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PubMed1983

Susceptibility of Rous sarcoma virus-specific sequences integrated into SR-C3H/He mouse ascites sarcoma cell chromatin to DNase I and DNase II.

The susceptibility of Rous sarcoma virus (RSV) genomes integrated in mouse ascites sarcoma cells (SR-C3H/He cells) to DNase I and DNase II was investigated. Approximately half of the viral sequences were sensitive to DNase I and DNase II when 17% and 7.4% of the chromatin DNA was rendered acid soluble, respectively. The results suggest that newly acquired exogenous proviral sequences are integrated into both transcriptionally active and inactive regions of chromatin in cells lacking related endogenous viral sequences.

Animals↗
PubMed1978

Effects of prophylactic treatment with the methanol extraction residue fraction of tubercle bacilli (MER) on the development of Rous sarcomas of chickens following challenge with the Rous sarcoma virus.

Three-month-old chickens were treated with the methanol extraction residue fraction of tubercle bacilli (MER) under different conditions, and subsequently challenged with living Rous sarcoma virus. The birds developed progressively growing sarcomas following viral challenge. A substantial proportion of the hosts which had been pretreated with MER under optimal circumstances (38 to 58%) showed complete and long-lasting regression of the neoplasms, and the survival of many of the animals that did succumb to progressively growing tumors was prolonged. An absolute condition for prophylactic efficacy of MER treatment in this model system was injection of the agent into the same body area (wing) into which subsequent viral challenge was introduced. The quantity of MER employed and the timing of the prophylactic administration were also decisive variables.

Animals↗
PubMed1985

Isolation of two transforming viruses from sarcomas obtained in chickens inoculated intraembryonally with a transformation defective mutant of Prague strain Rous sarcoma virus.

Sarcomas appeared after long latency with a frequency of about 2% in Brown Leghorn and (CB X IC)F1 chickens after intraembryonic and neonatal inoculation of transformation-defective mutants of ASVs subgroup C. Only the freshly isolated td mutants, td daPR-C and td daPR-C morphf, exhibited the tumorigenic activity, whereas the standard td mutants induced no sarcomas. Two (862 and 2257) out of four tumours could be transplanted in young chickens and produced low titres of transforming virus. The other two tumours were not transplantable and devoid of any transforming virus. Viruses 862 and 2257 are clearly defective in replication, virus 2257 cannot be complemented efficiently by any helper virus in vitro. The low titre of virus 2257 is not caused by interference with a helper virus of the same subgroup specificity. Both viruses are highly tumorigenic in vivo.

Animals↗
PubMed1979

Characterization of RNA polymerases from Rous sarcoma virus-induced mouse ascites sarcoma cells.

RNA polymerase was extracted from the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV)-induced C3H/He mouse ascites sarcoma cells (SR-C3H). RNA polymerase was separated into RNA polymerases I and II by DEAE-Sephadex chromatography. RNA polymerase I was separated into Ia and Ib fractions by phospho-cellulose chromatography. In SR-C3H cells RNA polymerase Ib was the main component of RNA polymerase I. At 0.05--0.1 M ammonium sulphate RNA polymerase I transcribed native DNA most actively, and RNA polymerase II transcribed denatured DNA most actively. Partial digestion of DNA by DNAase I enhanced RNA synthesis by RNA polymerases I and II. At ionic strength over 0.2 M ammonium sulphate, the initiation reaction of RNA polymerases I and II was inhibited. The initiation complexes of RNA polymerases I and II with native DNA were more stable against high salt concentration than with denatured DNA.

Animals↗
PubMed1986

[Fatty acid content in the muscles and liver of mice developing sarcomas induced by 3-methylcholanthrene and Moloney murine sarcoma virus].

A comparative analysis was made for the fatty acid composition of lipids in the malignant muscular tissue, muscle and liver under blastomogenesis induced in mice by the Moloney sarcoma virus and 3-methylcholanthrene. The relation of the found changes in the fatty acid composition to the blastomogenesis stages is shown. The development of the tumour node is accompanied by a decrease of the fatty acid amount in the animal tissues and by its increase in the tumour. A spontaneous regression of the Moloney sarcoma results in increased level of the fatty acid content in the animal tissues followed by its normalization.

Animals↗
PubMed2005

Infection with Kaposi's sarcoma-associated herpesvirus among families of patients with classic Kaposi's sarcoma.

BACKGROUND: Classic Kaposi's sarcoma (CKS) primarily affects elderly Mediterranean or Eastern European men. Incidence rates of CKS in Israel are among the world's highest. In practically all cases, antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) can be detected. A relatively high seroprevalence rate of KSHV in Israel generally correlates with the incidence of CKS. A sexual mode of virus transmission is recognized among homosexual men, whereas the precise transmission routes in the heterosexual population and those with CKS are still unclear. OBJECTIVE: To better assess the transmission routes of KSHV in Israeli patients with CKS and their first-degree relatives as compared with a control group. DESIGN: Serum was collected from all study participants and tested for KSHV antibodies by means of latent and lytic immunofluorescence assays. An open reading frame 65 (ORF65) Western blot assay was applied as a confirmatory tool. SETTING: Three dermatological departments in Israel. PATIENTS: Sixty-four Jewish patients with CKS, 143 of their first-degree relatives, and 186 hospital-based control subjects. RESULTS: Seropositivity to KSHV was detected in 62 (96.9%) of the patients with CKS, in 56 (39.2%) of their first-degree relatives, and in only 21 (11.3%) of the hospital controls (P<.001). The specific relationship with the index patient (spouse, offspring, or sibling) had no significant effect on the prevalence of serpositivity in the family members. CONCLUSION: Our serologic evidence of familial clustering of KSHV infection suggests a predominantly nonsexual horizontal transmission route of the virus.

Adolescent↗
PubMed1998

Follicular dendritic cell sarcoma and interdigitating reticulum cell sarcoma: a review.

Neoplasms of reticular dendritic origin are extremely rare and include the follicular dendritic cell sarcoma (FDCS) and the interdigitating reticulum (or dendritic) cell sarcoma (IDCS). In this article, we review the literature pertaining to the two diseases and describe clinical observations and salient pathologic features, including information provided by authors of FDCS and IDDCS reports. We performed a computerized database search for published articles regarding FDCS and IDDCS. The articles were evaluated critically by the authors. Simple descriptive statistics were used to analyze the data. There are 51 cases of FDCS and 21 cases of IDDCS that are well documented in the literature. The pathologic diagnosis of FDCS and IDDCS is often challenging and requires morphologic, immunophenotypic, cytochemical, and electron-microscopic analysis. Patients with FDCS usually present with cervical or axillary lymphadenopathy, but extranodal disease has been described. In at least some patients, preexisting Castleman's disease has been recognized. Resected localized disease may be prevented from recurrence by consolidative radiotherapy. Chemotherapy regimens have shown nondurable antitumor activity in FDCS. Patients with IDDCS usually present with lymphadenopathy. The clinical course of IDDCS has been variable, but it seems to be more aggressive than that of FDCS. Variable degrees of remission may be achieved with chemotherapy. FDCS and IDDCS are rare neoplasms that may pose difficulty in pathologic diagnosis. IDDCS seems to display a more aggressive behavior than FDCS. Patients with IDDCS and FDCS can eventually die of disease progression. The role of chemotherapy and radiotherapy is not clearly defined.

Dendritic Cells↗
PubMed1980

Intergroup Ewing's Sarcoma Study: local control related to radiation dose, volume, and site of primary lesion in Ewing's sarcoma.

One hundred ninety-three patients with localized Ewing's sarcoma treated at participating instutitions of the Intergroup Ewing's Sarcoma Study form the basis for this report. All patients received radiation therapy to the primary lesion and were randomized to receive vincristine, actinomycin-D, and cyclophosphamide (VAC) plus adriamycin (Regimen I); VAC alone (Regimen II); or VAC and bilateral pulmonary irradiation (Regimen III). Local control was achieved in 96% of the patients in Regimen I, and 86% of the patients in both Regimens II and III. The median duration of follow up was 83 weeks and median survival time was 172 weeks. Incremental doses of irradiation did not result in significant changes in the rate of local control of primary lesions. The local control rate was the same (92%) for tumors treated by means of whole-bone irradiation or with at least 5 cm of free margin around the lesion. The local control rate decreased to 79% for lesions treated with less than 5-cm margin. Excellent control was obtained for lesions involving the skull or spine (100%), and distal bones (fibula, 96% and tibia, 91%). Less favorable control rates were noted for pelvic and humeral lesions (84% and 79%, respectively). Bilateral pulmonary irradiation for subclinical disease played a role in lowering the incidence of lung metastases from 38% to 20% for patients treated with VAC. Lung metastases were similarly decreased (10%) when adriamycin was added to VAC chemotherapy.

Bone Neoplasms↗
PubMed1983

Primary Ewing's sarcoma of the ribs. A report from the intergroup Ewing's sarcoma study.

Thirty-six patients with primary Ewing's sarcoma of the ribs have been reviewed. Of these, 21 had clinically localized disease at diagnosis and were entered on protocol IESS 7299, eight had regional and seven metastatic disease at diagnosis and were entered on protocol 7450. The 21 with localized disease were treated with surgical excision or biopsy, followed by local radiotherapy (in all but one patient) and randomization to one of three chemotherapy regimens. Eleven patients (52%) remain disease-free for periods ranging from 18 to 64 months, respectively. Seven of eight patients who underwent complete surgical excision of the primary lesion remain disease-free, compared with four of 12 (excluding one patient who died disease-free) who remain disease-free after partial excision or biopsy. However, analysis of size of tumor at diagnosis reveals that smaller primary tumors have a better prognosis irrespective of extent of surgery. Protocol IESS 7450, consisted of radiotherapy to all areas of known disease and four drug chemotherapy. Four (50%) with regional disease but none with metastatic disease have remained alive and continuously disease-free. It is concluded that an aggressive approach to Ewing's sarcoma of the ribs is justified by the results, as even regional disease may be curable. The apparent prognostic advantage for those patients undergoing surgical excision may be explained by patient selection.

Adolescent↗
PubMed1984

Cyvadic in advanced soft tissue sarcoma: a randomized study comparing two schedules. A study of the EORTC Soft Tissue and Bone Sarcoma Group.

Two hundred forty-six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC-CYV) alternating at 4 weekly intervals. One hundred sixty-two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90-100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50-80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Adolescent↗
PubMed1991

Radiation therapy as local treatment in Ewing's sarcoma. Results of the Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86.

The Cooperative Ewing's Sarcoma Studies, CESS 81 and CESS 86, are multiinstitutional trials with more than 80 participating institutions from Germany, the Netherlands, Austria, and Switzerland. Treatment consists of four courses of multiagent chemotherapy and local therapy. Local therapy was not randomized and was either radical surgery or resection plus postoperative irradiation or definitive radiation therapy. Here results according to local therapy have been analyzed for 93 protocol patients with localized Ewing's sarcoma (ES) who have been recruited in CESS 81 from January 1981 to February 1985 and 122 protocol patients recruited in CESS 86 from January 1986 to November 1989. The 3-year relapse-free survival (RFS) was 55% in CESS 81 and 62% in CESS 86. In CESS 81, the RFS was better for surgically treated than for irradiated patients. In this study there was an extremely high incidence of local failures (50%) after definitive irradiation. In CESS 86, however, the results after radiation therapy have been improved markedly (3-year RFS 67% after radiation therapy, 65% after surgery, and 62% after resection plus irradiation). Possible explanations for the improvement of radiotherapeutic results are as follows: selections for patients for radiation therapy, start of local therapy, and quality of radiation therapy. In CESS 86, irradiated patients were randomized to receive either conventionally fractionated irradiation with less intense chemotherapy or hyperfractionated irradiation with simultaneous chemotherapy. There was no difference in treatment results at the time of analysis. The authors conclude that selection of patients for local treatment modalities and quality of treatment performance has an impact on local and overall treatment results in ES.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

The IVADo regimen--a pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma: a pilot study of behalf of the European pediatric Soft tissue sarcoma Study Group.

BACKGROUND: The role of doxorubicin (Doxo) as part of multidrug regimens used to treat children with soft tissue sarcoma (STS) is controversial. To evaluate the feasibility of combining Doxo with the well established ifosfamide, vincristine, and actinomycin D (IVA) regimen, the Italian STS Committee performed a pilot study on a series of children with metastatic STS. METHODS: Between July 2002 and February 2004, 29 evaluable patients were enrolled in this study; 19 patients had rhabdomyosarcoma, 5 patients had peripheral neuroectodermal tumor, and 5 patients had other types of STS. The IVA-Doxo (IVADo) regimen included ifosfamide 3 g/m(2) on Days 1 and 2, vincristine 1.5 mg/m(2) on Day 1, actinomycin D 1.5 mg/m(2) on Day 1, and Doxo 30 mg/m(2) on Days 1 and 2. Three courses of IVADo were to be administered in the initial part of treatment and analyzed for toxicity and tumor response. RESULTS: Overall, 92 cycles were delivered. Major regimen-related toxicity was myelosuppression, with Grade 4 neutropenia in 67% of cycles and fever and neutropenia in 37% of cycles. Nonhematologic toxicity included Grade 3-4 mucositis (6.5% of cycles), constipation (9.7%), and peripheral neuropathy (6.5%). Other manifestations of major toxicity were venoocclusive disease and seizures, which occurred in one patient each. All but 1 patient with a malignant schwannoma showed some degree of tumor volume reduction; however, considering only complete and partial remissions, the response rate was 76% (+/- 7.9%). CONCLUSIONS: The intensive IVADo regimen was effective against pediatric STS with acceptable toxicity. This combination will be investigated in high-risk patients with rhabdomyosarcoma in a randomized trial launched by the European pediatric Soft tissue sarcoma Study Group.

Adolescent↗
PubMed1996

Chemically induced sarcomas from nude mice are more immunogenic than similar sarcomas from congenic normal mice.

To detect possible differences in immunogenicity between tumors induced in T cell-deficient mice and phenotypically normal congenic mice, 16 sarcomas, 8 having developed in nude BALB/c mice and 8 having developed in congenic normal (nu/+) mice, were transplanted to normal BALB/c recipients and the rates of rejection or acceptance were registered. The 16 tumors were chosen randomly from a panel of 39 sarcomas induced with 0.5% or 0.1% 3-methylcholanthrene and maintained as cell lines in culture. Out of the tumors originating from nude mice, 66% were rejected by the normal BALB/c recipients, while only 30% of the tumors originating from normal mice were rejected. Tumors with short induction times from normal mice were more readily accepted than tumors with long induction times. Tumors originating from nude mice had significantly longer mean latency times after transplantation to both normal and nude recipients than tumors originating from normal mice. Contrary to what has been reported by others, there was no correlation between the rejection rates of the individual tumors and their Kd, Dd or Ld major histocompatibility complex (MHC) class I surface expression as measured by flow cytometric analysis of cultured tumor cells. The Kd, Dd and Ld proteins of the transplanted tumor lines were analyzed by isoelectric focusing for the occurrence of mutations resulting in altered charge of the MHC protein. No such mutations were found, ruling out MHC mutations of that kind as the source of immunogenicity in the cell lines used in these experiments. Our results suggest the existence of a T cell-mediated selection in the original tumor cell mass of tumors induced in normal mice, adapting the tumor to growth in a host with a functional T cell system, but apparently there is no connection between this loss of immunogenicity and loss of MHC class I expression.

Animals↗
PubMed2007

Reactivation of Kaposi's sarcoma-associated herpesvirus by natural products from Kaposi's sarcoma endemic regions.

Kaposi's sarcoma (KS) and its causative agent, Kaposi's sarcoma associated herpesvirus (KSHV/HHV-8), a gamma2 herpesvirus, have distinctive geographical distributions that are largely unexplained. We propose the "oncoweed" hypothesis to explain these differences, namely that environmental cofactors present in KS endemic regions cause frequent reactivation of KSHV in infected subjects, leading to increased viral shedding and transmission leading to increased prevalence of KSHV infection as well as high viral load levels and antibody titers. Reactivation also plays a role in the pathogenesis of KSHV-associated malignancies. To test this hypothesis, we employed an in vitro KSHV reactivation assay that measured increases in KSHV viral load in KSHV infected primary effusion lymphoma (PEL) cells and screened aqueous natural product extracts from KS endemic regions. Of 4,842 extracts from 38 countries, 184 (5%) caused KSHV reactivation. Extracts that caused reactivation came from a wide variety of plant families, and extracts from Africa, where KSHV is highly prevalent, caused the greatest level of reactivation. Time course experiments were performed using 28 extracts that caused the highest levels of reactivation. The specificity of the effects on viral replication was examined using transcriptional profiling of all viral mRNAs. The array data indicated that the natural extracts caused an ordered cascade of lytic replication similar to that seen after induction with synthetic activators. These in vitro data provide support for the "oncoweed" hypothesis by demonstrating basic biological plausibility.

Biological Assay↗
PubMed1991

Kaposi's sarcoma and non-Hodgkin's lymphoma in European AIDS cases. No excess risk of Kaposi's sarcoma in Mediterranean countries.

Prior to the AIDS epidemic, Kaposi's sarcoma (non-AIDS-KS) in Europe was mainly a disease of elderly Mediterranean men. In 1989 AIDS data from 15 European countries were collected to study proportional trends in AIDS-related Kaposi's sarcoma (AIDS-KS) in order to determine whether specific factors in Southern Europe might be important in the development of KS among AIDS patients. Another AIDS-related cancer, non-Hodgkin's lymphoma (NHL) was included as a malignancy control. Of 22,367 AIDS cases reported, 3,779 (16.9%) were KS and 741 (3.3%) were NHL. A significant, continuous fall in the percentage of AIDS-KS was seen for both homosexual men and other members of exposure groups during the period 1981-89 (p-trend less than 0.0001). The proportion with AIDS-KS decreased from 40.5% in 1983 to 26.5% in 1988 in homosexual men and from 12.2 to 3.6% in other exposure groups, respectively. No significant change was observed in the proportion of NHL cases among any of the risk groups over time, although a tendency towards a slight increase was noted for homosexual men. Comparing proportional trends of KS and NHL geographically, no significant difference was found overall, by time or by exposure group. In conclusion, a specific decline is observed over time for AIDS-KS. However, if geographically-restricted factors are important in the development of non-AIDS-KS in Europe, the same factors do not appear to affect the risk of AIDS-KS.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Molecular epidemiology of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 strains from Russian patients with classic, posttransplant, and AIDS-associated Kaposi's sarcoma.

We report the molecular characterization of 38 new Kaposi's sarcoma-associated herpesvirus (KSHV) strains from Russian patients with either classic (25 cases), epidemic/AIDS-associated (7 cases), or posttransplant/immunosuppressed patients (6 cases), or Kaposi's sarcoma (KS). While a complete sequence of the K1 gene (870 bp) was obtained from 30 strains, only partial sequences of the hypervariable regions VR1 (372 bp) and/or VR2 (381 bp) of the K1 gene were obtained from eight strains of KS paraffin blocks. Sequence comparison and phylogenetic studies indicate that the novel KSHV strains belong to either the A subtype (28 cases) or the C subtype (10 cases). Within the 28 strains of A subtype, 24 (86%) belong to the large A' subgroup, mostly A1 and A1' clades, and 4 belong to the A" subgroup, mostly A3 clade. Within the 10 strains of subtype C, 4 were of C' subgroup, and 6 of the C". Some molecular variants of subtype A' were observed, with 3 strains exhibiting an insertion of a single amino acid at the position 65 and 2 strains (both from AIDS-KS) with an unique deletion of 17 amino acids in the VR2 region. Polymerase chain reaction-based subtyping of the K14.1 genomic region indicated that most (23/32) of the novel strains belonged to the P subtype. The results indicate that despite a wide genetic diversity of A and C K1 subtypes of KSHV strains present in Russia, most are closely related and belong to the A1 or A1' molecular clades suggesting a common origin. This study also expands the data regarding the absence of any correlation between a K1 molecular subtype and a specific KS type (classic, epidemic, or posttransplant), as well as between the K1 and K14.1 molecular subtypes.

Acquired Immunodeficiency Syndrome↗
PubMed1980

Solid dendritic cell angiosarcoma: re-interpretation of extraskeletal sarcoma resembling Ewing's sarcoma.

Twenty cases of a type of extraskeletal tumour resembling Ewing's sarcoma (Angervall and Enzinger, 1975) were studied. The tumour affected mainly soft tissues in a variety of sites. Throughout the long follow-up period, there was only one instance of non-recurrence after excision. Most of the tumours became generalised within 3 years. One case developed general spread after 13 years. The tumour shows predominantly expansive growth and a solid architecture which, in places changes to reticular or sinusoidal structures. The predominant dendritic tumour cells show multiple junction complexes. Weibel-Palade granules can occasionally be demonstrated in their cytoplasm. In foci of peritheliomatous pattern the tumour cells become elongated, contain an abundance of endoplasmic reticulum and give rise to pericellular basement membranes, although typical collagen was rarely found. Judged by its structural and cytological features the tumour is a form of angiosarcoma, mostly of the endothelial type but with pericytic variations. Since neither its cellular features nor its biological behaviour correspond to those of Ewing's sarcoma, a change of name is proposed.

Adolescent↗
PubMed2004

Ewing's sarcoma and primitive neuroectodermal tumor of hand and forearm. Experience of the Cooperative Ewing's Sarcoma Study Group.

PURPOSE: Because Ewing's sarcoma (EWS) is extremely rare in the hand and forearm, only limited data are available for planning treatment or predicting prognosis. METHODS: Data of 33 patients with EWS of the forearm or hand who were enrolled in studies of the German Association for Paediatric Oncology/Haematology and the European Intergroup Cooperative Ewing's Sarcoma Study Group were analyzed. Patients received neoadjuvant multi-agent chemotherapy according to the valid protocol. Local treatment consisted of surgery (n=7), radiotherapy (n=7), or a combination of both (n=19). RESULTS: The 5/10-year overall survival rate was 84.1% (95% CI: 71.2-96.9)/74.1% (95% CI: 56.8-91.5), and both 5/10-year event-free survival rate were 71.3% (95% CI: 55.4-87.1). Only one of seven patients with secondary metastases was in remission at the time of analysis. One patient with local recurrence and another with primary metastases died. Altogether, eight of 33 patients died of their disease. The event-free survival rate was 80.6% in patients with good response to chemotherapy and 33.3% in patients with poor response. Surgery in combination with radiotherapy achieved a higher survival rate compared with radiotherapy or surgery alone. One out of two patients with non-wide margins of resection died of disease. CONCLUSIONS: The results demonstrate a remarkably high survival rate for patients with EWS of the hand and forearm.

Adolescent↗