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The differential effects of IL-1 and TNF-alpha on proinflammatory cytokine and matrix metalloproteinase expression in human chondrosarcoma cells.

OBJECTIVE AND DESIGN: Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinases (MMPs) play important roles in the pathogenesis of osteoarthritis (OA). In the present study, using Affymetrix oligonucleotide array technology and real-time quantitative RT-PCR we have investigated the molecular mechanisms underlying the differential effect of IL-1 and TNF-alpha on gene expression in the human chondrosarcoma cell line, SW1353. MATERIALS AND METHODS: SW1353 cells were stimulated singularly with IL-1alpha, TNF-alpha, Phorbol 12-myristate 13-acetate (PMA), or treated with the combination of cytokine and PMA. Total RNA was collected at multiple time points over a 24-h period followed by biotinylated cRNA target preparation and hybridization onto the Affymetrix HG-U95Av2 array. The differential expression patterns of several cytokine and MMP genes were further confirmed by real time quantitative RT-PCR, Western blot, and ELISA. RESULTS: Our microarray experiments have broadly confirmed previously published data on chondrocyte gene expression regulated by IL-1 and TNF-alpha. The expression pattern of proIL-1beta, MMP-1, and MMP-13 in chondrocytes is differentially regulated when stimulated with proinflammatory cytokines. IL-1, but not TNF-alpha, can induce IL-6, bone morphogenic protein 2 (BMP-2), and cyclooxygenase (COX-2) expression in SW1353 cells. Additionally, our Western blot results provide the first evidence that IL-1beta is produced in the proform in IL-1alpha-activated chondrosarcoma cells and that additional signals are required for its posttranslational processing/activation. CONCLUSIONS: IL-1 and TNF-alpha each activate a distinct set of genes in chondrosarcoma cells, and gene expression in these cells is regulated by groups of genes related in part by their function. Chondrocyte IL-1alpha appears to serve an important role in the pathogenesis OA contributing to joint inflammation and cartilage destruction.

Cell Line, Tumor↗

Extraskeletal myxoid chondrosarcoma of the knee.

Extraskeletal myxoid chondrosarcoma is an uncommon neoplasm, accounting for less than 2% of all soft tissue sarcomas. It affects adult males with a median age in the fifth decade at the time of diagnosis. The tumor usually arises in the deep soft tissues, especially in the lower extremities. Patients present with a gradually enlarging mass that may or may not be associated with pain. This report describes a 25-year-old man who initially presented with a 4- to 5-year history of right knee pain and an enlarging mass in the right knee. Evaluation revealed a cartilaginous neoplasm with no evidence of metastatic disease. The tumor was widely excised and an allograft reconstruction was performed. The patient was closely followed with an eventual above the knee amputation for recurrent myxoid chondrosarcoma. At 34 months, retroperitoneal metastases were noted on abdominal CT. The patient underwent a left radical nephrectomy, renal vein thrombectomy and enucleation of the mass in the right kidney, distal pancreatectomy, and splenectomy. The patient received postoperative chemotherapy. Forty-eight months after initial diagnosis, the patient was found to have recurrent abdominal and retroperitoneal lesions. At 64 months, the patient died from complications of extraskeletal myxoid chondrosarcoma.

Abdominal Neoplasms↗

Chondrosarcoma of the hyoid bone.

The CT and MRI findings in a case of chondrosarcoma of the hyoid bone are reported. Although chondrosarcoma is the second most common primary malignant bone tumor, only 10 % of chondrosarcomas occur in the head and neck region. The hyoid bone is a rare site of involvement with only seven cases reported previously.

Bone Neoplasms↗

Clear cell chondrosarcoma of the proximal femur with intrapelvic extension.

Clear cell chondrosarcoma is a rare tumor that can be easily confused with benign tumors. The aim of this report is to present a case that is rare, initially diagnosed as aneurysmal bone cyst and then chondroblastoma, and has an interesting extension pattern. A 41-year-old male patient was treated for an apparently benign cystic lesion of the right proximal femur by intralesional excision and bone grafting. The pathological diagnosis was aneurysmal bone cyst. Two years later, the patient presented with a pathological fracture at the same site and a total hip arthroplasty was performed. The pathological specimen was diagnosed as chondroblastoma. Three years later, clinical and radiological examination of the patient revealed a large mass located on the intrapelvic side of the acetabulum. There was no evidence of distant metastases. Both tumors were resected with a wide margin on the femoral side and a marginal margin on the intrapelvic side. The extremity was reconstructed with a resection-type total hip prosthesis. Again, the pathological diagnosis was chondroblastoma. The patient developed a deep infection that was treated by antibiotic therapy and surgical debridement. One year later, there was recurrence of the femoral and intrapelvic masses and right hemipelvectomy was performed; the specimen was reported as clear cell chondrosarcoma. Since then, the patient has been leading an active life, and there is no evidence of local recurrence or distant metastasis. Clinically and pathologically, clear cell chondrosarcoma may be confused with benign bone tumors. This caused a delay in the final diagnosis of this patient and he received inadequate surgical treatment, leading to a hemipelvectomy. We also found that the intrapelvic mass seemed to have developed independently on the intrapelvic side of the acetabulum. We were unable to find an exact explanation for this finding and postulated that tumor cells might have been seeded into the inner wall of the acetabulum during acetabular preparation of the total hip prosthesis.

Adult↗

Laryngeal chondrosarcoma: a report of five cases.

Laryngeal chondrosarcoma is a rare tumor that is known for its indolent course and its tendency to ultimate recurrence. According to the actually adopted classification, 95% of the reported cases are of a low-grade type. A consensus recognizing conservative surgery as the most reasonable treatment for these lesions has almost been reached. However, fear of jeopardizing the patency of the laryngeal airway as a result of a wide cricoid excision and also the fear of repeated recurrences could still push some surgeons to perform a total laryngectomy in the case of laryngeal chondrosarcoma. After a brief review of the literature, we will present five cases of laryngeal chondrosarcoma that were treated and followed at the Clermont-Ferrand University Medical Center over the last two decades. These cases exhibit many of the clinicopathologic features of the tumor and illustrate the pitfalls of diagnosis and treatment. In light of this presentation, we will discuss the widely accepted management as well as a newly suggested treatment modality for this disease.

Adult↗

Extraskeletal myxoid chondrosarcoma of the nasal cavity.

Extraskeletal myxoid chondrosarcoma presenting in the head and neck is extremely rare. Histologic diagnosis is difficult and close co-operation among clinician, radiologist and pathologist is recommended. The tumour has a better prognosis than myxoid chondrosarcoma of the bone but surgical resection may be difficult due to its gelatinous nature. We present a case of extraskeletal myxoid chondrosarcoma originating in the left nasal cavity of a 35-year-old woman.

Adult↗

Characterization of a newly established human chondrosarcoma cell line, CS-OKB.

A clonal cell line, CS-OKB, was derived from a human chondrosarcoma and characterized by cytogenetic study, immunocytochemical staining, and reverse transcriptase polymerase chain reaction (RT-PCR). Chromosomal abnormalities characteristic of malignant cartilaginous neoplasms were identified. CS-OKB cells were intensely stained with anti-type II collagen and anti-keratan sulphate antibodies. RT-PCR indicated that CS-OKB transcribes cartilage-specific genes such as type II, X procollagen, and aggrecan. This human chondrosarcoma cell line is stable and expresses well-differentiated chondrocyte-specific genes. It synthesizes well-differentiated chondrocyte-specific molecules in uncoated plastic dishes. CS-OKB may be useful for studies of human chondrocytes and in characterizing human chondrosarcomas.

Aged↗

Differential enhancement of collagen crosslink excretion in cases of osteosarcoma and chondrosarcoma.

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma ( n=20; age range 16-49 years) and chondrosarcoma ( n=15; age range 18-70 years). The values were compared with those obtained from 74 healthy controls (age range 16-83 years). The range and upper limit of normal values (HP(max) and LP(max)) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma ( p=0.001) and chondrosarcoma ( p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.

Adolescent↗

Mesenchymal chondrosarcoma of the sellar region.

BACKGROUND: It is known that, although rare, mesenchymal chondrosarcoma can originate intracranially. However, no such malignant tumour has been described in the sellar region. CLINICAL PRESENTATION: We report a case of mesenchymal chondrosarcoma in a 21-year-old man who presented with double vision, right blepharoptosis and facial pain. Upon initial admission, no endocrinological abnormalities were found, and computed tomography and magnetic resonance imaging revealed a mass with calcification in the sella and right cavernous sinus. INTERVENTION: For this malignant tumour, three surgical resections, two sessions of gamma-knife radiosurgery, one session of fractional irradiation, and one cycle of chemotherapy were performed, resulting in only brief arrest of the tumour growth. Pathologically, the tumour consisted of undifferentiated small cells of high cellularity, and islands of hyaline cartilage. The undifferentiated small cells showed immunoreactivity for vimentin and ultrastructural features suggesting a mesenchymal origin. Lacunar cells in the islands were immunopositive for S-100 protein and vimentin. CONCLUSION: Although malignant tumours in the sellar region are rare, they should be considered in the differential diagnosis of various sellar tumours typified by non-functioning pituitary adenoma, and mesenchymal chondrosarcoma is one possible candidate.

Adult↗

Chondrosarcoma of the mandibular condyle. Report of a case with special reference to radiographic features.

A case of chondrosarcoma of the mandibular condyle is described. With carefully taken tomographs, a diagnosis of chondrosarcoma of the mandibular condyle can be made with some degree of certainty, on radiological evidence alone. Chondrosarcomata of the mandibular condyle may manifest with the typical symptoms of the temporomandibular joint dysfunction syndrome. Tumours of the condyle can reach a large size without producing clinically obvious swellings. The literature pertaining to chondrosarcoma of the mandibular condyle is reviewed.

Adult↗

HNF transfection with chondrosarcoma DNA results in the development of a sarcoma cell surface-associated epitope.

High molecular weight DNA, which was isolated from a chondrosarcoma cell line, was transfected into human neonatal foreskin fibroblasts and NIH/3T3 cells. Both types of transfected cells expressed anchorage-independent growth in soft agar and produced tumors in nude mice. The tumors which developed in nude mice following injection of transfected human fibroblasts grew to approximately 0.8 cm in diameter in four weeks. The tumors which developed from transfected NIH/3T3 cells grew to greater than 2.0 cm in diameter in 6 weeks. After growth in soft agar the transfected human fibroblasts expressed a cell surface sarcoma-associated epitope recognized by the monoclonal antibody 345.134S. In addition to the transfected human fibroblasts, the original human chondrosarcoma tumor, the chondrosarcoma cell line derived from the tumor, and the nude mouse tumor which developed from transfected human fibroblasts all exhibited positive reactivity with the monoclonal antibody 345.134S. Transfected NIH/3T3 cells that exhibited anchorage-independent growth and tumorigenicity did not exhibit detectable reactivity with the monoclonal antibody. These results suggest that the expression of the tumor-associated cell surface antigen appears to be an early event correlated with transformation of the transfected human cells but not directly related to the tumorigenic potential of the DNA. The transfected cells which expressed anchorage independent growth exhibited the sarcoma cell surface antigen prior to attaining the potential for tumorigenicity.

Animals↗

Delayed mandibular reconstruction following removal of a mesenchymal chondrosarcoma. Report of a case.

An unusual case of mesenchymal chondrosarcoma is presented. Initially seen when the patient was 8 years old, the lesion was repeatedly biopsied and curetted with a diagnosis of odontogenic fibroma. In 1971 a diagnosis of osteosarcoma of the chondroblastic type was made. At that time, the patient underwent a partial mandibulectomy with immediate graft. The patient did well until 1981, when a recurrence of the lesion was noted. The microscopic diagnosis at this time was mesenchymal chondrosarcoma. The treatment of this lesion as a staged procedure with initial resection of the mandible and placement of a silicone rubber mandibular prosthesis is discussed. The second stage of the procedure was definitive mandibular reconstruction, with an allogeneic mandible as a crib for autologous particulate cancellous bone from the iliac crest. Although the prognosis of mesenchymal chondrosarcoma is usually grave, this case is unusual because of its long history of multiple procedures performed prior to the definitive treatment of the lesion 14 years after its discovery. Two-year follow-up since the definitive mandibular reconstruction shows adequate range of motion, excellent healing, and no recurrence.

Bone Transplantation↗

Chondrosarcoma of the ethmoid sinus extending to the anterior fossa.

A 27-year-old women with chondrosarcoma of the ethmoid sinus extending to the anterior fossa had initial symptoms of blurred vision on the left and slight proptosis. Neuroradiological examination, however, disclosed that the tumor extended not only to the anterior cranial fossa, but also to the orbit, nasal cavity, and maxillary sinus. It is difficult to predict the biological behavior of chondrosarcoma by means of histological examination. The effectiveness of radiotherapy, chemotherapy, or both is also a matter of controversy. Clinical aspects of chondrosarcoma are briefly discussed.

Adult↗

Molecular analysis of a myxoid chondrosarcoma with rearrangements of chromosomes 10 and 22.

Myxoid chondrosarcoma is a rare tumor of adulthood. An associated nonrandom reciprocal translocation between chromosome 9 and 22 was previously reported in this tumor. We performed cytogenetic and molecular genetic analysis of a myxoid chondrosarcoma derived from the sphenoid bone. Using restriction fragment length polymorphism (RFLP) analysis, we demonstrated rearrangement and a possible allele loss close to the chromosome 22 breakpoint. In addition, structural rearrangement in the chromosome 10q21.1 region and an allele loss in the chromosome 10q21-q23 region were also detected. In tumor DNA an additional hybridization fragment was detected by pAS-1 probe, which recognizes multiple pseudogenes of argininosuccinate synthetase dispersed in various chromosomes. We were unable to detect chromosomal abnormalities with two additional chromosome 9q probes. This study suggests that multiple gene rearrangements occurred in the myxoid chondrosarcoma and the significance of this is discussed.

Adult↗

Translocation (9;22)(q22;q12). A recurrent chromosome abnormality in extraskeletal myxoid chondrosarcoma.

Cytogenetic analysis of a case of extraskeletal myxoid chondrosarcoma revealed a reciprocal translocation between 9q and 22q in almost all metaphases analyzed. Structural rearrangements involving 9q and 22q have been reported previously in three cases of extraskeletal myxoid chondrosarcoma. The breakpoints on chromosomes 9 and 22 in the present case were in regions 9q22-q31 and 22q11-q12.2, respectively. The same breakpoints were present in all three previously reported cases. Thus, this recently identified rearrangement of 9q and 22q may serve as a critical cytogenetic parameter for the diagnosis and classification of extraskeletal myxoid chondrosarcoma, as well as being a primary chromosomal event in the course of development of this rare malignancy.

Chondrosarcoma↗

Cytogenetic analysis of dedifferentiated chondrosarcoma.

Cytogenetic analysis of a dedifferentiated chondrosarcoma with a fibrosarcomatous component revealed the following chromosomal complement: 47,XX,i(1)(q10), add(6)(q13),+7,+8,t(10;12) (p11.2;q11.2),+14,-15,-17, add(19)(q13,4). Chromosome studies of dedifferentiated chondrosarcoma are sparse. Three of the anomalies in the present study are similar to those previously described in dedifferentiated chondrosarcoma.

Chondrosarcoma↗

Mesenchymal chondrosarcoma of the craniocervical junction.

Mesenchymal chondrosarcomas are found with equal low frequency in bone and soft tissue. The CNS is the most commonly reported site of extraosseous origin of mesenchymal chondrosarcomas. This report concerns the CT, MRI, and pathologic findings as well as the operative management of a mesenchymal chondrosarcoma of the craniocervical junction.

Adult↗

Chondrosarcoma of the sphenoid sinus resected by an endoscopic approach.

Chondrosarcoma of the sinonasal tract is a rare neoplasm. Surgical excision is usually sufficient for low-grade lesions, whereas combined treatment is usually recommended for high-grade lesions. The oncologic outcome depends on a complete resection as well as the grade of the tumor. We present the case of a 35-year-old man presenting with an incidental finding of a chondrosarcoma of the posterior septum and rostrum of the sphenoid sinus. The tumor was completely resected using a transnasal endoscopic approach obtaining negative margins. Surgery is the mainstay treatment for low-grade chondrosarcomas. In selected patients, complete resection can be achieved using transnasal endoscopic approaches.

Adult↗