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PubMed2005

[Intimal sarcoma of the inferior vena cava].

INTRODUCTION: Primary sarcomas of the great vessels, that is, the aorta, pulmonary artery, and inferior vena cava, are rare. They can be classified according to the location of the sarcoma in the vessel wall and by their gross appearance. Most often they are leiomyosarcomas or fibrosarcomas. CASE: We report here a case of an intimal sarcoma of the inferior vena cava. Histological and immunohistochemical findings confirmed the diagnosis for this 17-year-old girl and distinguished it from leiomyosarcoma and angiosarcoma, both of which have better prognoses. DISCUSSION: Intimal sarcoma of the inferior vena cava is rare and difficult to diagnose before surgery or biopsy. Histologically, it is a poorly differentiated tumor with the worst prognosis among the primary vascular sarcomas. Pathologic findings and immunohistochemical staining are useful for a positive diagnosis.

Adolescent↗
PubMed1998

Expression of p21WAF1/CIP1 in soft tissue sarcomas: a comparative immunohistochemical study with p53 and Ki-67.

The p53 gene controls the cell cycle by transactivating p21WAF1/CIP1, a cyclin dependent kinase (cdk) inhibitor. By inhibiting cdks, p21WAF1/CIP1 regulates the cell cycle by blocking the G1 to S phase transition. In this study, we analyzed the immunohistochemical expression of p21WAF1/CIP1 in 66 soft tissue sarcomas and its relationship to p53 and the cell cycle proliferation antigen Ki-67. Expression of p21WAF1/CIP1, was detected in 76% of the tumors and p53 in 26%. All malignant schwannomas, synovial sarcomas, leiomyosarcomas and gastrointestinal stromal tumors expressed p21WAF1/CIP1. The majority of angiosarcomas, dermatofibrosarcomas, and fibrosarcomas showed low expression or were negative for p21WAF1/CIP1. Ewing's sarcomas, liposarcomas, and malignant fibrous histiocytomas were heterogeneous in their expression of p21WAF1/CIP1. Combining p53 and p21WAF1/CIP1 staining, the following four patterns were observed: 23% of the tumors showed the p53+/p21+ pattern; 53% showed the p53-/p21+ pattern; 3% showed the p53+/p21- pattern and 21% were negative for both p53 and p21WAF1/CIP1. There was no correlation between Ki-67 and p21WAF1/CIP1 or p53 staining. Our results show that soft tissue sarcomas, independent of their histologic subtype, frequently express p21WAF1/CIP1 which is probably important in their tumorigenesis. Additionally, p21WAF1/CIP1 may play a role in determining the efficacy of various cell cycle-directed therapies in soft tissue sarcomas.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1988

Glucocorticoid receptor-mediated effects on rat fibrosarcoma growth.

Glucocorticoid receptors are present in most normal and malignant mammalian cells. To examine the hypothesis that the growth of methylcholanthrene-induced malignant sarcoma is glucocorticoid dependent, we evaluated the behavior of malignant fibrosarcoma (MCA) in adrenalectomized rats treated with either normal saline or deoxycorticosterone acetate and in intact rats treated with placebo or with the glucocorticoid receptor antagonist RU 486. Survival, tumor weight, and loss of body weight (an index of cachexia) were measured. In MCA-bearing rats, neither survival nor loss of body weight was affected by bilateral adrenalectomy or by treatment with RU 486. Tumor weight and time-integrated tumor volume, however, were significantly less in bilaterally adrenalectomized rats without deoxycorticosterone acetate replacement than in animals treated with deoxycorticosterone acetate. Similarly, tumor weight and time-integrated tumor volume were less in intact animals treated with RU 486 than in intact animals treated with placebo. The glucocorticoid receptors in the tumor cells had similar binding capacity (Ro) and equilibrium dissociation constant (Kd) as in control rat fibroblasts. These results suggest that the growth of MCA sarcoma cells is partially dependent upon glucocorticoids. This effect of glucocorticoids, however, was not of sufficient magnitude to improve survival and prevent cachexia. We conclude that glucocorticoids appear to influence MCA sarcoma growth in the rat, and that glucocorticoid receptor blockade, perhaps in combination with other antitumor agents, merits future study in the treatment of malignant tumors.

Adrenalectomy↗
PubMed1995

Cytokeratin positivity in fine-needle aspirates of melanomas and sarcomas.

Cytokeratin (CK) positivity has been considered a specific marker for epithelial differentiation in cytologic specimens. After observing CK reactivity in fine-needle aspirate (FNA) specimens of melanoma and sarcoma, a retrospective study of melanomas and sarcomas was undertaken to investigate the frequency of anomalous CK staining in these neoplasms. Cell block sections and/or restained smears from 36 melanomas and sarcomas were retrospectively stained for CK. An appropriate internal positive control (HMB-45), S100 protein, or vimentin) was also used to insure antigen preservation. Of the smears from 19 melanomas, five revealed focal strong CK positivity of neoplastic cells, two cases showed faint or equivocal staining, 11 cases were negative for CK, and one could not be interpreted due to inadequate controls. Of the smears from 14 sarcomas, two showed positivity for CK (one fibrosarcoma and one condrosarcoma), 11 were negative, and one had inadequate controls. The number of CK positive cells was less than that observed with the appropriate internal positive control antibodies. Destained Papanicolaou smears were superior to Diff-Quik smears for retrospective immunocytochemical stains. Cell block sections from four of the melanomas and one sarcoma demonstrated no aberrant staining. Since cytokeratin positivity occasionally is seen in nonepithelial neoplasms, its presence alone cannot be used to make a definitive diagnosis of carcinoma. Therefore, a panel of immunocytochemical stains should be utilized in diagnosis of FNA specimens.

Biopsy, Needle↗
PubMed1984

Potentiation of anticancer agents by new synthetic isoprenoids. II. Inhibition of the growth of transplantable murine tumors.

The antitumor effects of combinations of synthetic isoprenoids-decaprenylamine.HCl, N-(p-methylbenzyl)decaprenylamine.HCl [N-(PMB)-decaprenylamine.HCl], and decaprenoic acid-with anticancer agents were studied in male ICR mice with ascites sarcoma 180 (S180) and in male BALB/c mice with fibrosarcoma Meth A. Decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl, and decaprenoic acid were tested in combination with bleomycin A2 (BLM) on S180. Decaprenoic acid was also examined in combination with BLM or 5-fluorouracil (FUra) for effects on fibrosarcoma Meth A. The dosages of synthetic isoprenoids used in the combination therapy were much below the median lethal dose. In the low-dosage schedule, decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl or decaprenoic acid considerably enhanced the antitumor effect of BLM on S180; e.g., the T/C value (mean survival time of treated mice/mean survival time of controls) for decaprenylamineHCl plus BLM, N-(PMB)-decaprenylamine.HCl plus BLM, or decaprenoic acid plus BLM was 294, 357, and 279% respectively, and the combinations increased life-span 2.4-fold, 2.3-fold, or 1.8-fold, respectively, as compared to the effects of BLM alone. The combination of BLM or FUra with decaprenoic acid, when administered by iv injection to mice with fibrosarcoma Meth A (solid tumor system), did not produce synergism. However, a preventive effect of decaprenoic acid monotherapy was observed: Decaprenoic acid at 3 mg/kg resulted in 38.9% suppression of tumor growth 21 days after inoculation.

Animals↗
PubMed1995

Sarcomas in organ allograft recipients.

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.

Humans↗
PubMed1985

Experimentally produced synovial sarcoma in mice.

BALB/c and C57 B1/6 mice which received weekly subcutaneous injections of a cannabinoid developed tumors at the points of injection. In the groin the tumors were fibrosarcomas, while in the interscapular region they were anaplastic sarcomas and synovial sarcomas. The latter developed faster and were larger in cannabinol - and cannabidiol-treated C57 B1/6 mice than in delta 9-tetrahydrocannabinol-treated BALB/c mice. This difference could not be attributed to strain differences. 2 cannabidiol- and 1 cannabinol-treated C57 B1/6 females with the fastest growing synovial sarcomas were pregnant and, in addition, 2 of them developed mammary adenocarcinomas, indicating that they were rich in estrogen. On the other hand, it is known that delta 9-tetrahydrocannabinol causes a decrease in the sex hormone. It is consequently thought that the cannabinoids are only initiators of synovial sarcoma, while growth or promotion of the latter is influenced partially or entirely by the sex hormone.

Adrenal Gland Neoplasms↗
PubMed1987

Inhibition of established rat fibrosarcoma growth by the glucose antagonist 2-deoxy-D-glucose.

Sarcoma cells exhibit higher rates of glycolysis than normal tissues and may be dependent on glucose utilization for growth. Accordingly, we tested the ability of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) to inhibit the growth of an established methylcholanthrene-induced rat fibrosarcoma in three groups of F344 rats with increasing subcutaneous inoculations of tumor (2 X 10(6) cells, 1 X 10(7) cells, and 1 mm tumor fragments). Rats were randomized to receive 2-DG or saline solution at doses of 0.75 gm/kg, 1.5 gm/kg, or 1.75 gm/kg, beginning 3 days after tumor implantation and continuing for 10 days. Tumors were removed and weighed on day 14. We measured tissue [14C]-2-DG levels in tumor, brain, liver, and muscle after intraperitoneal injection of radiolabeled 2-DG. In these same tissues we determined the activity of glucose-6-phosphatase (G-6-Pase), an enzyme which dephosphorylates the intracellular glycolytic inhibitor 2-DG-6-phosphate, thus reversing the antitumor effect of 2-DG. All groups treated with 2-DG had a significant reduction in tumor weight of 50% to 70% when compared with saline solution-treated controls. Toxicity was substantial at the highest dose of 2-DG, but minimal toxicity was noted at intermediate and low doses. Tumor had the greatest uptake of [14C]-2-DG, with low levels of G-6-Pase leading to prolonged retention and highest tissue levels of radiolabeled 2-DG. Use of 2-DG inhibits established sarcoma growth because it is rapidly transported into tumors, cannot be metabolized after phosphorylation, and is dephosphorylated and released slowly from tumor cells. Rat sarcoma growth is dependent on glucose utilization and can be effectively inhibited by glucose antagonism.

Animals↗
PubMed1990

Fractionation sensitivity and immunological status in radiation treated murine sarcomas.

The fractionation sensitivity of a strongly immunogenic murine fibrosarcoma (FSa1) was tested in highly immunosuppressed (18 Gy whole body irradiation, 10 fractions, 4 days and bone marrow salvage) and control mice (C3Hf/Sed). Radiation was delivered to extremity-transplanted tumors after reaching a volume of 250 mm3. Two, 4 and 10 fractions were used, delivering the radiation treatments to uniformly hypoxic tumors (by extremity clamping). Doses needed to attain a 10 day tumor-growth delay (TGD) over the volume range 250 mm3 to 1000 mm3, and doses necessary to reach a tumor-control probability of 50% (TCD50), were calculated for the three fractionation schedules. Immunosuppression influenced the TCD50 values profoundly: 56.2, 71.5, and 101.4 Gy in control mice versus 76.6, 104.2, and 141.1 Gy in immunosuppressed mice for 2, 4, and 10 fractions, respectively. The alpha/beta ratios estimated by reciprocal-dose analysis using the TGD and TCD50 assays were not significantly different, nor were the alpha/beta ratios of tumors grown in immunosuppressed mice (TGD 5.7 Gy; TCD50 5.3 Gy) as compared with tumors in control recipients (TGD 3.5 Gy; TCD50 4.9 Gy). In addition, direct analysis was used with the fractionated TCD50 data from control and immunosuppressed animals to calculate a immunity-related-cell-kill factor. For 250 mm3 tumors a 1.29 [0.99 . . . 1.59, 95% confidence interval] log10-kill factor was obtained.

Animals↗
PubMed1984

Macrophage activation and generation of tumoricidal activity by liposome-associated human C-reactive protein.

The effect of human C-reactive protein incorporated into multilamellar vesicles (CRP-MLV) was studied in assays of macrophage function. Peritoneal exudate macrophages from C57BL/6 mice phagocytosed CRP-MLV in vitro more rapidly than multilamellar vesicles bearing comparable amounts of immunoglobulin G. Exposure of peritoneal exudate macrophages in vitro to CRP-MLV resulted in development of tumoricidal activity against syngeneic T241 fibrosarcoma and B-16 melanoma cells and against allogeneic Sarcoma 1 cells. Peritoneal exudate macrophages obtained from mice given CRP-MLV i.p. demonstrated antitumor activity against the syngeneic T241 fibrosarcoma in a Winn-type assay, and when challenged in vitro with phorbol myristate acetate, they showed elevated superoxide anion production. Administration of CRP-MLV i.p. did not enhance natural killer activity of spleen cells, however. In superoxide anion assays, CRP-MLV were approximately 10 to 100 times more effective than free C-reactive protein. Results indicate that C-reactive protein is capable of activating macrophages, thus supporting the concept of C-reactive protein as an immunomodulator.

Animals↗