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H D Suit

Publications and source records attributed to H D Suit.

At least 73 records · Page 4Linked to original sources
PubMed1990

Metastatic ependymoma of the sacrum.

Ependymomas originating in the sacrum or extraspinal parasacral soft tissues are rare tumors. The majority are of the myxopapillary type and may be locally destructive. Even though metastases are not uncommon in retrosacral ependymomas, they have been rarely described in intrasacral locations. A case is reported of a large intrasacral ependymoma with metastases to several vertebrae. Radiologic and pathologic studies are presented. Treatment options are discussed.

Aged↗
PubMed1990

Residual immunity of athymic NCr/Sed nude mice and the xenotransplantation of human tumors.

This study assessed the residual immunity possessed by NCr/Sed (nu/nu) athymic nude mice and examined strategies to reduce it in order to enhance the transplantability of human tumors for experimentation. Adult (8-week-old) female mice had fewer T cells (11%) and more B and NK (asialo-GM1-positive [ASGM1+]) cells in their spleen than euthymic (nu/+) controls. The number of phenotypically mature T cells increased with age, peaking at 16 weeks. ASGM1+ cells also increased in number over time, although the NK-activity decreased after 12 weeks. B cells remained relatively constant in number. Athymic NCr/Sed nude mice displayed reactivity against a human squamous carcinoma xenograph (FaDu), in a Winn's test and TD50 assay. Immunity against xenografts (TD50 assay) was significantly lower (by a factor of 2) in 4-week-old than in 12-week-old nude mice. Similarly, a significant 2-fold reduction in TD50 was obtained after a single intraperitoneal injection of cyclophosphamide into 8-week-old animals. Chronic (greater than 8 weeks) exposure of the nude mice to subcutaneously administered beta-estradiol markedly reduced the number of splenic NK cells and their cytolytic activity, but the TD50 reduction was not statistically significant (p = 0.1). Six Gray whole-body irradiations (WBI) had been shown to produce a highly significant, 3-fold reduction in the TD50 for FaDu. Flow cytometric analysis of splenic lymphoid cells from whole-body-irradiated recipients revealed: (a) marked initial depletion in the absolute numbers of lymphoid cells; (b) marked and long-lasting depletion of T cells, with slow and minimal recovery only evident between 6 and 12 weeks; (c) rapid, almost complete, depletion of B cells with prompt and partial recovery after 2 weeks; (d) depletion of NK cells and NK activity, with recovery by 10 weeks. No change in the number or phagocytic capacity of resident peritoneal macrophages was seen. These data give further support to a postulated role for residual T cells in the xenoreactivity of NCr/Sed nude mice.

Age Factors↗
PubMed1990

Fibromatoses: from postsurgical surveillance to combined surgery and radiation therapy.

The results of management of two groups of patients with musculoaponeurotic (desmoid tumors) and plantar fibromatoses seen at Massachusetts General Hospital (MGH) during the period 1970-1985 are examined: (a) 26 patients who had had surgical resection for their primary fibromatosis but whose surgical margins were positive and who received no further treatment; and (b) 24 patients who were treated for their primary or recurrent fibromatosis by radiation alone or combined with surgery. For the 26 patients who were only observed, despite the positive surgical margins, 9 have recurred; the actuarial continuous local control rate at 5 years was 68% (a median follow-up of 70 months). Five patients had gross disease left after surgery and all of them failed. Seventeen of 21 patients who had grossly complete resection have local control; the four failures have been salvaged. This result supports the rationale for a no treatment but a thorough and close follow-up policy for patients with positive margins after grossly complete resection of a primary desmoid or fascial fibromatosis. There is no risk of metastasis in these patients and hence the effort toward a conservative policy which defers radiation merits interest and further study. Of the second group, 23 patients were treated for gross disease and one patient for microscopic disease after surgical resection. All of the 10 patients who were treated for primary desmoid tumor have local control. Among the 14 recurrent desmoid tumors there have been five local failures, after treatment by radiation alone or radiation + surgery. Three patients treated by radiation alone are currently scored as incompletely regressed tumors. Accordingly 16 of the 24 patients are scored as local controls without evidence of disease and 19 of the 24 are scored as local control (complete response or partial but stable response).

Adult↗
PubMed1990

The response of two human tumor xenografts to fractionated irradiation. The derivation of alpha/beta ratios from growth delay, tumor control, and in vitro cell survival assays.

A series of growth delay experiments was performed to derive alpha/beta ratios for two human neoplasms growing as xenografts in the hind limbs of NCr/Sed nude mice. The tumors were irradiated at 6 mm mean diameter under clamp-hypoxic conditions in one, two, four, or eight fractions, 2 fractions per day with a minimum intertreatment interval of 4 hr and a maximum overall treatment time of 3 days. The alpha/beta ratios derived for the high grade glioma U87 and the pharyngeal squamous carcinoma FaDu were 38 and 20 Gy, respectively. Comparably high values were derived from the same two tumors in a reanalysis of fractionated TCD50 data. The alpha/beta ratios were similarly high whether the TCD50 data were analyzed using the Full Effect plot or the Direct Method. For comparison, cell survival assays were performed on U87 and FaDu irradiated in vitro under plateau-phase, aerobic conditions. The alpha/beta ratios obtained were 9.2 and 15.0 Gy, respectively. Such high alpha/beta values suggest a therapeutic gain could result from the use of small doses per fraction.

Animals↗
PubMed1990

Radiation response of xenografts of a human squamous cell carcinoma and a glioblastoma multiforme: a progress report.

Human cell lines derived from squamous cell carcinomas of the pharynx (FaDu and HSCC6) and glioblastoma multiforme (U87, A2, A7, MMC-1, MMC-2) have been studied in vitro as monolayers in exponential (all 7 cell lines) or plateau phase (FaDu and U87), and as 1 mm diameter spheroids in vitro (FaDu and U87) and as 6 mm diameter xenografts growing in the legs of athymic NCr(nu/nu) nude mice (FaDu, HSCC6, U87, A7 cells). For SF2s and D values, there was broad overlap of values between SCC and glioma cell lines. In contrast, the D0 values were higher for U87, A2, A7, and MCC-1 than the two SCC cell lines, while the extrapolation numbers were greater for the two SCC lines than any of the glial tumor lines (these differences were not regularly significant). Complete dose response assays for local control of FaDu, HSCC6, U87, and A7 xenografts have been performed under conditions of normal blood flow and clamp hypoxia for tumors growing in mice which had received 6 Gy WBI at 24 hr before transplantation. Under the latter circumstances, irradiations have been performed on FaDu and U87 as single doses or as 2, 4, or 8 equal doses; for the fractionated irradiation, treatments were given on a BID basis with 4 hr between the treatments on any 1 day. For irradiation of 1 mm diameter spheroids, radiation was administered as single doses under conditions of equilibration with AIR. The TCD50 for the FaDu was significantly higher and the dose response curve steeper for tumors growing in immune suppressed (6 Gy WBI 24 hr prior to transplantation) than in control nude mice. Tumors, exponential or plateau phase cells, and spheroids derived from U87 were significantly and substantially more resistant under all conditions and fractionation schedules than for FaDu. Thus, the in vitro results do not indicate a clearly greater resistance by the glioma cell lines, while the more limited TCD50 data (single dose and 8 fractions irradiation) show more resistance in vivo by the glial tumors. We noted that the TCD50 values for U87 and A7 glial tumors overlap those for spontaneous tumors of the C3H mouse but are higher than the human squamous cell carcinoma xenografts in the nude mice. Substantial additional data from xenografts are needed to determine if the higher TCD50 values for GBMs, especially for fractionated irradiation, is a regular finding and is of sufficient magnitude to be pursued by studies to explain the observed differences.

Animals↗
PubMed1990

Fractionation sensitivity and immunological status in radiation treated murine sarcomas.

The fractionation sensitivity of a strongly immunogenic murine fibrosarcoma (FSa1) was tested in highly immunosuppressed (18 Gy whole body irradiation, 10 fractions, 4 days and bone marrow salvage) and control mice (C3Hf/Sed). Radiation was delivered to extremity-transplanted tumors after reaching a volume of 250 mm3. Two, 4 and 10 fractions were used, delivering the radiation treatments to uniformly hypoxic tumors (by extremity clamping). Doses needed to attain a 10 day tumor-growth delay (TGD) over the volume range 250 mm3 to 1000 mm3, and doses necessary to reach a tumor-control probability of 50% (TCD50), were calculated for the three fractionation schedules. Immunosuppression influenced the TCD50 values profoundly: 56.2, 71.5, and 101.4 Gy in control mice versus 76.6, 104.2, and 141.1 Gy in immunosuppressed mice for 2, 4, and 10 fractions, respectively. The alpha/beta ratios estimated by reciprocal-dose analysis using the TGD and TCD50 assays were not significantly different, nor were the alpha/beta ratios of tumors grown in immunosuppressed mice (TGD 5.7 Gy; TCD50 5.3 Gy) as compared with tumors in control recipients (TGD 3.5 Gy; TCD50 4.9 Gy). In addition, direct analysis was used with the fractionated TCD50 data from control and immunosuppressed animals to calculate a immunity-related-cell-kill factor. For 250 mm3 tumors a 1.29 [0.99 . . . 1.59, 95% confidence interval] log10-kill factor was obtained.

Animals↗
PubMed1990

Metastases after fractionated radiation therapy of three murine tumor models.

The incidence of lung metastases after fractionated radiation therapy was compared to single dose irradiation in a retrospective analysis of three murine tumor models. For FSaII and SCCVII 5 or 15 fractions over 5 days were given using curative and subcurative doses and photons and neutrons. Data were pooled from different experiments. In mice with locally controlled FSaII the incidence of lung metastases was the same after all treatments, whereas in mice with locally controlled SCCVII, metastases were enhanced after 15 fractions. Photon and neutron irradiations yielded similar results. Local recurrences were followed by increased metastases. MCaIV was subcuratively irradiated with 9 equal fractions followed by a top-up dose to achieve local control. Metastases were high if doses per fraction were low and interfraction time intervals long. The data on MCaIV indicate increased metastases if clonogenic cells during treatment represent a large proportion of the integral tumor burden. The results on FSaII and SCCVII indicate that fractionated treatments might differently influence distant metastasis in different tumor models.

Animals↗
PubMed1990

Response of human squamous cell carcinoma xenografts of different sizes to irradiation: relationship of clonogenic cells, cellular radiation sensitivity in vivo, and tumor rescuing units.

The relationship of clonogenic cells, cellular radiation sensitivity at tumor control does in vivo, and tumor rescuing units at different tumor sizes was investigated in the human squamous cell carcinoma FaDu growing in NCr/Sed nude mice. The composition of the tumors was determined in single cell suspensions and compared to tumor control data after single-dose irradiation. To avoid the influence of varying oxygen concentrations in the tumors, all irradiations were performed under clamp hypoxia. Nude mice and animals further immunosuppressed by 6-Gy whole-body irradiation were used to assess the immunological effects. The numbers of total cells, cells excluding trypan blue, host cells, and colony-forming cells increased linearly with the weight of FaDu tumors. Comparable results were obtained for cell suspensions prepared from tumors growing in nude of pretreated nude mice. The radiation dose required to control 50% of tumors (TCD50) of different sizes between 36 and 470 mm3 increased from 52.1 to 60.1 Gy when the tumors were maintained in normal nude mice and from 50.8 to 61.3 Gy in whole-body-irradiated mice. The D0 of FaDu cells in vivo was calculated by regression analysis of TCD50 vs the logarithm of the clonogenic cell number, assuming an oxygen enhancement ratio of 3.0. The resultant D0S of 1.1 and 1.2 Gy in vivo correspond well to the radiosensitivity of FaDu cells in vitro determined previously. Assuming the single-hit multitarget model of cell killing and extrapolation numbers between 2 and 20, the mean number of tumor rescuing units would be 10(5) to 10(6) for a 100-mm3 tumor growing in whole-body-irradiated nude mice. Comparison of the number of tumor rescuing units to the estimated number of clonogenic cells does not conflict with the assumption that every surviving clonogenic cell is able to repopulate FaDu tumors after irradiation; however, it seems more likely that more than one clonogenic cells is necessary. The proportion of tumor rescuing units in the clonogenic cell population is independent of tumor size.

Animals↗
PubMed1990

Increased efficacy of radiation therapy by use of proton beam.

Proton beam treatment techniques provide a powerful approach to improving dose distribution (decrease treatment volume towards target volume) and hence increasing dose to target with resultant higher tumor control rates and lesser morbity. To achieve these dose distributions in patients requires use of modern imaging techniques, rigid immobilization systems, confirmation of target position vis a vis the proton beam at each treatment session, treatment planning which feature beam's eye view, displays of uncertainty, dose at each anatomic point, boli based on accurate assessment of density along each pixel, etc. Experience at MGH/MEEI/HCL has yielded a disease-free survival of 78% for patients with chordoma/chondrosarcoma of base of skull. Local control is achieved by 98% of patients treated for choroidal melanoma.

Chondrosarcoma↗
PubMed1989

Comparative morphometric study of tumor vasculature in human squamous cell carcinomas and their xenotransplants in athymic nude mice.

When human tumor xenotransplants into nude mice are used as experimental models, it is important to know whether their microvascular anatomy is rather host or tumor specific. Therefore a morphometric comparison of the vascular network in human squamous cell carcinomas and their xenotransplants was carried out. Biopsies were taken from surgical specimens of three squamous cell carcinomas of the oral cavity. Part of the material was processed for histology and the rest was cut into 1-mm3 cubes and transplanted s.c. into the lateral thorax of athymic nude mice [NCr/Sed(nu/nu)]. The microvascular architecture of original tumors and of three first, one second, and one late generation xenografts was compared. Capillaries were identified in original human tumors by anti-factor VIII staining and in xenografts with antilaminin staining. The median distances between interphase tumor cells and blood vessels were determined and were found to be much longer in original human tumors than in xenografts, ranging from 81 microns to 99 microns and 53 microns to 65 microns, respectively. However, the characteristic qualitative histology of tumors appeared to be preserved in xenotransplants. Analysis of the topographic distribution of mitotic figures revealed that in both original tumors and xenotransplants proliferation of tumor cells was concentrated around blood vessels. Again, vascular distances in original tumors were significantly longer than in xenotransplants. In addition, xenotransplants into nude mice from a long passaged cell line from a human pharyngeal squamous cell carcinoma, FaDu, was investigated. FaDu showed a rare-fication of the capillary network with increasing tumor volume, but a constant median distance of mitotic figures from blood vessels. In conclusion, the pattern of spatial distribution of proliferating tumor cells as well as differentiation characteristics appear to be retained in xenograft tumors, but the density of the vascular system is host specific. This has to be taken into account when physiological parameters of blood supply are studied in xenotransplanted tumors.

Animals↗
PubMed1989

A morphometric study of the vascularity of oral squamous cell carcinomas and its relation to outcome of radiation therapy.

In 26 patients the vascular morphology of pretreatment biopsies from oral squamous cell carcinomas (scc) was studied. Patients had been treated by radiation alone and followed up for 25-73 months. Vascular endothelial cells were identified using antifactor VIII staining. The distances from 700 randomly selected tumor cells to the closet blood vessel were measured in each tumor. Stepwise logistic regression analysis revealed that tumors with fewer than 21% of the morphologically intact tumour cells located within 48 microns of the closest blood vessel had a better control rate than tumors with a higher proportion of tumor cells within this distance. Using the analysis as a predictive assay, local tumor control was predicted from a single histological section with a sensitivity of 81% and a specificity of 60%. In correctly predicted cases of local control, the average median distance between tumor cells and blood vessels was 105 microns. These tumors formed well differentiated avascular tumor cell nests that were surrounded by stroma and blood vessels. Mitotic figures were observed only in the outer rim of cell nests while the center was often keratinizing or necrotic. In cases of correctly predicted treatment failures the average median distance from intact tumour cells to capillaries was 76 microns. These tumors showed varying degrees of organization and capillaries penetrating tumor cell areas. Clinical outcome of radiation therapy of oral scc appears to be correlated with different patterns of tumor architecture and blood supply.

Carcinoma, Squamous Cell↗
PubMed1989

Quantitative transplantation assays of the rat rhabdomyosarcoma BA1112 isografts into the WAG/Rij Y rat and xenotransplantation into the athymic NCr (nu/nu) nude mouse.

Quantitative tumor cell transplantation assays have been performed to compare the transplantability of rat rhabdomyosarcoma BA1112 into isologous WAG/Rij Y rats and athymic NCr(nu/nu) nude mice. The end-point was the TD50 or the number of viable tumor cells which would transplant the tumors into half of the recipients. At Yale, two sets of 2-fold dilutions were prepared, one was sent to the MGH by Air Express. That afternoon, concurrent assays were performed at Yale using the WAG/Rij Y rat and at MGH using the NCr(nu/nu) mouse. The TD50 values were the same for iso- and xenotransplantation. Furthermore, the TD50s in rats and mice were unaffected by standard immunization procedures prior to challenge of the TD50 assay. The BA1112 (10(7) trypan blue excluding cells) grew to 10-12 mm and then completely regressed if transplanted into NCr(nu/+) mice which had received 6 Gy whole body irradiation but did not grow in control NCr(nu/+) mice. The times for the BA1112 to grow to 10 mm were the same in normal or preimmunized WAG/Rij Y rats or NCr(nu/nu) mice and in 6 Gy WBI NCr(nu/nu) mice. All of the experimental data show that the xenogenic NCr(nu/nu) mice accept the BA1112 as readily as do the isologous WAG/Rij Y rats.

Animals↗
PubMed1989

The growth and cell kinetics of a secondary tumor after radiation or surgical treatment of the primary tumor.

Early transplants of a spontaneous mouse fibrosarcoma (FSa II) were used to investigate whether radiation or surgical treatment of a tumor in the leg altered the growth or cell kinetics of a second tumor in the axilla. The volume doubling times and in vivo Bromodeoxyuridine labeling indices of the axillary tumors were the same in the control group and in the groups which received 70 Gy to the leg tumor or normal leg. After surgical removal of the leg tumor, there was small reduction in the time to reach 1500 mm3 (4.0 vs 4.6 days) and an increase in Bromo-deoxyuridine labeling index at Day 3 (18% to 24%) in the axillary tumors. In all groups, there was a fall in labeling index with time reflecting increasing tumor size.

Animals↗
PubMed1989

Radiation therapy in the treatment of difficult giant cell tumors.

Thirteen patients with giant cell tumors of bone have been treated by radiation therapy because surgery was not feasible or unacceptably disfiguring. Seven patients were treated for primary giant cell tumors of the bone, four for recurrent disease, and three for metastasis (one presented with both distant metastasis and local recurrence after primary surgery). The follow-up time ranged from 18 months to 13 years, with a mean of 6.5 years. All patients except one are alive. Local control was achieved in 11 patients (85%). One patient whose tumor was located in the sacrum had no gross response and at 5 months was subjected to a partial sacrectomy. A second patient had local regrowth 1 year after treatment; salvage surgery was successful. There have been no long-term complications of radiation therapy. This study confirms that for patients with giant cell tumor of bone, radiation therapy offers an effective alternative to complex or difficult surgery and constitutes a good treatment method to medically inoperable patients.

Adolescent↗
PubMed1989

Effects of hydralazine on in vivo tumor energy metabolism, hematopoietic radiation sensitivity, and cardiovascular parameters.

Energy metabolism of murine FSaII foot tumors was studied by in vivo 31P-MRS in C3Hf/Sed mice. Spectroscopy was performed following exposure to escalating doses of hydralazine (HYD) ip. At 0.25 mg/kg, HYD caused a 20% increase in PCr/Pi and had no significant effect on mean arterial blood pressure. HYD doses greater than or equal to 2 mg/kg lead to hypotension which was associated with a decrease in PCr, NTP, pH, and an increase in Pi (p less than 0.01 for control vs 10 mg/kg HYD). When mice were given ip injections of HYD (0.25, 1, 2 and 10 mg/kg) 10 min prior to whole body irradiation, spleen stem cell survival after 6 Gy was increased (2.19 colonies in control animals vs 6.74 colonies per spleen in animals treated with greater than or equal to 2 mg/kg HYD), as was the LD50/30 dose (6.49 Gy [control] vs 9.00 Gy [10 mg/kg HYD]). The data provide evidence that PCr/Pi is a useful indicator of perfusion efficiency (and indirectly of hypoxic cell fraction) in FSaII tumors. These observations suggest that HYD may be a useful adjuvant for hyperthermic treatment of tumors and for potentiation of agents specifically toxic to hypoxic or nutrient-deprived cancer cells. HYD should be used with care in patients receiving radiation treatments or other therapies for which hypoxia can unfavorably affect treatment outcome.

Animals↗
PubMed1989

Dermatofibrosarcoma protuberans treated with radiation therapy.

Dermatofibrosarcoma Protuberans is an uncommon soft tissue tumor that is locally aggressive, prone to recur locally following excision, and has a low propensity for metastasis. Ten patients have received radiation (both external beam and interstitial implant) as part of, or as their only treatment, at Massachusetts General Hospital from 1979-1987. Three patients received radiation alone (66.7-75 Gy) for gross palpable disease. One patient has slowly regressing nodules at 33 months; the other two had complete regression and are free of disease at 24 and 26 months posttreatment. Seven patients received radiation in conjunction with surgery. One received both preoperative and postoperative radiation and six received postoperative radiation (60-67 Gy) for microscopic residual disease following resection. Six of these seven patients are free of disease 16 to 105 months following treatment. One patient, with diffuse microscopic tumor infiltration of the scalp, had a local recurrence within the radiation field 16 months following 64.4 Gy. There has been no significant treatment related morbidity. Even though the present experience is limited and the follow-up brief, it does suggest that radiation can be considered a viable therapeutic option in the patient who has a lesion that is not resectable.

Adult↗