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PubMed1988

Radiotherapy of the rhabdomyosarcoma R1H of the rat: the influence of the number of fractions on tumor and skin response.

The influence of the number of fractions on tumor and skin response to fractionated irradiation was studied. R1H rhabdomyosarcomas of the rat (volume doubling time 3 days) were irradiated with 6, 18, 30, or 42 fractions in 6 weeks. Total doses of 45, 60, or 75 Gy were applied in each fractionation scheme, that is, the dose per fraction ranged from 1.07 to 12.5 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. A clearcut reduction of skin damage was observed with increasing number of fractions, whereas the tumor response was found to be the same whether the dose was given in 6, 18, 30, or 42 fractions. Thus, the fractionation regimens were more effective than expected from calculations based on single-dose in situ survival curves. This result can be explained by assuming that the clonogenic tumor cells become less hypoxic with increasing number of fractions. Since normal tissue damage decreases with increasing number of fractions, the therapeutic gain may be improved by applying a greater number of fractions.

Animals↗
PubMed1988

Radiotherapy of the rhabdomyosarcoma R1H of the rat: kinetics of cellular inactivation by fractionated irradiation.

The kinetics of cellular inactivation by fractionated irradiation in the R1H rhabdomyosarcoma of the rat was studied in the dose range of 1.07 to 12.50 Gy per fraction. Regimens of 1, 3, 5, 7, and 10 fractions per week for several weeks were compared. The number of clonogenic tumor cells per tumor in the course of the different treatment schedules was determined using an in vitro colony assay. The results show that the proliferation of clonogenic tumor cells is decelerated in the course of a fractionated radiotherapy. The deceleration persists for several days after end of treatment, until accelerated repopulation is initiated. The fraction of tumor cells inactivated per week was only dependent on the total dose per week, that is the cellular response was the same whether the weekly dose was applied in 1,3,5,7, or 10 fractions. Thus, the fractionation regimens were considerably more effective than expected from calculations based on single-dose in situ survival curves.

Algorithms↗
PubMed1989

Radiotherapy of the rhabdomyosarcoma R1H of the rat: hyperfractionation--126 fractions applied within 6 weeks.

The effect of a hyperfractionated irradiation treatment on the response of the rhabdomyosarcoma R1H of the rat was studied. Tumors were irradiated under ambient conditions with 126 fractions of X rays, applied in 3 fractions per day with a time interval of 8 +/- 1 hr between fractions on 7 days per week during 6 weeks. The total dose ranged from 54 to 90 Gy, that is the dose per fraction ranged from 0.43 to 0.71 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. The tumor response to the hyperfractionated treatment was found to be slightly more effective compared to the results obtained in a previous study where treatments with 6, 18, 30, and 42 fractions were applied. Since normal tissues are considerably spared with increased numbers of fractions, clinical studies with hyperfractionation seem to be very promising.

Animals↗
PubMed1989

Response of rat rhabdomyosarcoma tumors to split doses of mixed high- and low-let radiation.

Radiation-induced growth delay was measured in rat rhabdomyosarcoma tumors exposed to split doses of high-LET (linear energy transfer) neon ions in the extended-peak ionization region and low-LET X rays. Top-off doses of 7.5, 15, and 25 Gy of 225-kVp X rays were administered to the tumors at 0.5, 4.0, and 24.0 hr following priming doses of either peak neon ions or X rays. The priming doses used were 7 Gy of peak neon ions and 20 Gy of X rays, both of which produced a 10 day delay in tumor regrowth to a volume twice that measured on the day of irradiation. The tumor response to split doses of X rays indicated rapid repair of sublethal damage, with significant recovery occurring at 0.5 hr and complete recovery by 4 hr after the initial 20-Gy X ray dose. The top-off doses of X rays required to produce an additional 10 or 20 days of tumor growth delay were 18 and 7% larger, respectively, when the priming dose was 20 Gy of X rays as compared to 7 Gy of peak neon ions. This result indicates that relatively little interaction of the neon-ion and X ray radiations occurred, even when the time interval between split-dose irradiations was as short as 0.5 hr. Our data indicate that the interaction of high- and low-LET radiation modalities is small, and approaches a simple additivity of effects when the tumors repair a major portion of the sublethal radiation injury imparted by a priming dose before the second dose is administered.

Animals↗
PubMed1990

Radiotherapy of the rhabdomyosarcoma R1H of the rat: postoperative radiotherapy.

Rhabdomyosarcoma R1H of the rat was excised aiming for a complete macroscopic local excision. Adjuvant radiotherapy was performed from the third postoperative day on. Former tumor sites were locally irradiated with 200 kVp X rays 4 times per week over a period of 6 weeks. Total doses of 0, 15, 30, 45 and 60 Gy were applied. The tumor volume was measured and the time to regrow to initial volume was assessed. The results were compared to the effect of a standard radiotherapy alone with 30 fractions of 2 Gy applied within 6 weeks. All tumors recurred despite of the irradiation treatment. At high total doses (greater than 30 Gy), adjuvant radiotherapy was found to improve short term tumor response considerably, whereas no positive effect was seen at low doses. After a total dose of 60 Gy and long time intervals after start of treatment, radiotherapy alone and a combination of surgery and radiotherapy seem to be isoeffective in our tumor system.

Animals↗
PubMed1991

Reoxygenation in a rat rhabdomyosarcoma tumor following X-irradiation.

The paired survival curve technique was used to characterize the rate at which the fraction of hypoxic cells in rat rhabdomyosarcoma R-1 tumors returns to the preirradiation value of 37% following a single dose of 225-kVp X rays. Tumors were administered a conditioning x-ray dose of 15-Gy, followed at 0, 3, 6, 12, 24, or 48 hr by a 5-Gy, 10-Gy, or 15-Gy dose of X rays under air-breathing conditions or under hypoxic conditions produced by nitrogen-gas asphyxiation 5 min prior to irradiation. Cellular surviving fractions were determined by the tumor excision assay following in vivo irradiation. From the ratio of the survival fractions measured for tumor cells from air-breathing and hypoxic animals, the fraction of hypoxic cells was determined as a function of time postirradiation. These results indicated that immediately following a 15-Gy dose of X rays, essentially 100% of the viable cells remaining were hypoxic. The tumors reoxygenated rapidly, returning to the preirradiation level of 37% during the first 6 hr postirradiation.

Animals↗
PubMed1991

ASTRO (American Society for Therapeutic Radiology and Oncology) keynote address: Contributions of pediatric oncology: examples derived from advances made in the treatment of rhabdomyosarcoma and neuroblastoma.

A revolution in cure rates has occurred in the treatment of childhood cancer in the past 3 decades. Although scientific and technical improvements in surgery, anesthesia, radiation therapy, and chemotherapy have occurred in this time period, these striking improvements are also due to overall management approaches, such as the concept of multidisciplinary consultation prior to definite management, which have been pioneered in the pediatric patient. Using improvements in the treatment of rhabdomyosarcoma and neuroblastoma as examples, this paper reviews some of these approaches that have been of particular importance and have, in many instances, been exported to the adult clinic with success. The role that pediatric oncology has served in increasing our knowledge of cancer and the potential that pediatric cancer serves as a model for future gains in our understanding of cancer is also discussed.

Child↗
PubMed1992

Tumor and normal tissue response to interstitial photodynamic therapy of the rat R-1 rhabdomyosarcoma.

Interstitial photodynamic therapy (IPDT) using Photofrin II (PII) as photosensitizer has been studied in the rat rhabdomyosarcoma R-1, growing on the thigh or flank of WAG-Rij rats. A light dose-response relationship has been established, for 10 mg PII/kg i.v. and irradiation 24 hr later, with local tumor control as the end point for single IPDT treatments using four cylindrical diffusors simultaneously. A light energy fluence of 150-200 Joule/cm2 (wavelength 625 nm), measured in vivo at the tumor periphery, was required for tumor control. Comparison of tumor response at 5 and 2.5 mg PII/kg with the complete dose response relationship at 10 mg PII/kg suggests drug-light dose reciprocity and indicates that in our tumor model treatment failures are not likely to be caused by variations in (tumor) tissue photosensitizer level, but rather by insufficient light dose or inadequate light dose distribution. Increasing the interval between PII administration and irradiation from 24 hr to 48 hr had no great effect on tumor response to IPDT in this study. Inspection of the original tumor site 100 days after tumor control revealed obvious loss of thigh muscle tissue. Also, recurrent tumors showed a reduced growth rate. Therefore, the relationship between tumor (re)growth and PDT-induced normal tissue damage was studied and the existence of a tumor bed effect was confirmed. The present study indicates that tumor control after a single IPDT treatment is feasible, but that PDT induced damage to a margin of the adjacent normal tissue is probably required.

Animals↗
PubMed1995

Combined modality treatment of the rhabdomyosarcoma R1H of the rat: tumor and normal tissue response after cisplatin and conventional or accelerated irradiation treatment.

PURPOSE: To test the importance of the sequence of cisplatin and irradiation, either conventional or accelerated fractionated. METHODS AND MATERIALS: 30 fractions of 2 Gy were given in 6 or 3 weeks preceded or followed by (time interval between cisplatin and radiotherapy: 3 days) a single IP dose of 5 mg/kg cisplatin in the rhabdomyosarcoma R1H of the rat. Survival curves were generated, and comparisons were made by the log-rank test. RESULTS: After 60 Gy in 6 weeks, no local tumor controls were observed. If cisplatin was injected 3 days before start of 60 Gy/6 weeks, 11 +/- 10% (mean +/- SE) of the tumors were controlled. Cisplatin after radiotherapy resulted in 50 +/- 14% local controls. The difference was significant (p = 0.01) for cisplatin after radiotherapy in comparison to radiotherapy alone where no local controls were observed. After accelerated fractionation, 57 +/- 19% of the animals were cured with or without cisplatin before radiotherapy. If the drug was injected after end of 60 Gy/3 weeks, 86 +/- 13% survived recurrence free. The difference to accelerated radiotherapy alone was not significant. Accelerated radiotherapy produced significantly higher control rates than conventional radiotherapy (p < 0.001). CONCLUSIONS: Accelerated radiotherapy resulted in higher local tumor control rates as compared to conventional fractionated irradiation. Cisplatin combined with radiotherapy showed significantly better results if given after but not before irradiation, either conventional or accelerated fractionated.

Animals↗
PubMedDate not supplied

Importance of a post-therapeutic residue in the prognosis of head and neck rhabdomyosarcoma in children.

Enhanced contrast computed tomography (CT) was performed in 23 children treated for head and neck rhabdomyosarcoma (RMS). The CT studies were retrospectively reviewed by two senior radiologists. Analysis of these CT studies revealed to separate groups of patients. One group (12 patients) had a post-therapeutic residue defined as soft tissue thickening at the original site, which remained stable over a period of 3 months and caused no mass effect on adjacent structures. Of these 12, eight showed enhancement at the area of thickening. Nine of these 12 patients relapsed. The other group (11 patients) demonstrated no post-therapeutic residue; only three of these patients relapsed. In this study the presence of a post-therapeutic residue was significantly associated with a poor prognosis, using a Fischer's test (P = 0.04).

Adolescent↗
PubMed1993

MR imaging of late onset orbital rhabdomyosarcoma with intracranial extension.

Today, patients with alveolar rhabdomyosarcoma have a favorable prognosis with a survival rate of more than 80%, due to modern radiotherapy. However, those patients with secondary meningeal involvement are still afflicted with a mortality rate of 90% unless a different therapeutic approach is taken. We report a case of a young adult with invasion of the tumor into the anterior cranial fossa. MRI aided in the assessment of the intracranial tumor spread and allowed for a direct visualization of the meningeal membranes. The signal characteristics of the tumor and the adjacent tissue in unenhanced and postcontrast MRI is discussed. MRI was clearly superior to CT and indicative for the choice of treatment.

Adult↗
PubMedDate not supplied

Comparison of human rhabdomyosarcoma, HEp-2, and human foreskin fibroblast cells for the isolation of herpes simplex virus from clinical specimens.

The performance of locally produced human rhabdomyosarcoma (RD) cells was shown to be superior to human foreskin fibroblast (SF) and HEp-2 cells for the isolation of the herpes simplex virus (HSV) from clinical specimens. A comparison of sensitivity, clarity of cytophathic effect, and ease of growing the cells for the isolation of HSV was made on these cell lines. A total of 1351 fresh clinical specimens, submitted for the isolation of HSV, were inoculated into RD, HEp-2, and SF cell culture tubes. The cultures were incubated for 7 days at 35 degrees C on a roller drum and observed daily for cytophathic effect (CPE). Of these specimens, 318 (23.5%) were positive for HSV. In 287 (90%) of these positive specimens, the RD cell line was the first, either alone or simultaneously with another cell line, to display typical HSV CPE. This CPE was clearly recognized by the appearance of clusters of rounded cells and associated multinucleated giant cells. In 241 (76%) of the positive specimens, the RD cell line displayed CPE on the first or second day of incubation. These results demonstrate that the RD cell line was more rapid than the SF and HEp-2 cell lines for the detection of HSV and suggests that RD cells should be included in a tissue culture program designed for the detection of HSV.

Cell Division↗
PubMed1986

Regulation of viral persistence in human glioblastoma and rhabdomyosarcoma cells infected with coronavirus OC43.

Cultures of human rhabdomyosarcoma (RD) and human glioblastoma (U87-MG) were compared for their ability to sustain a persistent infection with coronavirus OC43. Within 28 days, infectious virus and hemagglutinin were being produced at high levels in both types of cells. Temperature sensitive plaque variants were recovered at 31 degrees C. In both cell types, the virus caused increased antigen synthesis and cell death, if the temperature was lowered to 31 degrees C. Infectious virus was lost if cells were treated with antiserum to whole virus or if the temperature was raised to 39.5 degrees C. Probing the cured cells with OC43-specific 32P-cDNA showed that cured cells contained no detectable viral RNA. The relative ease of establishment and cure of these persistent infectious makes them attractive as models to study coronavirus regulatory processes.

Coronaviridae↗
PubMedDate not supplied

Imaging of retroperitoneal rhabdomyosarcoma mimicking hypernephroma.

Malignant tumors that arise in the perinephric space often present a diagnostic dilemma. These retroperitoneal tumors may resemble renal carcinomas, extrahepatic lymphoma, metastatic disease, or tumors arising in other retroperitoneal organs. We present a case of a patient with a primary retroperitoneal rhabdomyosarcoma who had an extensive diagnostic workup prior to surgical intervention that was thought to be consistent with an aggressive renal cell carcinoma.

Aged↗
PubMed1993

Radioimmunoscintigraphy using [111In]antimyosin Fab fragments for the diagnosis and follow-up of rhabdomyosarcoma.

Between 1987 and 1992, 39 radioimmunoscintigraphic studies using 111In-labelled antimyosin Fab fragments were performed in 27 patients with rhabdomyosarcoma (RMS), 2 patients with leiomyosarcoma (LMS) and 1 with alveolar soft tissue sarcoma. 21 patients were children aged 3-14 years. These patients, who had histologically proven myosarcoma, were examined scintigraphically to search for local recurrences or metastases and to determine the response to treatment. The results of immunoscintigraphy were compared with histopathological parameters and other imaging modalities. The sensitivity of antimyosin scintigraphy in this series was 82% and the specificity was 73%. Although the technique appears to be not highly specific for RMS, it was found to be useful for the early detection of local recurrence and metastases, as well as for the evaluation of the response to therapy.

Adolescent↗
PubMed1991

Metabolism of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 by blood derived macrophages from a patient with alveolar rhabdomyosarcoma during short-term culture and 1 alpha,25-dihydroxyvitamin D3 after long-term culture.

We have examined the ability of blood-derived monocytes and macrophages isolated from a patient with alveolar rhabdomyosarcoma and hypercalcaemia, to form 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3). Adherent monocyte-macrophage cells incubated with 25(OH)D3 over the initial 2 days in culture synthesized 1.9 pmol 24,25(OH)2D3/h/incubation (representing 0.63 pmol/h/10(6) cells), whereas macrophages synthesized 1.03 and 1.15 pmol 1 alpha,25(OH)2D3/h/incubation after 1 and 4 weeks in culture respectively. In a further experiment synthesis of 1 alpha,25(OH)2D3 by long-term cultured macrophages fell from 2.25 to 0.04 pmol/h/incubation following exposure to 10 nM 1 alpha,25(OH)2D3 for 7 days, whereas 24,25(OH)2D3 synthesis was induced (0.46 pmol/h/incubation). The vitamin D3 metabolites were identified by co-chromatography with authentic 24,25(OH)2D3 or 1 alpha,25(OH)2D3 in three different high-performance liquid chromatography systems. Serum 1 alpha,25(OH)2D3 in the patient was markedly suppressed at 5 pg/ml (normal 20-50 pg/ml) indicating that raised 1 alpha,25(OH)2D3 was not the cause of the hypercalcaemia, but rather, that raised calcium may have suppressed renal 1 alpha,25(OH)2D3 synthesis. Administration of APD (3-amino-1-hydroxypropylidine-1,1-bisphosphonate) corrected the hypercalcaemia in the patient suggesting that increased bone resorption was responsible for the raised calcium. The results of this study show for the first time that immature blood derived monocyte-macrophage cells can synthesize 24,25(OH)2D3 before they mature into macrophages able to synthesize 1 alpha,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Comparative pharmacokinetic and photodynamic studies with zinc(II) phthalocyanine in hamsters bearing an induced or transplanted rhabdomyosarcoma.

Comparative pharmacokinetic studies in hamsters bearing an induced or first-generation transplanted rhabdomyosarcoma that were injected with liposome-incorporated zinc(II) phthalocyanine (ZnPc) show a higher drug concentration in the induced tumour. The selectivity of tumour targeting is underlined by the fact that, 24 h after injection, larger amounts of ZnPc are found in the tumour than in the liver. Photodynamic therapy investigations were carried out using 673 nm light from an argon-dye laser. On the basis of different assessment criteria (changes in mean tumour diameter with time, tumour mass regression, survival time of the treated groups of animals, and histological determination of the necrotic tissue) the photosensitizing effect of ZnPc appears to be comparable for both kinds of tumour in spite of the higher uptake of photosensitizer by the induced tumour.

Animals↗
PubMed1994

TNF receptor fusion proteins are effective inhibitors of TNF-mediated cytotoxicity on human KYM-1D4 rhabdomyosarcoma cells.

KYM-1D4 cells are a subline derived from a human rhabdomyosarcoma which are highly sensitive to TNF-mediated cytotoxicity. They were selected for this study because they express human TNF-R and are therefore a more relevant target for comparing the potential therapeutic value of human TNF-inhibitory agents than the usual murine cell lines. Two recombinant soluble TNF-R-IgG fusion proteins, one containing p55 TNR-R, the other containing p75 TNF-R, and a recombinant monomeric soluble p55 TNF-R were all found to block the cytotoxicity generated by human TNF-alpha and LT as well as also murine TNF. The p55 TNF-R-IgG fusion protein (p55-sf2) was the most effective of the antagonists tested, requiring an equimolar, (based on a monomeric configuration of TNF-alpha) or a 3-fold higher (based on a trimeric configuration of TNF-alpha) molar concentration to inhibit the cytotoxicity mediated TNF-alpha by 50%. p55-sf2 was also as effective at inhibiting the cytotoxicity mediated by LT or murine TNF in the KYM-1D4 assay. In contrast, the monomeric soluble p55 TNF-R was the least effective inhibitor, requiring a > 4000-fold higher molar concentration than p55-sf2 to achieve a similar degree of protection. The fusion proteins, particularly p55-sf2, may be useful as human therapeutic agents, as at low concentrations they can prevent both TNF-alpha-mediated and LT-mediated effects on human cells. As TNF-R-IgG fusion proteins also block the action of murine TNF in vitro, they may also be useful in the investigation of murine models of human inflammatory disease.

Animals↗