Suramin inhibits DNA damage in human prostate cancer cells treated with topoisomerase inhibitors in vitro

Suramin, a highly sulfonated drug, has been reported to be effective against several human malignancies in vitro and in vivo, and currently is undergoing clinical trials against prostate tumors. The biochemical and molecular mechanisms for suramin's antiproliferative activity are not clear. In order to define the biochemical basis for its antitumor activity and to enhance suramin's chemotherapeutic potential while decreasing its toxicity, we have examined interactions of suramin with topoisomerase I and 11 and several clinically active anticancer drugs against the human prostate (PC3 and LNCaP) cancer cell line. While etoposide, m-AMSA, camptothecin, and SN-38 (the active metabolite of CPT-11) were active in killing prostate cells as single agents, combinations of suramin and these agents were antagonistic against these cells. We found that suramin inhibited activities of purified topoisomerase I and II in vitro as measured by relaxation and cleavage assays. Further studies indicated that suramin also inhibited the drug-induced DNA damage in vitro and in isolated nuclei. These findings indicate that combinations of suramin with topoisomerase inhibitors, for example, VP-16, m-AMSA, or CPT, may not be beneficial to patients receiving suramin-containing chemotherapy. © 1993 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America

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A comparison of the effects of vasopressin and oxytocin with amphetamine and chlordiazepoxide on passive avoidance behaviour in rats

On the basis of results obtained from passive avoidance studies, we have argued that the neuropeptide vasopressin could act on arousal, rather than memory processes in rats (Sahgal et al. 1982). In this report, we examine the effects of substances that are known to increase (d-amphetamine) or decrease (chlordiazepoxide) behavioural arousal, and compare the data with those obtained after vasopressin or oxytocin treatment. All four substances yielded broadly similar bimodal results (although the oxytocin data failed to reach significance). We argue for an arousal interpretation which suggests that performance and arousal are related in an inverted-U manner. The data also indicate that care must be taken in selecting appropriate statistical tests.     

PET tomographic imaging of the human heart,pancreas, and liver with nitrogen-13 derived from [13N]-L-glutamate

The first commercial version of the Massachusetts General Hospital (MGH) positron camera was used to image the relative distributions of ¹³N (T _1/2=9.96min) in the human heart, pancreas, and liver after intravenous administration of [¹³N]-l-glutamate. The instrument was operated in two imaging modes. Conventional 2-dimensional (2-D) focal-plane images showed high concentrations of ¹³N in the heart and pancreas, and lower levels in the liver. Five PET tomographic transverse section (3-D) images were made through the heart and three through the pancreas. Our results suggest that further studies designed to gain an improved understanding of the biochemistry of [¹³N]-l-glutamate aided by PET imaging, especially with newer instrumentation, are worthy of further investigation.     

Educating allied health professionals to provide care for cancer patients and their families

From 1985 to 1988, a state-wide program of cancer education was offered to community-based allied health professionals (AHPs) at five different program sites in Pennsylvania. During this three-year period, 512 social workers, clergy, dieticians, physical therapists and others received training to increase their knowledge about cancer and counseling, improve their supportive attitude regarding cancer patients and families, and decrease stress related to their work with this population. Overall, the Program was successful in reaching AHPs working with cancer clients who had little formal training in the cancer field. At the beginning of training, it was observed that AHPs with initially higher levels of education and more years of work experience with cancer patients had higher levels of counseling knowledge. Those who were women, worked in hospitals, or had worked with cancer patients longer exhibited higher levels of cancer knowledge. Participants who were women and who had more education had reported lower levels of job stress. Among those AHPs who completed the training courses, cancer knowledge increased by 14 percent. In addition, knowledge related to counseling cancer patients and their families improved by 11 percentage points. Perceived job stress among the AHPs also declined by 10 percent. Finally, participant supportive attitude concerning cancer clients improved.     

A rejoinder to Professor Bruening

Point and Counterpoint

A rejoinder to Professor Bruening     

Blood lipid measurements. Variations and practical utility.

OBJECTIVE--To describe the magnitude and impact of the major biological and analytical sources of variation in serum lipid and lipoprotein levels on risk of coronary heart disease; to present a way to qualitatively estimate the total intraindividual variation; and to demonstrate how to determine the number of specimens required to estimate, with 95% confidence, the "true" underlying total cholesterol value in the serum of a patient. DATA SOURCES--Representative references on each source of variation were selected from more than 300 reviewed publications, most published within the past 5 years, to document current findings and concepts. Most articles reviewed were in English. STUDY SELECTIONS--Studies on biological sources of variation were selected using the following criteria: representative of published findings, clear statement of either significant or insignificant results, and acquisition of clinical and laboratory data under standardized conditions. Representative results for special populations such as women and children are reported when results differ from those of adult men. DATA EXTRACTION--References were selected based on acceptable experimental design and use of standardized laboratory lipid measurements. DATA SYNTHESIS--The lipid levels considered representative for a selected source of variation arose from quantitative measurements by a suitably standardized laboratory. Statistical analysis of data was examined to assure reliability. The proposed method of estimating the biological coefficient of variation must be considered to give qualitative results, because only two or three serial specimens are collected in most cases for the estimation. CONCLUSIONS--Concern has arisen about the magnitude, impact, and interpretation of preanalytical as well as analytical sources of variation on reported results of lipid measurements of an individual. Preanalytical sources of variation from behavioral, clinical, and sampling sources constitute about 60% of the total variation in a reported lipid measurement of an individual. A technique is presented to allow physicians to qualitatively estimate the intraindividual biological variation of a patient from the results of two or more specimens reported from a standardized laboratory and to determine whether additional specimens are needed to meet the National Cholesterol Education Program recommendation that the intraindividual serum total cholesterol coefficient of variation not exceed 5.0. A National Reference Method Network has been established to help solve analytical problems.     

Factors which regulate net hepatic glucose uptake in vivo

The regulation of net hepatic glucose uptake in vivo occurs by way of the hormonal milieu (insulin and glucagon), the glucose level, and the route of glucose delivery. Hyperglycemia in the absence of changes in pancreatic hormones (i.e., increased insulin and/or decreased glucagon) does not elicit significant glucose uptake by the liver. Net hepatic glucose uptake is augmented in a dose-dependent manner by a rise in insulin and is further stimulated by the presence of a "portal signal." The presence of coordinated changes in insulin, glucagon, and the glucose level in combination with the "portal signal" ensures adequate glucose uptake by the liver in response to a meal.