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PubMed2000

Effective adenoviral transfer of IkappaBalpha into human fibroblasts and chondrosarcoma cells reveals that the induction of matrix metalloproteinases and proinflammatory cytokines is nuclear factor-kappaB dependent.

OBJECTIVE: To determine whether, in human fibroblasts and chondrosarcoma cells, the regulation of interleukins (IL)-6, 8, and 11 and matrix metalloproteinases (MMP)-1, 3, and 13, and their tissue inhibitor TIMP-1, depends on the transcription factor nuclear factor-kappaB (NF-kappaB). METHODS: Fibroblasts and chondrosarcoma cells were effectively infected with an adenovirus encoding human IkappaBalpha, and inhibition of NF-kappaB function was observed. The induction of MMP and IL-6, 8, and 11 by various stimuli was assessed by ELISA. RESULTS: The induction of IL-6 and IL-8 clearly depended on NF-kappaB in both fibroblasts and chondrosarcoma cells, irrespective of stimulus, but IkappaBalpha overexpression had little effect on IL-11. MMP-1, -3, and -13 were also inhibited, but TIMP-1 was unaffected. CONCLUSION: NF-kappaB appears to play an important and selective role in MMP induction in human fibroblasts and chondrosarcoma cells. This suggests there are NF-kappaB dependent mechanisms of cartilage destruction in rheumatoid arthritis, and supports the concept that there are similarities in the regulation of inflammatory and destructive pathways in that disease.

Arthritis, Rheumatoid↗
PubMed2000

Proton radiation therapy for chordomas and chondrosarcomas of the skull base.

Most patients with conventional radiotherapy after surgery die with local disease progression. The superior local tumor control and overall survival achieved with fractionated proton RT can be attributed to improved dose localization characteristics of protons, resulting in higher doses delivered. Patients with base of skull neoplasms are increasingly considered for stereotactic radiosurgery. Recently, Muthukumar et al reported for the University of Pittsburgh group on cobalt-60 Gamma Knife (Elekta Instruments, Atlanta, GA) therapy for 15 patients with chordomas or chondrosarcomas of the base of the skull. With tumor volumes ranging between 0.98 and 10.3 mL (mean, 4.6 mL), doses to the tumor margin varying from 12 to 20 Gy (median, 18 Gy) were delivered. Two patients were treated without histologic tumor confirmation. After a median follow-up time of 40 months, 2 patients had died of disease, 2 patients had succumbed to intercurrent disease, and 1 patient surviving at the time of analysis had developed tumor progression. Neither actuarial local control nor actuarial survival data were presented. In the LLUMC series, most tumors exceeded sizes reportedly suitable for radiosurgery or were of a highly irregular configuration. Nevertheless, in 11 patients, tumors less than 15 mL in size remained locally controlled as did tumors sized between 15 and 25 mL in 11 additional patients; these patients were thus potential candidates for stereotactic radiosurgery. At present, too few reports on radiosurgery contain sufficient patient numbers and statistical analyses to permit one to draw conclusions about the feasibility of radiosurgery for chordomas and chondrosarcomas of the base of the skull. A principal difference between proton RT and radiosurgery as currently practiced in most centers concerns target definition. In proton RT, the GTV is treated. In addition, a clinical volume is defined, which is distinctly different from the GTV in size and shape, to include the operative site and other areas of microscopic risk. In many instances, only the GTV is targeted in radiosurgery. Although it is certainly appropriate to explore the role that radiosurgical techniques may have in treating these tumors, results should be evaluated against the excellent outcome that can be achieved with fractionated proton RT, particularly in patients with tumors small enough and of favorable configuration and location to make them candidates for radiosurgery. The present problem of particle therapy is its limited availability. In the United States, only two proton centers can currently provide treatment for base of skull lesions. The HCL is soon to be replaced by a hospital-based facility at the MGH. Several other proton centers in the United States are currently under active consideration. Proton RT is an evolutionary process. Recent developments in proton RT include intensity modulated therapy and improvements in beam delivery systems, namely, the introduction of active beam scanning. These should further increase the degree of dose conformity. In addition, other heavy particles are also being investigated so as to combine the physical advantages of protons with the differential increased biologic effectiveness of particles in tumor as compared to normal tissues. A report from the Heavy Ion Research Facility in Darmstadt, Germany, has not revealed any increased acute toxicities in the first 13 patients with skull base chordomas or chondrosarcomas treated using carbon ions. Several important factors have emerged from recently published results: Patients with low-grade chondrosarcomas and male patients with chordomas have an excellent chance of durable tumor control and long-term survival after proton RT. Severe complications are within the acceptable range considering the high doses delivered and given the major morbidity associated with uncontrollable tumor growth in such patients. Female patients with chordomas experience increased early and late failures

Chondrosarcoma↗
PubMedDate not supplied

Elevation of serum alkaline phosphatase in clear cell chondrosarcoma of bone.

BACKGROUND: Clear cell chondrosarcoma is a rare bone tumor, which is sometimes misdiagnosed as a different bone neoplasm. MATERIALS AND METHODS: The files of 6 patients with clear cell chondrosarcomas were reviewed. Histological slides, radiographic studies, and pre- and post-operative serum alkaline phosphatase (ALP) levels were evaluated. Molecular and histochemical analyses of ALP were documented in one case of clear cell chondrosarcoma. RESULTS: Pre-operative serum ALP levels were elevated in 3 patients, and were normal in another 3 patients. After removal of the tumors, the enzyme levels decreased in all patients and returned to normal in 3 patients, who had pre-operative high ALP levels. Enzyme histochemical and molecular analyses demonstrated that the tumor produced ALP. CONCLUSION: Clear cell chondrosarcoma produces ALP, which can be used as a tumor marker in diagnosis and follow-up.

Adolescent↗
PubMed2001

Mesenchymal chondrosarcoma of soft tissues of the calf.

Mesenchymal chondrosarcomas are distinct from conventional and dedifferentiated chondrosarcomas and are quite rare, making up less than 2% of all chondrosarcomas. We describe a mesenchymal chondrosarcoma of the soft tissues of the calf and review the differential diagnosis of this poorly understood entity.

Chondrosarcoma, Mesenchymal↗
PubMed2001

Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation.

Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma, and chondrosarcoma explants were cultured either alone or with the addition of ciprofloxacin at 1, 10, or 20 mg/L of medium. Samples were collected up to twenty-one days after treatment and were processed for electron microscopy and conventional light microscopy. The specimens were characterized morphologically with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat droplets, rough endoplasmic reticulum, and prominent Golgi apparatus; and a proteoglycan layer surrounding the cells. With prolonged ciprofloxacin treatment and with increased doses, there was an increase in dilated rough endoplasmic reticulum, the appearance of phagosomes, and disintegrated bundles of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition. Ultrastructural analysis demonstrated clumped glycogen, dilation of endoplasmic reticulum, numerous abnormal lysosomes containing degeneration products, and a decreased proteoglycan deposit surrounding the tumor cells. Treated chondrosarcoma cells and tissue specimens did not proliferate, and apoptosis was induced. In contrast, the in vitro growth of other noncartilaginous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin. Our results indicate that ciprofloxacin is toxic to chondrocytes. In vitro and in vivo treated chondrosarcomas are the most affected.

Anti-Infective Agents↗
PubMedDate not supplied

[Radiation therapy for chordomas and chondrosarcomas of the base of the skull and cervical spine].

PURPOSE: Prospective analysis of local tumour control, survival and treatment complications in 67 consecutive patients treated with fractionated photon and proton radiation for a chordoma or a chondrosarcoma of the base of the skull and of the cervical spine. PATIENTS AND METHODS: Between December 1995 and January 2000, 67 patients with a median age of 52.3 years (14-85), were treated using 201 MeV proton beam of the centre de protonthérapie d'Orsay (CPO), 49 for a chordoma and 18 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented 2/3 of the total dose and protons 1/3. The median total dose delivered within gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (60-70). RESULTS: With a mean follow-up of 32 months (4-71), the 3-year local control rates were for chordomas and chondrosarcomas of 70.8% and 85.2%, respectively and 4-year overall survival rates of 87.7% and 75%, respectively. Fourteen tumours (21.5%) failed locally (eight within the gross tumor volume, four into the CTV and 2 in an unknown site). Seven patients died of tumour and one of intercurrent disease. In univariate analysis, age inférieur ou égal à 52.3 years (p = 0.002), maximum tumoral diameter < 44.7 mm (p = 0.02) and GTV < 28.4 mL (0.02), at time of radiotherapy, influenced positively the local control. According to multivariate analysis, only age was an independent prognostic factor of local control. Only five (7.7%) patients presented grade 3 or 4 complications. CONCLUSION: In base of skull chordomas and chondrosarcomas, the combined photon and proton therapy offers excellent chances of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Adolescent↗
PubMed2002

Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation.

Human chondrosarcomas do not respond to current chemotherapies or radiation therapy, and their size and histological appearance do not reliably predict the risk of local recurrence and metastases, making selection of surgical treatment difficult. Identifying mechanisms responsible for the proliferation and invasive behavior of these tumors would be of immense clinical value. We hypothesized that telomerase expression is one of these mechanisms. We detected telomerase expression in 7 of 16 chondrosarcomas, but cells cultured from telomerase-negative chondrosarcomas acquired strong telomerase activity and lost tumor suppressor activity after their establishment in culture. These changes were associated with accelerated indefinite cell proliferation, morphological transition, and increased invasive activity, indicating that telomerase activation and loss of cell cycle control leads to the emergence of aggressive cells from chondrosarcoma cell populations. These observations may lead to better understanding of the factors responsible for malignant transformation, local recurrence, and metastases of cartilage neoplasms.

Adult↗
PubMed1976

Effect of aromatic retinoids on rat chondrosarcoma glycosaminoglycan biosynthesis.

Synthetic aromatic analogs of retinoic acid were administered i.p. and p.o. to Fischer F344 rats bearing a transplantable chondrosarcoma. 35CO4 incorporation into glycosaminoglycans were compared for neoplastic and normal cartilage explants after removal from animals given various analogs. There was a direct relationship between [35S]glycosaminoglycan synthesis by chondrosarcoma chondrocytes and inhibition of tumor growth. The degree of inhibition of [35S]glycosaminoglycan synthesis in the neoplastic cartilage was dependent on the dose of the retinoid administered. At 20-mg/kg/day doses of retinoid for 4 weeks, 35SO4 incorporated into glycosaminoglycan by treated tumor explants was reduced as much as 95%. There was no reduction of [35S] glycosaminoglycan produced in normal costal cartilage of the same animals. Retinoid treatment of 20-mg/kg/day doses for 4 weeks resulted in a 75% reduction in glycosaminoglycan per mg of chondrosarcoma; there was no reduction in costal cartilage glycosaminoglycan. Retinoid (10- to 20-mg/kg/day doses) elevated collagen levels per mg of chondrosarcoma but had no effect on costal cartilage collagen. Combined in vitro and in vivo studies showed that retinoid administration modified neoplastic chondrocyte function but had no measurable effect on normal chondrocyte function.

Animals↗
PubMedDate not supplied

[Chondrosarcoma of the hyoid bone. Follow-up and cytological study of a case].

The follow-up study of one chondrosarcoma of the hyoid bone is reported; the tumor was a well differentiated grade II chondrosarcoma that relapsed after 10 months and metastasized after 6 years. Fine needle aspiration cytologic method was utilized for the diagnosis of the lung metastases. Cytologic criteria in the differential diagnosis of the chondrosarcoma are discussed. Follow-up of the extra-skeleton chondrosarcoma has to be continued for a long time independently from the grade of differentiation.

Adult↗
PubMed2004

Chondrosarcoma of the epiglottis: report of a case treated with CO2 laser epiglottectomy.

Chondrosarcoma of the larynx is a rare slow-growing malignant tumour with approximately 240 cases reported in the literature: the cricoid cartilage is the most commonly affected site (72-75%), in rare case was described of epiglottis (1-2%). We report a case of a chondrosarcoma of the epiglottis treated with CO2 laser epiglottectomy. The patient was referred with dysphonia, dysphagia and halitosis that started four months before. Indirect laryngoscopy revealed a large smooth mass with a roundish appearance and a pearly-grey colour, as big as a nut, apparently arising from the laryngeal surface of the epiglottis, causing obliteration of the piriform fossa. The definitive histopathological report showed microscopically, the tumour was low-grade (grade I) chondrosarcoma. A literature review regarding chondrosarcomas of the epiglottis is presented. The diagnosis, histology and treatment of these tumours are discussed. In particular we examine the controversy of conservative surgery vs. total laryngectomy. A conservative surgical approach is typically appropriate in light of this tumour's low-aggressive nature.

Adult↗
PubMed2004

Dedifferentiated chondrosarcoma: the role of chemotherapy with updated outcomes.

BACKGROUND: There are very few published data on the survival of patients with dedifferentiated chondrosarcoma, or, more specifically, on the efficacy and role of chemotherapy, especially in the era of modern diagnostic and treatment modalities. The current study examines the influence of advancements in imaging and chemotherapy on outcome and serves as an extension to a previous study published in 1986. METHODS: Forty-two patients with dedifferentiated chondrosarcoma who had presented to our institution between 1986 and 2000 were identified, and a retrospective chart review was performed. The study group included twenty-four men and eighteen women with an average age of sixty-six years. The diagnosis of dedifferentiated chondrosarcoma was verified histologically, and data on treatment, adjuvant therapy, and survival were obtained from the medical records of all patients. All patients had been followed for a minimum of twenty-four months. RESULTS: The tumors were classified, according to the system of the Musculoskeletal Tumor Society, as grade IIA (five), grade IIB (twenty-six), and grade III (eleven). Three patients underwent biopsy only, eighteen had a limb-sacrificing procedure, and twenty-one had a limb-sparing procedure. In the group of patients who underwent resection, the surgical margins were classified as intralesional in three, marginal in two, wide in nineteen, and radical in fifteen. Twenty-seven patients received neoadjuvant therapy; of these, twenty-three received chemotherapy only, two received radiotherapy only, and two received combined therapy. The median survival time was 7.5 months, and the five-year rate of disease-free survival was 7.1%. With the numbers available, there was no significant difference in the rate of disease-free survival with respect to the use of chemotherapy (p = 0.54), the location of surgical margins (p = 0.14), the histological subtype (p = 0.87), the tumor stage at the time of diagnosis (p = 0.43), the tumor size (p = 0.79), or the performance of limb-sparing as opposed to limb-sacrificing procedures (p = 0.42). CONCLUSIONS: Despite advances in diagnostic modalities and adjuvant therapies, dedifferentiated chondrosarcoma continues to carry a poor prognosis. While local control is achieved in the majority of cases, distant disease remains the greatest clinical challenge, developing in 90% of patients. Efforts are needed to continue to encourage earlier diagnosis and to develop effective adjuvant therapies for the control of distant disease. The routine use of current adjuvant chemotherapy and its inherent risks in this population should be reconsidered.

Adult↗
PubMed2005

Evaluation of p16 and Id1 status and endogenous reference genes in human chondrosarcoma by real-time PCR.

Both the tumour suppressor, p16, and the helix-loop-helix transcription factor, Id1, have been assigned roles in tumour growth in general and appear to be involved in chondrosarcoma. Id1 has further been found to repress the expression of p16. Therefore, the mRNA expression of these two genes was studied by real-time PCR in a search for prognostic markers in human chondrosarcoma. To get reliable quantitative data, however, the choice of endogenous reference gene for use in the assay is important. Therefore, eleven different endogenous reference genes were evaluated in chondrosarcoma cells and articular chondrocytes. 18S rRNA appeared to be the best choice to use as endogenous reference gene, since it was suitable for both kinds of cells. Several of the other reference genes tested showed variation between individuals or between normal chondrocytes and chondrosarcoma cells. This demonstrates the importance of using a correct endogenous reference gene to get reliable results from quantitative measurements. Both p16 and Id1 showed varied gene expression patterns among the samples and none of these genes could be significantly correlated to prognosis.

Bone Neoplasms↗
PubMed2006

[Clinicopathology analysis of mesenchymal chondrosarcoma in soft tissue].

OBJECTIVE: To investigate the clinicopathological and immunohistochemical characteristics of soft tissue mesenchymal chondrosarcoma. METHODS: The clinical material, pathological and immunohistochemical characteristics (reaction to LCA, CD3, CD20, CD45RO, CD79a, CD99, NSE, S-100, Syn, CgA, CK7, CK19, EMA, Coll-II, Sarcomeric-Actin, Desmin, Ki-67,P53) of 2 cases of soft tissue mesenchymal chondrosarcoma in Jishuitan Hospital between 1995 and 2005 were reviewed and followed up. RESULTS: The two patients were both females. The tumors were located in the low extremity muscles. The main roentgenographical appearance was stippled calcification in tumor and calcification at the edge of the tumor. The histological characteristic features showed undifferentiated small cells together with islands of chondrosarcoma; there was hemangiopericytoma-like arrangement of small cells. The tumor cells were positive for CD99, NSE, Syn, CgA; The cells in chondroid matrix were positive for S-100; chondroid matrix was positive for Coll-II. All tumor cells were negative for LCA, CD3, CD20, CD45RO, CD79a,Sarcomeric-actin, Desmin and CK7, CK19, and EMA. The patient with followed radiotherapy was alive. and the other without radiotherapy dead. CONCLUSION: Mesenchymal chondrosarcoma of soft tissue has the characteristics of primary mesenchyme which differentiates to congenital cartilage. The pathological characteristics of bimophic pattern and roentgenographical appearance of tumor are useful for diagnosis. The prognosis is poor.

Adolescent↗
PubMed2006

[Retroperitoneal extraskeletal myxoid chondrosarcoma].

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor included by WHO in the group of tumors of uncertain differentiation because well formed cartilage is rarely seen in its setting; moreover some of the immunophenotype features of the tumor are still controversial. The reciprocal translocation t(9;22)(q22;q12) has recently been identified in many cases, and this chromosomal aberration is currently considered high specific of this tumor. CASE REPORT: We report the case of a 75-year-old female submitted to radical nephrectomy for a voluminous kidney tumor with radiological evidence of extrarenal extension. RESULTS: Grossly the lesion was set in the perirenal fat tissue. Histological examination revealed a malignant mesenchimal tumor with myxoid f eatures and areas of chondroid differentiation consistent with the diagnosis of extraskeletal myxoid chondrosarcoma. According with the diagnosis the tumor showed focal positivity to NSE by immunohistochemistry. DISCUSSION: Differentiated cartilage is seen in extraskeletal myxoid chondrosarcoma in about 30% of the cases. Our case is then interesting not only for the rare site of tumor location but also for the extension of chondroid differentiation areas found on histologic examination in the tumor setting. Moreover immunohistochemistry showed focal positivity of the neoplastic cells for NSE, according with recent studies demonstrating expression of some neural/neuroendocrine markers in extrascheletal myxoid chondrosarcoma.

Aged↗
PubMed1990

Mesenchymal chondrosarcoma. An immunohistochemical study.

Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle-specific actin, cytokeratin, and epithelial membrane antigen, and the avidin-biotin-peroxidase complex (ABC) method. The small cells of mesenchymal chondrosarcoma failed to express S100 protein, whereas all components of the tumors (small cells, lacunar chondroblasts, and chondroid matrix) stained for Leu-7 antigen in six cases. Neuron-specific enolase was identified in the small cells of four cases and in the lacunar cells of seven. None contained desmin, actin, cytokeratin, epithelial membrane antigen, or synaptophysin. The immunophenotype of mesenchymal chondrosarcoma resembled that of embryonic cartilage and thus did not contradict the premise that this tumor was the neoplastic counterpart of fetal chondroid tissues. However, immunohistologic studies are not overly helpful in the differential diagnosis between mesenchymal chondrosarcoma and other small round cell lesions.

Adolescent↗
PubMed1989

[Chondrosarcoma of the ribs: report of two cases].

Chondrosarcoma of rib origin is relatively rare in Japan. Two patients with chondrosarcoma of rib origin were treated surgically. Case 1: A 79-year-old male, 4 years ago, he noticed a tumor in the left anteroinferior part of the chest. The histological examination of the specimen obtained by incisional biopsy showed osteochondroma in another hospital and he had been under observation. Since the tumor has recently increased in size, he was referred to our department. Radical resection of the chest wall was performed. As expected, the tumor was found to be a secondary chondrosarcoma by postoperative histological examination. Case 2: A 49-year-old female. In the follow up studies after radical nephrectomy, Tc-MDP scintigram revealed an accumulation in the left second rib. Under the diagnosis of rib metastasis, radical resection was performed. The histological examination showed chondrosarcoma of rib origin postoperatively. This lesion was a primary central type, and is considered to have been resected in the earliest stage of all cases we have found in the Japanese literature.

Aged↗
PubMed1989

[Chondrosarcoma of the rib--a case report].

Chondrosarcoma is second in frequency only to osteogenic sarcoma as a malignant tumor of bone, and constitutes 17 to 22% of all bone tumors. However, chondrosarcoma is the most common malignant tumor of the sternum or rib. The natural history of chest wall chondrosarcoma is one of slow growth and local recurrence. Wide excision is the main treatment, but usually plastic surgery is needed for chest wall reconstruction. A 29-year-old male patient visited to local clinic due to URI symptoms (eg: cough, rhinorrhea). Routine chest X-ray examination showed a huge tumor within L't chest cavity and chondrosarcoma was proved via tissue biopsy. P't underwent surgery for total removal of the tumor and corresponding rib (3rd rib) and the chest wall defect was repaired with bovine pericardium. So far, after follow-up and treatment for 4 months, there is no evidence of recurrence.

Adult↗
PubMed1988

Skeletal myxoid chondrosarcoma with microtubular aggregates within rough endoplasmic reticulum.

A skeletal myxoid chondrosarcoma of the femur was examined by light and electron microscopy. Light microscopic features were characteristic for myxoid chondrosarcoma or "chordoid sarcoma." Electron microscopy disclosed crystalline arrays of microtubules within dilated rough endoplasmic reticulum, a feature previously described in extraskeletal myxoid chondrosarcomas. Tumors with the histologic characteristics of extraskeletal myxoid chondrosarcoma ("chordoid sarcoma") occurring in bone have been rarely reported. We describe herein such a tumor and document the existence of distinct microtubules within the endoplasmic reticulum.

Bone Neoplasms↗