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Single dose X-irradiation and concomitant hyperthermia on a murine fibrosarcoma.

The objectives of this study were to quantitate the effects of local tumor hyperthermia (LTH) and concomitant x-irradiation (RAD) on a moderately radioresistant murine fibrosarcoma in situ. Comparisons were made to the combined treatment response on the Ridgway osteogenic sarcoma, a radio sensitive tumor previously used in this laboratory and to establish the Meth-A fibrosarcoma as a model system for combined modality studies. 1.0 cm3 tumors were exposed to single doses of RAD ranging from 0.5-3.5 krad alone or 0.5-2.3 krad in combination with LTH (water bath at 43.1 +/- .05 C for 20 minutes) applied immediately postirradiation. LTH significantly enhanced the action of radiation as measured by tumor volume analysis, mean survival time and cures. The ratio of radiation doses vs. RAD + LTH required to produce an equivalent response ranged from 1.4 to 2.5 depending upon the endpoints evaluated. These findings are consistent with single dose studies on the radiosensitive Ridgway osteogenic sarcoma and suggest that the tumoricidal effectiveness of combination radiation and hyperthermia cannot be predicted on the basis of the radiation alone responsiveness of tumor.

Animals↗

Spindle cell sarcoma in the kidney of a dog.

A spindle cell sarcoma involving the left kidney was diagnosed in a 14-year-old male Basenji. Radiography and ultrasonography were used to define the extent and location of the mass. Metastatic disease was not detected. An 8 x 5-cm mass, involving the left kidney, was resected by performing nephroureterectomy. Signs of metastasis were not detected at 3 and 6 months after surgery. Shortly after the 6-month examination, the dog was euthanatized because of perceived signs of pain attributable to cervical disk disease. Postmortem examination was not performed. Histologic examination consisted of use of hematoxylin and eosin, Masson trichrome, and van Gieson stains, and 4 immunoperoxidase techniques. On the basis of the histologic findings, the final diagnosis was spindle cell sarcoma, with the 2 most likely possibilities being leiomyosarcoma and fibrosarcoma.

Animals↗

Diagnostic aspect of spindle-cell sarcomas by electron microscopy.

Spindle-cell sarcomas in the somatic soft tissue and soft parts, including fibrosarcoma, leiomyosarcoma, malignant fibrous histiocytoma (MFH), and malignant schwannoma were examined by electron microscopy in order to delineate the most reliable cellular features for their diagnosis. Fibrosarcoma consisted largely of fibroblastic cells and leiomyosarcoma cells were packed in forming small cell groups with constant junctional complexes of nexus and zonula adherens types. MFH showed variable cellular features containing the cells with myofibroblastic and histiocytic differentiation. Malignant schwannoma was characterized by tumor cells having slender cytoplasmic processes with overlapping or interdigitation and thick basement membrane. These ultrastructural features were contributory to the differential diagnosis of the sarcomas examined.

Adult↗

Primary brain sarcomas: light and electron microscopic features.

The following is a description of the diagnostic structural features in three neoplasms in which we diagnosed: primary intraparenchymal brain sarcoma. One appeared to have arisen de novo from the mesenchymal components of the brain parenchyma and was labeled fibrosarcoma. A second case, having mixed features of meningioma and fibrosarcoma, may represent an instance of sarcomatous changes in a prexisting intraparenchymal meningioma. The third sarcoma's ultrastructural characteristics were those of embryonal capillaries and a designation of hemangiosarcoma is proposed for that one. An angiographic, preoperative diagnosis of meningioma was suggested in all three instances. Two of the patients died a few weeks after craniotomy and the third one is alive and well eighteen months after resection of the neoplasm.

Adolescent↗

Immunohistochemical detection of bone morphogenetic proteins in bone and soft-tissue sarcomas.

BACKGROUND: Bone morphogenetic proteins (BMPs) are potent inducers of bone formation. Functional and immunohistochemical studies have identified BMPs in a subset of osteosarcomas. In the present study, the authors extend the analysis of BMP expression to other bone and soft tissue sarcomas. METHODS: Monoclonal antibody AbH3b2/17 against human BMP-2 and BMP-4 was used in avidin-biotin-immunoperoxidase assays with frozen sections of bone tumors (71 specimens), soft tissue sarcomas (69 specimens), and normal tissues. RESULTS: Among bone tumors, BMP was detected in osteosarcomas (17 of 29 samples), malignant fibrous histiocytomas (MFHs) (6 of 6), and the spindle cell sarcomatous components of spindle cell (dedifferentiated) chondrosarcomas (4 of 4), but not in conventional chondrosarcomas (0 of 10) or Ewing's sarcomas (0 of 14). Histologic subtypes of osteosarcoma differed for BMP expression, with 8 of 9 fibrohistiocytic, 9 of 13 osteoblastic, and 0 of 5 chondroblastic lesions showing immunostaining. In all BMP-positive bone tumors, immunostaining was localized in the cytoplasm of primitive mesenchymal cells, with little or no staining in tumor matrix and more mature osteoblastic/chondrocytic cells. Among soft tissue sarcomas, MFHs (11 of 12), liposarcomas (5 of 11), leiomyosarcomas (3 of 9), and malignant schwannomas (3 of 8) showed cytoplasmic BMP immunostaining. Synovial sarcomas (0 of 9), rhabdomyosarcomas (0 of 8), and fibrosarcomas (0 of 7) were BMP-negative. All normal human tissues tested, including the tissues of a 16-week-old fetus, lacked BMP immunoreactivity. CONCLUSIONS: Bone morphogenetic protein is expressed in a subset of osteosarcomas, a high proportion of MFHs of bone and soft tissue, and in spindle cell chondrosarcomas. In these tumors, BMP is localized predominantly to the cytoplasm of malignant cells with primitive mesenchymal features; no or little BMP is detected in the more differentiated elements of bone and soft tissue sarcomas. Different histologic types of bone and soft tissue sarcomas may mimic discrete stages of mesenchymal differentiation as defined by BMP expression and histologic criteria.

Antibodies, Monoclonal↗

Matrix assembly induction and cell migration and invasion inhibition by a 13-amino acid fibronectin peptide.

Fibronectin (FN) is an extracellular matrix (ECM) protein involved in tumor growth and metastasis. Five human FN cDNA segments encoding for FN fragments, all starting with the II1 repeat and ending with different C-terminal extensions, have been stably expressed in chick embryo fibroblasts (CEF). These FN cDNAs induce the formation of an organized ECM in CEF as long as they retain a sequence coding for a 13-amino acid stretch (FN13), with collagen binding activity, localized between type II2 and I7 repeats. An FN13 synthetic peptide induces in control CEF the assembly of an FN-ECM comparable with that observed in CEF-expressing FN fragments. The activity of FN13 is specific for its amino acid sequence, although the cysteine present in the 6th position can be substituted with a polar serine without affecting the induction of a fibrillar FN-ECM. A less fibrillar matrix is induced by FN13-modified peptides in which the cysteine is methylated or substituted by a non-polar alanine. FN13 induces the assembly of an FN-ECM also in Rous sarcoma virus-transformed CEF lacking the ECM and in hepatoma (SK-Hep1) and fibrosarcoma (HT-1080) human cell lines. FN13 also promotes the adhesion of CEF and Rous sarcoma virus-CEF at levels comparable with those obtained with purified intact FN. Finally, FN13 inhibits the migratory and invasive properties of tumorigenic cells, whereas intact FN favors their migration. All FN13-modified peptides show similar effects, although with reduced efficiency. None of these activities is supported by a scrambled peptide. These data suggest a possible role of FN13 in tumor growth and metastasis inhibition and its possible use as anti-tumorigenic agent.

Alanine↗

[Mesenchymal breast sarcomas: general review].

Breast sarcomas are rare, representing 1% of all malignant breast tumors. A variety of histologies are found, the main ones being fibrosarcomas and malignant fibrohistiocytomas. Nodal involvement is rare and, as in other sarcomas, hematogenous spread of metastases is more usual. Major prognostic factors are histological grade and mitotic activity; the three-year disease-free survival ranges between 40% and 60%. Surgery remains the treatment of choice of these tumors; for some authors adjuvant irradiation could improve local control, especially for patients treated with conservative surgery. The role of adjuvant chemotherapy remains undefined.

Breast Neoplasms↗

Late effects of radiotherapy for pediatric extremity sarcomas.

PURPOSE: To determine the long-term effects of radiotherapy (RT) in children treated for extremity sarcoma. PATIENTS AND METHODS: Between 1964 and 1997, 15 of 33 children treated with RT for extremity sarcomas at the University of Iowa have survived with a median follow-up was 20 years (range, 6-36 years). There were 10 boys and 5 girls with a median age of 13 years (range, 3.5-20 years) at the time of irradiation. The diagnosis was Ewing's sarcoma in 8 (53%), synovial sarcoma in 4 (27%), alveolar rhabdomyosarcoma in 2, and fibrosarcoma in 1. Location of primary tumor was lower extremity in 10 (67%) and upper extremity in 5 (33%). RT was given as the definitive therapy for 9 children (median dose, 55.8 Gy; range, 45-66 Gy) and as an adjuvant postoperative treatment in 6 (median, 63 Gy; range, 41.4-66.4 Gy). (60)Co was used in 6 (40%), 4 mV in 4, 6 mV in 2, and 250 kV photons in 2 patients; 1 child was treated with a combination of 12 and 15 MeV electrons for a Ewing's sarcoma of the distal femur. Another child had a 25 Gy intraoperative RT boost after 41.4 Gy conventional RT. Late effects to the muscle, soft tissue, and growing bone were assessed using the objective portion of the LENT-SOMA scale proposed by the Late Effects Consensus Conference. RESULTS: Late effects were seen in all patients and included atrophy in 12 (80%), fibrosis in 12 (80%), bone growth abnormalities in 10 (67%), impairment of mobility and extremity function in 6 (40%), edema in 3 (20%), and peripheral nerve injury in 2 (13%). Ten of 15 (67%) children had Grade 1 or 2 growing bone, muscle, soft tissue, or peripheral nerve complications. Two patients (13%) had a Grade 3 mobility and extremity function score and had moderate to severe limitation of movement. Two children (13%) required epiphysiodesis because of a shorter treated leg. The patient who received an intraoperative RT boost of 25 Gy developed sensory dysfunction of the ulnar nerve 11 years after RT. Another developed radial nerve palsy 3 years after marginal resection and postoperative RT and required tendon transfer repair. One patient had radiation-induced vasculitis with popliteal artery thrombosis 23 years after RT. Five (33%) developed a fracture of the irradiated bone at a median time of 8 years after RT (range: 9 months to 22.2 years); all had Ewing's sarcoma, and 3 of these patients were subsequently found to have a secondary bone cancer (osteosarcoma 2, malignant fibrous histiocytoma 1) in the RT field. One of these patients also developed breast cancer 26 years after lung RT for metastatic Ewing's sarcoma. Overall, 11 surgical procedures in 8 children were performed to correct a limb preservation treatment toxicity. CONCLUSIONS: Although most children treated with RT for a pediatric extremity sarcoma have minimal late toxicity by LENT-SOMA scale, approximately half required a surgical procedure to correct a late effect. A fracture in the irradiated bone may be the presenting sign or may precede a radiation-induced bone malignancy, as seen in 3 of the patients in this study.

Adolescent↗

Postirradiation fibrosarcoma following radical mastectomy.

A case of fibrosarcoma arising in the scar of the radical mastectomy with postoperative irradiation of breast carcinoma is reported. The tumors arose five times in spite of the extirpations including surrounding tissue since 11 years after radical mastectomy and postoperative irradiation. All of arisen tumors were diagnosed fibrosarcoma histologically and with every recurrence the aggravation of malignancy of tumors was shown. In this case, the primary tumor of the breast was infiltrating carcinoma and no sign of fibrosarcoma was noted histologically. The mastectomy scar was indicated the irradiation therapy postoperatively and fibrosarcoma developed 11 years after postoperative irradiation. Namely, this case agreed to the strict criteria of the postirradiation sarcoma proposed by Cahan et al. In this paper, a case of postirradiation fibrosarcoma arising in the scar of radical mastectomy for carcinoma is presented.

Breast Neoplasms↗