In patients with symptomatic proximal DVT, PEVI plus anticoagulation may be superior to anticoagulation-alone in the reduction of VTE and PTS at 6 months.
Multiplication-stimulating activity (MSA) produced by Buffalo rat liver cells in culture is related to the somatomedin family of growth regulatory polypeptides.MSA will stimulate glucose transport and DNA synthesis in normal chicken embryo fibroblasts (CIEF) at concentrations of 10-200 ng/ml. MSA found in BRL-3A-conditioned medium, like the somatomedins in serum, does not exist as the free hormone but is' bound to a specific high molecular weight carrier protein.In this report we demonstrate that purified MSA carrier protein (MCP) inhibits the biological activity of MSA on CEF as measured by the stimulation of glucose transport and'DNA synthesis. In addition, purified MCP competitively inhibits the binding of i25I1abeled MSA to these cells. In control experiments in which insulin was used as the mitogenic agent, MCP had no effect on these biological responses. These results indicate that the inhibitory effect of MCP'is the result of'specific interaction with MSA and support the hypothesis that cells may be unresponsive to somatomedins bound to their serum carrier proteins.
A B S T R A C T PurposeAll patients in phase I trials do not have equivalent susceptibility to serious drug-related toxicity (SDRT). Our goal was to develop a nomogram to predict the risk of cycle-one SDRT to better select appropriate patients for phase I trials.
Patients and MethodsThe prospectively maintained database of patients with solid tumor enrolled onto Cancer Therapeutics Evaluation Program-sponsored phase I trials activated between 2000 and 2010 was used. SDRT was defined as a grade Ն 4 hematologic or grade Ն 3 nonhematologic toxicity attributed, at least possibly, to study drug(s). Logistic regression was used to test the association of candidate factors to cycle-one SDRT. A final model, or nomogram, was chosen based on both clinical and statistical significance and validated internally using a bootstrapping technique and externally in an independent data set.
ResultsData from 3,104 patients enrolled onto 127 trials were analyzed to build the nomogram. In a model with multiple covariates, Eastern Cooperative Oncology Group performance status, WBC count, creatinine clearance, albumin, AST, number of study drugs, biologic study drug (yes v no), and dose (relative to maximum administered) were significant predictors of cycle-one SDRT. All significant factors except dose were included in the final nomogram. The model was validated both internally (bootstrap-adjusted concordance index, 0.60) and externally (concordance index, 0.64).
ConclusionThis nomogram can be used to accurately predict a patient's risk for SDRT at the time of enrollment. Excluding patients at high risk for SDRT should improve the safety and efficiency of phase I trials.
The lay health advisor (LHA) training program for breast cancer screening was conducted among Chinese- English bilingual trainees residing in Southeast Michigan. Guided by Bandura's Social Learning Theory, the development of the training curriculum followed the health communication process recommended by the National Cancer Institute. Data analysis based on questionnaires completed by 79 LHAs indicated that the breast cancer screening training program significantly increased LHAs' knowledge and self-efficacy (p < .01, t test, two-tailed) and LHAs had a positive perception with regard to the training manual. Regression analysis found that LHAs who were younger, employed, and demonstrated a positive perception of the training manual tended to have higher self-efficacy in promoting breast cancer screening (R(2) = .30). This study suggests that a culturally competent training program effectively increases LHAs' self-efficacy. The findings have implications for developing effective LHA training programs in Asian American communities where LHA interventions are rarely implemented.
Multiplication-stimulating activity (MSA) for chicken embryo fibroblasts was purified from serum-free medium conditioned by the growth of a line of rat liver cells (CRL). The biological activities of purified CRL MSA for chicken embryo fibroblasts were compared with those of calf serum to determine which activities are important for the stimulation of DNA synthesis and mitosis. In a balanced salt solution, only glucose and amino acids were needed in addition to purified CRL MSA to stimulate DNA synthesis maximally. Purified CRL MSA stimulated the rates of uptake of glucose and a-aminoisobutyric acid. Only the stimulation of the rate of glucose uptake appeared to be a primary response to purified CRL MSA since the stimulation was not inhibited by actinomycin D or cycloheximide. The stimulation of the rate of uptake of a-aminoisobutyric acid was inhibited by actinomycin D.CRL MSA differed from calf serum in its inability to commit cells irreversibly to synthesize DNA after the removal of CRL MSA and in its lack of the ability to stimulate the migration or prolong the survival of chicken embryo fibroblasts.Comparative studies indicated that purified CRL MSA had functional similarities to insulin and somatomedin. CRL MSA may be representative of a family of small polypeptide hormones having insulin-like activity which are involved in the control of cell multiplication.
Purpose
The NCI Cancer Therapy Evaluation Program sponsors hepatic dysfunction phase 1 clinical trials (HDCT) and phase 1 clinical trials (P1CT) to determine safe doses and schedules of antineoplastic therapeutics. We sought to compare clinical outcomes between these trial types while stratifying by hepatotoxic agents.
Experimental design
Individual subject data were extracted from the records of 51 NCI-sponsored HDCT and P1CT. The NCI’s Organ Dysfunction Working Group’s hepatic impairment categorization and two drug-induced liver injury (DILI) scales (FDA R ratio and Hy’s law) were used to classify subjects. The number of cycles administered and treatment discontinuation reason were also evaluated and compared between groups.
Results
There were 513 and 1328 subjects treated on HDCT (n=9) and P1CT (n=42), respectively. There were differing patterns of DILI with significant worsening of total bilirubin in subjects on HDCT, and worsening of ALT in subjects on P1CT. Cholestatic peak patterns of liver impairment (predominant increases in alkaline phosphatase rather than transaminases) were more frequent in HDCT. Criteria for Hy’s Law were met by 11 subjects on P1CT but not by any subjects on HDCT. Disease progression was the most common reason for treatment discontinuation, followed by adverse events at similar frequencies in both HDCT and P1CT.
Conclusions
The differential effects on hepatotoxicity suggest that underlying hepatic function may affect susceptibility to and patterns of DILI. The incorporation of additional measures of hepatic function may help identify those at highest risk of hepatotoxicity in future trials since baseline liver tests did not.
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