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PubMed1990

[Adjuvant chemotherapy of soft tissue sarcoma].

As the adjuvant chemotherapy of osteosarcoma has been proved highly effective, that of soft tissue sarcoma has been expecting. However, there is still some question as to its effectiveness. The indication and methods were studied on literatures and our own cases. A survey of the literature regarding to the chemotherapeutic effect upon advanced soft tissue sarcoma shows response rate ranging 20 to 50 per cent. On the other hand, soft tissue sarcoma has a variety of histological type and malignancy and the sensitivity to chemotherapy varies considerably according to each tissue type. The literatures and our results indicate that most effective sarcoma is rhabdomyosarcoma, which is absolutely advisable to apply adjuvant chemotherapy. The same is the sarcoma with similar histological pattern. As to other type sarcomas, the therapy has to be applied according to their grade, stage, age and the effect of chemotherapy evaluated by advanced tumor. Most prevalent agents used for soft tissue sarcoma are adriamycin, cyclophosphamide, actinomycin-D, vincristine and DTIC. These agents usually used as combination called VAC, CYVADACT, CYVADIC, BCD.

Adolescent↗
PubMed1989

Spontaneously metastasizing rat sarcomas LW13K2 and RPS: assessment by the immunogenetic test of malignancy, in vitro behaviour and karyology.

Populations of LW13K2 sarcoma derivatives were compared for their malignancy, patterns of cell behaviour in vitro (dynamic morphology and migration) and karyological pattern. The following tumour cell populations were used: the original LW13K2 sarcoma from inbred LEW/CUB rats, RPS sarcoma derived from it by neoplastic progression, four cell populations isolated in vitro from metastases of a syngeneic LEW-CUB strain rat with RPS tumour and four neoplastic cell populations isolated from spontaneous metastases shed by RPS sarcoma in allogeneic rats, differing from LEW/CUB in weak alloantigenic loci. Although RPS tumour did not grow progressively in MHC-different recipients (while the original LW13K2 tumour did), it grew progressively and metastasized in all groups of non-MHC allogeneic recipients. Parallel with the metastatic potential patterns of in vitro behaviour, such as an increased incidence of the quasi-stellate morphotype at slightly acid culture conditions endowed with enhanced changeability of the cell shape and migrational activity, were found. Cytogenetic analysis demonstrated rather stable chromosomal patterns over the cascade of neoplastic progression from LW13K2 sarcoma over RPS sarcoma to freshly isolated metastases. This indicated that the apparent neoplastic progression observed in the cell populations derived from LW13K2 sarcoma is with high probability not due to the selection at the chromosomal level.

Animals↗
PubMed1989

Cross-reacting tumor associated transplantation antigen on primary 3-methylcholanthrene-induced BALB/c sarcomas.

Immunization of adult, syngeneic BALB/c mice with irradiated, primary MCA-induced sarcomas conferred reproducible, nonisologous TATA-associated cross-protection against challenge with other primary MCA sarcomas or in vitro passaged MCA sarcoma cells. Isologous, individually specific TSTA-associated protection was also detected. Irradiated, normal BALB/c spleen or muscle tissues were not similarly protective. Pronounced cross-protection was best detected with secondary cultured, in vitro adapted sarcoma challenge inoculum, which could be accurately standardized. These findings paralleled the good cross-protection reported previously with long-term cultured MCA-induced sarcoma cell lines. OFA was expressed as a TATA on all syngeneic, primary MCA-induced sarcomas tested by syngeneic adoptive transfer experiments and on MuLv-free MCA-induced, syngeneic Meth A sarcoma cells.

Animals↗
PubMed1988

Soft tissue sarcomas in Auckland 1974-1984: a review of 105 cases.

We have reviewed the records of 105 patients with the diagnosis of soft tissue sarcoma seen in the Auckland region between January 1974 and December 1984. The mean age at diagnosis was 54 years and the average duration of symptoms prior to specialist assessment was 8 months. By the time of presentation 27% of patients had metastatic disease. Forty-six patients underwent biopsy-type procedures and of these only one patient was alive and apparently disease free at one year. Three were alive with disease at an average of 2.2 years, 29 of the 46 had died of their sarcoma at one year and five of the 46 died of other causes. Fifty nine patients had definitive reactions performed and 26 of were alive with disease at an average of 2.2 years, 29 of the 46 had died of their sarcoma at one year and five of the 46 died of these were alive and disease free at two years. Six were alive with recurrent disease and 15 had died of sarcoma 1.9 years after presentation. In terms of site of the primary, patients with limb sarcomas fared better than those with retroperitoneal lesions, whereas sarcomas in other locations had survival figures in between these two groups. Soft tissue sarcomas consitute an aggressive and unforgiving type of cancer, and to entertain any realistic chance of cure complete resection of the lesion must be achieved. However, the patients presented to specialist attention at a relatively late stage of their disease, and the chances of survival are dependent both on the site of the primary lesion and on whether or not definitive surgery and adjuvant therapy is employed.

Adolescent↗
PubMed1986

Estrogen and progesterone receptors in uterine sarcomas.

Estrogen and progesterone receptors were measured in tissues from 43 patients with various uterine sarcomas using the dextran-coated charcoal assay. Estrogen receptor was present in 55.5% and progesterone receptor in 55.8% of samples, at median estrogen and progesterone receptor concentrations of 10.7 and 15.8 fmol/mg cytosol protein, respectively. These median values are much lower than those in 30 consecutive endometrial adenocarcinomas and 50 breast carcinomas assayed in our laboratory. Progesterone receptor status correlated strongly with estrogen receptor status in uterine sarcomas (P = .001). Estrogen and progesterone receptor levels were not influenced by stage, grade, or mitotic count. Patients 50 years of age or less had significantly higher progesterone receptor than those over 50. No such age effect was seen for estrogen receptor. Endometrial stromal sarcoma had higher estrogen and progesterone receptor levels than other histologic types. Low-grade endometrial stromal sarcomas had higher median estrogen receptors (238.9 fmol/mg) and better survival (all patients alive at 6-12 months) than did high grade (N = 7) endometrial stromal sarcomas (median ER = 6.6 fmol/mg, all dead of disease at 8-27 months). For all histologic types, evaluable patients with stage I or II disease (N = 16) were more likely to survive longer than one year than those with stage III or IV disease (N = 13, P = .003). Evaluable patients with estrogen receptor-positive sarcomas were more likely to survive longer than one year than those with estrogen receptor-negative tumors (P = .006). With one exception, an endometrial stromal sarcoma, hormonal therapy exerted no beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Damaging action of human recombinant TNF on tumor vessels as an aspect of its anti-neoplastic action against Meth A sarcoma in mice].

Effect of human recombinant TNF (rHu-TNF) on tumor blood vessels was investigated in relation to its mode of anti-neoplastic action against Meth A sarcoma in BALB/c mice. The extent of the blood vessel lesion was evaluated by measuring the degrees of blueing and hemorrhage after intravenous injection of Evan's blue. When injected intravenously into mice bearing Meth A cells in the abdominal skin transplanted 8 days previously, rHu-TNF, at doses of 3000 and 10,000 units/mouse produced dose-related lesioning of blood vessels in the sarcoma and the adjacent skin but not in the skin distant from the sarcoma. Similar lesioning of blood vessels in the adjacent skin was seen after intravenous administration of 10,000 units/mouse of rHu-TNF in mice with the sarcoma in which the cells had been selectively killed by intratumoral injection of acetic acid (20%, 0.01 ml). On the other hand, rHu-TNF (10,000 units/mouse, i.v.) produced weak lesioning of blood vessels in the granuloma tissue caused by subcutaneous implantation of felt pellets and in the adjacent skin but not in the operation wound in mice with the sarcoma. These results suggest that rHu-TNF damages newly formed blood vessels, particularly those connected with the sarcoma, without influencing blood vessels in normal skin and healing wounds in mice with Meth A sarcoma.

Animals↗
PubMed1985

Vascular tumors produced by NIH/3T3 cells transfected with human AIDS Kaposi's sarcoma DNA.

Patients with the acquired immunodeficiency syndrome (AIDS) have a high incidence of Kaposi's sarcoma. The etiology, histogenesis, and neoplastic nature of this neoplasm have been controversial. We have therefore searched for transforming gene(s) associated with AIDS Kaposi's sarcoma. DNA from an AIDS patient's Kaposi's sarcoma was transfected into NIH 3T3 cells. Control DNA was derived from human fibroblasts or salmon sperm. Kaposi's sarcoma DNA, but not the control DNA, transforms NIH/3T3 cells with a frequency of approximately 0.02 foci per 5 X 10(5) cells/micrograms DNA. The primary and secondary transfectants contain human repetitive DNA sequences. The transfected clones produced hemorrhagic angiosarcomatous neoplasms when implanted in nude mice. The histology of the nude mouse tumors is very similar to human Kaposi's sarcoma. The tumor produced by some transfectants is highly invasive and metastatic in nude mice. No significant homologues of rasN, rasH, rasK, v-sis, v-src and v-fes oncogenes (known to transform NIH/3T3 cells) were identified in the Kaposi's sarcoma DNA-transformed cells. Thus, AIDS Kaposi's sarcoma DNA may contain a distinct transforming gene(s).

Acquired Immunodeficiency Syndrome↗
PubMed1984

[Treatment of Ewing's sarcoma with intensive initial chemotherapy. 1st evaluation of a French pediatric multicenter protocol].

From April, 1978 to December, 1982, 87 cases of Ewing's sarcoma were registered in 12 centres of paediatric oncology in France. The results of a therapeutic protocol consisting of intensive chemotherapy (vincristine, cyclophosphamide and actinomycin with or without adriamycin) prior to tumoral irradiation, followed by maintenance chemotherapy are reported after 3 years' follow-up from the beginning of treatment. In localized sarcomas, complete remission (66/70) persisted without relapse or metastasis in 54% of the cases (78% in sarcomas of long bones, and 37% in sarcomas of short bones). In non-metastatic sarcomas of the ribs, the first remission persisted in 7/14 patients (50%). All these patients had been initially treated with chemotherapy, radiotherapy and surgical excision. These preliminary results emphasize the value of co-operative therapeutic trials in a rare tumour, demonstrate the effectiveness of the initial chemotherapy used against Ewing's sarcoma and are in favour of a combined treatment, including systematic excision, for Ewing's sarcomas affecting the ribs.

Adolescent↗
PubMed1980

Provirus DNA sequences in Rous sarcoma cell genome.

Non-producer hamster and virus-producing chicken Rous sarcoma cells contain a complete avian sarcoma virus (ASV)-provirus DNA (pro-DNA). Unlike this, in normal hamster liver DNA to ASV--specific sequences are absent. Moreover, the nuclear chicken Rous sarcoma and chick embryo cell (CEC) DNA preparations contain practically all endogenous chicken virus (ECV)-specific sequences, while the hamster tumor DNA was annealed with only more than half of the ECV-RNA sequences. Thus, the pro-DNA of permissive hosts contains so-called "sarcoma-specific", "common" and "endogenous--specific" nucleotide sequences. The "sarcoma-specific" and "common" sequences are present in the hamster sarcoma pro-DNA, only. Both the pro-DNA of permissive cells and the pro-DNA of non-permissive cells consist of moderately reiterated and unique sequences. The "common" regions of pro-DNA are localized, mainly, in the unique zone, while "sarcoma-specific" and "endogenous-specific" sequences of pro-DNA - in the moderately reiterated and unique zones. The pro-DNA organization of permissive and non-permissive hosts is discussed.

Animals↗
PubMed1980

Karyological and isoenzyme characterization of established human sarcoma cell lines.

Six established human sarcoma cell lines (giant cell tumor of bone B-5GT, fibrosarcoma, B-6FS, cystosarcoma phylloides B-19CS, synovial sarcoma U-4SS and two osteogenic sarcomas U-20S and U-393OS) have been studied and compared to the normal B-41FB fibroblastic cells and the HeLa cells. For cytogenetic and isoenzyme characterization both conventional and G banding techniques as well as the mobility of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PD) were employed. All six sarcoma cell lines had karyotype and LDH patterns of human cells. A study of the chromosome counts distribution revealed a large variability from one sarcoma cell line to the other. There was no evidence of any cross-contamination between the lines or by HeLa cells. This conclusion is based on the detection of G-6-PD with B phenotype, the lack of HeLa marker chromosomes in all sarcoma lines and the presence of Y chromosome in U-4SS and U-393OS derived from male donors. In addition, each sarcoma cell line revealed a group of distinctive marker chromosomes which can serve to identify them and help to control cell line specificity during in vitro culturing.

Cell Line↗
PubMed1984

Prognostic features of sarcomas and mixed tumors of the endometrium.

A retrospective study of 103 patients with endometrial sarcomas treated at the University of Michigan Hospital includes 47 mixed homologous tumors, 32 mixed heterologous tumors, 21 pure homologous sarcomas (endometrial stromal sarcoma), and three pure heterologous sarcomas (rhabdomyosarcomas). Clinical characteristics appeared similar among the four patient groups. Fourteen percent of the patients had received previous pelvic irradiation. Twenty-nine percent of the patients with a clinical stage I or II tumor had extrauterine disease discovered at surgery. Extent of the tumor at the time of surgery strongly correlated with outcome, and only two patients with extrauterine disease were long-term survivors. Life table survival probability at five years was 58% with surgical stage I, 33% with surgical stage II, 13% with surgical stage III, 0 with surgical stage IV, and 5% in patients referred with recurrence. Risk factors predicting treatment failure were analyzed separately in surgical stages I and II using Cox model analysis. There was no difference in risk for treatment failure between pure endometrial stromal sarcoma, mixed homologous sarcoma, or mixed heterologous sarcoma. The strongest factor correlating with a poor outcome was deep myometrial invasion (P less than .001). An adverse trend was detected in those patients with previous pelvic irradiation, with advancing patient age, and with increasing uterine size, although these differences did not reach statistical significance. Neither the presence of heterologous tumor elements nor cervical involvement were found to be adverse prognostic factors.

Actuarial Analysis↗
PubMed1984

[Chemotherapy of advanced bone and soft tissue sarcoma].

The primary site of metastasis of bone and soft tissue sarcoma is the lung. Control of these sarcomas depends upon the prevention and treatment of their pulmonary metastasis. The introduction of a chemotherapy consisting mainly of Adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. However the effectiveness of chemotherapy has not yet been duplicated in soft tissue sarcomas except some childhood sarcomas. We analyzed the clinical data for pulmonary metastasis of osteosarcomas and soft tissue sarcomas. Based on these analyses, we tried to clarify the nature of pulmonary metastasis of these sarcomas and to evaluate its response to treatment, that this would yield clues to future treatment of these sarcomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

[Uterine sarcoma. Retrospective analysis of a series of 22 cases].

37 uterine tumors originally diagnosed as uterine sarcomas at Fondation Bergonié between 1970 and 1982 were histologically reclassified. 15 patients were excluded from this study because of inadequate data or not confirmed initial diagnosis. The 22 remaining cases were classified as leiomyosarcomas 13, endometrial stromal sarcomas 7 and mixed mesodermal sarcomas 2. The mean age of the patients was 56. The cases were classified according to the FIGO staging system. 5 patients had previously undergone (between 1 and 8 years) a subtotal hysterectomy for uterine leiomyoma. 5 patients had stage 1 sarcoma, 13 patients stage III and 2 patients stage IV. 13 patients are dead, 7 are alive without evidence of disease, 2 are alive with evidence of disease. The 5 year actuarial survival rate was 30%. Tumor extent at diagnosis was not correlated with survival. Analysis of failures revealed : 4 metastatic, 5 metastatic and pelvic and 6 isolated pelvic failures. Prognosis was not significantly different between leiomyosarcomas and endometrial stromal sarcomas. There was no pelvic failure in patients with stage I sarcoma (treated by surgery plus radiotherapy). Survival was not found to be correlated with histopathological grade as described in soft tissue sarcomas. Nevertheless a correlation (non significant) was found between survival and mitosis count. Chemotherapy (Cyvadic) was administered in 8 advanced tumors with partial response (always below 50% of the initial tumor) in 5 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Preoperative regional chemotherapy and rapid-fraction irradiation for sarcomas of the soft tissue and bone.

Conventional treatment for high grade and large sarcomas uses a radical surgical approach, including amputation, in many patients. We evaluated a limb-sparing treatment approach using preoperative regional Adriamycin chemotherapy and rapid-fraction radiation therapy. Thirty patients with soft tissue or skeletal sarcoma were treated in a prospective, nonrandomized clinical trial to evaluate local disease control and limb salvage in these patients who would otherwise require amputation or face a high risk of local recurrence with surgical excision. Almost all patients had large tumors with grade III histologic findings. All patients had a three day intra-arterial regional chemotherapy infusion with Adriamycin (100 milligrams total dose), followed within ten days by rapid-fraction irradiation (3,000 rads over a two week period) prior to surgical excision of the tumor. The size and location of the sarcoma permitted only a marginal resection in one-half of the patients, while the remainder could be excised in a three dimensional en bloc manner. Almost all patients received post-operative systemic Adriamycin chemotherapy (450 milligrams per square meter given intravenously over a six month period). Two of six patients with significant wound complications later required amputation. Only one patient (3 per cent) has had a local recurrence of sarcoma develop after a mean follow-up of 22 months (range nine to 42 months), and 90 per cent of the patients have a useful extremity. The three year survival rate was 68 per cent for soft tissue sarcomas, compared with an expected survival rate of 38 per cent for published historical control studies. The patient with osteogenic sarcoma has a projected 83 per cent survival rate at 18 months after treatment. This multimodality approach is an effective treatment for local disease control in patients with high risk sarcoma. It permits limb salvage in most patients without compromising the survival rates.

Adolescent↗
PubMed1983

Energy metabolism in nongrowing mice with sarcoma.

The time course of energy metabolism has been studied in weight-stable and nongrowing mice with a transplantable methylcholanthrene-induced sarcoma. Daily oxygen consumption and carbon dioxide production were measured in relation to the tumor growth from the time of tumor implantation. The time course of energy dynamics was related to the end-state changes in body composition. Freely fed sarcoma-bearing mice decreased their whole-body energy expenditure in proportion to the tumor growth. This was due to the accompanying anorexia. The alteration in oxygen consumption and carbon dioxide production was continuously evident 24 hr/day in sarcoma-bearing mice. The tumor-bearing mice lost body fat and had decreased respiratory quotient, while pair-fed controls maintained their body composition, and their respiratory quotients agreed with the food respiratory quotient. Loss of body lipids in freely fed sarcoma-bearing mice reflected a negative energy balance, accompanied with increased fat oxidation, while maintenance of body composition in pair-fed controls reflected a decreased metabolic rate. Sarcoma-bearing mice showed a significantly higher energy expenditure in relation to their food intake compared to that of pair-fed controls. Estimates of partition of oxygen uptake in sarcoma-bearing mice support that both the host and the tumor account for the elevated energy expenditure. This study has confirmed a small but significantly increased energy expenditure in sarcoma-bearing mice, which was continuously present 24 hr/day in spite of unlimited availability of food. This illustrates the fatal outcome of experimental cancer.

Animals↗
PubMed1982

Human tumor-associated antigens detected by serological techniques: analysis of autologous humoral immune responses to primary and metastatic human sarcomas by an enzyme-linked immunoabsorbent solid-phase assay (ELISA).

An enzyme-linked immunoabsorbent solid-phase assay was developed for measuring humoral immune responses to human sarcoma-associated antigens, and binding of autologous sera to 1-butanol extracts of fresh sarcomas was determined. Binding of autologous sarcoma patients' sera was reproducible and significantly greater than normal sera. Extensive quantitative competitive binding inhibition tests with normal tissue were unable to completely remove binding to autologous tumor extracts by sera from five of eight patients, thus demonstrating a quantitatively distinct specificity present on tumor tissue. An antibody in autologous sera recognizing a determinant on normal adult tissue was also identified. Autologous humoral immune responses to soluble 1-butanol extracts of paired primary and metastatic human sarcomas from six patients from this group were assessed. Antibody binding was observed to both primary and metastatic tumor extracts; however, binding was significantly greater to the primary extracts in 14 of 16 autologous serum-tumor combinations tested. Absorption and competitive binding inhibition studies demonstrated the presence of common sarcoma-associated antigens in extracts of both the primary tumor and its metastasis from all patients studied. Two individual metastases from the same patient also possessed antigens recognized in that patient's primary tumor extract in two cases. Autologous sarcoma patients' sera recognize sarcoma-associated antigens common to both the primary tumor and its metastasis.

Antibody Formation↗
PubMed1995

Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts.

Cytogenetic analysis of Ewing's sarcoma, primitive neuroectodermal tumors and Askin tumors revealed characteristic translocations t(11;22) or t(21;22). Molecular analysis of these translocations revealed 5'-region of EWS gene (from band 22q12) is fused to the 3'-region of either Fli-1 gene (from band 11q24) or erg gene (from band 21q22). Functional characterization of the EWS-Fli-1 and EWS-erg chimeric proteins suggested that they function as transcriptional activators. In order to develop therapeutic agents, it is essential to know whether expression of the EWS-fusion gene products is coupled to tumorigenicity of Ewing's sarcoma cells and if targeting the EWS-fusion products results in loss of tumorigenicity of Ewing's sarcoma cells. For this reason, we have made stable Ewing's sarcomas expressing antisense EWS-Fli-1 or EWS-erg expression plasmids. Expression of antisense EWS fusion transcripts resulted in a significant loss of endogenous EWS-Fli-1 and EWS-erg proteins in Ewing's sarcoma cells. These cells expressing antisense EWS fusion transcripts showed loss of anchorage independent growth and tumorigenicity in nude mice unlike the parental Ewing's sarcoma cells. These results demonstrate the necessity of a certain threshold level of expression of EWS-fusion products in the clonogenicity and tumorigenicity of Ewing's sarcoma cells and therefore emphasizes the importance of targeting the EWS-fusion products as a therapy for Ewing family of tumors.

Animals↗
PubMed1995

Effects of hyperbaric oxygen on S-180 sarcoma in mice.

The contents of oxygen free radicals (OFRs) and malondialdehyde (MDA) in S-180 sarcoma tissues were measured in four groups of mice: an untreated normoxic group, a normoxic hyperbaric group, a hyperbaric oxygen group, and an HBO group treated with superoxide dismutase (SOD). Measurements were done by electron resonance and spectrophotometry, and observations were made on the volume, weight, necrosis incidence rate of sarcoma tissues, and mortality in all groups. The OFR and MDA content in sarcoma tissues in the HBO group was significantly higher than those of the control groups (P < 0.001); necrosis incidence of sarcoma tissues and the survival rate of mice were higher; the time required for necrosis was shorter, and the volume and weight of sarcoma tissues were smaller and lighter than those of the control groups (P < 0.01). The results suggest that SOD cannot completely eliminate OFRs produced by hyperbaric exposure, although the role of HBO in producing more OFRs can be counterbalanced by SOD to a certain degree. Apparently HBO can check the growth rate of sarcoma and accelerate the necrosis of S-180 sarcoma cells.

Animals↗