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Immune response to leukemia virus and tumor-associated antigens in cats.

Cats represent an unusually valuable model for studying the role of the immune response to leukemia, lymphoma, and other mesodermal neoplasms. The agents that cause spontaneous feline leukemias, lymphomas, and fibrosarcomas, the feline leukemia and sarcoma viruses, are well characterized. A specific tumor cell membrane antigen, designated the feline oncornavirus-associated cell membrane antigen (FOCMA) has also been described. Feline leukemia and feline sarcoma viruses are antigenically indistinguishable, and FOCMA is common for both. Both laboratory-induced and spontaneous feline leukemias, lymphomas, and fibrosarcomas are available for study. A clear correlation has been shown between the resistance of cats to development of lethal tumors following inoculation of feline sarcoma virus and the presence of high humoral antibody titers to FOCMA. The geometric mean antibody titer to FOCMA for cats that resisted growth of fibrosarcomas was more than 20-fold higher than the mean for cats that succumbed to lethally progressing tumors. Cats with induced or spontaneous leukemia or lymphoma also have either no detectable FOCMA antibody or very low levels. Conversely, some cats resist development of leukemia or lymphoma following natural exposure to feline leukemia virus in leukemia cluster households, and these cats have high FOCMA antibody titers. These results support the concept of a natural immunosurveillance mechanism against leukemia or lymphoma development in an outbred mammalian species.

Animals↗

The use of daunomycin-antibody immunoconjugates in managing soft tissue sarcomas: nude mouse xenograft model.

Analysis of human fibrosarcoma cells exposed to radiolabeled monoclonal antibody 19-24, which recognizes sarcoma-associated antigen p102, revealed that over 54% of the cell surface-bound radioactivity was internalized. No modulation of cell surface p102 antigen by monoclonal antibody 19-24 was observed in human fibrosarcoma cells. Monoclonal antibody 19-24 coupled to daunomycin via a dextran bridge was found to be most effective. In different preparations, the daunomycin:total protein molar ratio ranged from 1.9 to 6.1. In vitro cytotoxicity studies using human fibrosarcoma cells showed that, at 10 micrograms/ml concentration, this immunoconjugate was 79.4% as efficient as free daunomycin and, at 1 microgram/ml concentration, 36.8% as efficient. Control nonspecific murine monoclonal antibody P3 immunoconjugates were relatively ineffective. The distribution of 14C-Adriamycin, 125I-labeled monoclonal antibody 19-24, and 125I-labeled 19-24 immunoconjugate was also evaluated over a 24-h period in tumor and normal tissues of athymic mice bearing a human fibrosarcoma xenograft. Poor uptake of radiolabeled Adriamycin by the tumor tissue was observed. The level of 14C radioactivity in the tumor tissue never exceeded 1% of the total injected dose and was 24.8-fold lower than the radioactivity found in the spleen tissue. Tumor tissue uptake of radiolabeled monoclonal antibody 19-24 was characterized by the high tumor tissue:blood ratio of 1.62 +/- 0.28 (SD). However, for monoclonal antibody 19-24 immunoconjugates, this ratio decreased to 0.66 +/- 0.05, which was still higher than normal (liver, 0.48 +/- 0.02; lung, 0.48 +/- 0.07; spleen, 0.28 +/- 0.01) or nonspecific monoclonal antibody P3 immunoconjugates (0.22 +/- 0.03). Thus, it appears that, compared to free daunomycin, monoclonal antibody 19-24 immunoconjugates may be more efficient and less cytotoxic to normal tissues.

Animals↗

The postoperative prognosis of primary pulmonary sarcomas. A review with a comparison between the histological forms and the other primary endothoracal sarcomas based on 474 cases.

On the basis of 41 personally observed cases from 1957 to 1974 and 435 case reports in the literature from 1957 to 1972, a scale of malignancy of the histological forms of primary pulmonary sarcomas is presented. A fairly continuous rise in the rate of malignancy according to the differentiation of the tissues can be convincingly recognized. The more mature a pulmonary sarcoma is, the better is the postoperative prognosis. The rate of malignancy increases from the relatively differentiated and tissue matured fibrosarcomas over the spindle cell sarcomas and round cell sarcomas, to the completely non-differentiated polymorph cell sarcomas. Primary myosarcomas, neurosarcomas and reticulum sarcomas of the lungs take an isolated position within this scale of malignancy. Primary lymphosarcomas are the most common and have clearly the best postoperative prognosis. The greatest malignancy is found with the carcinosarcomas. The characteristics of each of the histomorphological forms of primary sarcoma of the lungs are discussed. At the same time it is shown that the postoperative prognosis of endothoracal sarcomas is determined not only by their histological structure, but also by their localization in the lungs, mediastinum, or chest wall. Forty-one primary pulmonary sarcomas were compared with 22 sarcomas of the mediastinum and 17 sarcomas of the chest wall. Due to their long period of development, with rare symptoms and late diagnosis, sarcomas of the lungs and the mediastinum have a similar postoperative prognosis, in contrast to the endothoracal sarcomas of the chest wall which have a clearly more favourable prognosis.

Fibrosarcoma↗

Nonselective destruction of murine neoplastic cells by syngeneic tumoricidal macrophages.

The purpose of these studies was to select in vitro tumor cells that were resistant to macrophage-mediated lysis. Seven different heterogeneous murine neoplasms (four fibrosarcomas, a melanoma, a rhabdomyosarcoma, and an osteogenic sarcoma) and one cloned line of a fibrosarcoma were incubated in vitro with syngeneic tumoricidal macrophages. Surviving tumor cells were recovered and expanded to undergo subsequent interaction with tumoricidal macrophages. After six sequential interactions, all cell lines were examined for their susceptibility to lysis mediated by murine peritoneal exudate macrophages activated with liposomes containing muramyl tripeptide phosphatidylethanolamine. In all eight systems, no significant differences were detected between the parent tumor cells and cells that survived the sequential interactions. Neither macrophage infiltration into s.c. tumors nor the experimental or spontaneous metastatic potentials of the parental tumors differed from the lines established by cells surviving macrophage-mediated lysis. Collectively, the data suggest that tumor cell destruction by activated macrophages is nonselective and does not lead to the development of resistant tumor cells nor to cells with altered metastatic properties.

Animals↗

Two new retroviral onc genes, sea and jun.

Avian leukemia virus S13 induces erythroblastosis, granulocytic leukemia, fibrosarcoma, anemia, and endothelial neoplasia. It transforms chick embryo fibroblasts and primitive erythroid cells in culture and is defective in replication. Its onc gene, sea, is expressed as transformation specific env-sea fusion glycoprotein of 155 kDa. Gp155 is proteolytically processed into gp85env and gp70env-sea. The latter shows tyrosine specific protein kinase activity. Avian sarcoma virus 17 induces fibrosarcoma and transforms chick embryo fibroblasts in culture. Its cell derived onc gene, jun, is not related to known onc genes and appears to be expressed as a gag-jun fusion protein of 55 kDa. The amino acid sequence of jun shows homology in its C-terminal region to the C-terminal DNA binding region of the yeast regulatory protein GCN4, suggesting that the jun protein may bind to DNA.

Amino Acid Sequence↗

[Lung carcinosarcoma--a report of 15 cases].

Lung carcinosarcoma is a rare pulmonary mixed malignant tumor. From November 1979 to Sept. 1992, among 4251 cases of pulmonary malignant tumor operated in our department 15 were lung carcinosarcoma (0.35%). Pneumonectomy was done in 6 patients, lobectomy in 8, thoacotomy in 1. Pathologically, squamous carcinoma with fibrosarcoma was observed in 4, squamous carcinoma with chondrosarcoma in 1, squamous carcinoma with pleomorphic sarcoma in 1, adenocarcinomma with fibrosarcoma in 7, adenocarcinoma with chondrosarcoma in 1, and small-cell carcinoma with chondrosarcoma in 1. There was no operation death. Upon follow up, the 1-, 3-, 5-, and 7-year survival rates were 66.7%, 53.3%, 42.9% and 2/7, respectively. The longest survival was 97 months. The histologica origin, the relationship between pathological findings and clinical features and the diagnosis, treatment and prognosis are discussed.

Adult↗

Diagnostic and therapeutic problems of soft tissue tumors other than rhabdomyosarcoma in infants under 1 year of age: a clinicopathological study of 34 cases treated at the Institut Gustave-Roussy.

Thirty-four cases of soft tissue tumors (STT) other than rhabdomyosarcoma in infants under 1 year of age were seen in our institution between 1955 and 1985. All were diagnosed initially as malignant tumors except for three cases of fibromatosis, and, thus, they received therapy appropriate at that time. During a recent pathologic review, four were seen to have had hemangioma, six hemangiopericytoma, one hamartoma, seven fibromatosis, eight fibrosarcoma, and eight unclassified sarcomas. Of these 34 cases, the initial histological diagnosis was confirmed in only 17. Sixteen patients were believed to have received inappropriately aggressive therapy; indeed, four of these cases diagnosed prior to 1975 had been benign. Major long-term side effects were seen in 7/16 treated patients (six radiotherapy, one surgery), who, in retrospect, should have received less aggressive treatment. The reasons for these initial errors in diagnosis included doubtful histologic features associated in some cases with alarming clinical presentation. We believe that difficulties still remain in distinguishing benign from malignant STT in this age group by histological examination. Therefore, we urge extreme caution in using aggressive therapy before the diagnosis is certain.

Age Factors↗

Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas.

BACKGROUND: An excess risk of second malignancies has been reported in survivors of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewing's sarcoma and to identify possible causal factors. METHODS: Information was derived from a data base that included 266 survivors of Ewing's sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS: After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received > or = 60 Gy. CONCLUSION: The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.

Adolescent↗

Primary sarcomas of the jaw.

Nine cases of primary sarcoma of the jaw seen over a period of 14 years are presented. They consisted of four osteosarcomas, three fibrosarcomas, one myxosarcoma and one Ewing's sarcoma. The treatment of choice for osteosarcomas of the mandible is hemimandibulectomy with disarticulation at the temporomandibular joint. Bone graft reconstruction from the iliac crest should be done at a second stage. Palliative maxillectomy for extensive fibrosarcoma of the maxilla served to relieve one patient of local symptoms for more than a year. Myxosarcoma, a variant of fibrosarcoma, and Ewing's sarcoma of the jaw, are very rare conditions, and since these lesions are usually very extensive radiotherapy is the treatment of choice.

Adolescent↗

Use of immunohistochemistry and polymerase chain reaction for detection of oncornaviruses in formalin-fixed, paraffin-embedded fibrosarcomas from cats.

OBJECTIVE: To determine whether there was intralesional infection or expression of FeLV or feline sarcoma virus in suspected vaccine-associated fibrosarcomas in cats. DESIGN: Prospective case series. SAMPLE POPULATION: 130 suspected vaccine-associated fibrosarcomas from cats and 1 multicentric fibrosarcoma from 1 cat. PROCEDURE: Excisional biopsy specimens were fixed in formalin and embedded in paraffin. Expression of FeLV antigen was assessed, using a polyclonal goat anti-FeLV glycoprotein 70 (gp 70) serum and an avidinbiotin immunoperoxidase staining technique. The FeLV genome was detected with a polymerase chain reaction (PCR), using primers targeted to a conserved sequence in the untranslated region of the long terminal repeat (LTR) of the FeLV. RESULTS: FeLV gp 70 and LTR sequence were detected in a multicentric fibrosarcoma. All 130 of the suspected vaccine-associated fibrosarcomas were FeLV gp 70 negative on the basis of immunohistochemical test results: 100 fibrosarcomas also were examined by use of PCR and were negative for FeLV LTR region. CLINICAL IMPLICATIONS: Exogenous retroviruses, FeLV, and feline sarcoma virus were not detected in these suspected vaccine-associated fibrosarcomas, using immunohistochemistry and PCR. Additional testing will be required to determine the nature of genomic alterations that are involved in the oncogenesis of vaccine-associated fibrosarcomas in cats.

Animals↗

Effect of Nocardia rubra cell wall skeleton on T-cell-mediated cytotoxicity in mice bearing syngeneic sarcoma.

Cell-mediated cytotoxicity against syngeneic MC104 fibrosarcoma cells was detected in C57BL/6N mice 7 days after tumor inoculation in the hind foot. This cytotoxicity was undetectable by Day 14 in the Winn test using spleen and draining popliteal lymph node (DPLN) cells. Similar results were obtained with the 51Cr release assay following in vitro activation of these lymphoid cells with mitomycin C-treated tumor cells. The antitumor cytotoxicity was shown to be mediated by T-cells. Spleen but not DPLN cells from 14-day tumor bearers enhanced tumor growth in the Winn test, suggesting the presence of immunosuppressor cells in the spleen. Two intralesional injections of 50 microgram of cell wall skeleton (CWS) of Nocardia rubra on Days 2 and 7 resulted in apparent tumor growth inhibition and prolongation of the survival period of tumor bearers. DPLN cells from tumor bearers treated with N. rubra CWS exhibited significant recovery in the cytotoxicity tested on Day 14, whereas the recovery in that of spleen cells was not apparent. The cytotoxicity augmented by N. rubra CWS was specific to MC104 tumor cells and was shown to be mediated by T-cells. These cytotoxic T-cells were shown to be able to localize not only in DPLN but also in the spleen and tumor in mice receiving the intralesional immunotherapy with N. rubra CWS. These results suggest that T-cell-mediated cytotoxicity against syngeneic tumor can be augmented by N. rubra CWS and might play an important role in the systemic development of its antitumor effect, although the effector cell increase in the spleen might be suppressed by splenic suppressor cells during tumor growth.

Animals↗

Fibroblastic/myofibroblastic sarcoma of the skin: a report of five cases.

BACKGROUND: A number of malignant soft tissue tumors, particularly those of fibroblastic and fibrohistiocytic derivation, have been found to display myofibroblastic differentiation focally. The term myofibroblastic sarcoma, a controversial presumably distinctive entity, defines a malignant soft tissue tumor in which myofibroblasts are quantitatively the predominant cell type. METHODS: Five cases of cutaneous spindle-cell sarcomas showing fibroblastic-myofibroblastic differentiation with predominance of fibroblasts were retrieved from the files of three large centers of dermatopathology. Tumors were analyzed histopathologically, immunophenotypically, and, in two cases, ultrastructurally. Results were compared with those previously reported in fibrosarcoma, malignant fibrous histiocytoma, and myofibroblastic sarcoma. RESULTS: Immunophenotypic and ultrastructural profiles of the cases analyzed in this series were closer to fibrosarcoma and to malignant fibrous histiocytoma than to myofibroblastic sarcoma by virtue of quantitative predominance of fibroblasts over myofibroblasts. On the other hand, histopathologic findings were in keeping with those reported in myofibroblastic sarcoma. CONCLUSIONS: Our series highlights the intrinsic problems in attaching certain cutaneous sarcomas with fibroblastic-myofibroblastic differentiation to one of the recognized entities and gives support to the hypothesis that fibrosarcoma, malignant fibrous histiocytoma, and myofibroblastic sarcoma are related histogenetically.

Aged↗

Antitumor activity of Hypsizigus marmoreus. I. Antitumor activity of extracts and polysaccharides.

Antitumor activity of Hypsizigus marmoreus, one of the most popular Japanese edible mushrooms, was investigated. The aqueous and methanol extracts were tested against allogeneic tumor, solid sarcoma 180 and syngeneic tumor, Meth A fibrosarcoma. The aqueous extract was highly active in inhibiting growth of solid sarcoma 180, but not as much for Meth A fibrosarcoma. Fractionation of antitumor substances of the aqueous extract isolated four polysaccharides. Chemical analysis revealed one of them to be beta-(1-3)-glucan with a remarkable inhibitory effect against tumor-growth of sarcoma 180.

Animals↗