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H D Suit

Publications and source records attributed to H D Suit.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparison between the in vitro intrinsic radiation sensitivity of human soft tissue sarcoma and breast cancer cell lines.

The purpose of this study is to evaluate the radiation sensitivity of human soft tissue sarcoma cell lines in vitro and to compare with that of human breast carcinoma and glioblastoma cell lines. The intrinsic radiation sensitivity parameters of seven human soft tissue sarcomas and eight breast carcinoma cell lines were investigated in vitro by clonogenic assays for single-dose irradiation under aerobic conditions on cells in exponential phase of growth. The results for sarcoma cell lines showed that the mean surviving fraction at 2 Gy (SF2) was 0.39 (SD +/- 0.09) with a range of 0.24 to 0.53, and the average mean inactivation dose (MID) was 1.92 (SD +/- 0.35) range from 1.36 Gy to 2.49 Gy. These values were not different from that of breast cell lines examined concurrently and using the same experimental methods (mean SF2 0.38, SD +/- 0.09; MID 1.9 Gy, SD +/- 0.37). However radiobiological parameters of nine karyotyped human malignant glioma cell lines determined earlier in this laboratory were significantly higher (mean SF2 0.50 +/- 0.14; mean MID 2.61 +/- 0.60). In conclusion, the data presented here do not support the view that cells of sarcomas show unusual radiation resistance. To the extent that the in vitro determined cellular radiation sensitivity reflects the tumor response in vivo, the success rate for radiation applied against sarcoma and breast carcinoma of comparable size could be similar.

Breast Neoplasms↗
PubMed1996

Spontaneous metastasis, proliferation characteristics and radiation sensitivity of fractionated irradiation recurrent and unirradiated human xenografts.

PURPOSE: Do tumor cells which survive high dose fractionated irradiation exhibit modified metastasis activity, proliferation kinetics, and/or radiation sensitivity? To address this question experimentally, we have studied three recurrent human tumor xenograft systems. METHODS AND MATERIALS: Three models were derived from a soft tissue sarcoma (HSTS26T), a colon adenocarcinoma (HCT15), and a glioblastoma (HGL21) which had recurred after 90 Gy, 109 Gy, or 77.4 Gy administered in 30 equal doses, respectively. Their production of spontaneous metastasis and cell proliferation characteristics were studied in early generation xenografts in SCID mice, and were compared to those in their previously unirradiated counterparts. As a control, we have also studied each tumor as a post-surgical recurrence. Specimens from the irradiated recurrent and their unirradiated primary tumors were cultured in vitro and their radiation sensitivity determined by clonogenic assay. RESULTS: The three irradiated recurrent tumor systems retained the individual histological features of their unirradiated primary xenografts. A lower metastatic incidence was observed in two of the three irradiated recurrent tumor lines in comparison with their unirradiated control tumors and their surgical recurrent counterparts. No significant differences were found between the irradiated recurrent tumors and their unirradiated counterparts with respect to: volume doubling time, growth time, potential doubling time, mitotic index, PCNA index, and SF2 values. CONCLUSIONS: High dose irradiation given in 30 fractions did not increase the metastatic activity in the three human tumor xenograft systems. Furthermore, the fractionated irradiation did not significantly change their proliferation characteristics and cellular radiation sensitivity.

Adenocarcinoma↗
PubMed1995

Radiation dose-response of human tumors.

PURPOSE: The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined. These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting. The goal of this study was to compute the dose of radiation that locally controls 50% (TCD50) of tumors in human subjects. METHODS AND MATERIALS: Logit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. RESULTS: 90 dose response curves were calculated; 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control. The mean and median TCD50 for gross disease were 50.0 and 51.9 Gy, respectively. The mean and median TCD50 for microscopic disease control were 39.3 and 37.9 Gy, respectively. At the TCD50, an additional dose of 1 Gy controlled an additional 2.5% (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease. For both macro- and microscopic disease, an increase of 1% of dose at the TCD50 increased control rates approximately 1% (median) or 2-3% (mean). A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. CONCLUSION: Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease, and are about 79% of the dose required to control macroscopic disease. The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic microscopic disease, with a median value of approximately 1%/% and a mean of approximately 2.7%/%.

Dose-Response Relationship, Radiation↗
PubMed1995

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice.

PURPOSE: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-alpha with local radiation on the tumor control probability of this tumor model. METHODS AND MATERIALS: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm3, mice were randomly assigned to treatment: rHuTNF-alpha alone compared with normal saline control; or local radiation plus rHuTNF-alpha vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-alpha on this tumor. The TCD50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-alpha with local radiation. RESULTS: Tumor growth in mice treated with a dose of 150 micrograms/kg body weight rHuTNF-alpha, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-alpha also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-alpha starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD50 from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). CONCLUSION: rHuTNF-alpha exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD50 value in the treatment vs. the control groups.

Animals↗
PubMed1995

Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone.

PURPOSE: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. METHODS AND MATERIALS: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. RESULTS: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p = 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy there was a lower positive rebiopsy rate for arm 1 versus arm 2 patients (28 vs. 45%) and also for those with well and moderately differentiated tumors versus poorly differentiated tumors (32 and 50%). These differences were not statistically significant. Grade 1 and 2 rectal bleeding is higher (32 vs. 12%, p = 0.002) as may be urethral stricture (19 vs. 8%, p = 0.07) in the arm 1 versus arm 2. CONCLUSIONS: An increase in prostate tumor dose by external beam of 12.5% to 75.6 CGE by a conformal proton boost compared to a conventional dose of 67.2 Gy by a photon boost significantly improved local control only in patients with poorly differentiated tumors. It has increased late radiation sequelae, and as yet, has not increased overall survival, disease-specific survival, or total recurrence-free survival in any subgroup. These results have led us to test by a subsequent Phase III trial the potential beneficial effect on local control and disease-specific survival of a 12.5% increase in total dose relative to conventional dose in patients with T1, T2a, and T2b tumors.

Aged↗
PubMed1995

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice.

PURPOSE: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. METHODS AND MATERIALS: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. RESULTS: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.

Animals↗
PubMed1995

Cell proliferation kinetics in human tumor xenografts measured with iododeoxyuridine labeling and flow cytometry: a study of heterogeneity and a comparison between different methods of calculation and other proliferation measurements.

The influence of overall treatment time in the results of fractionated radiation treatment was initially established in experimental tumors and, subsequently, in the clinic. The availability of techniques (antibodies against halogenated thymidine analogues and flow cytometry) which permit determinations of the duration of the synthesis phase, the labeling index, and the tumor potential doubling time (Tpot) in a short period of time and requiring only a small biopsy of tumor tissue, has expanded interest in the relationship between tumor cell proliferation and response to irradiation. A valuable tool in the study of this relationship are human tumor xenografts. Previous studies have shown a substantial intratumoral heterogeneity in the determinations of Tpot. Different methods of calculation of the kinetic parameters have been published. We have conducted a heterogeneity analysis and an evaluation of the different calculation methods in order to define the validity of Tpot as a proliferation rate measurement in human tumor xenografts. Results show the intertumoral variability in Tpot [between different types of human tumor xenografts systems (coefficient of variation = 88.2%)] to be greater than mean intratumoral variation (coefficient of variation = 30.8%); this suggests that this variation is potentially adequate to serve as a predictor of response. The diverse calculation methods provided significantly different absolute values but not different tumor ranking, probably because the time interval between labeling and sampling was maintained, for all the samples, between 6 and 8 h. Our study has found significant differences between the labeling index and the S-phase fraction determined with the DNA profile in 9 out of 10 tumor types. No correlation was found between the DNA index of the tumors in this series and their proliferation rate.

Animals↗
PubMed1995

Quantitative comparison of xenotransplantation of a human soft tissue sarcoma into the subcutaneous tissue of normal, postincision, and postincision plus indomethacin-treated nude mice.

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound.

Animals↗
PubMed1995

Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice.

The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21-25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm3; mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (78% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme.

Adenocarcinoma↗
PubMed1994

Connective tissue tumors in patients with cutaneous melanoma.

BACKGROUND: A possible relation between cutaneous melanoma and connective tissue tumors has been described. OBJECTIVE: After the observation that a group of our patients had both cutaneous melanoma and a soft tissue sarcoma, we elected to review this formally. Eleven patients with both diagnoses were identified and are described. METHODS: A computer search through the Medical Records Department and the Tumor Registry of the Massachusetts General Hospital identified seven men and four women with the diagnoses of melanoma and malignant bone or soft tissue sarcoma. The medical records and pathology specimens of all tumors were reviewed. RESULTS: In three patients, the two tumors were diagnosed within 1 year of each other, in seven, the diagnosis of melanoma was made first, and in one, melanoma was diagnosed after the connective tissue lesion. The interval between the two diagnoses ranged up to 13 years. Although the locations and types of melanoma were typical, some of the connective tissue tumors were unusual; there were two sacral chordomas. In two instances, the melanoma and connective tissue tumor were anatomically close; the sarcoma developed at the edge of the resection of the prior melanoma in one patient. None of the tumors developed in previously irradiated tissues, and in no instance did the second tumor appear to be caused by the therapy received for the first. None of the patients had a family history of melanoma. Four patients had other cancers in addition to the melanoma and connective tissue tumor. CONCLUSION: Although these patients were seen in a referral center, it is our impression (based on the total number of patients with connective tissue tumors seen and the incidence of melanoma in the general population) that observing 11 patients with both types of tumors is greater than would be expected by chance.

Adult↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.

Animals↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the brain of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993) that the take rate of human xenografts in the s.c. tissue of severe combined immunodeficient (SCID) mice is significantly higher than that of nude mice. Earlier, this laboratory reported that the transplantability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of human and murine tumors in comparison with s.c. tissue in SCID mice; (b) the relative i.c. transplantability in SCID mice in comparison to nude mice; and (c) the influence of whole-body irradiation on i.c. transplantability of SCID and nude mice. The assay based on the number of cells required to transplant tumors into 50% of recipients (TD50) was used to describe the transplantability assays. Five human and four murine tumor cell lines were used. Concurrent TD50 assays were performed i.c. in whole-body irradiated and nonirradiated SCID and nude mice. Serial 2-10-fold dilutions of cells were injected in a 10-microliters volume into the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50S were significantly lower than the s.c. TD50S by a factor of 1.7-1580. The average enhancement ratio (s.c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No significant difference was found between the i.c. TD50S in SCID and in nude mice, contrary to the significant difference in s.c. TD50S between both strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID mice. In conclusion, despite the significantly lower s.c. TD50S of human xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immunoreactivities between nude and SCID mice in s.c. transplantability; however, for i.c. transplantability, nude mice behaved equally as well as SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immunoreactivity, although the immunoreactivity is significantly lower than that of nude mice.

Animals↗
PubMed1993

Intratumoral heterogeneity of malignant gliomas measured in vitro.

PURPOSE: To evaluate the extent of intratumoral heterogeneity of radiation sensitivity in malignant gliomas, by comparing the intrinsic radiation sensitivity of different glioma sublines derived from the same tumor. METHODS AND MATERIALS: The study was performed on five early established malignant gliomas (passage 3-10). Each specimen was quickly cut into three equal pieces (except for one specimen, where only two pieces were obtained). Each piece was processed independently, disintegrated into single cell suspension using a cocktail of enzymes. Survival curve assays, using colony formation as an end-point, were performed for each subline. Comparison between the intrinsic radiation sensitivity of sublines was calculated using the surviving fraction at 2 Gy and the mean inactivation dose as the measured parameters. The DNA content of the cell lines as well as their cell cycle analysis was determined using flow cytometry. RESULTS: The mean calculated surviving fraction at 2 Gy of all the sublines was 0.37 +/- 0.14, the mean mean inactivation dose was 1.98 +/- 0.63. The intertumoral coefficient of variation for the calculated surviving fraction at 2 Gy of all cell lines was 38%, while that for intratumoral heterogeneity was 25%. Three of the 5 tumors showed a statistically significant difference in the surviving fraction at 2 Gy and mean inactivation dose values of their sublines (p < 0.05). This difference in radiation sensitivity between sublines of the same tumor was not attributed to a difference either in the ploidy status or in the distribution of cells in the cell cycle. CONCLUSION: There is a significant intratumoral heterogeneity of radiation sensitivity in some malignant gliomas. This heterogeneity may limit the predictive power of surviving fraction at 2 Gy or mean inactivation dose, especially when their values are based upon a single measurement/single biopsy. In the meantime, this heterogeneity may be a factor in the discrepancy between unexpectedly sensitive tumor cell lines in vitro and their high clinical radiation resistance.

Brain Neoplasms↗
PubMed1993

Impact of stromal sensitivity on radiation response of tumors.

BACKGROUND: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e.g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. PURPOSE: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. METHODS: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. RESULTS: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). CONCLUSIONS: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression.

Animals↗