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At least 757 records · Page 42Linked to original sources
PubMed1996

Gene fusions encoding chimaeric transcription factors in solid tumours.

Analysis of chromosomal alterations in human malignancies has revealed recurring genetic changes that are often closely associated with specific subtypes of tumours. Among solid tumours, cytogenetic analysis of a group of primitive sarcomas occurring principally in children and young adults has identified specific non-random chromosomal translocations associated with these malignancies. A number of the translocation breakpoints have now been cloned, revealing the in frame fusion of genes located at each partner breakpoint. The common theme is the expression by these hybrid genes of chimaeric proteins containing functional domains from each fusion partner. These domains confer transcriptional activation or repression, DNA binding specificity, or other novel protein-protein interactions. The net result appears to be the expression of chimaeric oncoproteins that function in transformation by dysregulating gene transcription.

Cloning, Molecular↗
PubMed1994

Positron emission tomography with fluorine-18-fluorodeoxyglucose for the evaluation of therapeutic isolated regional limb perfusion in a patient with soft-tissue sarcoma.

METHODS: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. RESULTS: PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. CONCLUSION: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

Chemotherapy, Cancer, Regional Perfusion↗
PubMedDate not supplied

Fine needle aspiration cytology vs. needle core biopsy of soft tissue tumors. A comparison.

Fine needle aspiration (FNA) cytology is an effective modality in the diagnosis of soft tissue lesions. Previous studies compared FNA with surgical biopsies and reported high sensitivity and specificity rates. No study has evaluated the diagnostic yield of FNA to that of needle core biopsies (NCBs). One hundred seventeen FNAs were performed by our clinical staff for soft tissue lesions (1980-1992). The FNAs were divided into three categories: diagnostic 53 (37 sarcoma, 16 benign); unsatisfactory, 44; normal/inflammatory cells present, 20. Of these, 59 had concomitant NCBs: 37 on patients with sarcoma on FNA, 22 on unsatisfactory FNA and none on those with normal/inflammatory cells (followed clinically). There was 100% correlation between FNA and NCB when sarcoma was diagnosed. In 7 of these cases, the NCB further specified the type of sarcoma. No NCBs were employed to confirm the diagnosis of benign tumor on FNA; excisional biopsies showed a total correlation. The 22 NCBs for unsatisfactory FNA yielded 15 sarcomas, 2 fibromatosis and 5 benign lesions. Seventeen patients with unsatisfactory FNA had surgical biopsies (3 sarcoma, 14 benign), and 5 were lost to follow-up. In our experience, diagnostic FNA gave a yield identical to that of NCB, and the latter did not contribute to patient management. Core biopsies may have the advantage of subtyping selected sarcomas diagnosed by FNA. Unsatisfactory FNA should be evaluated further by a repeat aspirate or NCB. Performance of FNA by cytopathologists can reduce the number of unsatisfactory specimens and allow repeat aspiration. In our study most of the unsatisfactory FNAs were from retroperitoneal and pelvic lesions, were performed under radiographic guidance and could have been minimized by immediate cytologic assessment. Many of these lesions, however, may be as readily accessible via NCB as they are via FNA. Utilization of each of these modalities and of their full benefits ultimately depends on the proper clinical setting and the experience of the clinician and pathologist.

Adolescent↗
PubMed2004

Soft tissue sarcoma of the upper extremity.

Soft tissue sarcomas of the upper extremities are rare and hand surgeons typically encounter only one or two undiagnosed soft tissue sarcomas during their careers. It is incumbent on the physician to review repeatedly the characteristics of these tumors and remain suspicious, because these lesions typically are misdiagnosed and treatment is delayed. The most common soft tissue sarcomas of the upper extremity are the epithelioid sarcoma, synovial cell sarcoma, and malignant fibrous histiocytoma. Limb salvage surgery is the treatment of choice for soft tissue sarcomas to preserve upper extremity function. Following wide tumor resection, adjuvant therapies such as chemotherapy, external beam radiation therapy, and brachytherapy may lessen local recurrence rates, but their effect on overall survival remains unclear.

Arm↗
PubMed1994

Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma.

The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma, malignant melanoma, and other malignant cells and is, therefore, a potential target for therapeutic monoclonal antibodies. Intravenously administered R24, a murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously every other day for six doses to 10 patients with pulmonary metastases from a primary soft tissue sarcoma of the extremity for whom thoracotomy was planned. Resected tissue was available from 7 patients. All metastases expressed GD3; however, expression was heterogeneous within tumors, and in no tumor were more than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of mononuclear cells with T-cell markers was identified around or within pulmonary metastases in 6 patients. Tolerable acute allergic reactions occurred in all patients, but 3 patients had severe chest tightness and bronchospasm that limited the planned therapy. The setting of thoracotomy for metastatic disease provides an ideal system for studies on the pharmacology and biological effects of monoclonal antibodies that target soft tissue sarcoma antigens.

Adult↗
PubMed1985

Prognostic features of pediatric soft-tissue sarcomas.

Eight hundred ninety-two patients under 20 years of age with soft-tissue sarcomas histologically diagnosed between 1955 and 1971 (before the era of combined modality therapy) were reviewed to delineate important prognostic variables. Differing histologic findings, extent of disease at initial presentation, and site of the primary tumor correlated with prognosis; age, sex, and race did not affect survival significantly. Patients with fibrosarcomas, liposarcomas, and leiomyosarcomas had improved survival rates when compared with adults with the same histologic findings; patients with localized tumors and extremity primary sites had the best prognosis. Patients with rhabdomyosarcomas, disseminated disease, or retroperitoneal primary sites had the worst prognosis. These data suggest that some childhood sarcomas are not as aggressive as adult sarcomas or childhood rhabdomyosarcomas. Therefore they may not require the adjuvant therapy shown to be beneficial in childhood rhabdomyosarcomas.

Adolescent↗
PubMed1987

Doxorubicin and methotrexate on a weekly schedule in patients with sarcomas.

Fifty-five sarcoma patients with advanced measurable disease were treated with a doxorubicin and methotrexate combination in which both drugs were given on a weekly schedule. Patients received doxorubicin and methotrexate at three prospectively evaluated treatment levels with doxorubicin dosage ranging from 0.5 to 0.725 mg/kg/week and methotrexate dosage ranging from 0.25 to 0.375 mg/kg/week. Objective responses were seen in 11 of 39 (28%) patients receiving the two higher doxorubicin-methotrexate treatment levels where doxorubicin dose was greater than 0.5 mg/kg/week compared to only 2 of 16 (12%) patients receiving lower doxorubicin levels (p less than 0.05), suggestive of a dose-response relationship. Toxicity of this regimen was manageable but stomatitis was appreciable, seen in 30% of patients. These results support the activity of weekly doxorubicin in sarcoma therapy. However, no apparent improvement was associated with addition of conventional dose methotrexate to weekly doxorubicin treatment.

Adolescent↗
PubMedDate not supplied

Alternating administration of adriamycin (NSC-123127) and vincristine (NSC-67574)-actinomycin D (NSC-3053) in advanced sarcomas.

Fifteen patients with surgically incurable, advanced, and metastatic sarcomas were treated with courses of adriamycin and vincristine-actinomycin D alternating within a 7-week cycle. Three patients had objective partial responses for more than 3 months (liposarcoma, 4 months; fibrous histiocytoma, 15+ months; desmoid tumor, 19+ months) while two other patients (liposarcoma, leiomyosarcoma) had lesser responses. No beneficial effect could be attributed to therapy in two patients with leiomyosarcoma, two patients each with synovial cell sarcoma, fibrosarcoma, and chondrosarcoma, and one patient each with rhabdomyosarcoma and mesenchymoma. No additive effect of alternating full doses of these agents could be demonstrated over the published data on response to adriamycin or actinomycin D alone.

Adult↗
PubMed1994

On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors.

The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201 (81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas.

Adolescent↗
PubMed2001

Ectopic sequences from truncated HMGIC in liposarcomas are derived from various amplified chromosomal regions.

The HMGIC gene codes for an architectural transcription factor frequently rearranged by translocation in lipomas and other benign mesenchymal tumors. In sarcomas, malignant tumors of mesenchymal origin, the gene is also found to be rearranged, but in addition amplified and overexpressed. Here we report the sequence, chromosomal localization, and expression patterns of 11 novel ectopic sequences fused to exons 2 and 3 of HMGIC in seven different sarcoma samples. In addition, we identified a number of variant transcripts observed previously in benign tumors. Consistent with the suggested role of HMGIC in adipocytic differentiation, most of the novel ectopic sequences were observed in well-differentiated liposarcomas. These tumors are known to have complex marker chromosomes containing amplified segments from several chromosomes. Five novel sequences were derived from 12q14-q15, where HMGIC resides, two from 1q24, a region frequently amplified in these types of tumors, two from 11q14, and one from chromosome 2. All except one of the aberrant transcripts encoded truncated proteins with intact DNA-binding domains (AT hooks) but lacking the C-terminal acidic region, a target for constitutive phosphorylation by protein kinase CK2. Some of the ectopic sequences were transcribed in other tissues, and most of the ectopic sequences also showed recurrent amplification in liposarcomas.

Amino Acid Sequence↗
PubMed1988

Energy and protein metabolism in sarcoma patients.

We have performed a series of isotopic infusions both in normal volunteers (N = 16) and in sarcoma patients (N = 7). Using the primed-constant infusion of stable or radioisotopes we have determined the rates of glucose turnover, glucose oxidation, glucose recycling, and net protein catabolism (NPC). In addition, we have measured VO2 and VCO2. The values for VCO2 and VO2 were higher in the patients than in the volunteers (mean VO2 values in volunteers and patients: 107 +/- 13 and 158 +/- 13 mumol/kg/min, respectively). The basal rate of glucose appearance in the sarcoma patients was twice the value seen in the volunteers (28.3 +/- 3.5 vs. 13.9 +/- 0.3 mumol/kg/min). Glucose infusion in the volunteers resulted in virtually total suppression of endogenous glucose production, while in the patients glucose infusion induced only a 30% suppression of endogenous glucose production (p less than 0.01). The rate of glucose clearance in the patients was approximately twice the value seen in the volunteers [5.4 +/- 1.0 vs. 2.7 +/- 0.1 mL/kg/min (p less than 0.01)]. The per cent of glucose uptake oxidized in the patients was significantly less than in the volunteers [22% vs. 36% (p less than 0.05)], and the per cent of glucose uptake that was recycled was significantly higher in the patients [55% vs. 10% (p less than 0.01)]. In addition, the basal rate of net protein loss was increased twofold in the patients [3.2 +/- 0.5 vs. 1.4 +/- 0.4 g (protein)/kg/d (p less than 0.01)], and in contrast to the situation in the volunteers there was no suppression in the rate of net protein loss when the patients were infused with glucose. The basal insulin concentration and the insulin response to glucose infusion in the patients were similar to that of the volunteers, but the plasma cortisol level was similar in volunteers and in the patients (p less than 0.05). We conclude from these studies the following: (1) Sarcoma patients have significantly elevated rates of glucose production and glucose clearance, but they have an impaired capacity to directly oxidize either endogenous or infused glucose, coupled with an increased rate of glucose recycling. (2) Sarcoma patients have an elevated metabolic rate and are catabolic. In addition, in contrast with normal volunteers, glucose infusion does not result in a suppression of protein loss.

Adolescent↗