple numerical outcomes from randomized trials, the NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, it appears most of the clinical benefit associated with ANA in the first 2–3 years is in reducing the risk of local and regional relapses, while LET shows a pronounced impact in reducing distant metastases in these first 2–3 years. These findings are particularly relevant because distant metastases are associated with the lowest survival rates and represent a major economic burden to health care systems. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis
A first-in-human phase I study to evaluate GDC-0980, an oral PI3K/mTOR inhibitor, administered QD in patients with advanced solid tumors.
Authors: A. J. Wagner, J. C. Bendell, S. Dolly, J. A. Morgan, J. A. Ware, J. Fredrickson, K. E. Mazina, J. O. Lauchle, H. A. Burris, J. S. De Bono
Journal: Journal of Clinical Oncology (2011)

3020 Background: The PI3K-AKT-mTOR signaling pathway is deregulated in a wide variety of cancers. GDC-0980 is a potent, selective, oral inhibitor of class I PI3K and mTOR kinase with in vitro IC50 of 4.8 nM for p110α/p85α and apparent Ki of 17.3 nM for human mTOR. GDC-0980 demonstrates broad activity in xenograft cancer models (breast, ovarian, lung, and prostate). Methods: A phase I dose-escalation study (PIM4604g) using a 3+3 design was initiated in patients (pts) with solid tumors. GDC-0980 was given on Day 1, followed by 1 wk washout to study single-dose pharmacokinetic (PK) and pharmacodynamic (PD) markers. GDC-0980 was then dosed QD on a 21/28-day schedule. Steady-state PK and PD were evaluated after 1 wk of QD dosing. Objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT), evaluate PD endpoints (pAKT in platelet-rich plasma [PRP] and tumor FDG avidity by PET scan [FDG-PET]), and describe anti-tumor activity. Results: Thirty-three pts have been enrolled in 7 cohorts (2-70 mg QD). GDC-0980 demonstrates dose-proportional increases in fasting mean Cmax and AUC. Preliminary PD data show >90% inhibition of pAKT levels assayed in PRP at ≥16 mg GDC-0980. Drug-related adverse events reported in ≥10% of pts were fatigue, diarrhea, decreased appetite, nausea, rash, mucositis, hyperglycemia, vomiting, and constipation. The MTD was exceeded at 70 mg with DLT of Grade (Gr) 3 maculopapular rash and symptomatic Gr 3 hyperglycemia. Three pts at 70 mg experienced Gr 2-3 pneumonitis at the end of Cycle 2. One pt at 70 mg developed Gr 3 mucositis in Cycle 2. In all cases, symptoms associated with pneumonitis resolved with drug cessation and medical management. Anti-tumor activity was observed in 3 pts with mesothelioma treated at 8, 32, or 50 mg with 23 to 28% decreases by RECIST. Five of 6 patients evaluated by FDG-PET had a response (29 to 64% decreases) by SUVmax. A pt with GIST treated at 50 mg obtained a 58% decrease in tumor FDG-PET and continued on-study for >6 mo and a pt with adrenal cell carcinoma pt continues on-study for >1 year. Conclusions: GDC-0980 is generally well tolerated at doses below 70 mg QD. PK data support QD dosing. PD and anti-tumor activity were observed.
Sixty seconds on . . . Zika virus
Authors: Owen Dyer
Journal: BMJ (2016)

Who or what is Zika anyway?It's a forest in Uganda where this virus was first found, in a rhesus monkey in 1947.Since last year Zika fever has swept across South America and is now penetrating the Caribbean. 1Nine months after its arrival, the incidence of microcephaly in newborns has rocketed in South America.
Outcome of high risk (HR) stage 3 neuroblastoma (NB) with myeloablative therapy and 13-cis-retinoic Acid
Authors: J. R. Park, J. G. Villablanca, R. Seeger, H. Shimada, W. London, R. Gerbing, C. P. Reynolds, K. K. Matthay
Journal: Journal of Clinical Oncology (2005)

8503 Background: We assessed whether myeloablative chemotherapy with purged autologous bone marrow rescue (ABMT) compared to chemotherapy (CC) alone and whether subsequent treatment with 13-cis-retinoic acid (RA) compared to no RA therapy improved event-free survival (EFS) and survival (S) for patients with high risk (HR) stage 3 neuroblastoma (NB) defined as greater than 1 year of age with amplified MYCN copy number (MYCN-A), unfavorable Shimada histopathology or elevated serum ferritin level. Methods: Seventy-two of 539 patients enrolled onto CCG study 3891 had HR stage 3 NB. Patients were analyzed using a log-rank test. Results: The 5-yr EFS and S was 55 +/- 6% and 59% +/- 6%, respectively (n=72). MYCN-A (n=24) adversely effected prognosis with 5-yr EFS of 25% +/- 9% compared to 75% +/- 7% for patients without MYCN-A (n=38), p<0.0001. Partial response (PR) or less to induction chemotherapy (n=19) adversely effected prognosis with 5-year EFS of 26 +/- 11% compared to 66 +/- 8% for patients achieving complete response or very good PR (n=45), p=0.0043. Patients randomized to ABMT (n=20) had 5-yr EFS of 65% +/- 11% and S of 65% +/- 11% compared to 41% +/- 11 (p=0.21) and 46% +/- 11% (p=0.34) for patients randomized to CC (n=23), respectively. Patients randomized to RA (n= 23) had 5-yr EFS of 70% +/- 10% and S of 78% +/- 9% compared to 59% +/- 12% (p=0.52) and 62% +/- 12% (p=0.30) for patients randomized to no RA, respectively. Patients randomized to both ABMT and RA (n=6) had a 5-yr EFS 80 +/- 18% and S of 100%. Conclusions: Although there was insufficient statistical power to detect treatment differences within this small subset, the data suggest an improved outcome for HR Stage 3 NB randomized to receive ABMT and/or RA. MYCN amplification and poor response to induction chemotherapy predict for poor outcome. Additional tumor molecular analyses may further define subsets of stage 3 patients that require aggressive therapy. No significant financial relationships to disclose.
Interaction between the <i>DNAH9</i> gene and early smoke exposure in bronchial hyperresponsiveness
Authors: Marie-Hélène Dizier, Rachel Nadif, Patricia Margaritte-Jeannin, Sheila J. Barton, Chloé Sarnowski, Valérie Gagné-Ouellet, Myriam Brossard, Nolwenn Lavielle, Jocelyne Just, Mark Lathrop, John W. Holloway, Catherine Laprise, Emmanuelle Bouzigon, Florence Demenais
Journal: European Respiratory Journal (2016)

A previous genome-wide linkage scan of bronchial hyperresponsiveness (BHR) in the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) families, performed in the presence of a gene×early-life environmental tobacco smoke (ETS) exposure interaction, showed the strongest interaction in the 17p11 region where linkage was detected only among unexposed siblings. Our goal was to conduct fine-scale mapping of 17p11 to identify single nucleotide polymorphisms (SNPs) interacting with ETS that influence BHR. Analyses were performed in 388 French EGEA asthmatic families, using a two-step strategy: 1) selection of SNPs displaying family-based association test (FBAT) association signals (p≤0.01) with BHR in unexposed siblings, and 2) a FBAT homogeneity test between exposed and unexposed siblings plus a robust log-linear interaction test. A single SNP reached the threshold (p≤3×10 −3 ) for significant interaction with ETS using both interaction tests, after accounting for multiple testing. Results were replicated in 253 French-Canadian families, but not in 341 UK families, probably due in part to differences in phenotypic features between datasets. The SNP showing significant interaction with ETS belongs to DNAH9 (dynein, axonemal, heavy chain 9), a promising candidate gene involved in respiratory cilia mobility and associated with primary ciliary dyskinesia, a disease associated with abnormalities of pulmonary function.
Impaired in vitro polymorphonuclear function secondary to the chemotherapeutic effects of vincristine, adriamycin, cyclophosphamide, and actinomycin D.
Authors: M S Cairo, C Mallett, C VandeVen, P Kempert, G A Bennetts, J Katz
Journal: Journal of Clinical Oncology (1986)

The present study investigated the in vitro effect of four different chemotherapeutic agents, namely, cyclophosphamide (CTX), vincristine (VCR), Adriamycin (Adria Laboratories, Columbus, Ohio) (ADR), and actinomycin D (ACT-D) on human polymorphonuclear leukocyte (PMN) function. Human PMNs suspended in phosphate-buffered saline (PBS) at 1 X 10(7) cells/mL were incubated with increasing concentrations of CTX (0, 10(-5), 10(-4), 10(-3) mol/L) or VCR (0, 10(-7), 10(-6), 10(-5), 10(-4) mol/L), ADR (0, 10(-6), 10(-5), 10(-4), 10(-3) mol/L), or ACT-D (0, 5 X 10(-8), 1 X 10(-7), 5 X 10(-7), and 10(-6) mol/L). The cells were then tested for bacterial killing against Staphylococcus aureus, chemotaxis activity stimulated by Escherichia coli endotoxin, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated aggregation, and cytochalasin B (Cyto B)/FMLP-stimulated superoxide production and enzyme degranulation. High concentration of CTX, an alkylating agent, showed a significant depression of PMN superoxide production, (124 +/- 13 v 161 +/- 15 nmol/10(7) cells, 5 minutes, P less than or equal to .025). ADR, an intercalating agent and membrane inhibitor, showed a significant depression of PMN degranulation and lysozyme release at 10(-4) and 10(-3) mol/L (15.3% +/- 1.7% v 24% +/- 7%, P less than .01; and 15.0% +/- 2.5% v 24% +/- 7%, P less than or equal to .025). VCR, a microtubule inhibitor, showed a significant depression of PMN aggregation at 10(-6), 10(-5), and 10(-4) mol/L (P less than .05), lysozyme release at 10(-4) mol/L (P less than .004), and beta-glucuronidase release at 10(-4) mol/L (P less than .004). In addition, chemotaxis was inhibited by VCR in a dose-dependent manner at all concentrations (10(-7) mol/L, P less than .02; 10(-6) mol/L, P less than .007; 10(-5) mol/L, P less than .006, and 10(-4) mol/L, P less than .003). ACT-D showed no significant effect on the PMN functions tested. These studies conclude that chemotherapeutic agents have modulating in vitro effects on PMN function. Further in vivo studies are therefore needed to assess PMN abnormalities in patients receiving cancer chemotherapy to determine their role in infectious complications.
Impact of organization of colorectal cancer screening: Results of EDIFICE study
Authors: Y. Coscas, D. Serin, L. Cals, F. Eisinger, J. Blay, O. Rixe, X. Pivot, T. Bouillet, C. Roussel, J. Morere
Journal: Journal of Clinical Oncology (2006)

6078 Background: The EDIFICE study aimed to allow better understanding of population’s adhesion to the tests available for the 4 most frequent cancers: breast, colorectal, prostate and lung. In 1998 the French National Consensus Conference advocated for mass cancer screening (CS) using Hemoccult II. The departments are divided according to the existence or not of an organized program: this screening was organized in 22 departments (3 “scout” started in 1998, 9 “first wave” in 2003 and 12 “second wave” in 2004). Results are reported hereunder. Methods: This first nationwide observational study was carried out in France from January 18 th to February 2 nd , 2005 among a representative sample of 1504 subjects aged between 40 and 75 years and a representative sample of 600 general practitioners (GPs). Information about participating subjects included socio-demographic characteristics, attitude towards CS, and about GPs’ medical practice regarding CS. Results: Only 25% of the 970 subjects aged between 50 and 74 years had undergone a colorectal screening test. In the organized departments (OD), the rate of persons who self-report any colorectal cancer screening was 34% vs 20% in unorganized departments (UD) (OR=1.99, CI 95% 1.47- 2.69, p&lt;0.001). The rate of recent screening within a range of 2 years was 24% for OD vs 8% for UD (OR=3.35, CI 95% 1.91- 5.88, p&lt;0.01). The rate of “fear of the test and/or its results” was higher in OD: 11% versus 6% (OR=1.97, CI 95% 1.11–3.49). The rate of GPs who advocated systematically for screening was 40%, 29%, 26% and 13% for scout, first wave, second wave OD and baseline UD respectively. Organization reduced the rate of screening based on colonoscopy alone from 69% persons in UD to 35% in the OD. Conclusions: The main result of this survey comparing data in the same frame of time, in the same country, is that organized programs for colorectal cancer impact of health outcomes. No significant financial relationships to disclose.
Cytotoxic activities of fermented wheat germ extract on human gastric carcinoma cells by induction of apoptosis
Authors: S. N. Lee, H. Park, K. E. Lee
Journal: Journal of Clinical Oncology (2005)

4254 Background: The fermented wheat germ extract (code name:MSC, trade name: Avemar), is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. The objective of this study was to examine the in vitro cytotoxic activities of Avemar on 5 human gastric carcinoma cell lines and to test whether the mechanism involves induction of apoptosis. Methods: Cytotoxic activities of Avemar on 5 human gastric carcinoma cell lines (SNU-1, SNU-5, SNU-16, SNU-620, MKN-45) were examined using XTT cytotoxicity assay and apoptosis was measured by Sub-G1 fraction on flow histograms and annexin V- and propidium iodide-stained fraction on flow histogram. Results: Avemar dose-dependently suppressed the growth of all 5 examined gastric carcinoma cells by more than 90%, with ascending order of IC50 values: SNU-5 (0.37mg/mL), MKN-45 (0.49mg/mL), SNU-620 (0.52 mg/mL), SNU-1 (0.58 mg/mL) and SNU-16 (0.62mg/mL). Flow cytometry of Sub-G1 cells or annexin V- and propidium iodide-stained cells indicated that the growth inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Conclusions: Avemar was found to dose-dependently inhibit the growth of gastric carcinoma cells possibly via an apoptosis-dependent pathway and has a potential to be an additive or synergistic effect with cytotoxic agents. No significant financial relationships to disclose.
Phase II trial of neoadjuvant docetaxel with or without bevacizumab in patients with locally advanced breast cance
Authors: B. Overmoyer, P. Silverman, R. Leeming, R. Shenk, J. Lyons, N. Ziats, J. Jesberger, L. Dumadag, S. Remick, H. Chen
Journal: Journal of Clinical Oncology (2004)

727 Background: The anti-angiogenic agent, bevacizumab (rhuMAbVEGF) is a humanized monoclonal antibody against VEGF which, when combined with docetaxel in preclinical models, results in synergistic suppression of capillary vessel formation. Based on these data, a randomized phase II trial was developed to evaluate the vascular effects on tumor regression with combination bevacizumab/docetaxel vs. docetaxel in the treatment of locally advanced breast cancer. Methods: 33 patients (pts) were randomized to receive neoadjuvant therapy with bevacizumab (10 mg/kg qowk) and docetaxel (two 8-week cycles of 35 mg/m2 weekly x 6 with a 2 wk break) or docetaxel alone. Eligible pts had locally unresectable breast cancer with or without metastasis. Pts who responded underwent definitive surgery, radiation, 4 cycles of adjuvant conventional Adriamycin/cyclophosphamide, followed by tamoxifen (if ER/PR+). Results: 26 pts completed pre-operative treatment. 3 pts with inflammatory breast cancer were not operable at the conclusion of therapy because of residual disease. The median number of pathologically + lymph nodes (ln) was 1 (range 0–16); 40% were ln negative. The median size of residual tumor was 3.2cm (range 0–14cm). Toxicity included: grade 4 neutropenia-4; grade 3: anorexia-3; GI bleed-1; stomatitis-3; neuropathy-1; wound healing-1. There was no change in LVEF, no hypertension, protienuria, or thrombosis. Preliminary analysis of correlative studies suggests a reduction in tumor Kep by DCE-MRI and a reduction of tumor microvessel density. Conclusions: Neoadjuvant therapy for locally advanced breast cancer using docetaxel with or without bevacizumab is well tolerated and effective. This study requires a total of 60 pts before an analysis can be made of a treatment difference in vascular and disease response. Laboratory correlatives evaluating effects on tumor vasculature are ongoing. (Sponsored by grants: K23CA 87725–01, M01 RR 00080, UO1 CA 62502, P30 CA43703S NCI/Avon) No significant financial relationships to disclose.