摘要:

AbstractWe have examined the mechanism of activation of c‐raf‐1 and the expression of epidermal growth factor receptor (EGF‐R) gene in the three relatively radiation resistant human squamous cell carcinoma‐derived cell lines (SCC‐35, JSQ‐3, and SQ‐20B). The human c‐raf‐1 sequences were observed in the primary G418r, human Alu+NIH/3T3 clones transfected with these tumor cell DNAs. The humanraf‐1‐related sequences were truncated, rearranged, and amplified in the primary NIH/3T3 transfectants, and a majority of the clones revealed sequences corresponding to the carboxy‐terminus of the protein product of humanraf‐1 (Raf‐1). A highly tumorigenic potential of transfectant clones correlated with expression of the new (human)raf‐1‐related sequences. By contrast, the EGF‐R gene was amplified and aberrantly overexpressed in only the SQ‐20B tumor cells. The human EGF‐R‐related sequences were not detected in the human Alu+NIH/3T3 transfectant clones, including those derived following the SQ‐20B tumor cell DNA transfection. The levels of Raf‐1‐associated serine/threonine kinase activity were comparable in SCC‐35 and SQ‐20B cells. We have previously reported that the antisense c‐raf‐1 cDNA transfection is sufficient for the down regulation of tumorigenicity and radioresistance in SQ‐20B cells. The present data suggest that the role of c‐raf‐1 in the development of the tumor phenotype may be unrelated to the amplification and activation of EGF‐R in t

ISSN:1065-7541    

DOI:10.1002/roi.2970010103

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

年代:1993

数据来源: WILEY

摘要:

AbstractPerfluorochemical emulsions are highly biocompatible materials which carry and deliver oxygen when a high oxygen content atmosphere is breathed. The concentrated perflubron emulsionOxygent™CA (Oxygent) used in the current study is a second generation perfluorocarbon emulsion which is much more stable and much more concentrated (90% w/v perflubron) than the earlier preparations. In combination with single dose radiation, a range ofOxygentdoses corresponding to perfluorochemical levels from 4 to 12 g/kg led to dose modifying factors from 1.2 to 1.9, respectively. With daily fractionated radiation and dailyOxygentadministration over the same dosage range, dose modifying factors from 1.4 to 2.1 were achieved. In general, administration ofOxygentprior to each radiation fraction produced the greatest enhancement in tumor response, although the highest dose ofOxygentadministered (12 g/kg) on alternate days with daily carbogen breathing produced a comparable tumor growth delay to 4 g/kg of the perfluorochemical emulsion administered daily with carbogen breathing. Rapid administration of the emulsion was necessary to achieve maximal enhancement of tumor growth delay from this therapeutic adjuvant. These results indicate that dose, schedule of administration, and rate of infusion are important variables to consider in the design of clinical trials to maximize the therapeutic benefit achievable with perfluorochemical emulsions as adjuvants to radiation therapy. © 1993 Wiley‐Liss,

ISSN:1065-7541    

DOI:10.1002/roi.2970010104

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of tamoxifen on the radiosensitivity of an estrogen receptor positive (ER+) and an estrogen receptor negative (ER−) breast carcinoma cell line was studied in vitro. Tamoxifen concentrations of 1 and 5 μM inhibited the proliferation of ER+ MCF‐7 cells but had little effect on the growth of ER− MDA‐MB‐231. A 48 hr incubation in tamoxifen increased the proportion of G0/G1MCF‐7 cells, but minimally altered the cell cycle kinetics of MDA‐MB‐231 cells. Tamoxifen resulted in a small but significant increase in the mean inactivation dose of subconfluent cultures of the ER+ cells but had no effect on the ER− cells. The predominant change for MCF‐7 cells was a decrease in the linear damage coefficient, alpha. This was not associated with any enhanced capacity to recover from split radiation fractions. There was no difference in radiosensitivity comparing irradiated log‐phase to immediately plated plateau‐phase cells. However, 24 hr delayed plating of irradiated plateau‐phase cells resulted in decreased radiosensitivity of a magnitude comparable to that seen with tamoxifen. Quantitation of DNA strand fragmentation revealed no difference in the amount of single or double strand break induction nor the kinetics of strand break repair for cultures irradiated with or without tamoxifen. We conclude that tamoxifen results in a small decrease in the radiosensitivity of proliferating hormone responsive breast carcinoma cells and this effect appears to be most related to delay in cycle progression after release from tamoxifen inhibiti

ISSN:1065-7541    

DOI:10.1002/roi.2970010105

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

年代:1993

数据来源: WILEY

摘要:

AbstractFrom clinical experience, malignant melanomas are generally considered to be radioresistant. To explain this impression, the hypothesis had been advanced that the melanoma cells in a tumor are inherently resistant and that they are so because they are particularly effective in repairing potentially lethal damage. We have examined this idea with several lines of melanoma cells, and we have compared the responses of these cells to those of normal and ataxia telangiectasia fibroblasts (both SV40 transformed). The single‐dose responses of the melanoma cells were found to cover a large range. The most sensitive had a response similar to that of normal fibroblasts, but the most resistant required a dose for 10% survival to be 2–3 times larger. Correlated with this range in response, we found the sensitive melanoma cells to be deficient in both the fast and slow repair of potentially lethal damage compared to resistant melanoma cells. Sensitive and resistant melanoma cells survived ultraviolet light exposure equally well, however. We conclude that the repair of potentially lethal damage is important to the X‐ray response of melanoma cells, but that the degree of such repair correlates with the inherent sensitivity of such cells. Consistent with many other types of observations, we also note that the mechanism of lethality by ionizing radiation is fundamentally different from that of ultraviolet light. © 1993 Wiley‐L

ISSN:1065-7541    

DOI:10.1002/roi.2970010106

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe effects of recombinant interleukin‐6 (rIL‐6) and rIL‐3 on the radiation responses of myeloid [colony forming unit‐granulocyte‐macrophage (CFU‐GM)] and erythroid [burst forming unit‐erythroid (BFU‐E)]human pediatric bone marrow progenitor cells were analyzed. Cytokine exposure times of 30 min, 1 hr, 2 hr, 4 hr, 16 hr, and 24 hr were used prior to irradiation. The most notable observations were based on short exposure data, which provided unprecedented evidence that rIL‐6 increases the radiation damage repair capacity of both CFU‐GM and BFU‐E without affecting their radiation sensitivity, whereas rIL‐3 modulated the radiation responses of CFU‐GM only. The cytokine‐induced increase in radiation survival of CFU‐GM or BFU‐E at doses ≤200 cGy appeared to be primarily due to an increase in the ability of these hematopoietic progenitor cell populations to

ISSN:1065-7541    

DOI:10.1002/roi.2970010107

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

年代:1993

数据来源: WILEY

摘要:

AbstractPolyamines are ubiquitous polycations that interact with negatively charged macromolecules, including DNA. Since DNA is a target for radiation damage, we tested the hypothesis that radiation survival responses are polyamine‐dependent in cells derived from human tumors arising at different sites (lung [A549], cervix [HeLa], and brain [D54 and U251]). Untreated cultures displayed different growth rates (HeLa ≈ A549>D54>U251). Treatment with the specific ornithine decarboxylase inhibitor α‐difluoro‐methylornithine (DFMO) for 2 days or more suppressed putrescine and spermidine contents in all four cell lines. DFMO inhibited growth of each line, but to varying degrees (U251>HeLa ≈ A549>D54). Polyamine depletion generally suppressed γ‐ray‐induced sublethal and potentially lethal damage recovery. The degree of suppression of these recovery processes varied among cell lines (D54>A549 ≈ HeLa>U251), which correlated inversely with the ability of DFMO to suppress cell growth. These data suggest that agents such as DFMO, which suppress polyamine contents, may be useful adjuvants to radiation therapy by inhibiting either radiation recovery processes or cell proliferation, or both, during fractionated radiotherapy schedules. © 19

ISSN:1065-7541    

DOI:10.1002/roi.2970010108

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

年代:1993

数据来源: WILEY

摘要:

AbstractDNA‐ploidy and the percentage of S‐phase cells were measured by DNA flow cytometry in 171 primary squamous cell carcinomas of the head and neck. Of the analyzed tumors, 102 (60%) were aneuploid and 69 (40%) were diploid. Minimum follow‐up was 6 months (median: 37 months). For the whole population no difference of the 5‐year survival rate was found comparing diploid (18%) and aneuploid tumors (26%). Following sequential radiochemotherapy, aneuploid tumors revealed a better 5‐year survival (54%) than diploid tumors (7%;P<0.01). Accordingly, the locoregional control rate was higher for aneuploid tumors (57% vs. 28%; n.s.). By contrast, following surgery and radiotherapy or concurrent radiochemotherapy, diploid and aneuploid tumors had nearly the same survival rates. The analysis of recurrence demonstrated a lower rate of locoregional failures of diploid tumors (surgery + radiotherapy: 32% vs. 44%), but this was leveled out by a higher incidence of distant metastases of diploid carcinomas (surgery + radiotherapy: 36% vs. 17%). Relating to the fraction of S‐phase cells, slowly proliferating tumors (S‐phase

ISSN:1065-7541    

DOI:10.1002/roi.2970010109

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis retrospective analysis involved 453 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave‐Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to lymph node response, lymph node recurrence rate, distant metastasis rate, survival rate, tumor size, clinical N category, age, tumor dose, axillary dose, and internal mammary chain irradiation. Multivariate analysis permitted the definition of a risk score for axillary lymph node recurrence (RSLN) according to two independent factors: tumor size and clinical N category. It was shown that the RSLNwas a good single composite prognostic factor for lymph node control. Increase in axillary dose gave a similar effect on the axillary lymph node recurrence relative risk for all the RSLNgroups. According to the slope of the axillary dose‐effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of lymph node recurrence 2‐fold. A similar slope was previously described for tumor dose and local control. A risk score for distant metastases (RSM) was calculated according to three independent prognostic factors: tumor size, clinical N category, and age. The RSMwas not influenced by the tumor or the axillary dose but by the treatment of the internal mammary chain. Similar results were obtained for the risk score for death (RSD). The present data emphasize the role of the lymph node radiation dose in the lymph node control of locally advanced breast cancer. © 1993 Wiley‐L

ISSN:1065-7541    

DOI:10.1002/roi.2970010110

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

年代:1993

数据来源: WILEY

摘要:

AbstractFor the stereotactic irradiation of intracranial lesions with a linear accelerator, the use of a tertiary collimating system can be expected to confer several benefits in comparison to the use of the standard linac collimating jaw system. Moving the collimator closer to the patient should lead to reduced penumbra and reduced susceptibility to positioning error. In addition, the use of a circular rather than a square aperture should yield a more advantageous dose distribution for irradiation techniques which follow spherical geometry. An investigation using film dosimetry with a tissue‐equivalent head phantom demonstrated that the tertiary system was superior to the standard jaw system as expected. © 1993 Wiley‐Liss,

ISSN:1065-7541    

DOI:10.1002/roi.2970010111

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.2970010102

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

年代:1993

数据来源: WILEY