tbuckley/cabot-search huggingface dataset:
Polyadenylic Acid Metabolizing Enzyme Levels During Induction of Differentiation in a Human Leukemia T-Cell Line With Phorbol Ester&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Perez, T Trangas, D Kokkinopoulos, C M Tsiapalis, M Papamichail
Journal: JNCI Journal of the National Cancer Institute (1987)

Induction of differentiation of MOLT3 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to affect the activity levels of the polyadenylic acid [poly(A)] metabolizing enzymes. TPA administration at a concentration of 16 nM resulted in an increase of poly(A) exonuclease and poly(A) polymerase activities after 2 and 2.5 hours, respectively, and in a decline to control levels thereafter. Cordycepin, an inhibitor of poly(A) polymerization, prevented the increasing binding of OKT11A monoclonal antibody induced by TPA treatment, whereas TPA-induced reduction in OKT6 monoclonal antibody binding persisted. The alterations in the poly(A) metabolizing enzyme activities following treatment of the cells with TPA, as well as the inhibitory effect of cordycepin, may suggest that these enzymes may be involved in the regulation of the differentiation process.
Ten- to Fourteen-Year Effect of Screening on Breast Cancer Mortality&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Shapiro, W Venet, P Strax, L Venet, R Roeser
Journal: JNCI Journal of the National Cancer Institute (1982)

Results from the randomized trial conducted by the Health Insurance Plan (HIP) to determine the efficacy of breast cancer screening with mammography and palpation are reported for longer periods than previously available. By the end of 10 years after entry, the study group's mortality due to breast cancer was about 30% below the control group's. Arithmetic gains due to screening were maintained through year 14; relative gains declined. With increases in the period of follow-up, cumulative survival rates among cases detected by mammography alone (palpation negative during screening), decreased more rapidly than rates among other subgroups, but survival rates for mammography cases remained relatively high. Study women aged 40-49 years at entry began to show lower breast cancer mortality than those in the control group as duration of follow-up increased. Reservations are advanced about the acceptance of this finding as evidence of the efficacy of screening under age 50 under the conditions of the HIP study. The reservations are based on the observation that the decrease of mortality among the study group aged 45-49 at entry is concentrated entirely among cases diagnosed after they reached 50 years of age.
Short-term dynamic psychotherapy
Authors: J Marmor
Journal: American Journal of Psychiatry (1979)

Short-term dynamic psychotherapy is rooted in psychoanalytic theory. The author traces the historical background of brief psychotherapy, focusing on the contributions of Freud, Ferenczi, Rank, and Alexander and French, and then presents a synthesis of contemporary views. Selection criteria for patients who can benefit from short-term therapy, and the techniques used, are discussed. Similarities to and differences from crisis intervention techniques are pointed out. The trend of the future can be expected to be toward shorter-term therapies, but given the present state of psychiatric knowledge, long-term therapy will still be necessary for many patients.
A comprehensive profiling of colorectal cancer patients through multiplexed functional pathway signature and somatic mutation analysis for effective therapy selection.
Authors: H. C. Kim, P. S. Kim, F. Princen, G. Meyer, E. Webster, S. Brown, R. Kirkland, J. Zhou, C. Triggs, X. Liu, S. Singh
Journal: Journal of Clinical Oncology (2011)

e14103 Background: Colorectal cancer (CRC) is a leading cause of death in the developed nations. The development of effective forms of cytotoxic chemotherapy for colorectal cancer has been paralleled by the emergence of monoclonal antibodies against proteins that are thought to be important in the proliferation of malignant cells. Recent clinical studies showed that EGFR-targeting agent improved response rate when added to chemotherapy, however patients with KRAS mutations did not benefit from such treatment. Here we report a comprehensive profiling of pathwy signal proteins for their level of expression/activation and presence of somatic mutations in tumor tissues obtained from 136 CRC patients. Methods: The collaborative enzyme enhanced reactive immunoassay (CEER) is a multiplexed protein microarray platform requiring co-localization of two detector enzyme-conjugated-antibodies. Once target proteins are captured on the microarray-surface, channeling events between two detector enzymes in proximity enable the profiling of the target proteins with high sensitivity. In this study, tumor lysates were prepared from frozen tissues obtained from 136 CRC patients. In addition to a multiplexed analysis for panel of mutations in KRAS and BRAF genes, the level of expression and activation of HER1, HER2, HER3, cMET, cKIT, IGF-1R, PI3K, AKT, ERK and other pathway proteins were determined using CEER technology. Results: KRAS and BRAF mutations were found in ~40% (54/136) and ~5% (6/136) respectively in this cohort. The most frequent mutant alleles were G12D (14%) and G13D (13%). Varying levels of RTKs and associated activation patterns were observed. Levels of phosphorylated ERK and AKT correlated to expression/activation patterns of HER1, cMET, HER3 and prevalence of each biomarker along with pathway redundancy will be presented. Conclusions: A comprehensive profiling of multiplexed pathway/ somatic mutation analysis provides critical information needed to select the most effective targeted agents to overcome pathway redundancy /activating mutation related drug resistance through treatment combination or sequencing.
Plans of American medical oncologists (AMO) to order molecular testing before starting first-line therapy for patients with stage IV non-small cell lung cancer (NSCLC).
Authors: M. R. Green, A. J. Wozniak, J. Willey, K. E. Lemke, H. J. West
Journal: Journal of Clinical Oncology (2010)

7568 Background: Molecular testing can be used to predict the likelihood of response to specific treatments for patients with NSCLC. Different testing algorithms have been proposed by academic investigators or groups. We assessed plans among AMOs to incorporate marker testing into their treatment planning process for patients with advanced NSCLC. Methods: Between March and September 2009 we studied > 700 AMOs in 2 different research series using an extensively tested, live, case-based, market research vehicle to anonymously acquire data concerning marker testing plans. Here we report our findings related to testing before prescribing first-line therapy in advanced NSCLC. Results: In the setting of a 58 y.o. female former smoker (∼ 20 pack years total) with stage IV lung adenocarcinoma, PS 1, no contraindications to chemotherapy or bevacizumab use and adequate tissue for testing, the following testing plans emerged in the aggregate data set: No testing before prescribing 62%; EGFR mutation testing only 9.5%; KRAS and EGFR mutation testing 4.5%; KRAS mutation testing only 3.5%; ERCC-1 testing 2.5%; EGFR copy number by FISH 2.5%; EGFR expression by IHC 2%; 2 or all 3 of the following – KRAS mutation/EGFR by IHC/ ERCC-1 – 13.5%; other 1%. Conclusions: A “test all patients” paradigm to direct prescribing plans in the advanced NSCLC setting has been proposed by an increasing number of experts. There is thus far no consensus on exact testing algorithm. Currently a “do not test” paradigm is firmly in place in the treating community. Among AMOs who do plan marker testing there is no consensus about which test or tests should be ordered, though mutation testing is most preferred. Thus far, the multiple, overlapping, research findings on marker testing have not resulted in a clearly articulated testing algorithm that has been embraced by AMOs as broadly applicable to their prescribing plan decision making for their patients getting first-line therapy for advanced NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcenda, LLC Xcenda, LLC
Progression-free survival (PFS) as a surrogate for overall survival (OS) in patients with advanced colorectal cancer: An analysis of 3159 patients randomized in 11 trials
Authors: M. Buyse, T. Burzykowski, K. Carroll, S. Michiels, J. P. Pignon, P. Piedbois
Journal: Journal of Clinical Oncology (2005)

3513 Background: The traditional endpoint for efficacy in advanced colorectal cancer is OS, but this endpoint requires prolonged follow-up and the impact of first-line therapy on OS may be confounded by the effect of second-line therapies. We investigate whether PFS can replace OS as the primary endpoint in randomized trials on patients with advanced colorectal cancer. Methods: Individual patient data were available from 11 randomized phase III trials comparing 5-fluorouracil (5FU) + folinic acid (LV) to either 5FU alone (8 trials, 1814 patients) or raltitrexed (3 trials, 1345 patients). The correlation between PFS and OS was estimated through the bivariate distribution of these endpoints over the entire time range, or using Kaplan-Meier estimates of 6-month PFS and 12-month OS within each trial. The correlation between the treatment effects on PFS and OS was estimated using the hazard ratios over the entire time range, or up until 6 months for PFS and 12 months for OS. Correlation coefficients were estimated with their 95% confidence intervals (CI). Results: Median follow-up of alive patients was 13 months, median OS 11 months, and median PFS 5.5 months. A total of 1688 (53%) patients had progressed at 6 months, and 1659 (52%) had died at 12 months. The correlation between PFS and OS was 0.64 (CI 0.62 - 0.65). The correlation between 6-month PFS and 12-month OS was 0.19 (CI -0.26 - 0.65). PFS and OS were significantly longer with 5FU + LV than with 5FU or raltitrexed alone, with hazard ratios in favor of the combination of 0.78 (CI 0.72 - 0.85, P<0.001) for PFS and 0.86 (CI 0.79 - 0.93, P<0.001) for OS. The correlation between the log hazard ratios was 0.99 (CI 0.94 - 1.03). The correlation between the log hazard ratios up until 6-month for PFS and 12 months for OS was 0.93 (CI 0.84 - 1.01), and therefore the treatment effect on PFS at 6 months reliably predicted the treatment effect on OS at 12 months. Conclusions: PFS is poorly correlated with OS in patients with advanced colorectal cancer. In contrast, the effects of treatment upon PFS and OS are very strongly correlated, suggesting that PFS is a useful surrogate for OS in randomized trials on patients with advanced colorectal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Multicenter Phase II Trial of Temozolomide in Patients With Anaplastic Astrocytoma or Anaplastic Oligoastrocytoma at First Relapse
Authors: W.K. Alfred Yung, Michael D. Prados, Ricardo Yaya-Tur, Steven S. Rosenfeld, Michael Brada, Henry S. Friedman, Robert Albright, Jeffrey Olson, Susan M. Chang, Alison M. O'Neill, Allan H. Friedman, Janet Bruner, Nancy Yue, Margaret Dugan, Sara Zaknoen, Victor A. Levin
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m 2 /d. Patients previously treated with chemotherapy received temozolomide 150 mg/m 2 /d; the dose could be increased to 200 mg/m 2 /d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
The utility of dermoscopy-guided histologic sectioning for the diagnosis of melanocytic lesions: A case-control study
Authors: Emily A. Merkel, Sapna M. Amin, Christina Y. Lee, Alfred W. Rademaker, Pedram Yazdan, Mary C. Martini, Joan Guitart, Pedram Gerami
Journal: Journal of the American Academy of Dermatology (2016)
Effect of combination inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGF-R) on ovarian cancer cell lines
Authors: S. M. Kehoe, C. Ma, N. Rosales, T. Rao, J. Dupont, D. R. Spriggs
Journal: Journal of Clinical Oncology (2006)

13112 Background: Bevacizumab, a VEGF inhibitor, and cetuximab, an EGF-R inhibitor, have shown promising results in the treatment of solid tumors. The combination of these two antibodies and combinations with platinum chemotherapy is of interest for the treatment of ovarian cancer. Our objective is evaluate the mechanism of action and to determine the direct effect on tumor proliferation, the role of antibody dependent cell cytotoxicity (ADCC) with immune effector cells and the outcome in nude mouse xenografts with antibody treatment combinations. Methods: Five ovarian cancer cell lines were studied; SKOV3, SKOV8, OVCAR3, A2780, and CaOV3. VEGF secretion levels were determined for each cell line by standard ELISA. EGF-R, VEGF-R and VEGF surface expression was determined by flow cytometry. Cytotoxicity alamar blue 96-well plate assays were performed and cells were plated and exposed to bevacizumab or cetuximab alone, in combination and with cisplatin. Standard 51 chromium release assays were performed to determine if bevacizumab and cetuximab have a role in ADCC when combined with peripheral blood mononuclear cells (PBMC). Results: All ovarian cancer cell lines secreted VEGF ranging from 210 to 1,849 pg/ml. Flow cytometry studies demonstrated varying degrees of expression of VEGF-R and minimal surface expression of VEGF ligand. EGF-R was present on all cell lines. Five day alamar blue cytotoxicity assays using varying concentrations of single agent bevacizumab (0.1–10 μM) or single agent cetuximab (0.01–1.0 μM) had minimal to no cytotoxic effect on ovarian cancer cell lines. The IC 50 for cisplatin in these cell lines was obtained and ranged from 1–5 μM and was not altered by the addition of antibodies. In 51 chromium release assays, the combination of bevacizumab and cetuximab caused a trend toward increased SKOV3 cell lysis by PBMC. Conclusion: Bevacizumab or cetuximab alone or in combination with each other in vitro had minimal direct cytotoxic effect. ADCC may be a mechanism of cell lysis when these antibodies are combined with effector cells (PBMC) and further studies are underway. In vivo studies with nude mouse SKOV3 xenografts are being performed to evaluate the effect on combination antibody therapy on established tumors. No significant financial relationships to disclose.
An EORTC Gastrointestinal Group evaluation of the combination of sequential methotrexate and 5-fluorouracil, combined with adriamycin in advanced measurable gastric cancer.
Authors: J Wils, H Bleiberg, O Dalesio, G Blijham, N Mulder, A Planting, T Splinter, N Duez
Journal: Journal of Clinical Oncology (1986)

In a phase II multicenter trial, 71 patients with advanced measurable gastric cancer were registered to receive sequential high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (A [Adria Laboratories, Columbus, OH]). The response rate was 33% (22 of 67), including all eligible patients. There were nine complete responders (CRs). The median survival for all patients was 6 months. There has been one toxic death; however, three other patients died from toxicity associated with major protocol violations. It is concluded that this protocol is active in gastric cancer. Toxicity, partly because of nonprotocol adherence, is considerable and is now under further investigation in a randomized trial comparing this schedule with a combination of 5-FU, Adriamycin, and mitomycin C (FAM).
Phase II study of bevacizumab (Bev) combined with weekly paclitaxel (wPac) as first-line therapy for Japanese patients (pts) with HER2-negative metastatic breast cancer (MBC).
Authors: N. Masuda, K. Aogi, S. Ohno, H. Iwata, M. Kashiwaba, Y. Fujiwara, Y. Ito, T. Ueno, N. Saijo, S. Takashima
Journal: Journal of Clinical Oncology (2010)

1121 Background: Three phase III trials have shown significantly improved progression-free survival (PFS) and response rate (RR) when Bev is combined with first-line taxane or other standard therapy. As Bev data in Japanese populations are limited, we conducted a phase II study exclusively in Japanese MBC pts. Methods: Pts ≥20 years with HER2-negative measurable MBC, ECOG PS≤1 and no prior chemotherapy for MBC received Bev 10 mg/kg d1 and 15 with wPac 90 mg/m2, d1, 8, and 15 q4w, as in E2100. Coprimary endpoints were PFS and safety. Secondary endpoints included RR (RECIST v1) and overall survival (OS). Results: All 120 planned eligible pts were enrolled between April 2007 and July 2008. Median age was 55 years (17% aged ≥65), 28% had a disease-free interval (DFI) ≤24 months and 54% had received prior adjuvant chemotherapy. As of June 2009, 39 pts (33%) remained on therapy and 81 (68%) had discontinued. Disease had progressed in 50%. Median PFS was 12.9 months (95% CI 11.1-18.2). PFS results in clinically relevant subgroups (age, ER/PgR status, visceral metastases, prior chemotherapy, and DFI) were consistent with data from the randomized E2100 trial. The RR in 117 evaluable pts was 74% (95% CI 64.5-81.2). A further 11% had stable disease for ≥24 weeks. Median OS has not been reached; the 1- year OS rate is 89%. Median exposure to Bev and wPac was 10.6 months (range 0.3-24.7). The main reason for discontinuation was progression (45%). Grade 3 hypertension was reported in 17% (no grade 4); grade >2 proteinuria was absent; grade 3 or 4 bleeding occurred in 2% and 1%, respectively. There were no treatment-related deaths. Conclusions: The Bev-wPac combination in this large, single-arm Japanese study showed high activity, similar to that seen in E2100. No new safety signals were seen in this Japanese population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Takeda AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Takeda
Abstract P111: Serum and Dietary Magnesium and the Incidence of Atrial Fibrillation in Whites and African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Jeffrey R Misialek, Faye L Lopez, Rachel R Huxley, James M Peacock, Lin Y Chen, Elsayed Z Soliman, Sunil K Agarwal, Alvaro Alonso
Journal: Circulation (2012)

Background: Low serum magnesium (Mg) has been associated with a higher cardiovascular risk and other cardiovascular diseases (CVD) including ventricular arrhythmias. However, the association between serum or dietary Mg and atrial fibrillation (AF) has not been investigated to date. Methods: We studied 14,290 men and women (75% white, 53% women, mean age 54) free of AF at baseline participating in the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort in the United States. Serum Mg was assessed at baseline (1987-89) and a second visit (1990-92) while dietary Mg was assessed at baseline and a third visit (1993-95). The mean value of two Mg measurements were used for individuals who attended both visits while the baseline Mg measurement was used for individuals who did not attend another visit or were censored. Incident AF cases through 2008 were ascertained from electrocardiograms, hospital discharge codes, and death certificates. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for AF associated with serum and dietary Mg quintiles. Models were initially adjusted for age, sex, race, and ARIC field center, and additional models further adjusted for other cardiovascular risk factors and prevalent CVD. Dietary Mg analyses included correlated dietary covariates in all models. Interaction by race and sex was tested for serum and dietary Mg. Results: Over a median follow-up time of 19.7 years, 1,613 incident AF cases were identified. Higher serum Mg was associated with lower AF risk even after adjustment for cardiovascular risk factors and other CVD (table), with no evidence of significant interactions between serum Mg and sex or race. No significant association was identified between dietary Mg and AF. Conclusion: High serum Mg was associated with a lower AF risk, and this association was not different between whites and African Americans. Dietary Mg was not associated with AF risk. Funding(This research has received full or partial funding support from the American Heart Association, National Center)
Cardiac morphologic and functional changes induced by epirubicin chemotherapy.
Authors: M D Dardir, V J Ferrans, Y S Mikhael, M S el-Grindy, A B el-Aasar, H M el-Zawahry, D W Alling, S M Banks, N G el-Mawla
Journal: Journal of Clinical Oncology (1989)

Cardiac toxicity was evaluated in 24 patients who received epirubicin as a single chemotherapeutic agent, in doses of either 30 mg/m2 every week (11 patients) or 90 mg/m2 every 3 weeks (13 patients). The total doses of epirubicin ranged from 180 mg/m2 to 918 mg/m2 (mean, 491 +/- 187). No patient had prior heart disease, hypertension, mediastinal irradiation, or chemotherapy with other anthracycline agents. None of the patients developed overt heart failure, significant arrhythmias, ECG alterations, or roentgenographic changes in heart size. There was no significant change in the mean value of echocardiographic percent fractional shortening before and after epirubicin therapy. Patients receiving epirubicin doses less than 450 mg/m2 had minimal hemodynamic disturbances; however, no cut-off point separating two significantly different subpopulations could be demonstrated. Endomyocardial biopsy was performed on all patients; 20 biopsies were evaluable. Histologic and ultrastructural changes were similar to those caused by other anthracycline agents. A strong correlation was demonstrated between total dose of epirubicin and pathologic change as quantified using the Billingham scale (r = .7, P = .0006). A cut-off point beyond which there was a probability of increased pathologic damage was statistically defined at 450 mg/m2 of epirubicin. Severe pathologic alterations and moderate hemodynamic changes were observed in only one patient, who received 918 mg/m2 of epirubicin. Patients who are expected to receive epirubicin in excess of 450 mg/m2 should be monitored for cardiac toxicity, and continuation of epirubicin therapy beyond 900 mg/m2 should be based on the results of monitoring.
대간간학회지 제6차 춘계학술대회 초록집 : 구연 ; Dimethylnitrosamine 유발 간 섬유화 과정 중 간세포 및 Ito 세포에서의 세포 주기 조절 단백질 발현양상
Authors: 김미란 ( Kim Mi Lan ), 이민재 ( Lee Min Jae ), 정인평 ( Jeong In Pyeong ), 조은숙 ( Jo Eun Sug ), 장자준 ( Jang Ja Jun )
Journal: Clinical and Molecular Hepatology (2000)