Combined action of Rous sarcoma virus and chemical carcinogen in rats.
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Animals↗
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Results for “SARCOMA, FIBROSARCOMA”
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Genomic alterations in sarcomas: a histologic correlative study with use of oncogene panels.
Amplification and rearrangement of cellular proto-oncogenes are two of the several possible genetic alterations implicated in carcinogenesis and tumor progression. Although morphologically similar tumors may be heterogeneous at the level of the genome, some tumor types have shown relatively frequent and consistent abnormalities of specific oncogenes. In order to determine the frequency of oncogene amplification and rearrangement in several types of human sarcomas and to determine if histologically similar tumors have common genetic alterations, we analyzed 26 primary sarcomas by Southern hybridization. The oncogene probes utilized were N- and H-ras, sis, EGF-R (erb-B-1), neu (erb-B-2), fos, N- and c-myc, mos, and yes. The tumors studied included: five rhabdomyosarcomas (one alveolar, four embryonal), six malignant fibrous histiocytomas, six leiomyosarcomas, four liposarcomas, two Ewing's sarcomas, one osteosarcoma, and two fibrosarcomas. Oncogene abnormalities were identified in three tumors. One rhabdomyosarcoma showed 12-fold amplification and concurrent rearrangement of sis. This particular tumor also revealed rearrangement of H-ras and 15-fold amplification of c-myc. A second rhabdomyosarcoma revealed rearrangement of neu. A liposarcoma had a sis rearrangement. These findings suggest that many sarcomas show no common structural oncogene abnormalities. The presence of differing oncogene alterations within the rhabdomyosarcoma group indicates genetic heterogeneity among histologically similar sarcomas. The finding of a sis rearrangement in both a liposarcoma and a rhabdomyosarcoma, however, may suggest common oncogenesis among different tumor types.
Adolescent↗
Dual-colour fluorescence in situ hybridization analysis of synovial sarcoma.
Mounting cytogenetic evidence indicates that synovial sarcomas, regardless of histological conformation, share the specific reciprocal chromosomal translocation t(X;18)(p11.2;q11.2). Application of dual-colour fluorescence in situ hybridization (FISH) on interphase nuclei isolated from archival paraffin-embedded material to identify the specific translocation is of diagnostic importance for pathological practice and retrospective study. Five cases of well-characterized biphasic synovial sarcomas, two monophasic fibrous synovial sarcomas, one embryonal rhabdomyosarcoma, one fibrosarcoma, and one malignant peripheral nerve sheath tumour were analysed. To visualize the translocated chromosomal fragments and their topographic relationships with centromeres of chromosomes X and 18, nuclei from each case were hybridized concurrently with chromosome X centromeric and chromosome 18 painting probes, and chromosome 18 centromeric and chromosome X painting probes, respectively. Six out of seven synovial sarcomas showed chromosomal alterations consistent with t(X;18). One biphasic synovial sarcoma had trisomy 18 and lacked the chromosomal translocation t(X;18). The other three spindle cell sarcomas and the normal control tissues showed the normal numerical and structural composition for chromosomes X and 18. It is indicated from the present study that when histological differential diagnosis is difficult, FISH would be a crucial aid in detecting a known specific chromosomal alteration and that dual-colour FISH is an efficient stable diagnostic tool for pathological research and daily diagnosis. The results also suggest that rare synovial sarcomas may lack the chromosomal translocation t(X;18). 1998 John Wiley & Sons, Ltd.
Adult↗
The role of radiotherapy in the treatment of soft tissue sarcoma: a retrospective study 1958--73.
Survival and local control data are presented for a series of 109 cases of soft tissue sarcoma treated 1958--73. A five-year minimum follow-up period is available. The two-year and five-year survival rates for the complete series are respectively 80 and 68%. In a comparison of survival results for different histological subgroups we found a 94% two-year survival for liposarcomas compared with 80% for fibrosarcomas and 74% for synovial sarcomas; and five-year survivals of 73, 68 and 51% respectively. Sixty-two per cent of the series achieved local control of the disease after initial treatment, and this figure increased to 83% after further treatment. Eighty-six per cent of tumours of the extremities (66/77) were controlled locally without amputation. Of those in the complete series whose disease recurred, either locally or distantly, 50% experienced this recurrence within one year of initial treatment. In only 7% did the recurrence occur more than five years after initial treatment. These results are encouraging and we conclude that they justify an initial treatment policy of conservative surgery combined with radical radiotherapy.
Humans↗
Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature.
Primary sarcomas of the breast are extremely rare, with less than 0.1% of all malignant tumours of the breast. Mayo Clinic Surgical Pathology database was searched for all breast sarcoma from 1910 to 2000. Pathology reports and slides were reviewed and tumour types were determined. Metaplastic carcinomas and phyllodes tumours were excluded. There were 25 women ranging in age 24-81 years (mean 45 years). All but one patient presented with a palpable lump. Mastectomy was performed in 19 patients and lumpectomy in five patients. Histopathological diagnoses were fibrosarcoma (six), angiosarcoma (six), pleomorphic sarcoma (six), leiomyosarcoma (two), myxofibrosarcoma (three), hemangiopericytoma (one) and osteosarcoma (one). Tumour size ranged from 0.3 to 12 cm (mean 5.7). Low-grade lesions were observed in 10 cases and high-grade in 15. Overall, mean follow-up was 10.5 years. Local recurrence was observed in 11 patients and ranged from 2 to 36 months (mean 15 m), while distant metastasis was observed in 10 patients (40%) affecting lungs, bones, liver, spleen, and skin. Of the 25 patients, 12 have died of disease and six of other causes. Five-year overall (OS) and cause-specific survival (CSS) were 66 and 70%, respectively. OS and DFS at 5 years were 91% for tumours < or =5 cm and 50% for tumours >5 cm. Tumour size was significantly associated with OS (risk ratio=1.3 per 1 cm increase; 95% CI, 1.02-1.7; P=0.036). There was no significant difference in OS or CSS between low- and high-grade lesions. In this series, tumour size was a more valuable prognostic factor than tumour grade.
Adult↗
[Malignant neoplasms of the peripheral nerve sheaths with cellular immunophenotype of perineural cells (perineural sarcoma?)].
2 cases of soft tissue malignant tumors formally related to the group of spindle cell sarcoma are described. The majority of cells expressed an epithelial membranous antigen and vimentin but were S-100 protein unreactive, i.e. had a phenotype characteristic of perineural cells. Monoclonal antibodies to 5 types of filaments protein of intermediate type, neurone specific enolase and collagen type I, II, III, IV, V were also used as well as electron microscopic investigation. Problems of differential diagnosis from schwannomas, fibrosarcomas, monophasic spindle cell "synovial sarcoma" and validity of integrating these tumors into an independent variety of malignant peripheral nerve sheath tumors are discussed.
Adult↗
Effects of agents which inhibit the regulation of intracellular pH on murine solid tumours.
Cell killing can be achieved in an acidic environment in tissue culture (medium pH less than 7.0) by agents (nigericin, carbonylcyanide-3-chlorophenylhydrazone (CCCP)) which transport protons from the extracellular space into the cytoplasm. Cell killing is enhanced when these agents are used in combination with compounds (amiloride, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)) which inhibit the membrane-based exchangers responsible for the regulation of intracellular pH (pHi). We describe experiments which assess the ability of these agents to kill tumour cells in spheroids and in vivo. Both nigericin and CCCP were observed to penetrate tissue based on their ability to kill tumour cells in spheroids. The mean extracellular pH (pHe) of the KHT fibrosarcoma and the EMT-6 sarcoma were observed to be 0.21 and 0.32 pH units more acidic than the mean pHe in muscle tissue. Intraperitoneal (i.p.) administration of the vasodilator hydralazine (10 mg kg-1) caused a reduction of the mean pHe of the KHT but not the EMT-6 tumour. Nigericin (2.5 mg kg-1, i.p.) plus amiloride (10 mg kg-1, i.p.) followed 30 min later by hydralazine (10 mg kg-1, i.p.) reduced the surviving fraction of cells in the KHT and EMT-6 tumours, but had minimal effects on growth delay. When KHT tumours were treated with 15 Gy X-rays followed immediately by nigericin plus amiloride and hydralazine a reduced surviving fraction as well as an increase in tumour growth delay was observed compared to radiation alone. The administration of nigericin (2.5 mg kg-1, i.p.) or the combination of nigericin (2.5 mg kg-1, i.p.) followed by hydralazine (10 mg kg-1, intravenous (i.v.)) resulted in reductions of tumour pHi of 0.27 and 0.29 pH units respectively as determined by 31P magnetic resonance spectroscopy (MRS). Our results show that the combination of nigericin and hydralazine (with or without amiloride) can kill cells in rodent solid tumours and that cell killing is associated with a reduction in the mean pHi of tumour cells.
Amiloride↗
[Radiotherapeutic treatment in muscle sarcomas and connective tissue streaks in the extremities].
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Connective Tissue↗
Taurolidine inhibits tumour necrosis factor (TNF) toxicity--new evidence of TNF and endotoxin synergy.
The use of recombinant tumour necrosis factor (TNF) in the treatment of solid tumours has been limited by life threatening toxicity. In addition TNF may be a major mediator of the effect of endotoxins. Recent evidence suggested that a synergism between endotoxin (at the picogram level) and TNF may contribute to this toxicity. The use of the anti-endotoxin taurolidine may reduce TNF toxicity by interfering with this synergy. C57/BL6 mice (n = 140) received toxic doses (12 micrograms/mouse IV) of TNF. Four groups were studied. Group A received taurolidine 200 mg/kg IV 30 minutes before TNF, group B received TNF followed 30 minutes later by taurolidine 200 mg/kg IV, group C received an identical volume (0.5 ml) of normal saline 30 minutes prior to TNF, and group D taurolidine 200 mg/kg IP 45 minutes before TNF. The mortality rate of those mice receiving intravenous taurolidine 30 minutes prior to TNF was 8.8%. This was significantly less (P < 0.005) than the mortality rate achieved in groups B, C and D (33% vs 39.4% vs 50%). Further experiments employing an MTT (3-(4,5-dimethylthinzol-2-microliters)-2,5-diphenyl tetrazolinm bromide) assay showed that this was not due to direct interaction of taurolidine with TNF but is likely to be due to interference with the synergistic effects of endotoxin and TNF. It was also demonstrated in cotherapy studies in a murine model that taurolidine did not reduce the anti-tumour efficacy of TNF against the TNF sensitive mouse fibrosarcoma cell line Meth-A sarcoma.
Animals↗
Modular megaprosthesis for distal femoral tumors.
We treated 48 patients with distal femoral tumors by resection and limb salvage with an uncemented megaprosthesis (Howmedica Modular Replacement System). Diagnoses included: 32 osteosarcomas, five chondrosarcomas, six giant cell tumors of the bone, three fibrosarcomas, and two Ewing's sarcomas. The mean follow-up was 5.6 years (2-10 years). The overall complication rate was 39%. Seven patients died of their disease, but none from complications related to the surgery. Five patients were revised to arthrodesis, and one required amputation because of complications. The mean postoperative Musculoskeletal Tumor Society score (MSTS) score was 21 (6-28) for the remaining 35 patients. The most frequent complications were infection (14.6%) and aseptic loosening (4.8%). Ten-year survival of the prosthesis was 65%.
Adolescent↗
Carcinosarcoma of the prostate. Report of 21 cases.
BACKGROUND: Carcinosarcoma of the prostate is an unusual malignancy characterized by adenocarcinoma intimately admixed with sarcoma. METHODS: The authors reviewed the clinical and pathologic findings of 21 cases of carcinosarcoma of the prostate from the files of the Mayo Clinic. RESULTS: Patient age ranged from 50 to 89 years (mean, 68 years). Ten patients (48%) had a previous diagnosis of prostatic acinar adenocarcinoma 2-73 months (mean, 33 months) before the diagnosis of carcinosarcoma, 8 of whom had received androgen deprivation therapy and/or radiation therapy in the interim. The Gleason score of adenocarcinoma ranged from 7 to 10 (mean, 9; median, 9). The sarcomas consisted of osteosarcoma (13), leiomyosarcoma (5), fibrosarcoma (1), malignant fibrous histiocytoma (1), and rhabdomyosarcoma (1), and the grade of the sarcoma component ranged from 2 to 4 (mean, 4; median, 4). Adenocarcinoma was the dominant histologic pattern in 7 cases and sarcoma in 14. Immunohistochemical staining revealed cytoplasmic reactivity for prostate specific antigen or keratin in 16 of 16 cases in the adenocarcinoma component. The sarcoma component was positive for vimentin in 16 of 16 cases, actin in 8 of 16 (focal in 2), S-100 protein in 2 of 16, and desmin in 1 of 16. At the time of diagnosis of carcinosarcoma, 11 patients had metastases, including 4 with metastatic adenocarcinoma before the diagnosis of carcinosarcoma. Treatment varied, and nonsurgical therapy was ineffective. Sites of metastases included lung (10 cases), bone (7), brain (4), liver (1), and peritoneum (1). Follow-up ranged from 1 to 107 months after the diagnosis of carcinosarcoma (mean, 34 months; median, 10 months). Mean time to tumor progression was 23 months (range, 1-96 months; median, 18 months). Eighteen patients died of carcinosarcoma from 2 to 107 months (mean, 34 months; median, 9.5 months) after diagnosis. Five-year survival was 41%, and 7-year survival was 14%. Progression and survival were not affected by histologic pattern. CONCLUSIONS: Carcinosarcoma of the prostate is an aggressive malignancy, regardless of histologic type.
Aged↗
Modular megaprosthesis for proximal femoral tumors.
Fifteen patients with proximal femoral tumors had resection and limb salvage with an uncemented Kotz (HMRS) megaprosthesis. There were five osteosarcomas, four chondrosarcomas, one hemangioendothelioma, three fibrosarcomas, and two Ewing's sarcomas. The mean follow-up was 6.7 (range 3-10) years. Two patients died of causes not related to the prosthesis. The postoperative Musculoskeletal Tumor Society score (MSTS) score was 19 (range 12-26) for the remaining 13 patients. There were one aseptic loosening, two infections, and one local recurrence. The most frequent complication was hip dislocation at 20%. Reconstruction of proximal femoral tumors with a modular megaprosthesis is a good procedure, but hip instability remains a major problem.
Adolescent↗
[Combination therapy of a new platinum complex, DWA2114R with various antitumor agents against mouse tumors in vivo].
In vivo antitumor activity of (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) monohydrate (DWA2114R) in combination with various antitumor agents was examined using mouse leukemia P388, Meth-A fibrosarcoma and M5076 reticulum cell sarcoma. The combination treatment of DWA2114R with cyclophosphamide, 5-fluorouracil, adriamycin, etoposide or vindesine showed synergistic effects on the prolongation of survival time of mice bearing P388. Among these combinations, combination of DWA2114R with adriamycin or vindesine showed a good synergism. In the combination treatment with vindesine against Meth-A which is not so sensitive to platinum agent, DWA2114R showed a synergistic or additive effect, but cis-diamminedichloroplatinum (II) (CDDP) showed subadditive. Three-drug combination of DWA2114R or CDDP with cyclophosphamide and adriamycin was examined in mice inoculated i.p. or s.c. with M5076. In both models, the combination of DWA2114R was more active than that of CDDP at the dose less than 1/16-fold of the dose of CDDP which is the ratio of two drugs in clinical trial.
Animals↗
Soft-tissue sarcomas of the chest wall: prognostic factors.
OBJECTIVE: To evaluate factors that are predictive of outcome for patients with chest wall soft-tissue sarcomas. PATIENTS AND METHODS: A retrospective review of 55 surgically treated patients, from March 1964 to October 1996. RESULTS: The median age of the patients was 47.5 years (age range, 15 to 76.3 years), and 56.4% were men. The most common presenting symptom was chest wall mass in 29 patients (52.7%). The median symptom duration was 12 months. Tumor size ranged from 1 to 26 cm (median size, 9.7 cm). The most common histologic type of tumor was fibrosarcoma (52.7%). Twenty-three sarcomas (41.8%) were high-grade, and 32 sarcomas (52.8%) were low-grade. Of the 55 patients, 27 (49.1%) had previously been treated elsewhere (surgical resection, 23 patients; radiation therapy and surgery, 3 patients; chemoradiation therapy, 1 patient). Previously treated patients presented either with residual disease (10 cases) or recurrence of disease (17 cases). All 55 patients underwent surgical resection, 15 patients (27.3%) were treated by neoadjuvant chemoradiation therapy, and 2 patients were treated by adjuvant radiotherapy. Wide surgical resection was performed in 45 patients (81.8%), and marginal resection was performed in 10 patients (18.2%). The median follow-up time was 51.9 months. Local recurrence of disease developed in 6 patients, and metastases developed in 10 patients. The overall survival rates at 5 and 10 years were 87.3% and 79.3%, respectively. Tumor size < 5 cm and low histologic grade were determinants of better survival at univariate analyses. Multivariate analyses disclosed only histologic grade as an independent predictor for the risk of death. Disease-free survival rates at 5 and 10 years were 75.3% and 64.2%, respectively. Tumor size < 5 cm, performance of wide surgical resection, and low histologic grade were determinants of a better disease-free survival rate. Independent prognostic factors for disease-free survival were histologic grade and type of surgical resection. CONCLUSION: The clinical behavior of chest wall soft-tissue sarcomas is similar to that of extremity sarcomas. Thoracic wall soft-tissue sarcomas are best controlled by wide surgical resection.
Adolescent↗
[Prostate sarcoma: a report of 14 cases].
OBJECTIVE: To discuss the diagnosis and effective treatment of prostate sarcoma. METHODS: We analysed the clinical materials of fourteen patients with prostate sarcoma treated in our hospital from Jan. 1991 to Jun. 2004. RESULTS: Prostate sarcoma accounted for 3.21% of all the prostatic malignant tumors treated in our hospital during that period. The average age was 39.5 years old (ranging from 17 to 62). Twelve cases came to our hospital because of dysuria. Large soft prostate tumors were found in all the patients in physical examination. The serum AKP, ACP and PSA levels were normal in all the 10 patients who had received the test. Pathological test revealed: 7 cases leiomyosarcoma, 1 case rhabdomyosarcoma, 4 cases fibrosarcoma, 2 cases spindle cell sarcoma. Different kinds of prostate sarcoma each his its own immuno-histochemical staining features. Two cases were at Ghavimi Stage I, 5 at Stage II, 3 at Stage III, and 4 at Stage IV. All the patients received surgery, chemotherapy and/or radiotherapy. One case failed to be followed up, 11 died 2 approximately 12 months after diagnosis. Two patients are still alive, 1 for 18 months without recurrence, and the other for through with relapse. CONCLUSION: Dysuria is always the first symptom of prostate sarcoma. DRE test may suggest prostate sarcoma but needle biopsy contributes to a definite diagnosis. The immuno-histochemical dyeing helps to differentiate the disease. The prognosis of prostate sarcoma is very poor and the main treatment is surgery followed by chemotherapy and/or radiotherapy.
Adolescent↗
Accuracy of cytological grading of spindle-cell sarcomas.
Spindle-cell sarcomas constitute an important component of soft-tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle-cell sarcomas on fine-needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle-cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle-cell sarcomas, unclassified (2 cases), were graded according to a three-tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle-cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle-cell sarcomas. The cytological and histological concordance was better (75%) in high-grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases.
Adult↗
Cancer cell progression and chemoimmunotherapy--dual effects in the induction of resistance to therapy.
To determine whether resistance to chemoimmunotherapy is acquired during therapy, we investigated the effects of chemotherapeutic agents and anti-tumour polysaccharide, lentinan, on the progression of Rous sarcoma virus-induced S908.D2 fibrosarcomas. The chemoimmunotherapy was effective against the parental S908.D2-bearing mice. Nearly all the mice that were treated with cyclophosphamide (CY) and lentinan achieved complete tumour regression. Only a few of the mice that achieved complete regression of the primary tumours showed a recurrence of the tumour in regional lymph nodes. S908.D2-vp.1 was established from metastatic tumours that developed in the regional lymph nodes of parental S908.D2-bearing mice during therapy. S908.D2-vp.2-or vp.3 cells were sequentially derived in a similar way from S908.D2-vp.1-or-vp.2-bearing mice respectively, in which complete tumour regression at each primary site was achieved during therapy. These lines acquired resistance to CY and lentinan and also to 5-fluorouracil (5-FU)/5'-deoxy-5-fluorouracil and lentinan. No significant difference in either the sensitivity to 5-FU or 4-deoxycyclophosphamide in vitro or in the susceptibility to immune effector cells was observed between the parental and progressed lines (S908.D2-vp1 -vp3). There was an increase in the level of prostaglandin E2 (PGE2) in the progressed lines during repeated therapy (parental, 1171 pg ml(-1); vp.1, 2199 pg ml(-1); vp.2, 5500pg ml(-1); vp3, 16187 pg ml(-1)). There was no significant increase in the production of transforming growth factor beta (TGF-beta). The amount of interleukin-2 (IL-2) produced by spleen cells isolated from the S908.D2-vp.2-bearing mice was decreased compared with the amount produced by the parental S908.D2- bearing mice. Furthermore, combination therapy with lentinan and IL-2 achieved complete tumour regression in all the mice transplanted with S908.D2 progressed tumour lines, although IL-2 alone did not show any anti-tumour effects in either the S908.D2 parental or progressed lines. The findings suggest that the reduced production of IL-2 induced an increase in the production of the PGE2 by progressed tumour lines is involved in the acquisition of resistance.
Animals↗
[Resections in primary sarcoma of the lungs].
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Fibrosarcoma↗