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At least 415 records · Page 23Linked to original sources
PubMed2003

Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study.

The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI-571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). Patients with measurable lesions and adequate organ function were entered. They were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). All tumours were subject to a stringent pathological review by an expert panel. Immunohistochemical expression of KIT expression was evaluated. A total of 51 patients (27 GIST, 24 other STS), median age 53 years, median World Health Organization (WHO) performance score 1, were entered. 71% of the patients had received prior chemotherapy. The most frequent side-effects were anaemia (92%), periorbital oedema (84%), skin rash (69%), fatigue (76%), nausea (57%), granulocytopenia (47%) and diarrhoea (47%). Most of these side-effects were mild to moderate and no patient was taken off study due to side-effects. Skin rash and periorbital oedema frequently seem to be self limiting, despite continued treatment. In GIST patients, the current response rates (RRs) are 4% complete remission (CR), 67% partial remission (PR), 18% stable disease (SD) and 11% progression (PD). 73% of GIST patients are free from progression at 1 year. In the other STS group, there were no objective responses. The median time to progression in this subgroup was only 58 days. Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KIT-positive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit.

Adult↗
PubMed2005

Radiosensitization, after a combined treatment of survivin siRNA and irradiation, is correlated with the activation of caspases 3 and 7 in a wt-p53 sarcoma cell line, but not in a mt-p53 sarcoma cell line.

Survivin, a member of the inhibitor-of-apoptosis family is an essential protein for regular mitosis and is involved in an anti-apoptotic pathway. In some studies, an association between survivin expression and radiosensitivity has been described for tumor cells, but the relationship between p53 and survivin regarding radioresistance remains to be clarified. In order to increase the effect of irradiation on two sarcoma cell lines, A-204 with wt-p53 and US 8-93 with mt-p53, siRNA was applied to knock down survivin expression. The effects of combined treatment of siRNA treatment and irradiation were investigated by clonogenic survival assay, measurement of activity of caspases 3 and 7, Western blot hybridization for survivin and p53, and morphological analysis of apoptosis. Survivin knock down caused radiosensitization in the cell line A-204 (wt-p53) with an enhancement factor of 1.8 at 2 Gy (p=0.05) and 2.5 at 4 Gy (p=0.02), respectively. No radiosensitization was found in the cell line US 8-93 (mt-p53), when clonogenic survival was analyzed. These findings were supported by an increase in activity (up to 5.2-fold) of caspases 3 and 7 in cell line A-204 (wt-p53), but not in cell line US 8-93 (mt-p53) after a combined treatment of siRNA and irradiation. Our findings suggest that the wt-p53-caspase pathway is of importance for the radiosensitization induced by targeting survivin, which may have an impact on future gene therapeutical treatments.

Apoptosis↗
PubMedDate not supplied

Radiotherapy of classic Kaposi's sarcoma in Taiwan, an area where classic Kaposi's sarcoma is not prevalent.

BACKGROUND: Classic Kaposi's sarcoma (KS), a neoplastic disease of vascular endothelial cells of the skin, is relatively prevalent in Eastern Europe and the Mediterranean region and radiation is one of the standard therapies. The clinical presentation and treatment results of classic KS from other regions have rarely been reported. PATIENTS AND METHODS: Between 1994 and 2006, patients who had histologically confirmed KS and no immunodeficiency status due to human immunodeficiency virus infection or organ transplantation, and were treated with radiotherapy at Department of Oncology, National Taiwan University Hospital, Japan, were reviewed. RESULTS: A total of 17 classic KS patients, with a median age of 69 years, were studied over a period of 12 years. All classic KS lesions involved lower extremities. Radiotherapy was delivered with either a 60Co unit or a linear accelerator, with the most commonly prescribed treatment being 3 Gy per fraction to a total dose of 39 Gy. In addition, several techniques using bolus were adopted to improve the radiation distribution over the skin of lower extremities. All irradiated KS lesions responded, with a complete response rate of 76%. The overall survival and progression-free survival rates of the group at 5 years were 85% and 58%, respectively. CONCLUSION: Radiation therapy for classic KS patients in a non-prevalent area, such as Taiwan, is safe and effective.

Aged↗
PubMed1986

Separation of sarcoma growth inhibitor from avian sarcoma virus-transformed rat cells.

A cell growth inhibitor was isolated from an avian sarcoma virus-transformed rat cell line (77N1), from which we had previously obtained a novel transforming growth factor, TGF gamma 2. The growth inhibitor (named SGI) was found in cell extract of 77N1 cells and was separable from TGF gamma 2 by means of ion exchange chromatography. SGI inhibited the DNA synthesis of serum-starved, TGF gamma 2-stimulated BALB3T3 cells as well as the spontaneous and TGF-induced colony formation of various cells in semisolid agar. We present evidence that SGI is distinct from the ubiquitous growth modulator TGF beta, and we discuss the possible role of SGI in the neoplastic cell proliferation.

Animals↗
PubMed1985

[Genital sarcoma of the female with special reference to sarcomas of the uterus].

It is reported on 101 sarcomas of the female genitals which have been treated in the gynaecological department of the county hospital Dresden-Friedrich-stadt from 1950 to 1984. 79 of them had their origin at the corpus uteri. Results of treatment are discussed. The low frequency of the disease demands a centralized treatment. There is no optimal accompanying post-operative therapy, therefore it has to be found in future.

Adolescent↗
PubMed1984

In vitro reeducated T helper cells from sarcoma-bearing mice inhibit sarcoma growth in vivo.

Spleen cells from BALB/c mice bearing a small, but already clinically evident transplantable methylcholanthrene-induced sarcoma (CE-2) are not able to release interferons, proliferate and perform a cytotoxic response against CE-2 cells, nor able to inhibit their growth in vivo in a Winn-type neutralization assay. They can, however, be reeducated to be efficiently active against the tumor. Spleen cells (25 X 10(6) ) and 10(6) mitomycin C-treated CE-2 cells were cultured in 20 ml of medium for 6 days. The surviving spleen cells were then cultured for another 5 days under the same conditions plus 10% interleukin 2-rich supernatant from a clone of EL-4 thymoma cells stimulated with phorbol-12-myristate-13-acetate. Reeducated spleen cells were then able to inhibit the growth of a 100% lethal dose of CE-2 tumor cells in a Winn-type assay, even when the lymphocyte to tumor cell ratio was 5:1. In vitro, they released interferon-gamma when restimulated by CE-2 cells, and displayed a marked cytotoxicity in an 18-hr assay. Their in vivo tumor-neutralizing activity was not affected by the removal of Lyt-2.2+ lymphocytes, nor by the absorption of cytolytic cells on CE-2 monolayers. The absorbed cell population no longer contained cytotoxic cells nor cytotoxic cell precursors, but still contained CE-2-specific helper cells, which assist the in vitro induction of cytotoxic cells by normal thymocytes. Lyt-2.2-, noncytotoxic, reeducated spleen cells from tumor-bearing mice thus play an important role in tumor neutralization in vivo.

Animals↗
PubMedDate not supplied

Treatment of advanced soft tissue sarcoma with chlorozotocin: a phase II trial of the EORTC soft tissue and bone sarcoma group.

Chlorozotocin, 120 mg/m2 every 4 weeks, was administered to 22 patients with advanced soft tissue sarcoma. All patients had received extensive prior chemotherapy and had measurable progressive disease at the time of entry in the study. No objective responses were observed. The best individual results were in three patients with disease stabilization lasting 2--4 months. Toxic effects included nausea in one half of the patients and sweating episodes in one. One patient developed temporary leukopenia and three had thrombocytopenia that lasted for 3 weeks, 4 weeks, and 4 months. Blood sugar levels were unaffected by the treatment. No renal or hepatic toxicity was recorded.

Adult↗
PubMed1978

Studies on Crocker sarcoma 180 under the effect of alkylating agents. IV. Morphological studies of sarcoma 180 during treatment with the antitumour drug cytoxan.

The effect of one massive dose of cytoxan (150 mg/kg), as an alkylating agent, on the morphology of sarcoma 180 cells was followed after 1, 3, 6, 12, 24, 48, 96, 120, and 168 h. After 1 h the cells of treated tumour showed clumping and a decrease in their size. In addition, statistical analysis manifested significant decrease in all phases of mitotic figures. All mitotic figures were completely stopped after 3 h from cytoxan treatment. After 6 and 12 h from cytoxan treatment the hyaline degenerations became more marked in the treated tumour tissue. Chromosomal bridge formation, nuclei aberrations and polynuclear cells were more prominent in 24, 48, and 96 h from cytoxan treatment. Increase in the nuclear size and hyaline degeneration were observed in treated section of 120 and 168 h.

Alkylating Agents↗
PubMed1982

[Studies on the tissue culture of murine sarcoma (Dunn sarcoma)--a fix cell line established in vitro (DSK) and its cytokinetic findings (author's transl)].

Dunn osteosarcoma, transplanted successively from the original spontaneous murine osteosarcoma, was cultured for generations and serial changes of cultured cells were observed morphologically and also from the view points of chromosomes and cytokinetics. 1) In the early generations of subculture, the cultured cells were predominantly of spindle shape, proliferating in a mesh-like pattern. However, with generations the epitheloid cells became dominant with a slight increase in their proliferating rate, and from 16th generation thereafter, the cellular pattern became almost uniform. The nuclei, being in the center of the cytoplasm, varied in their size and number, and several mitoses were also noted. In the 8th and 9th generations, the multinucleated giant cells were greatest in their size, and their nuclei were most numerous. 2) The cells of each generation, inoculated into the mice, developed tumors in the mice with the same histological appearance as that of original tumors. From the 17th generation thereafter, these inoculations (in vivo back inoculation) were constantly successful in producing tumors. Meanwhile, the cells of the tumor induced by in vivo back inoculation could be cultured, and showed the same morphological patterns as that of the serially cultured cells. 3) The chromosomes of the cultured cells were prepared by treating the tissue with colchicine followed by 0.2% hypotonic saline. From the primary culture to the first ten generations, the mode of the chromosome number varied from diploidy to high diploidy, while it became stable in high diploidy from 16th generation thereafter. The shapes of the chromosomes were various, and there were a few bar-shaped chromosomes. No constant marker chromosome was detectable. 4) The mouse spleen cells, cultured with the inactivated cultured tumor cells were activated by the target, recognizing the tissue specific transplantation antigen of the target. Considering these findings, this series of tissue culture is regarded as a fixed cell line. Therefore, it is concluded that an experimental system of Dunn osteosarcoma has been established in vitro, and it could be named as DSK (Dunn sarcoma in vitro, KITASATO) by the author. The duration of cell cycle of DSK, using the cumulative labeling method, is 11 hours, which is about two hours shorter than that of in vivo.

Animals↗
PubMedDate not supplied

Results of the Royal Marsden Hospital second soft tissue sarcoma schedule (STS II) chemotherapy regimen in the management of advanced sarcoma.

Forty-eight patients with advanced soft tissue sarcoma were treated with a five-drug combination regimen consisting of vincristine, actinomycin D, and cyclophosphamide (Day 1) followed by doxorubicin and an infusion of methotrexate (Day 22). Thirty-seven of the 48 patients were fully evaluable. Of the 37 evaluable patients, two achieved a complete remission and three achieved a partial remission, with an overall response rate of 13.5%. These results compare unfavorably with previously reported series from this and other centers, and the regimen has now been superseded.

Adult↗
PubMed1995

Inflammatory cytokines induce AIDS-Kaposi's sarcoma-derived spindle cells to produce and release basic fibroblast growth factor and enhance Kaposi's sarcoma-like lesion formation in nude mice.

Homosexual males often present signs of immune activation and are likely to have increased levels of inflammatory cytokines such as IL-1 beta, TNF-alpha, and IFN-gamma. These individuals develop Kaposi's sarcoma (AIDS-KS) more frequently than other HIV-1-infected groups. Our previous work demonstrated that inflammatory cytokines stimulate the growth of spindle cells derived from AIDS-KS lesions (AIDS-KS cells) and that these cells produce high levels of bFGF that mediate autocrine and paracrine (endothelial) cell growth and angiogenesis. Here we show that AIDS-KS cells constitutively produce and release bioactive bFGF in the absence of cell death, and that extracellular bFGF exist in both a soluble and a bound form; the latter can be released by treatment with trypsin, heparin, or heparinase I. Inflammatory cytokines stimulate both the synthesis and release of biologically active bFGF from KS cells and enhance their ability to induce angiogenic KS-like lesions in nude mice. Because bFGF is highly expressed in primary KS lesions, and is a mediator of KS-like lesion formation, these results suggest that the export of bFGF induced by inflammatory cytokines may play a critical role in the induction and progression of KS in HIV-1-infected homosexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cyclophosphamide versus ifosfamide: a randomized phase II trial in adult soft-tissue sarcomas. The European Organization for Research and Treatment of Cancer [EORTC], Soft Tissue and Bone Sarcoma Group.

Ifosfamide (5 g/m2) was compared with its parent analogue cyclophosphamide (1.5 g/m2) in a randomized phase II study. Both drugs were given by 24-h intravenous (i.v.) infusion every 3 weeks along with i.v. bolus infusions of mesna (400 mg/m2), which was given every 4 h for nine administrations. Eligibility criteria included an age of 15-75 years, biopsy-proven advanced metastatic soft-tissue sarcoma, and a World Health Organization performance status of 0-2. Exclusion criteria were prior treatment with classic alkylating agents, a creatinine level of > 150 mumol/l, a bilirubin level of > 20 mumol/l, a leukocyte cell count of < 3.5 x 10(9)/l, and a platelet count of < 100 x 10(9)/l. A total of 171 patients were entered, 24 of whom were ineligible and 12, inevaluable, leaving 135 patients evaluable. In all, 67 patients were treated with cyclophosphamide, and the overall response rate was 7.5%. All responders to cyclophosphamide were patients who had not received prior chemotherapy (13% of 38 patients). Another 68 patients were given ifosfamide, 18% of whom responded to treatment. Of the 28 ifosfamide-treated patients who had received prior chemotherapy, 7% were responders. The response rate for the remaining 40 patients was 25%. The higher overall response rate (P = 0.13) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy.

Adolescent↗
PubMed1995

[Surgical therapy of soft tissue sarcomas II. Sarcomas of the extremities and their surgical resection].

In the past, the rate of amputation for soft tissue sarcomas of the extremities was 40-50%. In recent years this rate has declined to about 50%. The improved rate of limb salvage with improved rates of local control, compared to those of the past, has been due to the development of surgical techniques allowing often satisfactory resection with limb preservation and to the use of adjuvant radiation in the presence of inadequate surgical margins. Below, the surgical techniques of limb preservation, as well as those or the major amputations are described.

Amputation, Surgical↗
PubMed1997

Kaposi's sarcoma cells express the macrophage-associated antigen mannose receptor and develop in peripheral blood cultures of Kaposi's sarcoma patients.

The mannose receptor (MR) is a surface 175-kd C-type lectin expressed by macrophages and dendritic cells. MR is involved in removal of effete cells, phagocytosis of mannose-coated particles, pinocytosis, and antigen presentation. Expression of MR was investigated in 17 biopsies of Kaposi's sarcoma (3 AIDS KS, 13 classical KS, and 1 transplant-associated KS) using three anti-MR monoclonal antibodies (3.29, D547, and PAM1). Immunostaining for MR was detected in 94 +/- 7% KS cells with spindle morphology. In normal tissues, MR was expressed by sinus-lining cells of spleen and lymph nodes, but it was not detected in endothelial cells lining normal hematic and lymphatic vessels, hemangioma, hemangioendothelioma, and lymphangioma. Expression of MR in KS cells prompted us to investigate the possibility that they derive from a circulating precursor cell. Peripheral blood mononuclear cells from 16 patients with KS (10 classical, 1 transplanted, and 5 AIDS) were cultured in PHA-conditioned medium for 10 to 14 days. Confluent monolayers of adherent spindle cells were detected in 8 of 11 classical KS, in 5 of 5 AIDS KS patients, and in 0 of 34 control patients. Peripheral-blood-derived KS-like cells were characterized by co-expression of macrophage and endothelial antigens being positive for CD45 (60%), CD68 (98%), MR (70%), CD14 (25%), VE-cadherin (70%), and von Willebrand factor (10%). When the immunophenotype of peripheral-blood-derived adherent cells was compared with that of KS spindle cells of tissue biopsies, it was found that both cell types are VE-cadherin+/MR+/CD68+, that peripheral-blood-derived spindle cells are CD34- and are less frequently stained for CD31 and von Willebrand factor, and that lesional KS cells do not express the leukocyte markers CD45 and CD18. Our findings are consistent with the possibility that KS lesions derive from tissue accumulation and local proliferation of a special subset of macrophages with endothelial features the normal counterpart of which are the sinus-lining cells of spleen and lymph nodes.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Enhancement of gp130-mediated tyrosine phosphorylation of STAT3 and its DNA-binding activity in dexamethasone-treated AIDS-associated Kaposi's sarcoma cells: selective synergy between dexamethasone and gp130-related growth factors in Kaposi's sarcoma cell proliferation.

The soluble IL-6R (slL-6R alpha)/IL-6 complex and oncostatin M (OM), which exert biologic activities through the signal-transducing protein gp130, are potent growth factors for AIDS-associated Kaposi's sarcoma (KS) cells. Clinical observations indicate that glucocorticoid therapy is a possible risk factor in KS; however, little is known of specific interactions in KS cells between glucocorticoid and gp130-related growth factors. We obtained evidence that dexamethasone (Dex), in a synergistic manner, enhances gp130-mediated growth of KS cells. Anti-gp130 Abs or the glucocorticoid antagonist RU-486 abolished this synergistic effect. In addition, Dex had additive but not synergistic effects on stimulation of KS cell growth with IL-1beta or TNF-alpha, the signals of which are not mediated through gp130. Immunoblot analysis revealed sIL-6R alpha/IL-6- or OM-induced tyrosine phosphorylation of a similar set of proteins in KS cells, and which was augmented significantly in Dex-treated KS cells. Stimulation of KS cells with sIL-6R alpha/IL-6 or OM induced rapid tyrosine phosphorylation of the transcription factor STAT3, and Dex significantly enhanced the accumulation of tyrosine-phosphorylated STAT3. Electrophoretic mobility shift assays showed sIL-6R alpha/IL-6- or OM-induced DNA-binding activity of STAT3 in KS cells, and Dex further increased this activity. Thus, Dex appears to participate in the gp130-STAT3 signaling and transcriptional events by enhancing STAT3 activation, thereby leading to selective synergistic stimulation of KS cell growth with Dex and the gp130-related growth factors.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Endogenous basic fibroblast growth factor is essential for cyclin E-CDK2 activity in multiple external cytokine-induced proliferation of AIDS-associated Kaposi's sarcoma cells: dual control of AIDS-associated Kaposi's sarcoma cell growth and cyclin E-CDK2 activity by endogenous and external signals.

AIDS-associated Kaposi's sarcoma (KS) cell, a key element for development of KS lesions, proliferates in response to external cytokines, such as oncostatin M, the soluble IL-6R-IL-6 complex, TNF-alpha, and IL-1beta. In addition, the KS cell-produced basic fibroblast growth factor (bFGF) was reported to function as an autocrine growth factor. However, little is known of the exact roles of these external growth factors and endogenous bFGF on proliferation of KS cells, and underlying intracellular events have remained to be defined. We obtained evidence that anti-bFGF Ab abolished growth of KS cells by preventing S phase entry of the cell cycle, even in the presence of the external growth factors. Blockade of the FGF action profoundly inhibited cyclin E expression and cyclin-dependent kinase-2 (CDK2) activity, but not D-type cyclin expression and CDK4 activity. Exogenously added acidic FGF (aFGF), which generated a rapid tyrosine phosphorylation of FGFR1 and FGFR2 on KS cells, reversed the inhibitory effects of anti-bFGF Ab. Thus, FGF actions are essential for cyclin E-CDK2 activity and S phase entry. We also observed that the presence of external growth factors markedly induced cyclin E-CDK2 activity and S phase entrance, while the addition of aFGF or bFGF alone was insufficient to induce these responses. All this evidence shows that integration of the activities of external growth factors and endogenous bFGF is required for full activation of cyclin E-CDK2 activity and KS cell proliferation.

Acquired Immunodeficiency Syndrome↗