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PubMed1995

Translocation t(9;22)(q22;q12) is a primary cytogenetic abnormality in extraskeletal myxoid chondrosarcoma.

The cytogenetic and in vitro growth characteristics of 3 cases of extraskeletal myxoid chondrosarcoma (EMC) are described. In cell culture, the tumor cells retained the immunocytochemical and ultrastructural characteristics of EMC. Cytogenetically, 2 of the cases showed an apparently identical t(9;22)(q22;q12). In one case, the t(9;22) was found together with a dup(I)(q12q44), and in the other case it was found together with several other aberrations. The third case had an inv(10)(p11.2q22) as the sole karyotypic abnormality. Of 4 cases of EMC previously analyzed, 2 showed a t(9;22)(q22;q11-12) and one case of a t(9;22;15)(q31;q12.2;q25). Thus, 5 out of 7 cases of EMC showed recombination between 9q22-31 and 22q11-12, indicating that this represents a tumor specific abnormality. The breakpoints on 22q were in all 5 cases cytogenetically indistinguishable from those seen in Ewing's sarcoma with t(11;22), clear-cell sarcoma with t(12;22), and desmoplastic small round cell tumors with t(11;22). Molecular cloning of these translocation breakpoints revealed involvement of the EWS gene (located at 22q12) in all 3 tumor types. These observations raise the intriguing question of whether the EWS gene might also be involved in the t(9;22) in EMC.

Aged↗
PubMed2003

Alternative splicing of fibronectin mRNAs in chondrosarcoma cells: role of far upstream intron sequences.

The fibronectin (FN) gene encodes multiple mRNAs through the process of alternative splicing, and production of certain isoforms is characteristic of a given cell type. Chondrocytes produce FNs that completely lack alternative exon EIIIA, and loss of inclusion of the exon is tightly linked to chondrogenic condensation of mesenchymal cells. The inclusion of a second exon, EIIIB, is high in embryonic cartilage, but declines with age. Multiple exons are omitted to produce the (V + C)-form that is highly specific for cartilage and chondrocytes. A rat chondrosarcoma cell line, RCS, was identified that preserves key features of the cartilage-specific splicing phenotype. RCS cells, which exclude exon EIIIA, and HeLa cells, which include exon EIIIA similar to mesenchymal cells, were used to assess the contribution of intron sequences flanking exon EIIIA to splicing regulation. Deletion of most of the intron downstream of the exon had little effect on splicing in either cell type. However, deletions within upstream intron 32-A reduced inclusion of the alternative exon in both cell types. The sequences involved lie more than 200 nucleotides away from the exon, but could not be localized to a single region by deletion mapping. These intronic sequences contribute to the efficiency of exon EIIIA recognition, but not to cell-type specific regulation. The normally inhibitory factor polypyrimidine tract binding protein promotes exon EIIIA inclusion in a manner that is partially dependent on the regulatory sequences within intron 32-A.

Alternative Splicing↗
PubMed1984

Characteristics of the core protein of the aggregating proteoglycan from the Swarm rat chondrosarcoma.

A ternary complex of hyaluronic acid-binding region and link protein bound to hyaluronic acid was isolated from limit clostripain digests of proteoglycan aggregates isolated from the Swarm rat chondrosarcoma. Under these conditions, the hyaluronic acid-binding region has a molecular weight of approximately equal to 65,000 (HA-BR65). N-terminal amino acids in the complex were selectively 14C-carbamylated. The resulting derivatized HA-BR65 was isolated, and tryptic peptide maps were prepared and developed on two-dimensional TLC sheets. A single, labeled peptide was obtained which gave a Mr by approximately equal to 8,000 by SDS-PAGE. Chymotrypsin digestion of the ternary complex reduced the molecular weight of HA-BR65 to a polypeptide of approximately equal to 55,000 (HA-BR55) which still retains the same N-terminal tryptic peptide. Partial digestion of proteoglycan aggregates with clostripain generated a series of larger intermediates with the hyaluronic acid-binding region. Direct SDS-PAGE analysis revealed one major intermediate with approximately equal to 109,000 (HA-BR109) as well as HA-BR65. After chondroitinase digestion, two additional prominent intermediates were observed on a SDS-PAGE gel at Mr approximately equal to 120,000 (HA-BR120) and approximately equal to 140,000 (HA-BR140). All the intermediates were recognized by a monoclonal antibody specific for the hyaluronic acid-binding region, and all of them contained the same N-terminal tryptic peptide. The results indicate that the N terminus of the core protein is at the hyaluronic acid-binding end of the proteoglycan and that the chondroitin sulfate chains are first present on the core protein in a region between 109,000 and 120,000 molecular weight away from the N terminus.

Amino Acid Sequence↗
PubMed1984

Studies on the biosynthesis of cartilage proteoglycan in a model system of cultured chondrocytes from the Swarm rat chondrosarcoma.

Biosynthesis of cartilage proteoglycan was examined in a model system of cultured chondrocytes from a transplantable rat chondrosarcoma. Extensive modification with the addition of chondroitin sulfate glycosaminoglycan, N-linked oligosaccharide, and O-linked oligosaccharide is required to convert a newly synthesized core protein precursor into a proteoglycan. Kinetic analyses revealed the presence of a large pool of core protein precursor (t 1/2 approximately 90 min) awaiting completion into proteoglycan. The large t 1/2 of this pool allowed kinetic labeling experiments with a variety of radioactive precursors to distinguish between early biosynthetic events associated primarily with the rough endoplasmic reticulum from late events associated primarily with the Golgi apparatus. The results of a series of experiments indicated that the addition of N-linked oligosaccharide chains occurs early in the biosynthetic process in association with the rough endoplasmic reticulum, whereas the initiation and completion of O-linked oligosaccharides occurs much later, at about the same time as chondroitin sulfate synthesis. This also indicated that keratan sulfate chains, when present in the completed molecule, are added in the Golgi apparatus, as they are probably built on oligosaccharide primers closely related to the O-oligosaccharide chains. Furthermore, when 3H-glucose was used as the precursor, the entry of label into xylose, the linkage sugar between the core protein and the chondroitin sulfate chain, was found to occur within 5 min of the entry of label into galactose and galactosamine in the remainder of the chondroitin sulfate chain. This indicated that the initiation and completion of the chondroitin sulfate chain occurs late in the pathway probably entirely in the Golgi apparatus. Thus, proteoglycan synthesis can be described as occurring in two stages in this system, translation and N-glycosylation of a core protein precursor which has a long half-life in the rough endoplasmic reticulum, followed by extensive rapid modification in the Golgi complex in which the majority of glycosaminoglycan and oligosaccharide chains are added to the core protein precursor with subsequent rapid secretion into the extracellular matrix.

Animals↗
PubMed1986

Immunoreactive fibroblast growth factor (FGF) in a transplantable chondrosarcoma: inhibition of tumor growth by antibodies to FGF.

Using a radioimmunoassay for bovine pituitary fibroblast growth factor (FGF), we have established the presence of the immunoreactive mitogen in extracts of a transplantable mouse chondrosarcoma. Both neutral and acidic extracts of the tumor contain an immunoreactive FGF (ir-FGF) that cross-reacts in a parallel and dose-dependent fashion in the radioimmunoassay. The ir-FGF is retained on heparin-Sepharose affinity columns and can be detected in the same molecular weight forms as rat pituitary FGF. Mice (C57/Bl) inoculated with the tumor (10 mg, im) show a decreased rate of tumor growth when passively immunized with the antiserum to FGF. The results establish the presence of FGF in this tumor and implicate its role in the etiology of its development.

Animals↗
PubMed1977

Mesenchymal chondrosarcoma of the rectus sheath case report with ultrasonic findings.

The ultrasonic findings in a 54 year old white male with a rare tumor, mesenchymal chondrosarcoma, involving the rectus sheath are described. The sonogram confirmed the tumor's location in the anterior abdominal wall and provided useful information regarding its extent. An interesting feature was the lesion's relative sonolucency, apparently due to its myxoid content.

Abdominal Muscles↗
PubMed2002

Chondrosarcoma of bone: functional outcome and quality of life.

BACKGROUND AND OBJECTIVES: Outcome studies of chondrosarcoma have so far only reported oncological and functional results. Quality-of-life assessment becomes more important because more long-term survival after treatment of malignant diseases occur. The objective of this study is to analyze functional outcome and quality of life. METHODS: Functional evaluation of the patients was carried out according to the MSTS functional scoring system. For assessment of quality of life, questionnaires were used. RESULTS: Response of the questionnaires sent to 45 disease-free patients was 84%. The mean functional score of these 38 patients was 74% (20-100%). Best functional results were seen after bone graft reconstruction and curettage and cryosurgery with reconstruction. Quality-of-life analysis revealed a mean global health status of 75 (66-84). Furthermore, 24% of the patients experienced severe fatigue. Patients reported more problems with regard to physical functioning and sleep in comparison with healthy controls. No correlation was found between global health status scores and functional scores. CONCLUSIONS: Functional scores depend on the type of treatment with best results after curettage and cryosurgery. Quality-of-life analysis reveals problems on several domains, including fatigue, physical functioning and sleep.

Adolescent↗
PubMed1979

Pseudo-chondrosarcoma: solitary osseous metastases from atypical bronchogenic carcinoma.

A patient with bronchogenic carcinoma with a solitary metastases to the femur in whom the clinical, radiologic, and pathologic setting suggested that the primary tumor was the bone lesion (chondrosarcoma) and the pulmonary lesion was a solitary metastasis is presented. This case is added to the limited literature indicating that mucin-secreting tumors metastatic to bone may simulate primary bone tumors radiographically.

Adenocarcinoma, Mucinous↗
PubMed1992

An extraskeletal chondrosarcoma arising in the brachial plexus.

A case of extraskeletal chondrosarcoma of the left brachial plexus is described with emphasis on the diagnostic and therapeutic difficulties of this site. With combination therapy the patient survived 6 years. Recurrent disease in the plexus region and adjacent spinal cord resulted in a painful, flail limb.

Brachial Plexus↗
PubMed1980

Amianthoid fibres in a chondrosarcoma.

Amianthoid fibres up to about 1000 nm thick were found in the matrix of a chondrosarcoma. Our findings support the idea that this is a degenerative change and that these fibres are probably formed by coalescence of collagen fibrils.

Adult↗
PubMed1988

Extraskeletal myxoid chondrosarcoma characterized by microtubular aggregates in the rough endoplasmic reticulum and tubulin immunoreactivity.

A case is reported of a 66-year-old female with an extraskeletal myxoid chondrosarcoma which had originated in the lateral region of the right knee. The tumour tissue of the primary, recurrent, and metastatic deposits in the lungs was examined by electron microscopy and immunohistochemistry. Almost all the sarcoma cells in every tumour specimen harboured immunoreactivity to both alpha- and beta-subunits of S-100 protein. A large population of cells in the subcutaneous tumour at autopsy had numerous parallel arrays of microtubules within the rough endoplasmic reticulum in addition to the well-described ultrastructural features indicative of chondroblastic origin. These structures were present in round to polygonal, but not in fibroblastic, tumour cells. Tubulin immunoreactivity in the tumour cells showed the same tendency, being frequently positive in the large cells of the subcutaneous tumour but weakly positive in the fibroblastic and medium-sized cells of the recurrent and metastatic tumours. The parallel arrays of intracisternal microtubules therefore may be composed of tubulin protein, as in ordinary cytoplasmic microtubules.

Chondrosarcoma↗
PubMed2005

The gene expression profile of extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.

Adult↗
PubMed2007

Decreased EXT expression and intracellular accumulation of heparan sulphate proteoglycan in osteochondromas and peripheral chondrosarcomas.

Mutational inactivation of EXT1 or EXT2 is the cause of hereditary multiple osteochondromas. These genes function in heparan sulphate proteoglycan (HSPG) biosynthesis in the Golgi apparatus. Loss of heterozygosity of the EXT1 locus at 8q24 is frequently found in solitary osteochondromas, whereas somatic mutations are rarely found. We investigated the expression of EXT1 and EXT2 (quantitative RT-PCR) and of different HSPGs (immunohistochemistry) in solitary and hereditary osteochondromas and in cases with malignant progression to secondary peripheral chondrosarcoma, in relation to possible mutations and promoter methylation. The mutation status of patients with multiple osteochondromas correlated with decreased EXT1 or EXT2 expression found in their resected tumours. We could not show somatic point mutations or promoter hypermethylation in 17 solitary tumours; however, EXT1 expression was decreased in 15 cases, whereas EXT2 was not. Intracellular accumulation of syndecan-2 and heparan sulphate-bearing isoforms of CD44 (CD44v3) was found in most tumours, which concentrated in the Golgi apparatus as shown by confocal microscopy. This contrasted with the extracellular expression found in normal growth plates. In conclusion, mutational inactivation of either EXT1 or EXT2 leads to loss of mRNA expression of the corresponding gene. We hypothesize that loss of EXT expression disrupts the function of the EXT1/2 complex in HSPG biosynthesis, resulting in the intracellular accumulation of HSPG core proteins that we found in these tumours.

Adolescent↗
PubMed1998

Differential effects of Staphylococcus aureus alpha-hemolysin on the synthesis of hyaluronan and chondroitin sulfate by rat chondrosarcoma chondrocytes.

The plasma membranes of rat chondrosarcoma chondrocytes were permeabilized by treatment with alpha-hemolysin, the major toxin produced by Staphylococcus aureus, which forms small, stable, heptameric, transmembrane pores (1-2 nm in diameter) permitting influx/efflux of low-molecular-mass molecules (< or = 2000 Da). Treated chondrocytes were permeable to entry of trypan blue and exit of ATP. We describe the effects of alpha-hemolysin on the synthesis of hyaluronan (HA) and chondroitin sulfate (CS) by chondrocytes using the simple sugar [3H]glucosamine as a metabolic precursor. Chondrocytes permeabilized with alpha-hemolysin in serum-free media decreased intracellular ATP and synthesis of CS to approximately 5% of control within 2-4 h, but synthesized HA (80% of control for 8 h; approximately 65% of control at 24 h). Adding fresh medium (with or without serum) to permeabilized cells increased ATP significantly and increased HA synthesis to near initial control values. Under the same conditions, the recovery of CS synthesis approached initial levels in control but not permeabilized cells. Our model demonstrates that the biosynthesis of HA by these cells in vitro is remarkably stable to cellular perturbations which drastically inhibit synthesis of CS on proteoglycans.

Adenosine Triphosphate↗
PubMed2000

Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells.

Green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG)-is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In this study we describe a novel observation that EGCG displayed strong inhibitory effects on the proliferation and viability of HTB-94 human chondrosarcoma cells in a dose-dependent manner and induced apoptosis. Investigation of the mechanism of EGCG-induced apoptosis revealed that treatment with EGCG resulted in DNA fragmentation, induction of caspase-3/CPP32 activity, and cleavage of the death substrate poly(ADP-ribose)polymerase (PARP). Pretreatment of cells with a synthetic pan-caspase inhibitor (Z-VAD-FMK) and a caspase-3-specific inhibitor (DEVD-CHO) prevented EGCG-induced PARP cleavage. The induction of apoptosis by EGCG via activation of caspase-3/CPP32-like proteases may provide a mechanistic explanation for its antitumor effects.

Antineoplastic Agents↗
PubMed1996

Extraskeletal mesenchymal chondrosarcoma of the labium majus.

Extraskeletal mesenchymal chondrosarcoma is a rare tumor. It has been noted to occur most commonly in muscle and the central nervous system. It has never been reported to occur in the soft tissues of the anogenital region. We report the first such case, occurring in a 40-year-old woman who presented with a 1-year history of a mass originating in the left labium majus. After extensive local resection and lymph node dissection she remains disease free after 40 months follow-up.

Adult↗
PubMed1993

Chondrosarcoma of the larynx.

Chondrosarcoma of the larynx is a rare, slow-growing malignant tumor. One hundred and fifty cases of this entity have been reported in the literature. In 75% of cases the site of involvement was the cricoid cartilage, while 20% have involved the thyroid cartilage. The tumor presents as a space-occupying lesion in the subglottic region, or as a neck mass. An insidious, slowly progressing disease course associated with hoarseness and dyspnea accounts for usual delays in arriving at a diagnosis. We report our experiences with six cases of this entity and discuss a diagnostic and therapeutic approach. Whenever possible a conservative surgical management should be attempted.

Adult↗
PubMed1993

Chondrosarcoma of the nasal septum: surgical considerations on Le Fort I osteotomy.

A case of chondrosarcoma of the nasal septum extending into the entire nasopharynx sphenoid sinus and skull base is presented. These cartilaginous tumors are rate in the head and neck, with only 28 reported in the nasal septum. They arise in tissues known to be formed of cartilage, and in the present case tumour presumably originated from the perpendicular lamina of the septum. The treatment of choice is wide surgical excision, which requires an adequate approach for gaining the widest possible exposure of tumor. Surgical considerations are discussed.

Chondrosarcoma↗