Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Men, medicine and machines

PURPOSE: To examine the management and possible causes of primary valve malfunction of the Krupin eye valve with disk. METHODS: The authors reviewed the results of 113 patients undergoing implantation of the Krupin eye valve with disk and identified eight patients with primary valve malfunction requiring surgical revision. RESULTS: Valve revision involved manipulation (n = 1 case), explantation of the malfunctioning valve and implantation of a new valve (n = 2), and amputation of the valve (n = 5). Six of eight patients had final intraocular pressures of < 21 mmHg on one or no medications at a mean interval of 15.9 months (range 5-36) after surgical revision. Transient postoperative hypotony was noted in three patients and chronic hypotony with loss of light perception in one patient. One explanted valve was examined and found to have partially fused leaflets. CONCLUSIONS: Surgical revision in cases of primary valve malfunction of the Krupin eye valve with disk may be accomplished relatively safely with an acceptable level of postoperative complications. The etiology of primary valve malfunction may be related to the sterilization process and prolonged storage before implantation.     

Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo

The purpose of this study was to identify the optimal knot construction for interrupted dermal sutures. A synthetic braided absorbable suture, sizes 3-0 and 5-0, was selected for this evaluation. With reproducible mechanical performance tests, we determined that the construction of secure knots without ears required one additional throw as compared with secure knots with 3-mm ears. The direction of applied tension did not alter knot security, with the exception of granny knots, which required an extra throw when tension was applied parallel to the suture loop. Because interrupted dermal knot construction is accomplished without knot ears and with an applied tension parallel to the wound, one additional throw must be added to the knot to ensure knot security.     

Thermal image analysis for polygraph testing

We have designed, developed, and tested a very promising thermal image analysis method for polygraph testing. The method achieved a correct classification rate of CCR= 84% on the test population to our avail. This method, once refined, can serve as an additional channel for increasing the reliability and accuracy of traditional polygraph examination. We extract subtle facial temperature fluctuation patterns through nonlinear heat transfer modeling. The modeling transforms raw thermal data to blood flow rate information. Then, we use the slope of the average periorbital blood flow rate as the feature of a binary classification scheme. The results come to support our previous laboratory findings about the importance of periorbital blood flow in anxious states.     

The Kitty Genovese murder and the social psychology of helping: The parable of the 38 witnesses.

This article argues that an iconic event in the history of helping research--the story of the 38 witnesses who remained inactive during the murder of Kitty Genovese--is not supported by the available evidence. Using archive material, the authors show that there is no evidence for the presence of 38 witnesses, or that witnesses observed the murder, or that witnesses remained inactive. Drawing a distinction between the robust bystander research tradition and the story of the 38 witnesses, the authors explore the consequences of the story for the discipline of psychology. They argue that the story itself plays a key role in psychology textbooks. They also suggest that the story marks a new way of conceptualizing the dangers of immersion in social groups. Finally, they suggest that the story itself has become a modern parable, the telling of which has served to limit the scope of inquiry into emergency helping. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lizards as hosts for immature Ixodes scapularis (Acari: Ixodidae) in North Carolina

Previously archived museum specimens of lizards collected throughout North Carolina were examined for Ixodes scapularis (Say). Lizards (n = 1,349) collected in 80 of North Carolina's 100 counties were examined. Lizards with ticks were collected in 23 (29%) of the 80 counties from which lizards were examined. I. scapularis was detected on 8.7% (n = 117) of the lizards and was the sole species of tick obtained from lizards. Immature ticks were most frequently found on the southeastern five-lined skink, Eumeces inexpectatus, and the eastern glass lizard, Ophisaurus ventralis. Larvae were most frequently found on the six-lined racerunner, Cnemidophorus sexlineatus. One C. sexlineatus harbored 177 larvae and 2 nymphs. Nymphs were most frequently observed on E. inexpectatus. The majority of counties (chi 2, P < 0.01) where ticks were found on lizards were in the Coastal Plain.     

An extended panel of hamster-human hybrids for chromosome 2q

A hamster-human hybrid containing only the q arm of chromosome 2 has been used to construct a panel of hybrids bearing reduced regions of chromosome 2 using the technique of irradiation fusion gene transfer. The human chromosome 2 carried the Ecogpt gene and all hybrids were selected using this marker. The integrated Ecogpt gene was localized to the region 2q33-34, resulting in the selective retention of this region in the hybrids. These data were combined with another previously constructed panel of hybrids containing regions of 2q, which were enriched for the region 2q36-37. The combined hybrid panel is useful for the mapping of new markers to defined regions of chromosome 2 and for the cloning of genes located on 2q by a positional strategy.     

Fetus-in-fetu with malignant recurrence

Fetus-in-fetu is an unusual condition in which a vertebrate fetus is enclosed within the abdomen of another fetus. These occurrences are usually benign. This report describes an instance of malignant recurrence after resection of a fetus-in-fetu.