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Soft-tissue sarcomas of the head and neck in adults and children: experience at a single institution with a review of literature.

Ninety-four soft-tissue sarcomas of head and neck occurring among 10,700 malignancies, seen during the period 1953-1980 in the head-and-neck surgical department, were studied with reference to age, sex, ethnic origin, site, histological type and survival. The objective was to review our own experience with sarcomas in these sites seen in the Department of Pathology, A.C. Camargo Hospital. The predominant site was the head. Fibrosarcoma was the most frequent type in adults and rhabdomyosarcoma, located exclusively in the head, was the most frequent in children.

Adolescent↗

Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice.

The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect.

9,10-Dimethyl-1,2-benzanthracene↗

[Significance of radiotherapy in the treatment of soft tissue sarcomas].

Postoperative photon- or electron irradiation has been well established in the treatment of soft tissue sarcomas. For further improvement of these results, neutron- or neutron-boost irradiation was introduced at several centres of radiation therapy. In this report, the 3.5 year results of 112 patients are analysed. The majority (62%) had T3-tumours (UICC classification, Geneva 1978). 58 patients presented with gross tumour at the beginning of radiotherapy, and 54 patients without clinical evidence of tumour. 39 patients (35%) had recurrent tumours. A highly statistical difference in local tumour control was found between the group of patients with gross tumour (47%) and the group of patients without clinical evidence of tumour (81%). A statistical difference in local control and survival was also found between the group of patients with T1-tumours (100%), T2 tumours (76.8%) and T3 tumours (44.5%), whereas no differences were found in terms of grading. The high complication rate of 25%, which was found after neutron therapy, was reduced to 7% after introduction of a neutron boost. The statistical significance of this treatment modality is presently being evaluated in a randomised EORTC trial. Adjuvant chemotherapy is recommended für all G3 tumours.

Adolescent↗

Preparation of stable target cells for anti-herpes simplex virus cytotoxic T lymphocytes.

Using an avirulent strain of herpes simplex virus (HSV), SKa, and a methylcholanthrene induced sarcoma cell line, Meth A cells, we have developed a reliable target cell system for detection of cell-mediated cytotoxicity directed against HSV-infected cells. SKa-infection in Meth A produced no progeny virus but induced HSV-specific surface antigens as revealed by radioimmunoassay using 125I-labeled HSV antibody. Spontaneous release of 51Cr from the SKa-infected Meth A cells was no more than that from uninfected control cells but a strong spontaneous 51Cr release was produced in Meth A cells infected with KOS, a virulent strain which produced a progeny virus in Meth A and was lytic for the cells. When used as a target, SKa-infected Meth A cells could detect HSV-specific cytotoxicity by spleen and lymph node lymphocytes of mice immunized with SKa and KOS. This system also detected effector cytotoxic lymphocytes stimulated in vitro by mixed cultures of immune spleen cells and KOS-infected Meth A cells. Thus, the system should be valuable in studies of cell-mediated cytotoxicity directed against HSV-infected cells.

Animals↗

Differential effect of hyperthermia and x-irradiation on regrowth rate and tumour-bed effect for a rat sarcoma.

The regrowth rate of the rat sarcoma SSB1a was assessed, following treatment with either X-rays or hyperthermia. The growth rate of untreated tumours implanted in pre-irradiated or pre-heated normal tissue was also measured. For treatments giving similar levels of tumour regrowth delay, the regrowth of irradiated tumours was markedly slower than that of untreated tumours, whilst the regrowth rate of tumours subjected to hyperthermia did not differ from that of untreated tumours. The growth rate of untreated tumours implanted in pre-irradiated skin was also slower than that of control tumours, though the growth-rate reduction was less dramatic than for regrowth following tumour irradiation in situ. Tumours implanted in pre-heated skin grew at the same rate as control tumours. Slower regrowth in situ after X-rays than after hyperthermia would produce a larger growth delay for X-rays than for hyperthermia, for equal levels of tumour-cell kill or probability of tumour sterilization. This effect could lead to a systematic underestimation of the efficacy of hyperthermia relative to X-rays, when efficacy is assessed by growth delay.

Animals↗

Postradiation sarcoma of bone in Hodgkin disease.

We report 16 cases seen in the Memorial Sloan-Kettering Cancer Center (MSKCC) during the past 50 years. These patients had been treated with external radiation for Hodgkin disease and had developed sarcomas in the field 4-31 years after the diagnosis of Hodgkin disease. Most of the tumors (12 of 16) occurred in the chest wall. There were three tumors of the pelvis and an unusual osteosarcoma of the femur following treatment for a primary Hodgkin disease of the femur. The tumors were predominantly osteosarcomas (9). In addition, there were five malignant fibrous histiocytomas, one fibrosarcoma, and one chondrosarcoma. Prognosis was poor; the mean survival was 12 months. Survival of patients with other primary cancers who developed radiation sarcomas was not significantly different from that of patients with Hodgkin disease. Hodgkin disease is now the most common tumor among radiation-induced sarcomas in previously normal bone and has surpassed breast cancer, which was previously the most common original tumor.

Adolescent↗

Specific overexpression of P53 in sarcoma derived from Rat-1 cells transformed by cigarette smoking condensate-treated human fetal lung DNA.

The p53 protein is highly expressed in fibrosarcoma derived from Rat-1 cells transfected with cigarette smoke condensate-treated human fetal lung DNA but expressed low in the counterparts of nitroso-N-methylurea and dimethyl sulfoxide groups. Our results denoted that a high expression of p53 protein specifically contributes to the initiation of human lung carcinogenesis induced by cigarette smoke condensate. High expression and missense mutation of p53 may probably be a potential biomarker of initiation of human lung carcinogenesis.

Animals↗

Distribution of alpha 1-antitrypsin in normal, granuloma, and tumor tissues in rats.

Purified rat alpha 1-antitrypsin and albumin were radiolabeled, and their distribution and catabolism in various tissues were studied in rats with inflammatory granuloma or transplanted sarcoma. Intravenously administered labeled alpha 1-antitrypsin accumulated remarkably in extravascular spaces of the granuloma or sarcoma tissues. Among the normal organs examined, the lung preferentially incorporated alpha 1-antitrypsin. Furthermore, most of the alpha 1-antitrypsin accumulated in these three tissues remained in a TCA-precipitable form throughout the observation period. Since alpha 1-antitrypsin is incorporated in large amounts into inflammatory or tumor tissues, it could play a role in regulation of inflammatory processes or in controlling the proliferation of a tumor. The studies on TCA fractionation also suggest that liver and kidney provide the main sites for degradation of this protein. Although the accumulation of labeled albumin in granuloma and sarcoma was less marked, it showed essentially the same distribution and degradation pattern as alpha 1-antitrypsin in both morbid states.

Animals↗

Sarcoma cells engineered to secrete IFN-gamma or IL-2 acquire sensitization to immune cell killing via different mechanisms.

The murine fibrosarcoma FS29 can be more efficiently killed by syngeneic lymphocytes when it has been engineered to secrete either interferon gamma (IFN-gamma), or interleukin 2 (IL-2). The mechanisms by which the two cytokines enhance target sensitivity differ. Supernatant from IFN-gamma-secreting cells can enhance the sensitivity of unmodified cells. The enhanced sensitivity correlates with MHC upregulation observed on both the IFN-gamma-secreting and supernatant-treated cells. In contrast, supernatant from IL-2-secreting cells does not affect the sensitivity of unmodified cells. IL-2 can be detected, by a bioassay, bound to the extracellular matrix of the secreting tumour cells.

Animals↗

Modulation of extracellular proteolytic activity and anchorage-independent growth of cultured cells by sarcoma cell-derived factors: relationships to transforming growth factor-beta.

We have previously described a factor(s) produced by 8387 fibrosarcoma cells, which can affect plasminogen activator (PA) activity of cultured cells. Since then, transforming growth factor-beta (TGF beta) has been established as a major growth factor/growth inhibitor that regulates both the expression and activity of PAs and their endothelial-type inhibitor (PAI-1). The present study was undertaken to characterize the 8387 fibrosarcoma cell-derived factor(s) and to investigate its relationships to TGF beta by analysis of modulation of PA activity and cell growth. The fibrosarcoma cell-derived proteins were partially purified from serum-free conditioned culture medium using Bio-Gel P-10 chromatography. Two separate fractions with apparent molecular weights of 16,000 and 12,000 contained activities that both decreased the secretion of PA activity by human lung fibroblasts and inhibited the soft agar growth of A549 lung adenocarcinoma cells. Both factors affected similarly the production of urokinase-type PA and PAI-1 in various cell lines and enhanced anchorage-independent growth of murine AKR-2B fibroblasts. The effects of these factors thus resembled those of TGF beta. The immunological relationships between the Mr 16,000 and Mr 12,000 factors and TGF beta were therefore studied using neutralizing anti-TGF beta antibodies. The TGF beta antibodies efficiently inhibited the effects of the Mr 16,000 factor but not those of the Mr 12,000 factor in cell culture assays. The results suggest that 8387 fibrosarcoma cells produce two major growth inhibitors, one of which is closely related to TGF beta.

Animals↗

Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas.

Caveolae are plasma membrane microdomains that have been implicated in the regulation of several intracellular signaling pathways. Previous studies suggest that caveolin-1, the main structural protein of caveolae, could function as a tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated mesenchymal cells including adipocytes, endothelial cells, and smooth muscle cells. To study whether caveolin-1 is a possible tumor suppressor in human mesenchymal tumors, we have analyzed the expression using immunohistochemistry in normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors. Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues. The expression of caveolin-1 was slightly reduced in four of six well-differentiated liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of 20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight synovial sarcomas. The immunohistochemical findings were confirmed by Western blot analysis in a number of tumors. High levels of both the 24-kd [alpha]- and the 21-kd [beta]-isoform of caveolin-1 were detected in the nontumorigenic human fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells, caveolin-1 is strongly down-regulated. We show that the [alpha]-isoform of caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen-activated protein kinase-signaling pathway with the specific inhibitor PD 98059, whereas the specific inhibitor of DNA methylation 5-aza-2'-deoxycytidine only marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we conclude that caveolin-1 is likely to act as a tumor suppressor gene in human sarcomas.

Blotting, Western↗

Computed tomography of retroperitoneal and mesenteric sarcomas: a pictorial essay.

Retroperitoneal and mesenteric sarcomas are rare tumours that often do not present until they are very large. Computed tomography (CT) is helpful for diagnosis and for planning therapy. This pictorial essay illustrates the spectrum of CT manifestations of these tumours that the authors have encountered and includes a review of the various aspects of clinical presentation and treatment.

Fibrosarcoma↗

Isolation of a murine retrovirus with a temperature-sensitive src gene.

A murine retrovirus containing the src gene of avian sarcoma virus ts LA31A was generated. In contrast to the avian sarcoma virus, our recombinant murine retrovirus can efficiently infect mammalian cells. Transformation of NIH3T3 cells by the recombinant murine retrovirus is temperature sensitive. At the permissive temperature of 34 degrees, cells form foci of rounded cells. At the nonpermissive temperature of 39 degrees, the infected cells remain flat and exhibit contact inhibition. No disease was observed following infection of newborn NFS/n mice with the ts mutant virus. In contrast, infection of newborn NFS/n mice with a recombinant murine retrovirus containing the wild-type src gene causes fibrosarcomas and hepatosplenomegaly.

Animals↗

Cell-mediated suppression of tumor immunity has a non-specific component. I. Evidence from transplantation tests.

We have first demonstrated that the growth of a transplanted, 3-methyl-cholanthrene-induced BALB/c sarcoma, MCA-1425, in specifically immune syngeneic mice, was facilitated when the MCA-1425 tumor cells were injected together with either a mixture of irradiated MCA-1425 cells and thymus cells from mice immune to MCA-1425 or a mixture of irradiated cells from an antigenically different BALB/c sarcoma, MCA-1460, and thymus cells from mice immune to MCA-1460. We then performed Winn assays to study the induction of an immune response that could prevent the outgrowth of MCA-1425 cells in irradiated syngeneic recipients. Tumor immunity was found to be suppressed, if the mice immunized by a subcutaneous transplant of MCA-1425 cells and used as lymphocyte donors, were injected intraperitoneally with cells from either a different sarcoma, MCA-1460, or from 12-day BALB/c embryos. We tentatively attribute our finding to antigen-non-specific suppressor effector cells and postulate that an antigen-specific event is often involved in their induction.

Animals↗