摘要:

AbstractPoly(adenosine diphosphate ribose) [poly(ADP‐ribose)] polymerase is a mammalian enzyme which synthesizes long chains of ADP‐ribose attached to various nuclear proteins in response to DNA strand breaks. A role for this enzyme in cellular radioresistance has been postulated due to the radiosensitizing effect of chemical inhibitors of the enzyme on some cell lines. Inhibitor studies, however, lack specificity and direct evidence for involvement of the enzyme in radioresistance is still needed. In experiments described here, intracellular levels of the enzyme were modulated using vectors to express sense and antisense human cDNA transcripts of poly(ADP‐ribose) polymerase in stably transfected NIH/3T3 mouse fibroblasts. Although antisense constructs failed to lower enzyme levels, sense transcripts increased enzyme levels. None of the transfectants, however, showed any difference in either radiation sensitivity or DNA strand break repair rates. These results suggest that simple elevation of poly(ADP‐ribose) polymerase does not affect the intrinsic cellular radioresistance of these cells. © 1993 Wiley

ISSN:1065-7541    

DOI:10.1002/roi.2970010402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe hearts of Wistar rats were locally irradiated with 15–30 Gy single doses of 300 kV X‐rays or animals were intravenously injected by single doses of 1–3 mg/kg body weight of adriamycin. Animals were followed until death or for between 320 and 710 days. After irradiation, congestive heart failure occurred with a dose‐dependent latency, which was significantly longer if the atria were excluded from the irradiation field. Cardiac output started to decrease after about 3 months, well before myocardial degeneration was noted, but it did not depend on radiation dose. After adriamycin, cardiac output showed a dose‐dependent drop within 2 weeks to plateau and never recovered to the control values. Capillary density 400 days after treatment was reduced both after irradiation and after adriamycin. Irradiation with 20 Gy 6 months after adriamycin decreased capillary density even further. © 1993 Wiley

ISSN:1065-7541    

DOI:10.1002/roi.2970010403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThree recently synthesized 2‐nitroimidazole‐linked acridine DNA intercalators (NLA‐1, NLA‐2, and NLA‐4) have been studied as potentiators of the cytotoxic effect of melphalan (L‐PAM), 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (CCNU),cis‐diamminedichloroplatinum (II) (cis‐DDP), and doxorubicin in V79 cells. In vivo studies have also been performed with all three sensitizers and L‐PAM, while NLA‐1 alone was examined for potentiation ofcis‐DDP, using C3H/HEJ mice, bearing a murine ovarian tumor. Significant chemosensitization was observed in vitro with L‐PAM, CCNU, andcis‐DDP after hypoxic preincubation treatment of the cells (37°C) at negligible concentrations of each sensitizer, while inhibition was observed with doxorubicin. Long hypoxic preexposure times at relatively low sensitizer doses were more effective than short hypoxic preexposure times at high sensitizer doses for potentiation. Glutathione depletion studies in vitro with diethyl maleate (DEM) showed that only less than half of the enhanced toxicity observed with NLA‐1 or NLA‐4 and L‐PAM is due to glutathione depletion by the sensitizer. The LD50/35value in C3H/HEJ mice for NLA‐1, NLA‐2, and NLA‐4 was 45, 25, and 63 mg/kg, respectively. Significant antitumor effect was observed in vivo when 25 mg/kg of NLA‐1 was administered i.p. to tumor‐bearing mice 2 hr before L‐PAM administration (2.5 mg/ kg, i.p.). With this combination pattern of sensitizer:antineoplastic drug, 50% cures were observed in mice followed for>150 days; no long‐term survivors were

ISSN:1065-7541    

DOI:10.1002/roi.2970010404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractHuman brain tumors are clinically very resistant to radiation therapy. Recent clinical trials of combined simultaneous brachytherapy and mild hyperthermia have shown great promise. In this study two relatively radioresistant human glioma cell lines have been irradiated in plateau growth phase under low dose‐rate (LDR) conditions (<1 cGy/min) with and without concurrent mild (39–41°C) hyperthermia. The large degree of LDR sparing observed at 0.88 cGy/min (LDR1) was almost completely inhibited by concurrent heating at 41°C, resulting in a thermal enhancement ratio (TER) of 1.6 and 1.8 at the 1% survival level for U‐87MG and U‐373MG, respectively. At 0.41 cGy/min (LDR2) concurrent heating at 41°C resulted in greater thermoradiosensitization for U‐87MG (TER 2.1) and less thermoradiosensitization for U‐373MG (TER 1.5). For U‐87MG, thermoradiosensitization with LDR2at 39 and 40°C was similar and suboptimal compared with concurrent 41°C hyperthermia. For U‐373MG, thermoradiosensitization was nearly absent at both 39 and 40°C. The direct cytotoxicity of 39, 40, and 41°C heating was similar in both cell lines. Survival after 48 hr of heating at 41°C was not less than 30% for either cell line. Hyperthermia delivered prior to LDR irradiation has shown varying degrees of sensitization both in vitro and in vivo. In this study, preheating with 8 hr at 41°C did not sensitize 9 Gy LDR2at 37°C; however, 1 hr at 43°C did result in some thermoradiosensitization with a survival reduction factor (SRF) of 1.4. With 9 Gy LDR2delivered at 41°C, preheating did result in additional thermoradiosensitization (SRF of 1.6, 3.5, respectively). The significant degree of thermoradiosensitization seen with concurrent LDR irradiation and 41°C hyperthermia with or without preheating supports the promising results seen in recent clinical tr

ISSN:1065-7541    

DOI:10.1002/roi.2970010405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractPublished local control and survival rates strongly suggest the superiority of concurrent chemotherapy (CT) and radiotherapy (RT) over RT alone in the management of esophageal cancer, at least in the first 2–3 years after treatment. It is not yet known, however, if these promising early results will be sustained at 5 years and beyond. The present report updates a series that includes 103 patients with clinical stages I—III esophageal cancer treated with combined RT (44–64 Gy) and CT (5‐fluorouracil or etoposide plus cisplatin or carboplatin) either as definite therapy (n = 45) or as pre‐esophagectomy treatment (n = 58). Five year actuarial local control was 53% in the surgery group and 39% in the group without surgery (P<0.01). Overall survival of both groups was 14% at 5 years. Late local failures and deaths beyond 3 years occurred in both groups. These results, combined with the few other series documenting 5 year outcomes, are not substantially different from 5 year results reported after RT alone. We conclude that extended follow‐up of 5 years or more is necessary before any combined modality regimen can be considered to be superior to single modality therapy for esophageal cancer. © 1993 Wil

ISSN:1065-7541    

DOI:10.1002/roi.2970010406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractFor clinical cases with difficult combinations of patient parameter values, treatment selection may be complex or controversial and require considerable time. Treatment selection may be affected by a clinician's experience with a disease and expertise with a treatment, existing protocols, capabilities of local medical facilities, and patient preference. We discuss the concepts and clinical applications of an interactive statistical package (isp) software shell which can create systems that reproduce the judgment of one or more expert clinicians in the management of a patient. An isp system can 1) be taught, verified, updated, and tailored to local facilities quickly and easily by an individual clinician, 2) compute and rank treatment selection probabilities for a presented case in accord with the treatment preferences of its human teacher and explain to a clinician the logical and statistical basis of each step of the decision process, 3) identify sensitive variables of a case for additional verification and to allow questions of the type “what would be the treatment preferences if the value of this variable were changed?”, 4) accumulate statistics for unusual cases (rare combinations of patient parameter values), and 5) continue to learn and achieve further (statistical) insight by recognizing variable combinations (joint variables) whose values are more sensitive to the selection of a particular treatment. An isp system can be used for 1) second opinions, by estimating the treatment preferences of one or more clinical experts for a particular case, 2) allowing patient involvement in the treatment decision in cases for which several treatment options may provide the same outcome, 3) quality assurance, by helping a clinician to identify and review critical patient parameter values and pivotal questions, and to check a treatment decision with his own isp system and those of colleagues, 4) avoiding unnecessary diagnostic tests, by identifying parameters that do not affect the treatment selection for a case, 5) documenting the decision factors of a case, 6) finding the reasons for differences among experts in treatment selection for different types of cases, and 7) teaching residents. The concepts and clinical application of an isp system are discussed. © 1993 Wiley‐Lis

ISSN:1065-7541    

DOI:10.1002/roi.2970010407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:1065-7541    

DOI:10.1002/roi.2970010401

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY