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At least 217 records · Page 12Linked to original sources

Diagnostic implication of Kaposi's sarcoma-associated herpesvirus with special reference to the distinction between spindle cell hemangioendothelioma and Kaposi's sarcoma.

OBJECTIVE: To assess the diagnostic utility of recently identified Kaposi's sarcoma-associated herpesvirus (KSHV, also referred to as human herpesvirus 8) in distinction between Kaposi's sarcoma (KS) and other types of vascular lesion, especially spindle cell hemangioendothelioma (SCH). DESIGN: We conducted a polymerase chain reaction analysis of KSHV in 93 cases of benign and malignant vascular lesions, using DNA extracted from archival specimens. RESULTS: All five cases of Kaposi's sarcoma examined, including cases related and cases unrelated to acquired immunodeficiency syndrome, were positive for KSHV. Vascular lesions other than KS, including 6 SCH, 1 kaposiform hemangioendothelioma, 8 angiosarcomas, 46 hemangiomas (15 cavernous, 12 capillary, 7 venous, 6 intramuscular, 2 sinusoidal, 2 epithelioid, 1 microvenular, 1 glomeruloid), and 7 glomus tumors were consistently negative, except for 1 of the 20 pyogenic granulomas examined. CONCLUSIONS: Our data support the previous finding that KSHV is confined almost exclusively to KS, irrespective of human immunodeficiency virus infection, and suggest that KSHV is a reliable diagnostic marker to differentiate KS from other vascular lesions, including those with KS-like morphology, such as SCH.

Base Sequence↗

Proliferative activity (MIB-1 index) is an independent prognostic parameter in patients with high-grade soft tissue sarcomas of subtypes other than malignant fibrous histiocytomas: a retrospective immunohistological study including 216 soft tissue sarcomas.

AIMS: To evaluate the prognostic value of tumour proliferative activity, p53 accumulation and bcl-2 expression in a retrospective series of 216 patients with soft tissue sarcomas (STS). METHODS AND RESULTS: The immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was assessed by use of the monoclonal antibody MIB-1 and evaluated in multiple, random systematic sampled fields of vision. The percentage of proliferating cells (the MIB-1 index) ranged between 1% and 85% (median 12%). A significant increase in mean MIB-1 index was seen with increasing histological malignancy grade. Variation in the incidence of p53 accumulation and bcl-2 positivity among different histological subtypes was observed. p53 accumulation was frequent in synovial sarcomas and leiomyo- and rhabdomyosarcomas, whereas bcl-2 preferentially was expressed in synovial sarcomas. Univariate analysis identified patient age, tumour size, histological grade of malignancy, MIB-1 index and p53 accumulation as significant prognostic parameters. Multivariate Cox analysis, including tests for interaction terms between histological subtypes and MIB-1 index, showed independent prognostic effect of MIB-1 index and tumour size in patients with high-grade tumours of other subtypes than malignant fibrous histiocytoma (MFH). CONCLUSIONS: Histopathological malignancy grading is the most important single prognostic factor for overall survival in STS, but estimation of MIB-1 index is useful for identifying the least favourable subgroup of high grade STS of other subtypes than MFH, for whom adjuvant therapy may be indicated.

Adolescent↗

Homologies between a brain-specific identifier (ID) sequence and regions of Harvey murine sarcoma virus and Rous sarcoma virus genomes. Putative role of identifier sequences in the tissue specificity of malignant transformation by RNA tumor viruses.

As a step toward understanding of the tissue specificity of cellular transformation by RNA tumor viruses were looked for the presence of a putative brain specific regulatory (identifier) sequence (C82B) in the genome of various oncornaviruses. The genomes of Harvey murine sarcoma virus and Rous sarcoma virus contain sequences flanking the viral oncogenes with greater than 80% and greater than 60% homology to C82B, respectively. We suggest that identifier sequences acquired by oncoviruses may determine the potential target cells of malignant transformation after virus penetration.

Animals↗

Establishment of a novel granulocytic sarcoma cell line which can adhere to dermal fibroblasts from a patient with granulocytic sarcoma in dermal tissues and myelofibrosis.

A novel human myeloid cell line, designated HSM-1, has been established from the pleural effusion of a patient with granulocytic sarcoma (GS) who had been followed as having primary myelofibrosis for 10 years. When he was diagnosed as having granulocytic sarcoma in dermal tissues, no evidence of malignant transformation into leukaemia was found in both the peripheral blood and bone marrow. The established cell line was positive for myeloperoxidase, Sudan black B, Naphthol AS-D chloroacetate esterase. Surface marker analysis revealed that HSM-1 expressed CD4, CD13, CD11a, CD11b, Leu8, CD49b, CD49d, CD49e, CD29 and HLA-DR. To clarify why the unusual myeloid tumours developed in non-haematopoietic tissues, we examined the capability of HSM-1 to bind to skin fibroblast layers. The HSM-1 cells were found to bind to both bone marrow stromal layers and skin fibroblast layers. Among the other myeloid cell lines tested, none was found to bind to skin fibroblast layers. These findings suggest that the GS cell line may be derived from a haematopoietic precursor cell which can bind to skin fibroblasts and is localized in non-haematopoietic tissues resulting in the formation of extramedullary myeloid metaplasia. HSM-1 is a useful tool for analysing the characteristics of granulocytic sarcoma and homing receptors for haematopoietic stem cells.

Antigens, Surface↗

Phase II study of cisplatin in advanced osteogenic sarcoma. European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

The activity of cisplatin (CDDP) against advanced osteogenic sarcoma was evaluated in 37 of 50 patients registered by the members of the European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group between 1979 and 1982. All patients had measurable lung metastases. Thirty-one patients (84%) had received previous chemotherapy consisting mainly of high-dose methotrexate, doxorubicin, and vincristine. CDDP (100 mg/m2) was given as a 24-hour continuous infusion every 3 weeks for a minimum of two cycles, with appropriate fluids and diuretics. In the absence of impairment of the renal function and/or myelosuppression, the dose could be escalated by 20%. The overall response rate was 19% (seven responses among 37 patients), with one complete remission for 51 weeks and six partial remissions from 12 to 26 weeks. The median number of courses of CDDP administered was three, ranging from two to 11. Of 143 courses administered, only 18 (12%) had to be modified because of toxicity. In 16% of the patients some transient impairment of the renal function was observed. CDDP adds to the limited number of chemotherapeutic agents with useful properties in osteogenic sarcoma, and CDDP-containing combination chemotherapy regimens should be actively investigated.

Adolescent↗

[Primary reticulum-cell sarcoma (Parker-Jackson sarcoma) of the rib. Report of a case with a five-year survival after surgery, radiation therapy and chemotherapy (author's transl)].

A case of primary reticulum-cell sarcoma of the rib is reported. This rare tumor arose in an unusual site and was revealed by an exceptional clinical picture. Extensive hemothorax was the initial manifestation. Follow-up exceeds five years. Prognosis is not as poor for reticulum-cell sarcoma as for Ewing sarcoma. After radical surgery, radiation therapy and chemotherapy, the five-year total remission rate approximates 50%.

Adult↗

In vivo radiolocalization of antiosteogenic sarcoma monoclonal antibodies in osteogenic sarcoma xenografts.

Monoclonal antibodies Ost6 and Ost7 (mouse Immunoglobulin G1) to human osteogenic sarcoma were isolated from ascitic fluid and labeled with radioiodine. After injection into athymic nu/nu mice with s.c. xenografts of human osteogenic sarcoma, the uptake of radioactivity in tumors, visceral organs, and blood was determined. Five days after injection, Ost6 and Ost7 showed preferential accumulation in tumors (tumor:blood ratio, 4.3). Furthermore, with testicular and bladder tumors, both unreactive with Ost7, there was no localization of radiolabeled Ost7 in xenograft growths. When Ost7 was labeled with 131I, its accumulation into human osteogenic sarcoma could be clearly visualized by whole-body gamma-scintigraphy without computer-assisted data processing.

Animals↗

Time dependence of prognostic factors for patients with soft tissue sarcoma: a Scandinavian Sarcoma Group Study of 338 malignant fibrous histiocytomas.

BACKGROUND: Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown. METHODS: The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint. RESULTS: On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years. CONCLUSIONS: Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations.

Adult↗

Epithelioid sarcoma in children and adolescents: a report from the Italian Soft Tissue Sarcoma Committee.

BACKGROUND: Epithelioid sarcoma (ES) is an uncommon malignant soft tissue tumor. To the authors' knowledge, little information is available to date concerning its clinical features and management in children and adolescents, particularly with regard to the recently described proximal-type variant. The current study concerns 30 patients age<18 years who were enrolled in the Italian Soft Tissue Sarcoma Committee protocols. METHODS: Histopathologic specimens, clinical data, and treatment modalities were reviewed for the current analysis. Nineteen patients had classic ES and 11 had proximal-type ES. Surgery was the mainstay of treatment; radiotherapy was given to six patients considered to be at risk of local disease recurrence due to incomplete resection, and chemotherapy was administered to eight patients. RESULTS: With a median follow-up of 66 months, the 5-year event-free survival (EFS) and overall survival (OS) rates were 61.7% and 92.4%, respectively, but the OS rate dropped to 86.9% and 72.4%, respectively, at 10 years and 15 years. Local disease recurrence was the major cause of treatment failure. The most significant finding influencing both EFS and OS was tumor site, with a tumor location in the extremities predicting a favorable outcome. Initially unfavorable clinical findings and a worse outcome were associated with the proximal-type variant of ES. A response to chemotherapy was noted in three of the seven patients with measurable disease. CONCLUSIONS: The current study confirms some typical features of ES (i.e., the peculiar superficial distal location [i.e., the hand, fingers], indolent growth, and a tendency to recur locally). The current study data do not clearly confirm the strong tendency for the lymph node involvement described in adult ES patients. Further studies are needed to better define the clinical behavior and biology of the proximal-type variant of ES.

Adolescent↗

Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue to the transforming protein of simian sarcoma virus.

Several human normal and neoplastic cell lines were screened for production of PDGF receptor competing activity. Conditioned medium from two sarcomas and one glioma blocked 125I-PDGF binding to human foreskin fibroblasts in a dose-dependent manner. In each case this effect was abolished when the conditioned medium was pretreated with PDGF-antiserum, indicating that the receptor competing activity was immunologically related to PDGF. Direct evidence for de novo synthesis of a PDGF-like component in the cultures was afforded by 35S-cysteine labeling of the three cell lines, followed by immunoprecipitation with PDGF antiserum. This resulted in the specific precipitation of a 31,000 molecular weight labeled protein, which upon reduction was split into two polypeptides of molecular weights 17,000 and 16,500. The significance of these findings in view of the recently discovered structure homology between PDGF and the transforming gene product of simian sarcoma virus, p28sis, is discussed.

Binding, Competitive↗

Characterization of two strains of avian sarcoma virus isolated from avian lymphatic leukosis virus-induced sarcomas.

Two replication-defective avian sarcoma viruses, S1 and S2, which were independently isolated from tumors of chickens inoculated with avian lymphatic leukosis virus (LLV) were characterized. The genomes of S1 and S2 contain src-related sequences and are, respectively, about 3.9 and 4.5 kilobases long. pp60src-related proteins with molecular weights of 62,000 (p62) were detected in cells infected with these viruses, and protein kinase activity was found to be associated with these proteins. No other viral proteins, such as gag, pol, and env gene products, were detected. These results suggested that the c-src sequence in normal chicken cells was incorporated into LLV genomes by recombination at the expense of most of the viral genes to generate highly defective new sarcoma viruses.

Alpharetrovirus↗

Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients.

The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy. Two different schedules of ifosfamide were investigated in a randomised manner: Ifosfamide was given either at a dose of 5 g/m(2) over 24 h (5 g/m(2)/1 day), every 3 weeks or at a dose of 3 g/m(2) per day, administered over 4 h on three consecutive days (3 g/m(2)/3 days), every 3 weeks. Both schedules were given as first-line or second-line chemotherapy. A total of 182 patients was entered, 103 in first- and 79 in second-line, of whom 8 patients were ineligible, 5 in the first- and 3 in the second-line study. Most patients had a leiomyosarcoma, 46 of the 98 in the first-line and 34 of the 76 in the second-line. The two study arms were well balanced in both the first- and second-lines with respect to sex, age and performance status. In first-line treatment, 5 g/m(2)/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m(2)/3 days. As second-line treatment, the 24-h infusion yielded: one CR and one PR (RR 6%) and the 3-day schedule one CR and two PR (RR 8%). Survival did not differ between the two regimens. The major World Health Organization (WHO) grade 3 and 4 toxicities encountered were: leucopenia in 19% of all courses in the first-line and 32% in the second-line with the 5 g/m(2)/1 day, while for the 3 g/m(2)/3 days schedule the rates were 57 and 63% respectively. Grade 3 or 4 infections were seen in 4% of patients treated with 5 g/m(2)/1 day first-line and 10% of patients given 3 g/m(2)/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m(2)/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m(2), given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m(2) over 24 hours schedule resulted in a disappointing response rate.

Adult↗

Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group.

In a phase I study conducted by the EORTC Soft Tissue and Bone Sarcoma Group, 40 patients with advanced soft tissue sarcomas, most of whom had gastrointestinal stromal tumors (GISTs), received imatinib at doses of 400 mg q.d., 300 mg b.i.d., 400 mg b.i.d., or 500 mg b.i.d. Dose-limiting toxicities, including severe nausea, vomiting, edema and rash, were seen at the highest dose level; the maximum tolerated dose was therefore 400 mg b.i.d. Imatinib was active in the group of 35 patients with GISTs, producing partial responses in 19 (54%) patients and stable disease in 13 patients (37%). Responding patients have now been followed for a minimum of 10 months. The most common side effects seen in patients continuing on therapy have been periorbital edema (40%), peripheral edema (37.5%), fatigue (30%), skin rash (30%) and nausea/vomiting (25%). Severe late myelosuppression has also been seen occasionally. Eighteen (51%) GIST patients continue to have partial responses and 11 (31%) continue with stable disease. Thus, 82% of patients with GISTs are still obtaining clinically important benefits with continued imatinib therapy. Some patients showed accelerated progressive disease shortly after starting imatinib. On the other hand, following drug withdrawal, 2 patients had reductions in tumor burden and remain alive without drug therapy. In summary, imatinib is generally well tolerated and has significant activity during long-term treatment of patients with advanced GISTs.

Adult↗

Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children.

71 children with sarcomas were treated in a prospective pilot study to determine whether granulocyte colony stimulating factor (G-CSF) permits compression of the interval between chemotherapy cycles. Patients had Ewing's sarcoma/primitive neuroectodermal tumour (PNET), rhabdomyosarcoma, non-rhabdo soft tissue sarcomas or other advanced soft tissue tumours. The chemotherapy alternated vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, with G-CSF between courses. Therapy had two phases: induction (six cycles) and continuation (six cycles), which included primary tumour treatment with surgery and/or radiation. Chemotherapy cycles began every 14 days, or upon absolute neutrophil count (ANC) and platelet count recovery. The median chemotherapy cycle interval was 16 (11-48) days in the induction phase, with a median average relative dose intensification (ARDI) of 1.27 compared with every-21-day therapy. In the continuation phase, the median cycle interval was 21 days, with a median ARDI of 1.10. Radiation therapy prolonged chemotherapy intervals, whilst erythropoietin shortened them. Toxicity was modest for such chemotherapy. Event-free survival is comparable with or superior to that in recent large studies. G-CSF permits intensification of this regimen through interval compression. The impact of this approach on efficacy remains to be determined in a randomised trial.

Adolescent↗

The malignant histiocytosis sarcoma virus, a recombinant of Harvey murine sarcoma virus and Friend mink cell focus-forming virus, has acquired myeloid transformation specificity by alterations in the long terminal repeat.

The malignant histiocytosis sarcoma virus (MHSV), in contrast to other viruses with the ras oncogene, induces acute histiocytosis in newborn and adult mice. Molecular structure and function studies were initiated to determine the basis of its unique macrophage-transforming potential. Characterization of the genomic structure showed that the virus evolved by recombination of the Harvey murine sarcoma virus (Ha-MuSV) and a virus of the Friend-mink cell focus-forming virus family. Structural analysis of MHSV showed two regions of the genome that are basically different from the Ha-MuSV: (i) the ras gene, which is altered by a point mutation in codon 181 leading to a Cys----Ser substitution of the p21 protein, and (ii) the U3 region of the long terminal repeat, which is largely derived from F-MCFV and contains a deletion of one direct repeat as well as a duplication of an altered enhancer-like region. Biological studies of Ha-MuSV, MHSV, and recombinants between the two viruses show that the U3 region of the MHSV long terminal repeat is essential for the malignancy and specificity of the disease. A contributing role of the ras point mutation in determining macrophage specificity, however, cannot be excluded.

Amino Acid Sequence↗

Differential expression of viral Bcl-2 encoded by Kaposi's sarcoma-associated herpesvirus and human Bcl-2 in primary effusion lymphoma cells and Kaposi's sarcoma lesions.

Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.

Herpesvirus 8, Human↗

Supplemental arginine increases thymic cellularity in normal and murine sarcoma virus-inoculated mice and increases the resistance to murine sarcoma virus tumor.

Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.

Adrenal Glands↗

Radio-induced sarcomas in survivors of Ewing's sarcoma.

Of 255 cases of Ewing's sarcoma recorded at the Bone Tumor Center of the Rizzoli Orthopaedic Institute, 78 patients (irradiated and with a follow-up of longer than 3 years) were considered "at risk" for the development of a second radio-induced sarcoma (RIS). Three of the 78 patients developed an RIS in the irradiated field. Theoretical and statistical analyses were carried out considering different modalities of local treatment. Statistically, the only significant factor was related to the irradiation dose. Surgical resection seems to prevent RIS.

Adolescent↗