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Thorotrast-induced extraskeletal osteosarcoma of the cervical region. Report of a case.

This is the seventh reported case of soft tissue sarcoma attributed to thorotrast extravasated during the course of an injection for arteriography. An extraskeletal osteosarcoma occurring the cervical region of a 51-year-old man 30 years after a cerebral arteriogram is presented. The other reported cases include a fibrosarcoma, two neurofibrosarcomas, two spindle cell sarcomas, and an extraskeletal chondrosarcoma. The latency period has varied from 5 to 30 years. The thorotrast granules are readily identified in macrophages near or adjacent to the tumor, and the demonstration of alpha tracks on autoradiographs is diagnostic.

Humans↗

Karyological and isoenzyme characterization of established human sarcoma cell lines.

Six established human sarcoma cell lines (giant cell tumor of bone B-5GT, fibrosarcoma, B-6FS, cystosarcoma phylloides B-19CS, synovial sarcoma U-4SS and two osteogenic sarcomas U-20S and U-393OS) have been studied and compared to the normal B-41FB fibroblastic cells and the HeLa cells. For cytogenetic and isoenzyme characterization both conventional and G banding techniques as well as the mobility of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PD) were employed. All six sarcoma cell lines had karyotype and LDH patterns of human cells. A study of the chromosome counts distribution revealed a large variability from one sarcoma cell line to the other. There was no evidence of any cross-contamination between the lines or by HeLa cells. This conclusion is based on the detection of G-6-PD with B phenotype, the lack of HeLa marker chromosomes in all sarcoma lines and the presence of Y chromosome in U-4SS and U-393OS derived from male donors. In addition, each sarcoma cell line revealed a group of distinctive marker chromosomes which can serve to identify them and help to control cell line specificity during in vitro culturing.

Cell Line↗

Oncostatic and immunomodulatory effects of a glycoprotein fraction from water extract of abalone, Haliotis discus hannai.

The liquid from heat-treatment of an abalone, Haliotis discus hannai, which is normally discarded as waste, was found to contain a new glycoprotein antineoplastic agent. A fraction of the liquid obtained from chromatography that was 22% carbohydrate and 44% protein was injected locally or systemically into ICR mice or BALB/c mice inoculated s.c. with allogeneic sarcoma 180 or syngeneic Meth-A fibrosarcoma, and growth of the tumors was strongly inhibited. There was an optimum dose range for the inhibition of the growth of sarcoma 180, and optimum timing. The fraction did not have antitumor activity in T cell-deficient nude mice (CD-1 nu/nu or BALB/c nu/nu mice), and administration of carrageenan in vivo decreased its activity in ICR mice. This fraction activated the cytostatic activity of peritoneal and alveolar macrophages in vivo. These results suggest that the antitumor activity is not due to a direct toxic effect but to stimulation of a host-mediated response.

Adjuvants, Immunologic↗

The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma (LGFMS) is a variant of fibrosarcoma that was recognized as a distinct tumor entity only quite recently. We previously described a translocation, t(7;16)(q33;p11), that resulted in a fusion of the FUS and CREB3L2 (also known as BBF2H7) genes in two soft tissue tumors that fulfilled morphologic criteria for LGFMS. To delineate the spectrum of tumors that may harbor the FUS/CREB3L2 gene, we selected 45 low-grade spindle cell sarcomas for reverse transcriptase polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH) analyses; none of these tumors had originally been diagnosed as LGFMS. Furthermore, also included were two benign soft tissue tumors and nine high-grade sarcomas with supernumerary ring chromosomes or 7q3 rearrangement and three tumors diagnosed as LGFMS prior to the genetic analysis. Of the 59 tumors analyzed, 12 were FUS/CREB3L2-positive, all of which were diagnosed at histopathologic re-examination as being LGFMS, of both the classical subtype and the subtype with giant collagen rosettes. The breakpoints in the fusion transcripts were always in exons 6 or 7 of FUS and exon 5 of CREB3L2. The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.

Adolescent↗

Antitumor activity of KW-2170, a novel pyrazoloacridone derivative.

5-(3-Aminopropyl)amino-7,10-dihydroxy-2-(2-hydroxethyl)-aminoethyl -6H-pyrazolo[4,5,1-de]acridin-6-one dihydroxy-chloride (KW-2170), a novel derivative of pyrazoloacridone, was selected and evaluated for its antitumor activity and toxicity in mice. KW-2170 exhibited antitumor activity superior to adriamycin (ADM) against Sarcoma 180, breast carcinoma MM102 and fibrosarcoma Meth A inoculated s.c. in mice. Its therapeutic index (LD10/ED50) was higher than that of ADM on two murine carcinoma models, MM102 and Meth A. KW-2170 showed significant antitumor activity against 17 human tumor xenografts of a total of 24 tumors tested and the total tumor response rate by treatment with KW-2170 was significantly higher than that by ADM (70.8 versus 58.3%). In particular, human lung carcinoma was highly sensitive to KW-2170, and a marked tumor regression was observed on Lu-65 and Lu-99 human lung carcinoma xenograft models. Ovary and pancreas carcinomas were also sensitive to the drug. Additionally, its therapeutic index was also high on these human carcinoma models in comparison with that of ADM. The best antitumor efficacy of KW-2170 was observed by a weekly treatment schedule followed by a single treatment schedule and a successive administration schedule also tended to be toxic to the hosts. KW-2170 exhibited very low cross-resistance against four lines of multidrug resistant tumors expressing high levels of P-glycoprotein, and the drug showed significant antitumor activity against ADM-resistant human ovary carcinoma A2780/ADM and against nasopharynx carcinoma KB-A1 xenografts which were not sensitive to ADM. These results indicate that KW-2170 has a very potent antitumor activity and is feasible as a new antitumor drug against ADM-refractory solid tumors in clinics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Inability of leucovorin to rescue a naturally methotrexate-resistant human soft tissue sarcoma cell line from trimetrexate cytotoxicity.

A human lymphoblastoid line (RPMI-1788), a methotrexate-sensitive human fibrosarcoma cell line (HT-1080), and a naturally resistant mixed mesodermal human sarcoma cell line with impaired methotrexate polyglutamylation (HS-42), recently established in our laboratory, were used to compare the ability of leucovorin to prevent trimetrexate cytotoxicity. Growth inhibition and an in situ thymidylate synthesis activity assay showed that inhibitory effects of trimetrexate (1 to 10 microM), 24-h exposure, were prevented by 10 microM leucovorin in the RPMI-1788 and HT-1080 cell lines but not in the HS-42 cell line. Total intracellular reduced folates increased about 2-fold in the three cell lines after exposure to leucovorin (10 microM) for 4 h, and after a 6-hour efflux remained elevated (1.5- and 1.3-fold of control levels) in RPMI-1788 and HT-1080 cells but decreased to 80% of control levels in HS-42 cells. Although uptake of leucovorin and levels of N5,N10-methylenetetrahydrofolate achieved after leucovorin administration were similar in RP-MI-1788 and HS-42 cells, polyglutamylate forms of this coenzyme were less in the HS-42 cells as compared to RPMI-1788 cells. Based on these studies, the combination of trimetrexate with leucovorin should be further investigated as a way to increase the therapeutic index in some patients with soft tissue sarcomas.

Drug Resistance↗

Monophasic synovial sarcoma--a histological entity?

Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.

Collagen↗

Rhabdomyosarcoma of the oral and paraoral region.

Oral rhabdomyosarcoma (RMS) was studied by analysis of eight such cases which presented over a 25-year period. Rhabdomyosarcoma was the fourth most common oral sarcoma (7.5%) from this period after osteosarcoma (32%), fibrosarcoma (19%), and chondrosarcoma (9%). In patients younger than 20 years, RMS was the second most common sarcoma (six cases) after osteosarcoma (ten cases). Combined analysis with 113 further cases documented in the literature showed the majority of cases (71.2%) were embryonal. The alveolar subtype was considered a distant second in frequency (12.3%) even though the pleomorphic subtype was apparently more common (16.4%). However, the pleomorphic cases were diagnosed before histologic criteria were established to discern this entity from other pleomorphic sarcomas and this data is probably unreliable. Site predilections were found for the soft palate, maxillary sinus and alveolus, posterior mandibular region, cheek and lip and possibly tongue. The gingiva and floor of mouth were uncommon sites. There was a predilection for occurrence in the first two decades with a decline in the third decade. Documentation of recent cases treated with a multidisciplinary approach indicated that lesions in the oral soft tissues have a good prognosis; 17 of 21 such cases showed no evidence of disease after a mean follow-up period of 7.2 years (SD = 4.4). In contrast, four of five cases in the posterior mandible resulted in death after a mean period of 1.1 years (SD = 0.3).

Adolescent↗

Primary intracranial fibrosarcoma with intratumoral hemorrhage: neuropathological diagnosis with review of the literature.

Primary intracranial sarcomas are rare tumors of mesenchymal origin in the central nervous system (CNS). Spontaneous hemorrhage, while not an uncommon presentation of brain tumors, has not been described in primary cerebral sarcoma. We report the case of a 43 year old woman presenting with spontaneous hemorrhage into a primary cerebral fibrosarcoma, and discuss this case in the context of the diagnostic criterions of these rare tumors previous reports of intracranial sarcomas and mechanisms of intratumoral hemorrhage.

Adult↗

Murine xenograft model of Spirocerca lupi-associated sarcoma.

Nodular masses and granulomas of the esophagus are among the most frequent lesions caused by Spirocerca lupi, a nematode parasite of dogs, and neoplastic transformation of these granulomas to osteosarcoma or fibrosarcoma has been described. In this study, we developed a xenograft murine model of S. lupi-associated sarcoma. Samples of esophageal fibrosarcoma and osteosarcomas were excised from three dogs diagnosed with spirocercosis. These sarcomas were inoculated into three groups of 6-week-old NOD/SCID mice to create three tumor lines of S. lupi-associated sarcomas. Mice in all groups developed tumors after inoculation, and the cell lines could be further propagated as second-generation xenografts. We successfully established xenograft murine models of three different lines of S. lupi-associated sarcoma that offer readily available sources of these tumors for further experiments. This resource will facilitate studies on the malignant transformation of the granulomas, establishment of efficient chemotherapy and radiotherapy regimens, and identification of diagnostic molecular markers.

Animals↗