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[Analysis of the TNF receptor in KYM cells by affinity cross-linking].

We investigated the identity of the TNF receptor on the KYM cell membrane by cross-linking 125I-TNF and the presumed receptor site with DSS, and subjecting the TNF-receptor complex to electrophoresis. Four specific bands were observed at 145 K, 50 K, 35 K, and 17 K, and those at 50 K, 35 K and 17 K being consistent with trimers, dimers and monomers of TNF, respectively. The 145 K band disappeared after addition of excess unlabelled TNF or anti-human recombinant TNF monoclonal antibody (IV3-E), which quenched the cytotoxic activity of TNF and inhibited the TNF binding to the receptor. The molecular weight of native TNF as estimated by gel filtration was 45 K and this observation showed that native TNF existed only as the TNF trimer. These results confirmed that 95K, i.e., the difference between 145 K and 50 K, is the molecular size of the TNF receptor.

Antibodies, Monoclonal↗

Characterization of a monoclonal antibody directed to a T cell suppressor factor.

A monoclonal antibody raised by fusion of immune BALB/c splenocytes with NS1 cells is described. BALB/c mice were immunized with a T suppressor factor (TsF) raised in DBA/2 mice with specificity for the P815 tumor. The TsF had been purified by affinity chromatography before its use as an immunogen. The monoclonal antibody (B16G) was shown to affect the course of P815 growth in DBA/2 mice if administered i.v. on days -2 to 0 before tumor cell inoculation. Mice treated with B16G demonstrated slower tumor development and growth than controls, and a small number of animals (about 10%) did not develop tumors; all controls did. It was also shown that B16G did not exhibit total specificity for the P815 tumor in that it had similar effects on the growth of an unrelated myosarcoma (M-1) of DBA/2 mice. The general immunopotentiating effect of the B16G monoclonal was demonstrated by the fact that spleen cells of DBA/2 mice that had received B16G showed significantly higher MLC than did equivalent controls. When spleen cells of DBA/2 mice were depleted of B16G-reactive cells by panning in vitro, it was also found that cells so treated gave rise to elevated MLC reactions in comparison to appropriate controls. When an immunoadsorbent was prepared with B16G and cell lysates from splenocytes of immunosuppressed mice were passed over it, the immunosuppressive properties of the lysate in MLC were eliminated. The conclusion that the B16G recognizes a marker common to a group of regulatory T cells in DBA/2 mice is discussed.

Animals↗

Antibody specific to muscle actins in the diagnosis and classification of soft tissue tumors.

A series of soft tissue tumors, melanomas, carcinomas, and lymphomas were studied immunohistochemically for the presence of muscle actins (MA) with the monoclonal antibody HHF-35, and for the presence of desmin for comparison. In nonneoplastic tissues, MA immunoreactivity was present in skeletal and smooth muscle cells, in the pericytes of small vessels, and in the myoepithelial cells. Desmin immunoreactivity had a similar distribution, except that the pericytes of small vessels and myoepithelial cells were negative. All 17 rhabdomyosarcomas were positive for both MA and desmin. Of leiomyosarcomas, 31/32 were positive for MA, and 29/32 for desmin. In pleomorphic undifferentiated sarcomas (malignant fibrous histiocytomas) MA and desmin-positive cells were present in 9/35 and 5/35 cases, respectively. Three of five pleomorphic liposarcomas showed MA-positive tumor cells, which were also desmin-positive in one case. Desmoid tumors often showed a moderate number of both desmin- and MA-positive cells. Hemangiopericytoma, Kaposi's sarcoma, and endometrial stromal sarcoma showed MA-positive staining only in the pericytes and not in the neoplastic cells. In various types of carcinomas, melanomas, and lymphomas, MA- or desmin-positive neoplastic cells were not identified. MA, but not desmin, was present in the desmoplastic stroma in many carcinomas. Both MA and desmin are good markers for muscle differentiation and especially serve to identify rhabdomyosarcomas and leiomyosarcomas. These markers are also present in some sarcomas currently regarded as nonmuscle tumors. This may suggest that some of these tumors have differentiation properties related to true myosarcomas. The absence of muscle actin, a pericytic marker, in hemangiopericytoma does not confirm the concept of pericytic nature of this tumor.

Actins↗

Radio-immunodetection of myosarcoma using 111indium antimyosin.

Radio-labelled antimyosin-monoclonal antibodies (AMA) have been introduced to demonstrate myocardial necrosis after cardiac infarction or in cardiac allograft transplants. As rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS) are tumors of myogenic origin, thus often containing myosin, we decided to use the 111In-labelled Fab fragment of AMA (Centocor) in scintigraphic tumor detection. We examined 13 children with histologically-confirmed RMS and LMS, and five other children with other types of soft tissue sarcomas. Conventional techniques were used to determine the extent of the tumor. An uptake of the tracer was observed in all known tumor sites in seven RMS patients. As the scans were negative in three RMS patients who were in complete remission (CR) and in two other patients (fibrosarcoma and haemangiopericytoma) with a measurable tumor mass, we considered them to be "true negative". In the three remaining CR patients (1 RMS, 2 LMS) the scans were positive but weak in the primary tumor site in two cases and in a distant site (bone) in the third respectively. We considered them to be "false positive" as no tumor cells were evident in the biopsy specimen. In one case, the antimyosin uptake was presumably the result of damage to the muscles after radiation. Interestingly, in three patients with other malignancies such as rhabdoid and peripheral neuroectodermal tumors there was a noticeably strong uptake of the tracer in the primary tumors and the scans turned negative after complete remission was achieved. The diagnostic AMA scanning showed no side-effects. The reason why antimyosin antibodies permeate the membrane of the tumor cells is yet undetermined.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tenosynovial giant cell tumors: evidence for a desmin-positive dendritic cell subpopulation.

Diffuse tenosynovial giant cell tumor (DGCT) could present as a large intra-articular mass (pigmented villonodular synovitis, or PVNS) or as an extraarticular mass, which might be confused with a sarcoma, particularly when growth is destructive and giant cells are few. Prompted by a DGCT in which a subpopulation of cells was desmin positive and in which an erroneous diagnosis of myosarcoma was made, we analyzed the frequency of desmin, myogenin, MyoD1, and muscle-specific actin immunoreactivity in 45 well-characterized GCTs. We also analyzed a subset of these cases with antibodies to smooth muscle actin, as well as macrophage, follicular dendritic cell, extrafollicular dendritic cell, and dermal dendrocyte-associated antigens. Sections from 45 cases of formalin-fixed GCTs (22 DGCTs, 13 cases of PVNS, and 10 localized GCTs) were immunostained for desmin, myogenin, MyoD1, and muscle-specific actin. The eight cases that showed the largest number of desmin-positive cells were immunostained for smooth muscle actin, CD45, CD68, CD21, CD35, cytokeratin 8, and Factor XIIIa. Desmin-positive cells were seen in 20 (43%) of 45 cases: 10 (43%) of 22 DGCTs, 5 (38%) of 13 cases of PVNS, and 5 (50%) of 10 localized GCTs. In contrast, none were positive for any of the other muscle-associated proteins. In almost all of the cases, the desmin-positive cells were large and dendriform, with long processes that interdigitated between adjacent round cells. Desmin immunoreactivity was found in almost 50% of all GCTs, in the absence of positivity for other muscle markers. Desmin immunoreactivity in GCT seemed to be confined to a variably sized subpopulation of large dendritic cells whose exact identity remains uncertain.

Actins↗

Histopathological studies on experimentally induced pulmonary, pleural and peritoneal neoplasms in mice by intraperitoneal injection of chrysotile asbestos and N-methyl-N-nitrosourethane.

The cocarcinogenic effects of asbestos are presented. In lung carcinomas induced in mice, the number of carcinomas and the time of detection of the first carcinoma per tumor-bearing animals were greater and faster in the group with chrysotile plus MNU than either chrysotile or MNU alone. This suggested that chrysotile asbestos had a promoting or cocarcinogenic effect on some carcinogens in the respiratory tract. In the group treated with chryotile alone, a tumor was found in the right pleural cavity at 15 months. This tumor microscopically was similar to the biphasic form of the human diffuse mesothelioma. Microvilli, basement membrane, and junctional apparatus were seen by electron microscope, but other cytoplasmic organelles of the tumor cells were relatively scanty. Two peritoneal tumors developed in gastric and intestinal serosa at 11 and 12 months. Light and electron microscopic studies suggested that the tumors were probably myosarcomas or fibrosarcoms.

Adenocarcinoma↗

Postradiation high-grade myofibroblastic sarcoma of the prostate -- a rare entity of prostatic tumors -- responding to liposomal Doxorubicin.

BACKGROUND: Prostatic postradiation sarcoma (PRS) is a very rare malignant disease with a dismal prognosis. Aggressive surgical resection is the most widely used therapy for PRS. Chemotherapy so far has been unsatisfactory, with doxorubicin being the only drug with established activity. Liposomal doxorubicin has been shown to have comparable activity and a more favorable toxicity profile compared with unpegylated doxorubicin. CASE REPORT: A 78-year-old man presented with high-grade myofibroblastic sarcoma 13 years after curatively intended pion irradiation of the prostate with 30 Gy. He was treated with liposomal doxorubicin 40 mg/m(2) every 4-6 weeks up to now with a total dose of 800 mg. Partial remission has been achieved after 17 months of treatment with liposomal doxorubicin. Toxicity is minimal with palmoplantar erythrodysesthesia WHO grade 1, resolving completely after extending treatment intervals to 6 weeks. RESULT: Liposomal doxorubicin led to a sustained tumor stabilization over 17 months in a patient with prostatic postradiation high-grade sarcoma. Postradiation sarcoma (PRS) usually has a dismal prognosis and only very limited therapeutic possibilities. As in sarcomas of different origin, anthracyclines including liposomal doxorubicin seem to have potential antitumor activity in postradiation sarcoma of the prostate.

Adenocarcinoma↗

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↗

[Human ovarian myosarcoma and its cell culture (author's transl)].

One case of a very rare myosarcoma of ovarium origin was observed and establishment of its cell lines from the fluid obtained by paracentitis was accomplished. This report is on the determination of the tumor and the biological characteristics of its cultured cells. (Determination of the tumor) (1) This tumor was diagnosed as a malignant of the right ovary, using bimanual examination, selective angiography of the uterine artery, ultrasonic tomography, and abdominal ascitic cell examination. (2) The morphological type of tumor was based findings of hematoxylin eosin. Silver, Mallory and phosphotungstic acid hematoxylin stainings. The tumor was diagnosed as an ovarian sarcoma and probably myogenic. However, a clear cross strain could not be demonstrated. (Cell biological characteristics) (1) Morphological characteristics of cultured cells: a) Phase-contrast microscopy and Papanicolaou staining revealed round or short and spindle shaped cells, with markedly enlarged nucleoli. These proliferated without exhibiting any tendency of contact inhibition. Also frequently recognized were giant cells, multinuclear cells, an some bizarre such as a starfish-shaped cell. b) Electron microscopy revealed that bundles of fibrils regarded as myofibrils existed in the cytoplasma, with dense patches within them, but a cross strain could not be demonstrated. (2) Morphological characteristics of the tumor cells grown in a nude mouse: a) The tumor cells demonstrated similarities to the original tissues by of H.E., Silver, and Mallary stainings. b) A number of fibrils recognized by the electron microscopic observation were 100 A in width and were arranged in a concentric circles. In addition to the light microscopic findings, the above findings indicated that this cell line originated from myogenic sarcoma. (3) Biological characteristics of the cultured cells: a) The number of chromosomes varied widely and spread aneuploidically, the highest chromosome number was 76. b) Doubling time, Saturation density, and plating efficiency was 31.2 hr, 1.2 x 10(5)/cm2 and 43.9% respectively. c) These cells had a high sensitivity for trypsin and started morphological change rapidly.

Animals↗

[Cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion for peritoneal carcinomatosis caused by recurrent inflammatory myofibroblastic sarcoma: a case report and review of the literature].

Peritoneal carcinomatosis is a fatal diagnosis, associated with poor prognosis and quality of life. Survival is usually estimated in month. Traditionally surgery for peritoneal carcinomatosis was indicated only for palliative effort. Advances in tumour biology, cytoreductive surgery and pharmacology have improved the approach for this condition. An aggressive combined approach to peritoneal surface malignancy involves peritonectomy and intraperitoneal perioperative hyperthermic chemotherapy. Cytoreductive surgery reduces carcinomatosis to microscopic residual disease so that intraperitoneal hyperthermic chemotherapy is able to eradicate cancer. Hyperthermic chemotherapy enhances the cytotoxicity of the drugs and increases their penetration into the cancerous tissue. Careful patient selection is crucial for this multimodality approach. Quantitative prognostic indicators are useful in the assessment of outcome, like peritoneal cancer index and completeness of cytoreduction score. Cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy improves survival but is associated with significant morbidity and mortality. This review is based on a case report of a 22-year-old female patient who had peritoneal carcinomatosis of inflammatory myofibroblastic sarcoma and was treated by cytoreductive surgery and intraperitoneal hyperthermic chemotherapy at our department.

Adult↗