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PubMed1987

[Demonstration of complex dysregulation of anti-cytomegalovirus T-cellular immunity in Kaposi's sarcoma following renal transplantation].

An increased incidence of Kaposi's sarcoma is well known in renal transplant recipients in whom it may represent up to 3 p. 100 of all de novo tumours. This sarcoma has a close relationship with the potential oncogenicity of the cytomegalovirus (CMV) and with chronic immunological deficiency. Anti-CMV immunity is based on the integrity of cytotoxic cellular functions such as those of cytotoxic T lymphocytes (CTL), "natural killers" cells, and K cells which function in the antibody-dependent cell cytotoxicity (ADCC) system. Two cases of Kaposi's sarcoma were observed out of a total of 700 renal transplant recipients; they underwent the following investigations: lymphocyte sub-group counts by murine monoclonal antibodies, lymphocyte proliferation to lectins and allogenic cells, NK activity and generation of specific auxiliary and cytotoxic anti-CMV cells. Both cases of Kaposi's sarcoma were seropositive for CMV and seronegative for LAV. In one case, an abnormal number of peripheral OKT9 + lymphocytes (normally a thymocytic marker) was observed with small numbers of OKT4/OKT8, a reduced proliferative response to mitogens and allogenic cells. All these in vitro changes persisted despite reduction of immunosuppressive therapy and clinical improvement. A clinical and biological cure was only obtained after withdrawal of immunosuppressive therapy and return to haemodialysis. In the second case of Kaposi's sarcoma, the initial biochemical changes were minimal and a clinical cure was obtained by decreasing the immunosuppressive therapy. These two cases illustrate the complex dysregulation of the immune system in Kaposi's sarcoma.

Adult↗
PubMed1989

Intravenous recombinant tumor necrosis factor in the treatment of AIDS-related Kaposi's sarcoma.

Tumor necrosis factor (TNF) has demonstrated antitumor activity against a variety of tumors and is particularly cytotoxic to capillary endothelial cells, which are the presumed cell of origin of Kaposi's sarcoma. We evaluated the toxicity and clinical antitumor and antiretroviral effects of recombinant TNF administered at a once weekly dose of 100 micrograms/m2 intravenously for 8 weeks in five men with AIDS-related Kaposi's sarcoma and without prior opportunistic infection. One patient was removed from study at week 4 due to rapid progression of Kaposi's sarcoma, another patient with stage IV disease and a pretreatment CD4 count of 11 developed fever, hypotension, and pneumonia at week 7 and died 8 days after discontinuing recombinant TNF. No pathogenic organisms were isolated. He had marked eschar formation of his Kaposi's sarcoma lesions, particularly in areas previously exposed to radiation therapy. Uniform toxicities included fevers, rigors, and headaches during drug infusion that were ameliorated by prophylactic meperidine hydrochloride and acetaminophen. All experienced fatigue and three had arthralgias. One patient had transient hypotension which corrected with i.v. fluids. No significant hematologic, hepatic, or renal toxicities were seen. All patients had some progression of their Kaposi's sarcoma on study. There was no change in CD4 or CD8 count or in CD4:CD8 ratios. Serum human immunodeficiency virus (HIV) p24 antigen levels increased greater than 50% in three patients. We conclude that, as a single agent, at a dose of 100 micrograms/m2 recombinant TNF by i.v. infusion has no obvious antitumor or antiretroviral effects in patients with AIDS-related Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Myofibroblastic differentiation of a primary intracerebral sarcoma with gliomatous reaction.

Microscopic examination of an intracerebral tumor removed from a 50 year-old man revealed a gliomatous rim surrounding a sarcoma. The sarcoma had central necrosis and vascular hyperplasia. Sarcomatous cellular elements consisted of medium-sized undifferentiated cells together with spindle cells associated with a loose collagenous matrix. Although grossly circumscribed, the sarcoma microscopically invaded the brain along an ill-defined border. Adjacent, and encompassed cerebral parenchyma had undergone gliomatous changes consisting of swollen body astrocytes with cellular and nuclear pleomorphism, hyperchromatism and cellularity, and the presence of multinucleated giant cells. The sarcomatous cells were unreactive to antibodies for carcinoembryonic antigen (CEA), keratin, glial fibrillary acidic protein (GFAP), S 100, actin and factor VIII although the endothelium and muscularis of neovascular areas were positive for factor VIII and actin respectively. The gliomatous rim and encompassed glial elements were strongly positive for GFAP. Ultrastructure of the spindle cell component, found only in the sarcoma, revealed well-formed myofibroblasts with dilated cisternae of rough endoplasmic reticulum (RER) and bundles of myofilaments with dense bodies. The medium-sized cells of the sarcoma were generally undifferentiated. However some of these cells had bundles of microfilaments with areas of condensation although these cells lacked the configuration and dilatations of the RER characteristic of myofibroblasts. Transitional cells between the mature and immature components also occurred. These findings suggest that this sarcoma originates from mesenchymal stem cells undergoing myofibroblastic differentiation.

Brain Neoplasms↗
PubMed1988

[Surgical treatment for bone and soft tissue sarcomas of the shoulder part].

Since 1977 we have treated 18 bone sarcomas and 16 soft tissue sarcomas of the shoulder part. For 10 bone sarcomas of the proximal humerus, four fore-quarter amputations, two curative wide resections, and four wide excisions were performed as radical operations. The reconstructive procedures after the six resections were two spacer insertions, one total shoulder replacement, and three arthrodeses with autografts. Considering the functional result, the arthrodesis is the most-recommended method. For eight bone sarcomas of the scapula, three total resections and four partial resections of the scapula, and one debulking operation were performed. For 16 soft tissue sarcomas, we performed two ablative operations, three curative wide resections, five wide excisions, and six conservative operations after adjunctive chemo-and/or radiotherapy. Among all 34 bone and soft tissue sarcomas, the success rate for limb salvage was 74%, while the recurrence rate was 18%. The functional result of the limb salvage operations was far better than that of ablative operations of the shoulder part. In fact the rate of satisfactory ADL (excellent and good) was 81% among the limb salvage cases, while for ablative operations, the ADL ratings were all poor.

Bone Neoplasms↗
PubMed1986

The epidemiology of sarcomas of the uterus.

Data from nine population-based cancer registries (1973-81) were analyzed to examine the demographic characteristics that are related to the occurrence of sarcomas of the uterus. Leiomyosarcoma and mixed mesodermal sarcoma accounted for 86% of 1,452 uterine sarcomas reported, and both were more common in black women than in white women. The incidence of mixed mesodermal sarcoma was low through middle age, after which it rose sharply. The incidence of uterine leiomyosarcoma, however, was highest in middle-aged women and declined thereafter. The age-incidence pattern of uterine leiomyosarcoma resembles that of carcinomas of the female reproductive tract, unlike the pattern of other uterine sarcomas or sarcomas occurring elsewhere. This suggests that one or more factors that play a role in the etiology of carcinomas of the reproductive tract may be involved in the etiology of this tumor as well.

Adult↗
PubMed1987

Role of insulin in development of cancer cachexia in nongrowing sarcoma-bearing mice: special reference to muscle wasting.

This study evaluated whether altered insulin metabolism is a key factor behind weight loss during sarcoma growth in nongrowing mice (C57BL/6J). Fasted sarcoma-bearing mice had decreased blood glucose concentrations but unchanged levels of insulin, compared with those in pair-weighed and freely fed controls. During refeeding, insulin levels were inappropriately low for the degree of glycemia in sarcoma-bearing mice compared with those of pair-weighed and freely fed controls. Injections ip of glucose to tumor-bearing animals resulted in insulin levels comparable to postabsorptive values in healthy control animals, indicating that hypoinsulinemia in freely eating tumor-bearing animals was due to a reduced glycemic sensitivity for pancreatic insulin release. Insulin supplementation at doses [4 IU/100 g (body wt)] that increase body fat in normal animals could not protect the tumor-bearing host from progressive loss of body fat or lean tissues. Exogenous insulin in excess of endogenous insulin production did not stimulate tumor growth. Nitrogen and RNA-DNA content were significantly decreased in the quadriceps muscle of tumor-bearing mice. This reduction was independent of altered insulin levels and could not be prevented by exogenous insulin. The depressed capacity of protein synthesis in extensor digitorum longus (EDL) muscle could be entirely attributed to the state of malnutrition in tumor-bearing animals. The sensitivity and responsiveness of protein synthesis in EDL muscles to insulin were normal in tumor-bearing mice, regardless of whether exogenous insulin exerted its effect in vivo or in vitro. This study confirms insulin resistance for glucose metabolism in an experimental sarcoma animal model. Such changes are concluded to be secondary to anorexia and necessary to counteract hypoglycemia. In non-growing sarcoma-bearing mice, malnutrition and anorexia account entirely for depressed muscle protein synthesis, which is not explained by insulin resistance at the translational level. Insulin metabolism is not a key factor behind progression of wasting in sarcoma-bearing mice, but anorexia is.

Animals↗
PubMed1987

Resting energy expenditure and body cell mass alterations in noncachectic patients with sarcomas.

Resting energy expenditure (REE), body cell mass (BCM), and body fat (BF) were measured in six male and seven female volunteers and in a homogeneous group of noncachectic patients with sarcoma, (n = 7). The patients all had large localized tumors, no history or clinical evidence of decreased food intake or weight loss, and had received no prior treatment for cancer. Indirect calorimetry (for REE), K40 analysis (for BCM), and anthropometric measurements (for BF) were performed in accordance with established methods. Physical activity and nutritional status were also assessed. As expected, female control subjects had 50% greater percent BF (p less than 0.001) and 13% less percent BCM (p less than 0.01) than male controls. Male patients with sarcoma had equivalent percent BF, but significantly less percent BCM than controls matched for age, sex, and body surface area (BSA) (p less than 0.05). The REE corrected for BSA was similar in male and female controls but was 25% greater in male sarcoma patients than in male controls (p less than 0.05). This difference was doubled when REE was corrected for BCM (p less than 0.01). In patients with sarcomas, REE/BSA varied inversely with percent BCM (r = -0.782; p less than 0.05) while a similar relationship was not observed in healthy volunteers. We conclude that both REE and vital, functional BCM can be significantly altered in sarcoma patients before any overt signs of cachexia develop. The results support the contention that sarcoma alters host energy metabolism and causes abnormal body composition.

Adult↗
PubMed1985

[Bone sarcoma and malignant tumors of the retina].

Secondary bone sarcomas are frequent among children who have been treated previously for a retinoblastoma. The main point is that these bone sarcoma occur almost always after a bilateral retinoblastoma and more often in the irradiated area; from these, the classical concept of "radiocancer" was generally admitted. However, since many authors reported bone sarcomas occurring in a different location from the irradiated area, radiotherapy cannot be by itself the causative factor of these secondary bone sarcomas. Therefore the genetical factor is probably one of the predisposing factor. The authors report 6 cases of bone sarcomas with a review of the literature of bone sarcomas occurring in the irradiated field or not, for children "cured" of retinoblastoma.

Bone Neoplasms↗
PubMed1977

Bone sarcomas: etiology and immunology.

The etiology of skeletal sarcomas is found in induced by viruses in man (as they are in exogenous agents (irradiation, oncornavirus) acting in a peculiar setting of host factors. Patients with skeletal sarcomas react immunologically to autologous and allogeneic sarcoma cells, but reactors can be found among the healthy persons with or without exposure to patients with sarcomas. Various modalities of immunotherapy are available to increase the patient's immune reactivities in general or to sarcoma cells in particular, but immunotherapy of skeletal sarcomas has not yet brought about clear-cut and substantial benefits in addition to or beyond the results of conventional treatment.

Adolescent↗
PubMedDate not supplied

Serum ceruloplasmin concentrations in rats with primary and transplanted sarcomas induced by nickel subsulfide.

Ceruloplasmin (CPN) concentrations were measured by p-phenylenediamine oxidase assay in serums from (a) 30 control Fischer rats; (b) 5 rats with primary sarcomas induced by i.m. injection of nickel subsulfide (alpha Ni3S2), and (c) 12 rats at intervals up to six weeks after s.c. transplantation of four alpha Ni3S2-induced sarcomas. Serum CPN concentrations were not significantly increased in rats with primary sarcomas (mean = 0.38 g per liter) (S.D. +/- 0.05), versus 0.35 g per liter (S.D. +/- 0.04) in controls. In contrast, serum CPN concentrations were increased within 11 to 21 days in all rats with transplanted sarcomas. Maximum concentrations of serum CPN occurred at 31 to 34 days after tumor transplantation, (mean = 0.56 +/- 0.05 g per liter), equivalent to 1.6 +/- 0.2 times the initial CPN concentrations in serums obtained prior to treatment (P less than 0.001). The development of hyperceruloplasminemia in rats with transplanted sarcomas and not in rats with primary sarcomas is attributed to greatly enhanced growth-rates of the transplanted neoplasms.

Animals↗
PubMed1979

[Contribution to aetiology by the primary pulmonary sarcoma in comparison to the pulmonary carcinoma (author's transl)].

On 41 primary pulmonary sarcomas in the years 1957 till 1974 and on 192 pulmonary carcinomas in the year 1969 cancerogene noxes and endogene factors were analysed, compared and discussed with literature. Smoking of cigarettes, chronic bronchitis and radioactive radiation at underground mining are also significantly accumulated in our study and are recognized as cancerogenes. There is no correlation between pulmonary sarcomas and these exogene factors. The constant frequency in the last decades, the non-existing sex disposition, the ten till fifteen years lower sarcoma manifestation with a continuous increase already in the second decade of life and the protected position of the mesenchyme do not suggest a causal connexion between exogene cancerogene influence and pulmonary sarcoma formation. Rather make us suppose an endogene tumour disposition. Pulmonary sarcomas correlate as to localisation, sex relation and not provable exogene cancerogena with the adenocarcinoma of the lungs. The causal connexion between trauma and sarcoma formation in a thoracotomy cicatrice as well as the possibility of a sarcomatous degeneration are discussed.

Asbestosis↗
PubMed1978

[Radiotherapy of the soft tissue sarcomas (author's transl)].

Although 82,5% of the total body weight consist of mesenchymal tissues, only 1%--3% of all malignant tumors are soft tissue sarcomas. The necessary irradiation dose can only be determined after an exact histopathological diagnosis; therefore this diagnosis has to be made prior to the radiotherapy. Except the fibro- and liposarcomas, all sarcoma form very early lymphogenic metastases. All sarcomas show a remarquable tendency to form recurrences. Surgery is the primary therapy. After that, an irradiation of the tumor region and the regional lymph nodes should be effected under all circumstances. We have treated and checked up 749 patients. After this therapeutic method, the five-year survival rate in the stages T1 and T2 is 60% for the myxosarcoma, 67% for the angiosarcoma, 41% for the fasciculated sarcoma, 40% for the globocellular sarcoma, 30% for the polymorphous sarcoma, 69% for the fibrosarcoma, and 61% for the leiomyosarcoma.

Fibrosarcoma↗
PubMed1982

Serological analysis of cell surface antigens on methylcholanthrene-induced mouse sarcomas with antisera produced against the tumors.

Out of 9 cell lines from methylcholanthrene-induced fibrosarcomas in BALB/c, 4 lines without expression of murine leukemia virus (MuLV) were selected for immunization of three different F1 hybrids with mitomycin C-treated in vivo sarcoma cells. Antibody activity was tested by immune adherence (IA) and protein A (PA) assays after the 8th immunization. Two sarcomas, CMC-11 and CMC-12, produced antibodies detectable by IA in (BALB/c x C3H/He)F1, but no antibodies were detected by PA. (BALB/c x C3H/He)F1 anti-CMC-11 was tested against CMC-11 and three other MuLV- sarcomas as well as against the skin fibroblast (C-11) from a BALB/c mouse, in which the primary CMC-11 sarcoma was induced. CMC-11 line reacted up to 1/80, but other lines were weakly positive or negative. Absorption analysis showed that the antigen defined by anti-CMC-11 was present on CMC-11 as well as on many other sarcoma cell lines, but not on BALB/c thymocytes and spleen cells, nor on leukemia and myeloma cells. Among 5 fibroblast cultures tested, C-14 showed complete absorption. It seems significant that only C-14 produced tumor nodules in BALB/c mice, in contrast to 4 other fibroblast cultures. This suggested that this antibody was directed against antigens present on transformed fibroblasts and sarcoma cells. The specificity of (BALB/c x C3H/He)F1 anti-CMC-12 serum indicated that this antiserum also seemed to detect transformation-related antigens, although it showed a broader specificity with regard to the tissue representation detected.

Animals↗
PubMed1978

[Primary sarcomas of the gastrointestinal tract (author's transl)].

From 1952 to 1976 2203 malignant tumours of the gastrointestinal tract were seen at the Surgical Clinic of the M.H.L., 18 of them were sarcomas. There was a predominance of carcinomas of the stomach (Sa: Ca = 1:229) and of the colon (1:162), whereas sarcomas of the small intestine were found in a relation of 1:0,9. X-ray diagnosis of the gastric sarcomas is difficult, only those with endogastric growth can be recognized by gastroscopy. The postoperative prognosis of gastric sarcomas is better than that of gastric carcinomas. Sarcomas of the small intestine have a high mortality rate because of a high rate of ileus and perforation. Sarcomas of the colon - normally localized in the caecum or rectum - have a better prognosis, seldom stenosis can be seen.

Adult↗
PubMed1980

Levels of cytotoxic reactivity to cultured normal skin fibroblasts in sera from normal and sarcoma-bearing patients.

Human sera possess complement-dependent cytotoxic reactivity against autologous and allogeneic cultured normal skin fibroblasts. Previous studies indicated that the natural antibody reactivity is directed against fetal antigens expressed on these cells in tissue culture. The reactivity was further characterized in the present study. Chromatographic analysis of a normal serum indicated that its reactivity belonged to the immunoglobulin M (19S) class of immunoglobulins. Sera from 22 preoperative tumor-bearing osteogenic sarcoma patients, 30 tumor-bearing soft-tissue sarcoma patients, and 52 age- and sex-matched normal individuals were tested against allogeneic skin fibroblasts. The patient and normal groups displayed wide, overlapping ranges of cytotoxicity. The osteogenic sarcoma group showed a small but significant increase in mean cytotoxicity compared to the controls, whereas the soft-tissue sarcoma sera were not significantly different from the controls. Reactivities in the sera of patients whose tumors recurred were not significantly different from those of the patients who remained disease free. Cytotoxic levels in sera from eight osteogenic sarcoma patients followed throughout the clinical course remained constant up to the time of documented recurrence and were not affected by surgical removal of the primary tumor or Bacillus Calmette-Guérin immunotherapy. In three of four patients whose tumors recurred, cytotoxic levels fell, but only after documented recurrence. The natural antibody reactivity against normal fibroblasts does not appear useful as a marker for diagnosis, prognosis, or monitoring tumor presence in sarcoma patients.

BCG Vaccine↗
PubMed1982

Fracture-associated sarcoma in the dog.

Seven fracture-associated sarcomas developed in large-breed dogs after stabilization of comminuted long bone fractures with stainless steel plates and screws. In most cases, the healing pattern of the fractures was disturbed. The mean interval between fracture occurrence and tumor diagnosis was 5.5 years. Radiographically, the sarcomas were typified by smooth-bordered subperiosteal proliferation and soft tissue mineralization. Cortical destruction was variable. Several histologic subtypes of osteosarcoma were seen. Four sarcomas had a marked inflammatory cell component and 5 of the dogs had clinical evidence of chronic infection. These findings were similar to those in 35 previously reported fracture-associated sarcomas, even though many types of fixation devices in addition to plates, as well as no fixation at all, were represented in these cases. Fracture-associated sarcomas most frequently were found to be diaphyseal, and the femur accounted for almost half of the sarcomas reported.

Animals↗
PubMed1981

Immunoprecipitation of membrane proteins of cultured human sarcoma cells.

Human sarcoma associated antigens (HSAA) have previously been identified by indirect immune fluorescence in human sarcoma cells in culture using sera from patients bearing different types of sarcoma. To further characterize these HSAA, surface proteins of cultured cells were labeled with 125Iodine, [3H]-glucosamine and [35S]-methionine and solubilized. After immunoprecipitation labeled proteins were detected in immune complexes by SDS polyacrylamide gel electrophoresis and autoradiography, which allowed comparison with antigens described by other groups. A surface protein (Mr 96 000) was precipitated with sera from sarcoma bearing patients, and two glycoproteins (Mr 115 000 and 85 000) were preferentially precipitated with antisera from rabbits immunized with membranes from two human sarcoma cell lines. At least two of these proteins were found in each of five human sarcoma cell lines studied (U-4SS, U-3930S, U-20S, B-5GT and B-6FS). None of the proteins were precipitated with three human control sera, and only occasionally a faint band was observed in immunoprecipitates from control cells (B-25F, B-41B, B-42FC, U-2S, and U-393S with the immune sera. These proteins are probably some of the antigens responsible for the immune fluorescence observed in determination of HSAA. However, purification of the proteins and competition experiments are needed before this can be finally established.

Antigens, Neoplasm↗
PubMed1995

Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies.

We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chlorophenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkin's lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subject's case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (CI) = 1.2-91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1-28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (OR = 5.2; 95% CI = 0.85-32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkin's lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.

Case-Control Studies↗