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PubMed1988

Induction of synthesis of tumor necrosis factor in human and murine cell lines by exogenous recombinant human tumor necrosis factor.

Treatment of sensitive human myosarcoma cells (KYM-S) with exogenous tumor necrosis factor (r-TNF) resulted in the production of TNF by the cells. The newly synthesized cellular TNF was identified immunologically on Western blots and as a single 1.8-kilobase band on Northern blots. TNF synthesis began within 2 h of administration of the exogenous TNF in a dose-dependent manner. r-TNF also induced TNF synthesis in mouse tumorigenic fibroblasts (L-M). Resistant sublines of these cells as well as TNF nonsensitive human diploid fibroblasts possessed TNF mRNA without pretreatment, indicating an inverse correlation between levels of TNF expressed and sensitivity to the cytotoxic effects of exogenous TNF. It is conceivable that the newly synthesized cellular TNF functions in some protective manner to block cytolytic effects of exogenous TNF.

Animals↗
PubMed1978

[Cytology of metastases of rare tumors in the pleura (author's transl)].

In the Oncocytological Center of Zala Country were investigated in the recent years 2378 cases from effusions of pleural cavity. Ten of the tested cases had been proved to be metastases of sarcomatous lesions. Three of them were myosarcoma, two of them were malignant melanoma and one fibromyosarcoma, reticulosarcoma, osteosarcoma and sarcomatous stage of Hodgkin disease, each. The author gives a review of the cytological characteristics of metastatic sarcomatous lesions. Up to the opinion of the author there are some characteristics which can help in the typing.

Adolescent↗
PubMed1983

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↗
PubMed1983

Abnormalities of cobalt-activated acylase from human sarcoma, carcinoma and the adjacent tissue.

Cobalt-activated acylase form-2 from human uterine myosarcoma, lung adenocarcinoma and the adjacent tissue was isolated, purified and characterized. It was found, that the enzyme from the malignant neoplasms differed both from the normal tissue and benign tumor acylase-2 in its Km value, temperature optimum and effect of some ions. Some abnormal properties (pH dependence, activation by cobalt and thermostability) were common for benign and malignant tumors. In lung tissue adjacent to adenocarcinoma, some deviations of acylase properties were observed, similar to that found in tumor, indicating that biochemical changes may be present also in tissues unaffected by the neoplastic growth by the histopathological criteria.

Adenocarcinoma↗
PubMed1984

[Correlation between cell cycle and cell morphology of RKN cells].

UNLABELLED: In order to study the changes in the morphology of each phase of the cell cycle, RKN cells, derived from a human ovarian myosarcoma, were synchronized by a mitotic selection method and studied under time-lapse cinematography, light microscopy, scanning and transmission electron microscopy. RESULTS: M-phase: The cells with relatively a few cytoplasmic organelles were small and spherical, and chromosome were seen in them. The cell surface was covered with numerous mivilli. Late G1,S and early G2 phase: The large, thin cells were flat and polygonal with various organelles inside and had central nuclei. Most of the chromatin patterns were finely granular. No microvilli were found on the cell surface. Early G1-phase: The paired daughter cells were fanshaped and the nuclei were eccentric with finely granular chromatin patterns. At the edges of the cells, rufflers which were related to cell movements were often seen. Late G2-phase: The thick cells were of a spindle shape and the chromatin patterns were a coarse granular type. Again on the cell surface microvilli increased and the slender filopodia were often seen.

Cell Cycle↗
PubMed1981

Growth pattern and differentiation of human soft tissue sarcomas in nude mice.

Tumor suspensions prepared from 62 human soft tissue sarcomas were injected into the peritoneal cavity and subcutis of 124 nude mice. The sarcomas included were ten malignant fibrous histiocytomas, 15 fibrosarcomas, six tendosynovial sarcomas, five liposarcomas, nine myosarcomas, six angiosarcomas, six malignant schwannomas, and five miscellaneous sarcomas. Sixty-two percent of the sarcomas showed progressive growth in nude mice either subcutaneously (46%), intraperitoneally (14%), or at both sites (40%). Fifty-one percent of the primary sarcomas, 71% of the recurrent tumors, and 78% of the sarcomas that were metastatic grew in the animals. Sarcomas that were grafted into the subcutis appeared as solitary nodules and showed a more accelerated growth as well as better differentiation than those that were injected into the peritoneal cavity. The intraperitoneal tumors were multifocal and dedifferentiated growths. It appears that simultaneous subcutaneous and intraperitoneal grafting of human sarcomas into nude mice offers a model to study the histogenesis and morphologic variations of soft tissue sarcomas.

Animals↗
PubMed2005

Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review.

BACKGROUND: Sarcomas are a rare complication of radiotherapy for breast carcinoma and patients have a poor prognosis. The incidence, histology, and management of patients with sarcomas were reviewed in the current study. METHODS: The authors reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233 were treated without at the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50-55 grays (Gy) in 25-27 fractions were delivered to the whole breast over a period of 5-5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16-26-Gy boost to the tumor or tumor bed. Treatment of radiation-induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy. RESULTS: Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The median follow-up was 9.3 years (range, 1-22.4 years). The latency period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5- in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumulative RIS incidence was 0.07% (+/- 0.02) at 5 years, 0.27% (+/- 0.05) at 10 years, and 0.48% (+/- 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confidence interval, 9.03-11.59) for irradiated patients and 1.3 (0.3-3.6) for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years (mean, 34.2 +/- 0.7 months). The 5-year actuarial survival rate after diagnosis of RIS was 36% (+/- 0.11). CONCLUSIONS: The current study confirmed the rarity of RIS. However, it showed that the risk increased with time. Therefore, careful, long-term follow-up of patients treated with radiotherapy is needed for early detection and efficacious treatment of these malignancies.

Adult↗
PubMed2001

DNA copy number amplifications in sarcomas with homogeneously staining regions and double minutes.

To identify DNA amplifications in sarcomas, comparative genomic hybridization was performed on 27 cases that were likely to display high-level DNA copy number gains. In all cases, chromosome banding analysis had revealed homogeneously staining regions or double minutes, i.e., cytogenetic signs of gene amplification. In most cases, gains predominated over losses. Low-level amplifications (ratio 1.3:1.5) were seen in 20 cases. High-level amplifications (ratio >1.5) exceeded the frequencies seen in published, unselected sarcomas of similar histotypes and were detected in 16 tumors: 4/4 osteosarcomas, 5/8 malignant fibrous histiocytomas, 3/7 leiomyosarcomas, 1/2 myosarcomas, 0/1 liposarcoma, 0/1 rhabdomyosarcoma, 1/1 pleomorphic sarcoma, 0/1 myxofibrosarcoma, 1/1 malignant mesenchymona, and 1/1 malignant schwannoma, with two to four chromosomal regions involved in nine tumors. Recurrent amplifications involved 1p33-p32, 5p15-p14, 7pter-p12, 7q21-qter, 8q21.3-qter, 11q22-q23, 16p13.2-p12, 19q12-q13.1, 20q11.2-qter, and 22q12-q13. Most of the recurrent gains/amplifications we detected have been reported in sarcomas previously. A novel gain/amplification was seen at 2q14.3-q21 in five cases of four sarcoma types. The disparate pattern of amplified sequences, the poor correspondence between the localization of low- and high-level amplifications, and the chromosomal position of homogeneously staining regions suggest the involvement of many genes in the amplifications and that the genes rarely maintain their native position in these tumors.

Adolescent↗
PubMed1995

Polar agents with differentiation inducing capacity potentiate tumor necrosis factor-mediated cytotoxicity in human myeloid cell lines.

Cotreatment or pretreatment of several human myeloid cell lines (KG1, HL60, U937, THP1) with the differentiation inducer DMSO was found to potentiate the antiproliferative and cytotoxic effects of TNF. In addition, TNF-resistant monocytic cell lines could be sensitized to TNF cytotoxicity by DMSO treatment. Other highly polar molecules, known to be potent differentiation inducers, showed similar effects to those of DMSO. The potentiating effect of DMSO was related neither to an up-regulation of TNF receptor expression nor to an alteration in the rate of TNF internalization and degradation. We present evidence that the TNF activities are p55 TNF receptor-mediated and are not due to insertion of TNF into lipid bilayers, an effect that could be susceptible to DMSO, as this component has been described to modify cell membrane characteristics. DMSO-induced potentiation of TNF cytostasis/cytotoxicity was restricted to myeloid leukemia cell lines. In non-myeloid cells such as fibrosarcomas, myosarcomas, thymomas, or carcinomas, DMSO was found either not to alter or to inhibit TNF-induced cell death. The latter results are in good agreement with data reported by others who suggested that DMSO could act as a scavenger of TNF-induced toxic radical formation. The potential correlation in myeloid cells between DMSO-induced changes in the cells' differentiation status and DMSO-enhanced TNF-susceptibility is discussed.

Animals↗
PubMed1995

[Sarcomatoid carcinoma of the bladder in a 25-year-old man].

A 25-year-old patient with a rapidly growing sarcomatoid carcinoma of the urinary bladder is reported. The diagnosis was made on the basis of extended atypical proliferations of spindle or pleomorphic cells in the area of pelvic floor and the radix of the penis. The tumor showed invasion of the blood and a high Ki-67 growth fraction up to 40%. Immunohistochemically, the reactions with antibodies against cytokeratin, EMA, and vimentin were positive, while negative results were obtained in reactions with antibodies against desmin, actin, PSA, S 100, human epithelial antigen (Ber-EP4), and cytokeratin 13. The differential diagnosis against myosarcomas, pseudosarcomatous lesions, and inflammatory pseudotumours is discussed. After radical surgery a pelvic recurrence and pulmonary metastases developed, which led to the patient's death 3 months later. This case shows that sarcomatoid carcinomas of the urinary bladder can be found even in young people.

Adult↗
PubMed1982

Leiomyosarcoma of the uterus.

A series of 43 cases of uterine leiomyosarcoma was reviewed. Forty-one of the 43 patients were followed up 2 or more years. The overall 5-year survival was 73%. Favorable prognostic features included the premenopausal status of the patient, the confinement of the tumor within a myoma, the low mitotic count (less than four mitotic figures in any one high-power field or less than four mitotic figures per 10 high-power fields), the absence of necrosis, and the presence of hyalinization in the adjacent tissue suggesting confinement. Special cases such as those in which only myomectomy was performed and those receiving adjunctive chemotherapy are discussed. The differential in survival between patients with primary myosarcoma and those with lesions arising in a leiomyoma is stressed.

Adult↗
PubMed1991

Angiomatoid "malignant fibrous histiocytoma": an immunohistochemical study indicative of myoid differentiation.

Six cases of angiomatoid malignant fibrous histiocytoma (MFH), the rarest subtype of MFH, have been studied immunohistochemically using a broad panel of commercially available antisera in formalin-fixed, paraffin-embedded tissue in an attempt to define the pattern of differentiation shown by this unusual tumor. As has been reported in the more common types of MFH, no evidence of histiocytic differentiation was found. However, five cases strongly expressed desmin (DER-11) and two also expressed muscle actin (HHF 35). All tissues examined were negative for myoglobin and alpha-smooth muscle actin. These results provide good evidence for some sort of myogenic or possibly myofibroblastic differentiation in angiomatoid MFH. Given its clinicopathologically and immunohistochemically distinctive features, which are very different from the other variants of MFH, redesignation of angiomatoid MFH as a low-grade myogenic sarcoma of uncertain histogenesis is tentatively proposed. The new term angiomatoid myosarcoma is suggested.

Actins↗
PubMed1979

Carcinogenic activity in Sprague-Dawley rats of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-gluco-pyranose (chlorozotocin).

Sprague--Dawley rats of both sexes received 2 mg/kg body wt (group 1) or 0.4 mg/kg body wt (group 2) of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) intraperitoneally in weekly injections for life. A dose-dependent carcinogenic effect of chlorozotocin was found (animals with malignant tumors in group 1: males 88%, females 89%, in group 2: males 83%, females 63%, in controls: males 10%, females 24%). Chlorozotocin reduced the life expectancy of treated animals significantly, compared to solvent controls. Histologically, the chlorozotocin-induced tumors were shown to be mesotheliomas or sarcomas of the peritoneal cavity (undifferentiated type, fibrosarcomas, myosarcomas).

Animals↗
PubMed1993

Radioimmunoscintigraphy using [111In]antimyosin Fab fragments for the diagnosis and follow-up of rhabdomyosarcoma.

Between 1987 and 1992, 39 radioimmunoscintigraphic studies using 111In-labelled antimyosin Fab fragments were performed in 27 patients with rhabdomyosarcoma (RMS), 2 patients with leiomyosarcoma (LMS) and 1 with alveolar soft tissue sarcoma. 21 patients were children aged 3-14 years. These patients, who had histologically proven myosarcoma, were examined scintigraphically to search for local recurrences or metastases and to determine the response to treatment. The results of immunoscintigraphy were compared with histopathological parameters and other imaging modalities. The sensitivity of antimyosin scintigraphy in this series was 82% and the specificity was 73%. Although the technique appears to be not highly specific for RMS, it was found to be useful for the early detection of local recurrence and metastases, as well as for the evaluation of the response to therapy.

Adolescent↗
PubMed1975

Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry.

Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour.

Animals↗
PubMed1998

Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.

Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies. Here we review the currently available results of this evaluation. Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of topotecan evaluation in phase II study showed antitumour activity in neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma, neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma, ependymoma, malignant glioma and juvenile colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo biotransformation involving several enzyme systems, such as carboxylesterase, UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.

Animals↗
PubMed2004

New chromanone acids with antibacterial activity from Calophyllum brasiliense.

Six novel chromanone acids (1-6) were isolated from the bark of Calophyllum brasiliense Cambess. Their structures were elucidated on the basis of 1D and 2D NMR experiments, as well as mass spectrometry. All compounds showed moderate to strong antibacterial activity against Bacillus cereus and Staphylococcus epidermidis, with 1 and 2 being most active. None of the compounds were cytotoxic against KB, Jurkat T, and myosarcoma cancer cells up to 20 microg/mL.

Anti-Bacterial Agents↗