摘要:

AbstractThe isoquinoline sulfonamide H‐7 has been shown to delay the onset of radiation‐induced G2 arrest suggesting its possible application as a radiosensitizer. The effectiveness of H‐7 as a radiosensitizer and its toxicity in HeLa cells were evaluated. Cells were treated with either 10 or 100 μmM H‐7 and exposed to gamma radiation (0–6 Gy). H‐7 was toxic to cells at concentrations greater than 10 μM. Addition of H‐7 had no effect on the overall dose response of the HeLa cells to gamma radiation. These results suggest that the use of agents which inhibit protein kinase C activity does not necessarily result in decreased cell survival. © 1995

ISSN:1065-7541    

DOI:10.1002/roi.2970030502

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe found no significant decrease in the colony forming ability (clonogenicity) of either HeLa or S91/6 melanoma cells in hybrid spheroids incubated for 24 hr at 37°C with up to 30 μM chloroquine, nor for incubations of up to 9 hr at either 37 or 41°C with 30 μM chloroquine. Incubation for 24 hr at 41°C with chloroquine caused spheroids to disintegrate. When heating was applied to hybrid spheroids intermittently for 3 hr at the beginning and at the end of a 24 hr period of incubation with 30 μM chloroquine, there was no effect on HeLa cells but there was a highly significant decrease in the clonogenicity of S91/6 melanoma cells. Short‐term treatment (3 hr) with a combination of mild hyperthermia and 30 μM chloroquine which is non‐toxic to unirradiated cells in hybrid spheroids is, nevertheless, effective in decreasing the clonogenicity of irradiated cells of both lines. A similar increase in radiation lethality [radiation potentiating factor (RPF) of about 1.6] was obtained in both HeLa and in S91/6 cells. RPFs did not change significantly after correction of survival curves for cellular multiplicity, nor were they different from those previously reported by us for these cell lines in two versions of dense suspension cultures. Since many cells from biopsies will not grow in conventional culture systems but will do so in hybrid spheroids, the finding of similar RPF values in both systems for cell lines which will grow under both conditions suggests that hybrid spheroids may be useful for radiopotentiation studies. © 1995 Wile

ISSN:1065-7541    

DOI:10.1002/roi.2970030503

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

年代:1995

数据来源: WILEY

摘要:

AbstractPulsed low dose rate (PDR) irradiation is being investigated as an alternative to continuous low dose rate (CLDR) irradiation for the treatment of certain malignancies. Mathematical modeling by Brenner and Hall suggests that the two irradiation regimens will be equivalent under certain conditions. We are testing these predictions directly by using the mouse/SCC VII in vitro‐in vivo tumor model. This study involved in vitro irradiations that would not be expected to severely stress the assumptions of the mathematical model. The cytotoxicity of CLDR was compared to that for PDR regimens consisting of hourly radiation pulses of 5, 10, or 20 minutes and a 20‐minute radiation pulse every 2 hours. A total dose of 15.7 Gy of60Co γ‐rays was delivered over the same total time for all irradiations. Confluent cultures were irradiated in low serum at room temperature to minimize the effects of cell proliferation and cell cycling. Flow cytometric analysis demonstrated that an average of ≧80% of cells were in G0/G1phase, with ≦5% incorporating bromodeoxyuridine. Also, mitotic indices averaged<0.2%. There were no significant differences between the mean values for these cell cycle measures between CLDR and PDR or between PDR regimens. All PDR regimens showed increased cell kill relative to the CLDR, but in no case were the increases statistically significant. The increase in cell kill was by factors of 1.14–2.00, with the greatest increase in cell kill in the PDR regimen using 5‐minute pulses once per hour. The increase in cell kill, even if it was real, would not appear to be sufficient to violate the criteria for being “clinically indistinguishable,” as suggested by Brenner and Hall. Although these results generally support the modeling of Brenner and Hall, this experimental model does show increased cell killing in the PDR regimens, and this in vitro model does not stress the assumptions of the Brenner‐Hall model as severely as in vivo models would. ©

ISSN:1065-7541    

DOI:10.1002/roi.2970030504

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

年代:1995

数据来源: WILEY

摘要:

AbstractProgrammed cell death or apoptosis has recently been recognized as an important mode of cell death in the response of tumor cells to cytotoxic treatments associated with chemotherapy or radiation therapy (RT). We previously showed that both cisplatin and radiation induced substantial apoptosis in the murine mammary tumor MCA‐4 when administered as single agents in vivo. Moreover, the levels of apoptosis correlated with tumor response measured as tumor growth delay. In the current study a role for apoptosis in a combined treatment with cisplatin and radiation was evaluated. Mice bearing MCA‐4 tumors were irradiated at different times following an injection with cisplatin, and tumor growth delay was assessed. Apoptosis was scored from histological sections of the tumors. The results showed that whereas the cisplatin sensitized the MCA‐4 tumor to a subsequent irradiation in terms of the growth delay, the apoptotic index never rose above the maximum level characteristic of either agent when used singly. Thus, there was no indication that cisplatin sensitized the tumor cells to radiation‐induced apoptosis. We conclude that apoptosis is not the only important mechanism for cell killing in tumors following cytotoxic treatment and that tumor response is a complex composite of many different factors. © 1995 Wiley

ISSN:1065-7541    

DOI:10.1002/roi.2970030505

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

年代:1995

数据来源: WILEY

摘要:

AbstractUse of the anti‐estrogen tamoxifen (TAM) has been demonstrated to contribute a survival advantage in postmenopausal women with early stage or advanced breast cancer. Although conflicting results exist in the literature, some reports have suggested that TAM may exert potential deleterious effects on radiation sensitivity and response of breast cancers to radiotherapy (RT). A new non‐steroidal anti‐estrogen, ICI 182,780, which, unlike TAM, is without any estrogenic properties, has been used in European clinical trials in place of TAM. This study reports the effects of ICI 182,780 on radiation sensitivity and potentially lethal damage repair (PLDR) in estrogen‐receptor positive (ER+) MCF‐7 human breast carcinoma cells irradiated in vitro. At a concentration of 10−7M, ICI 182,780 can inhibit the growth‐stimulatory effect of 10−10M 17β‐estradiol (E2). Growth‐arrested MCF‐7 cells were divided into four treatment groups: estradiol‐deprived (−E2) and estradiol‐stimulated (+E2) cultures incubated in the presence or absence of ICI 182,780 (10−7M). Five days later each group was exposed to γ‐irradiation and cell survival was measured by clonogenic assay in complete medium containing E2. In one series of experiments, the cells were harvested immediately after irradiation, while in a second series, the cells were held at 37°C for an additional 24 hr prior to harvesting. No statistically significant survival difference was detected between groups plated immediately after irradiation or 24 hr later, although a trend toward improved survival for the delayed plating groups was routinely observed. ICI 182,780 did not significantly alter radiation sensitivity of MCF‐7 cells regardless of their hormonal status (+/−E2), nor did it change the sensitivity of cells harvested immediately or allowed 24 hr to express PLDR. These results suggest that ICI 182,780 may be used as an adjuvant in the treatment of breast cancer without altering the radiation sensitivity of breast cancer cells to

ISSN:1065-7541    

DOI:10.1002/roi.2970030506

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

年代:1995

数据来源: WILEY

摘要:

AbstractTumor size has been reported to be a limiting factor in both radiotherapy (RT) and gene therapy. Therefore, we assessed the effects of tumor necrosis factor‐alpha (TNF‐α) gene therapy and radiation in relatively large tumors in a human xenograft system. We linked DNA sequences from the promoter region of the radiation‐inducible gene Egr‐1 to the cDNA sequence that encodes human TNF‐α, a radiosensitizing cytokine. The Egr‐TNF construct was transfected into the human hematopoietic cell line HL525. Stable transfectants, exhibiting radiation inducibility of TNF‐α in vitro (clone 2 cells), were directly injected into xenografts of a radioresistant human squamous cell carcinoma cell line, SQ‐20B. In a previous study, 100 mm3tumors treated with radiation and clone 2 cells demonstrated significant tumor control (P<0.0001) when compared with tumors treated with clone 2 alone or radiation alone. In the present study, 450 mm3xenografts treated with clone 2 cells and radiation were significantly smaller (P<0.01) at the nadir of regression than tumors treated with radiation alone. Because the radiation dose was held constant (40 Gy) in both 100 and 450 mm3xenografts, only one cure was noted in the larger tumors. These data support an interactive anti‐tumor effect in vivo between radiation and TNF‐α gene therapy which is equal in both small and large human tumor xenograft models.

ISSN:1065-7541    

DOI:10.1002/roi.2970030507

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

年代:1995

数据来源: WILEY

摘要:

AbstractA measurable improvement in the efficacy of the three‐dimensional radiotherapy (RT) of primary lung cancer patients with unresectable disease will require the development of a technique that increases the therapeutic ratio of dose delivered to the tumor volume relative to functional lung. A full course of definitive RT dose was delivered to six consecutive primary lung cancer patients using multiple fields with treatment portals tightly conformed to the tumor shape in beams‐eye‐view, using multileaf collimation. For each patient, a treatment planning dose/volume histogram (DVH) was constructed considering the most anatomically normal tissues in both the ipsilateral and contralateral lungs. When compared to a standard anteroposterior‐posteroanterior (AP‐PA) treatment plan followed by parallel‐opposed oblique fields with conventional blocks, the five‐field conformal technique yielded a significantly lower integral lung dose as determined by cumulative DVH data. We compared the data for total lung capacity in cubic centimeters from the treatment planning DVH with that obtained by pulmonary function tests and found good concordance. The present RT technique and patient evaluation program should provide a valuable approach toward improving the quality of life in irradiated lung cancer patients, and may also guide efforts by which to escalate the dose to a tumor volume in the chest. © 1995 W

ISSN:1065-7541    

DOI:10.1002/roi.2970030508

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

年代:1995

数据来源: WILEY

ISSN:1065-7541    

DOI:10.1002/roi.2970030501

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

年代:1995

数据来源: WILEY