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Comparative genomic hybridization as a tool to define two distinct chromosome 12-derived amplification units in well-differentiated liposarcomas.

Well-differentiated liposarcomas (WDLPS) are frequently characterized by a near-diploid karyotype with supernumerary ring and/or giant rod-shaped marker chromosomes. We have shown, using fluorescence in situ hybridization (FISH) and molecular strategies, that these markers contain chromosome 12-derived sequences. Here we report the analysis of six WDLPS for the presence of amplified DNA segments by means of the recently developed comparative genomic hybridization (CGH) strategy. Two distinct chromosome 12-derived amplification units could be identified in all tumors examined, one located in the q14-q15 region as expected, the second unexpectedly mapping to q21.3-q22. Our results indicate that the concerted amplification of these two distinct regions on the long arm of chromosome 12 may be a consistent characteristic of WDLPS. These amplifications are most likely directly related to the presence of supernumerary ring and/or giant marker chromosomes in this group of soft tissue tumors.

Cell Differentiation↗

Tumor suppressive activity of a variant isoform of manganese superoxide dismutase released by a human liposarcoma cell line.

A cell line derived from a pleiomorphic liposarcoma, named LSA, was previously reported to secrete (a) factor(s) exhibiting oncotoxic properties. The present article describes the isolation, purification and sequence analysis of a protein released by LSA cells into conditioned culture medium. This protein proved to be a variant isoform of manganese superoxide dismutase (MnSOD), hence its designation as LSA-type-MnSOD. This LSA-type-SOD differed from conventional SODs in its secretion by producer cells, contrasting with the normal localization of SODs in the mitochondrial matrix. Interestingly, during the protein purification process, LSA-type-SOD cosegregated with a cytotoxic activity directed against a number of tumor cell lines, as determined under in vitro conditions. This cytopathic effect was most likely due to LSA-type-SOD, since it could be fully reproduced using recombinant SOD that was expressed from cDNA clones isolated from LSA cells mRNA preparations and henceforth designated L-rSOD. In addition to its manifestation in cell lines kept in tissue culture, the oncotoxicity of LSA-type-SOD was further reflected in a remarkable capacity of this protein for suppression of mammary tumors in Balb-C-FR(III) mice. Animals subcutaneously injected with L-rSOD in the tumor area showed a complete disruption of established mammary carcinomas, as monitored by nuclear magnetic resonance (NMR) scanning. Moreover, metastatic spreading, which was readily detected in the control group, was suppressed in the treated animals. Altogether these data suggest that LSA-type-SOD interferes with survival and spreading of neoplastically transformed cells and deserves to be future validated as a therapeutic agent against cancer, either alone or in combination with conventional treatments.

Amino Acid Sequence↗

Effect of treatment with interferon and cyclophosphamide on the growth of a spontaneous liposarcoma in rats.

A spontaneous non-immunogenic transplantable liposarcoma in BN rats was found to be sensitive to the antitumor effects of rat fibroblast interferon (RIF) when it was administered from the day of tumor implantation onwards. Treatment with RIF starting at 7 days after implantation was not effective. Tumor growth was markedly inhibited by cyclophosphamide (Cyclo). At the time and dose schedules used, Cyclo was more effective than RIF. When the growth of the tumor was inhibited by Cyclo, subsequent treatment with RIF did not lead to an additional retardation of tumor growth. Administration of RIF interfered with the beneficial effect of Cyclo when both agents were given concomitantly. RIF and Cyclo gave similar results to those obtained with RIF alone and these were inferior to those obtained with Cyclo alone.

Animals↗

Secondary liposarcoma of the ovary.

This report is the first description of a secondary ovarian liposarcoma. The primary growth was in the mediastinum. The growth rate of the ovarian tumor was very rapid, but the patient died of cardiopulmonary causes. The mode of spread is discussed, and it probably occurred by transcelomic migration and surface implantation.

Adult↗

Contralateral displacement of abdominal viscera by a retroperitoneal liposarcoma: ultrasonic demonstration.

Occasional reports have described contralateral displacement of the kidney, gall bladder, or liver by masses, but no ultrasonographic description of this phenomenon has been published. To our knowledge, this is the first report of contralateral displacement of all three structures by an encapsulated, well-differentiated low-grade liposarcoma. The significance to the ultrasonographer lies in the fact that he may be the first physician, as we were in this case, to have the opportunity to recognize the true anatomical relationships of all three organs and to suggest that this tumor is more likely to be benign or slowly growing rather than a highly infiltrative process.

Adult↗

Liposarcomas: prognosis and management.

Fifty-one evaluable patients with liposarcomas were reviewed. Two-thirds of the patients were referred after local recurrence. One-third with primary surgery at RPMI had local recurrence rate of 31.6%. Overall, one or more local recurrences presented in 78% of patients. Pulmonary metastases, occurred in 45%, while liver metastases in 13.6%. Most common primary sites were the lower extremity, followed by the retroperitoneal area and upper extremity. Median survival is better for upper and lower extremities than other areas (P less than 0.01). The medium survival was longer in the group that received radiation after resection although the difference was not statistically significant. The high rate of local recurrences suggests the adjuvant use of radiation postoperatively when the surgical margins have not been adequate. Sixteen patients are alive and disease-free, with 10 of them having had five years or longer follow-up.

Adolescent↗

Myxoid liposarcoma mimicking fluid density.

A case of liposarcoma of the liver capsule initially presenting as massive pleural effusion and ascites is reported. The chest radiograph, computed tomographic scan, and sonogram are emphasized.

Aged↗

Myxoid liposarcoma of the spermatic cord.

The clinical and pathological features of one new and eight previously reported myxoid liposarcomas of paratesticular origin were reviewed. This kind of tumor was seen in an older population (average age 64 years), most of whom had scrotal masses of long duration (average 3.3 years). The tumors are large, usually painless, and are frequently misdiagnosed as hydroceles or inguinal hernias. All patients were treated by radical inguinal orchiectomy and are alive with follow-ups of 1-9 years.

Aged↗

Limb-sparing treatment with surgery and intraoperative radiotherapy (IORT) for a second local recurrence of myxoid liposarcoma in the popliteal region, after previous surgery and high-dose radiation.

A 46-year-old man with a second local recurrence of a myxoid liposarcoma in the fossa poplitea, after surgery and high-dose external beam radiotherapy, was successfully treated by a limb-sparing procedure combining marginal excision, intraoperative radiotherapy and reconstructive surgery. After a 48-month follow-up, there was no evidence of disease, and the function of the leg and knee was normal.

Cobalt Radioisotopes↗

Cardiac metastasis of liposarcoma.

The authors describe a retroperitoneal liposarcoma with secondary involvement of the left ventricle. Therapy has been disappointing, and is guided by the nature of the primary tumor, previous therapy, extent of metastatic spread, and feasibility of cardiac resection. In selected patients whose primary tumor is well-controlled and progressing slowly, with no evidence of widespread disease, resection of the cardiac metastases can be performed when technically feasible.

Echocardiography↗

Frequent alteration of p16(INK4a)/p14(ARF) and p53 pathways in the round cell component of myxoid/round cell liposarcoma: p53 gene alterations and reduced p14(ARF) expression both correlate with poor prognosis.

In myxoid/round cell liposarcoma (MLS/RCLS), the presence of a round cell (RC) component has been reported to correlate with a worse prognosis for the patients. However, little is known about the molecular genetic differences between conventional myxoid (MX) components and RC components in this tumour. The aim of this study was to investigate the possible implications of molecular alterations of G1 to S-phase check-point genes, especially in the RC component. We evaluated the immunohistochemical expression of p53, MDM2, p14 and p16 protein and assessed proliferative activities using MIB-1 in 29 RC components and 81 MX components from 90 cases. Mutation of the p53 gene, amplification of the MDM2 gene, homozygous deletion, methylation status and mutation of the p16(INK4a)/p14(ARF) genes were also investigated, using concordant paraffin-embedded and frozen material. The data were analysed together with clinicopathological factors to assess their prognostic implications in MLS/RCLS. Immunohistochemically, the over-expression of p53 protein (p = 0.01366) and the reduced expression of p14 (p < 0.0001) and p16 (p < 0.0001) proteins were significantly more frequently observed in RC components than in MX components. Reduced expression of p14 protein correlated significantly with hypermethylation of the p14(ARF) gene promoter (p = 0.0176) and over-expression of p53 protein (p = 0.00837). By univariate analysis, reduced expression of p14 and p53 missense mutation were found to reduce the rate of survival significantly (p < 0.05). Multivariate analysis, including clinicopathological factors, revealed that tumour site (p = 0.0251), the presence of an RC component (p = 0.0113), high MIB-1 labelling index (p = 0.0005) and p53 missense mutation (p = 0.0036) were adverse prognostic factors. In MLS/RCLS, reduction of p14 protein expression and p53 mutation were related to poor prognosis. Accordingly, the p14(ARF)/p53 pathway may contribute to the presence of an RC component and malignant progression in this tumour.

Adolescent↗

Primary myxoid-type mediastinal liposarcoma.

In this paper we present a case of primary mediastinal liposarcoma and describe CT findings of this malignant tumor. In light of the literature we also discussed the mediastinal fatty masses.

Aged↗

Retroperitoneal liposarcoma simulating a prolapsed intervertebral disc. A case report.

A metastatic liposarcoma presented with the clinical features of a prolapsed intervertebral disc. The tumour had spread from the retroperitoneal space in front of the sacrum by way of the first sacral foramen and along the dural sleeve of the first sacral root. Such a presentation has not previously been reported, and we make the point that it is important always to send material removed during operation on discs for histological examination.

Adult↗

Thymus-related liposarcoma: report of a case and review of the literature.

We report herein the case of a 77-year-old woman who was admitted to our hospital for further evaluation of an abnormal shadow in the right upper mediastinum that had been revealed by a routine chest X-ray. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed the presence of a thymic tumor, but did not show any evidence of invasion into the central vessels or adjacent structures. Thus, an extended thymectomy with resection of the tumor was performed. Microscopically, normal thymic tissue was found among the tumor cells, and a pathological diagnosis of well-differentiated liposarcoma was established. From the operative and microscopic findings, it is apparent that the tumor was related to the thymus. Postoperative irradiation of 60 Gy was delivered to the operative site and the patient has remained free of disease for 29 months since the operation.

Aged↗

Myxoid liposarcoma. An electronmicroscopic study: biological and histogenetic considerations.

Ten myxoid liposarcomas (ML) were studied ultrastructurally in an attempt to determine the histogenesis of this neoplasm and structural associations which might contribute to their relatively benign clinical behavior. The findings were compared with normal and neoplastic adipose tissue. Three cell types were observed, i.e., "primitive" mesenchymal cells, intermediate cell types, and lipoblasts at various stages of development. The principle differences between the lipoblastic elements were the number and the size of intracytoplasmic fat vacuoles, the development of basement membrane-like material, micropinocytotic vesicles along the plasma membrane and the quantity and pleomorphism of mitochondria. The tumor vasculature was complex but consistently demonstrated a multilayered basal lamina. This finding has been described in neoplasms associated with a relatively good prognosis. This study demonstrates that the better differentiated lipoblasts in ML share some features with normal brown fetal fat and hibernoma. It is, thus, suggested that ML may be derived from brown adipose tissue.

Adipose Tissue, Brown↗

Myxoid liposarcoma. Light and electron microscopic investigation.

Liposarcoma is an important soft tissue sarcoma. It requires careful classification into types, since prognosis varies considerably with histological appearance. In this case a myxoid sarcoma is shown to contain cells resembling fetal fat with active pinocytosis, and some scanty signet-ring cells. Their ultrastructural appearances are described.

Adult↗

Liposarcoma of the head and neck.

Liposarcomas of the head and neck are rare. Two patients are described and 52 cases from the literature reviewed. The histological type of differentiation mainly determines the prognosis. Radical surgery is the form of treatment advised, but postoperative irradiation is also recommended. Experiences with chemotherapy are limited so far.

Aged↗

The primary liposarcoma of the bone.

The typical criteria of the osseous liposarcoma will be discussed by means of a case report of a 69-year-old patient. The clinical symptoms as well as the macroscopic, light- and electron microscopic results justify a specification of this rare and controversially described form of a primarily malignant bone tumor.

Aged↗