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PubMed1976

Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus.

The hypothesis that surface modulating assemblies containing microfilaments and microtubules and altered after cellular transformation was tested on cells infected with temperature-sensitive mutants of avian sarcoma virus. Untransformed cells (mouse 3T3 and chick fibroblasts), cells transformed by simian virus 40 (SV 3T3), and chick fibroblasts infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV-A-infected cells) were first compared for differences in microfilament and microtubule patterns after treatment with fluorescein-labeled antibodies to actin and tubulin. Transformed cells showed disappearance of ordered stress microfilaments and thickened or diffuse alterations of microtubular arrays. At restrictive temperatures (41 degrees), chick fibroblasts infected with a temperature-sensitive mutant (ts 68) of Rous sarcoma virus showed normal patterns of stress fialments and radial microtubular arrays originating in 1 or 2 centrioles. At permissive temperatures (37 degrees), these patterns were disordered and resembled those of SR-RSV-A-infected cells. After a shift from 41 degrees to 37 degrees, the changes in microtubules were observed in the majority of cells within 1 hr. These changes were reversible and did not result from the inability of tubulin to polymerize. In ts 68-infected cells at permissive temperatures, concanavalin A induced much less surface modulation (inhibition of receptor mobility) than at restrictive temperatures. These results suggest that cellular transformation alters both the structure and function of surface modulating assemblies and prompt the hypothesis that products of viral transforming genes may affect these assemblies with a consequent loss of growth control.

Actins↗
PubMed1994

Comparison of fibrosarcomas that developed at vaccination sites and at nonvaccination sites in cats: 239 cases (1991-1992).

Questionnaires were sent to veterinarians who had submitted a fibrosarcoma from a cat to the surgical pathology services of the veterinary schools of the University of Pennsylvania and Tufts University between Jan 1, 1991 and June 30, 1992. Questionnaire items included signalment, FeLV and feline immunodeficiency virus status, site of sarcoma, vaccination site, vaccines used, treatment, biologic behavior of the tumor, and final outcome. Data were analyzed, using Student's t-test for continuous data, chi 2 test for categoric data, and log-rank test for survival estimates. Comparing results for cats with vaccination-site (VS) tumors and nonvaccination-site (NVS) tumors, we determined that VS tumors developed in younger cats and were larger than NVS tumors. Although VS sarcomas were biologically aggressive and redeveloped more often than NVS sarcomas, metastasis was not detected, and cats with VS tumors survived longer than cats with NVS tumors. Vaccination-site sarcomas developed in cats after injection of many types of vaccines, administered singularly or in combination. Of the cats in the VS group administered a single vaccine, 37% were given rabies, 33% were given feline viral rhinotracheitis/calicivirus/panleukopenia virus, and 30% were given FeLV vaccines. Cats with VS tumors were more likely to have received FeLV vaccine and less likely to have received rabies vaccine than those with NVS tumors. Although vaccines produced by certain manufacturers were used most often in cats with VS and NVS sarcomas, it was believed that this probably represented marketing practices and brand popularity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1995

Homozygous deletion frequency and expression levels of the CDKN2 gene in human sarcomas--relationship to amplification and mRNA levels of CDK4 and CCND1.

Homozygous deletions of the putative tumour-suppressor gene CDKN2, which encodes an inhibitor of cdk4, have been detected in a high percentage of cancer cell lines of various histological types. In the present study, 109 human sarcomas were examined for homozygous deletions and for mRNA expression levels of the CDKN2 gene. Altogether, deletions were found in only eight (7%) of the cases, but, interestingly, in two (of eight) malignant Schwannomas and in two (of five) rhabdomyosarcomas. In comparison, such deletions were seen in only one (of 21) osteosarcomas and in none of 20 MFHs and 21 liposarcomas. Notably, highly elevated CDKN2 mRNA levels were found in 33% of the sarcomas, whereas no detectable transcript was present in 12 normal tissues. Amplifications of CDK4 and CCND1 (cyclin D1) were observed in 11% and 4% of the sarcomas respectively, but never in tumours with CDKN2 deletions. The level of CDK4 mRNA expression was increased in nine tumours in addition to the 12 samples with CDK4 amplification. Increased levels of the cyclin D1 transcript was found in 37 cases, four with and 33 without amplification. The data indicate that aberrations of these functionally related genes, or in regulation of the expression of the kinase, the activator or the inhibitor, may participate in sarcoma development. Furthermore, the data suggest that homozygous CDKN2 deletions may be of dissimilar significance in different sarcoma subtypes.

Animals↗
PubMed1976

Collagenolytic enzyme in solid Tawa sarcoma.

In order to demonstrate a collagenolytic enzyme in a tumor, solid Tawa sarcoma was subjected to a tissue culture technique. Salt- and acid-soluble collagen used as substrate was extracted from the rat skin and tail tendon. The tumor mass used was obtained on the 5th, 8th, and 11th days after subcutaneous transplantation of ascites Tawa sarcoma cells. Each tissue fragment in the inner and outer layers of the tumor mass was incubated on collagen gel at 37 degrees for 4 days, and collagenolytic activity was determined by comparing the relative content of hydroxyproline in the attacked collagen which was separated by means of centrifugation. All fragments were found to possess collagenolytic activity with some variation. Higher activity was observed in the outer layer than in the inner layer. Tumor fragments were cultured, and the collagenolytic enzyme was isolated from the culture medium and concentrated by ammonium sulfate precipitation and acrylamide disc electrophoresis. Collagenolytic enzyme activity was examined for its mode of attack on native collagen.

Animals↗
PubMed1989

[Increase in the generation of superoxide radicals and in the inhibitory effect on Yoshida sarcoma of anthracycline antitumor agents by ultrasound].

The antitumor effects of ultrasonic (US) irradiation in combination with the administration of an anthracycline drug, such as adriamycin and THP-adriamycin, were investigated from a viewpoint of the generation of superoxide radicals (SOR). In the in vitro experiments, the generation of SOR by US irradiation was measured by the amount of cytochrome c reduced. The addition of the drug stimulated the generation of SOR by US irradiation. In the in vivo experiments, Donryu rats inoculated subcutaneously by Yoshida sarcoma were treated with US irradiation in combination with the drug. During US irradiation, the temperature of the rat tissue irradiated was kept below 37 degrees C to avoid thermal effects. To know the optimum timing of US irradiation after the administration of the drug, the drug concentrations in the tumor and blood were determined and the time course of drug concentrations was analyzed pharmacokinetically. The effects of drugs and/or US irradiation showed antitumor activity judged by the growth of the tumor size or the survival time of rats. The combination treatments of US irradiation with the drug marked additional or synergistic effects on Yoshida sarcoma. Considering the relationship between the antitumor effect in vivo and the generation of SOR in vitro, the increase of anti-tumor effect of US irradiation by the anthracycline drug may be caused by the stimulation of the generation of SOR.

Animals↗
PubMed1979

Induction of osteogenic sarcomas and tumors of the hepatobiliary system in nonhuman primates with aflatoxin B1.

The carcinogenicity of aflatoxin B1 (AFB1) has been under evaluation in nonhuman primates for the past 13 years. A total of 47 Old World monkeys, chiefly rhesus and cynomolgus, have received AFB1 i.p. (0.125 to 0.25 mg/kg) and/or p.o. (0.1 to 0.8 mg/kg) for 2 months or longer, and 12 are currently alive and without evidence of tumor. Thirteen of the 35 monkeys necropsied to date (37%) developed one or more malignant neoplasms, yielding an overall tumor incidence of 28%. Five of the neoplasms were primary liver tumors (2 hepatocellular carcinomas and 3 hemangioendothelial sarcomas), and 2 cases of osteogenic sarcoma were found. Other tumors diagnosed were 6 carcinomas of the gall bladder or bile duct, 3 tumors of the pancreas or its ducts, and one papillary Grade I carcinoma of the urinary bladder. The tumors developed in animals receiving an average total AFB1 dose of 709 mg (range, 99 to 1354 mg) for an average of 114 months (range, 47 to 147 months). Fifteen of the 22 necropsied monkeys (68%) without tumor showed histological evidence of liver damage, including toxic hepatitis, cirrhosis, and hyperplastic liver nodules. These animals had received an average total AFB1 dose of 363 mg (range, 0.35 to 1368 mg) for an average of 55 months (range, 2 to 141 months). Our results indicate that AFB1 is a potent hepatotoxin and carcinogen in nonhuman primates and further support the hypothesis that humans exposed to this substance may be at risk of developing cancer.

Aflatoxins↗
PubMed1994

[Diagnostic imaging in immunosuppressed subjects: malignant tumors].

Each state of immunodeficiency is complicated by an increased incidence of certain types of cancer. The risk factors in the development of malignancies increase in a time-dependent relationship with the age of the defect in cell-mediated immunity and some tumors will develop at fairly distinct time intervals during immunodeficiency. Thus, Kaposi's sarcoma appears mostly when the degree of immunodeficiency is slight (average time: 23 months), non-Hodgkin's lymphoma is prevalent in an intermediate phase (average time: 37 months) and some carcinomas will appear only if immunodeficiency lasts many years. Many hypotheses have been suggested as to the biological mechanisms by which an immunity defect contributes to the development of malignancies: the most credible of them is the one suggesting the action of some oncogenic viruses which are not sufficiently controlled by the immune system. Kaposi's sarcomas and non-Hodgkin's lymphomas are the most common types of tumor in AIDS patients. Other tumors--except for Hodgkin's lymphoma--are seldom reported in HIV patients. However, the incidence of carcinomas is thought to be likely to increase in the next few years, because the longer survival of HIV patients, without strengthening their immune system, will unfortunately allow the tumors with longer onset time to develop. As for Kaposi's sarcomas and non-Hodgkin's lymphomas, the major epidemiological data are reported, together with some etiopathogenetic hypotheses and the main clinical and radiologic patterns. Other solid tumors in HIV patients and their clinical and radiologic features are reported too. Our series of cases was collected by the GICAT (Italian Cooperative Group on AIDS-related Tumors) which coordinates epidemiological studies, supports medical research and standardizes the treatment of patients suffering from HIV-related tumors.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Sarcomas of the great vessels. A clinicopathologic study.

BACKGROUND: There are few reports comparing the clinicopathologic features of sarcomas of the aorta (SA), sarcomas of the inferior vena cava (SIVC), and sarcomas of the pulmonary artery (SPA). METHODS: The authors retrospectively reviewed 11 SA, 16 SIVC, and 16 SPA, and compared clinical, pathologic, and immunohistochemical findings. RESULTS: The mean age at presentation for SA was 62.3 +/- 17.3 years versus 41.3 +/- 17.1 for SPA; mean age for SIVC was 49.9 +/- 18.8. Nine of 11 SA and 14 of 16 SPA were grossly confined to the lumen, compared with only two SIVC. Luminal sarcomas were classified as poorly differentiated (intimal), angiosarcoma or leiomyosarcoma. Eight SA, 13 SPA, and one SIVC were of the intimal type and were composed of fibroblastic or myofibroblastic cells; five had "storiform" areas typical of malignant fibrous histiocytoma, and all had areas of necrosis. Intimal SPA were more likely myxoid than SA, and osteosarcomatous differentiation was present only in SPA (three cases). Intimal sarcomas were negative for desmin, Factor VIII-related antigen, S-100 protein, and CD34/QBend; all were positive for vimentin and most showed positive cells for smooth muscle actin. One luminal SA and one luminal SPA were histologically typical of angiosarcoma. Two SPA, 2 SA, and 14 SIVC were predominantly mural, most of which were leiomyosarcomas. The mean survival of intimal SA was poor (5 months), compared with 37 months for SIVC and 23 months for intimal SPA. CONCLUSION: SA, SPA, and SIVC differ in their clinical presentation and survival. Most SA and SPA sarcomas are aggressive, probably derived from intimal cells that show myofibroblastic differentiation. SIVC are usually derived from medial smooth muscle and are relatively well differentiated leiomyosarcomas.

Adolescent↗
PubMed1996

Clinical phase I and pharmacokinetic trial of vinorelbine administered as single intravenous bolus every 21 days in cancer patients.

We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine administered as a bolus injection every 21 days. The aim was to evaluate a schedule with longer treatment intervals than one week and to determine the toxicity pattern of such a schedule. A total of 13 patients (pts) with solid tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2 pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were entered [9 male, 4 female, median age: 56 years (range: 37-69)]. Dose levels were 35, 40 and 45 mg/m2 with a total of 26 cycles administered. At 40 mg/m2, 2/6 pts developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m2 developed a grade 4 leuko- and granulocytopenia. Non-hematological toxicities were mild to moderate. Neurologic toxicity except for constipation was mild. Constipation occurred at 35 mg/m2 in 1/6 pts WHO grade 4, at 40 mg/m2 in 2/6 pts WHO grade 3 and at 45 mg/m2 in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor response was observed. Vinorelbine pharmacokinetics were analysed in whole blood and plasma and were similar to previously published studies using < or = 30 mg/m2. Our results confirm a high affinity of vinorelbine to corpuscular blood elements. We conclude that the MTD of vinorelbine administered once every 21 days as bolus injection is 40 mg/m2, the dose-limiting toxicities are constipation and granulocytopenia and the recommended dose for subsequent Phase II trials is 35 mg/m2.

Adult↗
PubMed1991

DNA ploidy of spindle cell soft-tissue tumors and its relationship to histology and clinical outcome.

With the use of fresh cell suspensions, the DNA ploidy of 11 benign and 27 malignant spindle cell soft-tissue lesions was determined by flow cytometry (37 cases) and/or image cytometry (35 cases). Of the 27 malignant lesions, 10 were low- or intermediate-grade sarcomas, and 17 were high-grade sarcomas. In the malignant lesions, the DNA ploidy was correlated with the histologic grade and the clinical outcome. Of the 11 benign lesions, six had a diploid DNA ploidy pattern, and five were nondiploid by either flow cytometry or image cytometry. All benign cases had a favorable outocome regardless of ploidy. Eight of the 10 low- or intermediate-grade malignant lesions were diploid, whereas two were nondiploid. Of the 17 high-grade sarcomas, 15 were nondiploid by either method of measurement and nine by both. Of the 10 diploid malignant tumors, only one had an unfavorable outcome (malignant mesothelioma with biopsy only), whereas of the 17 malignant lesions that were nondiploid, five had no evidence of recurrent disease, three cases recurred, eight patients died of disease, and one patient died of an unrelated cause. We concluded that (1) ploidy does not differentiate benign from malignant spindle cell soft-tissue tumors, (2) the nondiploid DNA pattern is more common in high-grade than in low- or intermediate-grade sarcomas, and (3) there is a statistically significant relationship between nondiploidy and a worse clinical outcome in sarcomas.

Adult↗
PubMed2005

[Thermoradiochemotherapy of inoperable soft-tissue sarcoma].

Three groups of patients with inoperable soft-tissue sarcoma received preoperative radiotherapy (57), thermoradiotherapy (102) and thermoradiochemotherapy (16) (n=175). Five year recurrence-free survival in group 1 was 37+/-7%, group 2 48+/-6%, and group 3 - 56+/-1,7%. Patients survived 5 years and more in group 3 (60+/-2%), group 2 - 50+/-7%, and group I 44+/-8% (p>0.05). Local hyperthermia used in conjunction with radio- and chemoradiotherapy was followed by a significant rise in the rate of complete and partial tumor regression.

Adult↗
PubMed1977

[Therapeutic results in sarcoma of the uterus (author's transl)].

60 cases of sarcoma of the uterine body were treated at the Ist Department of Obstetrics and Gynaecology, Vienna University, during the period 1960 to 1971. Treatment consisted of combined surgery and irradiation (37 cases), surgery alone (8 cases) and irradiation only (14 cases). The 5-year survival rate was 53.3%.

Adult↗
PubMed1994

Soft-tissue sarcoma of the extremity. Experience with limb-sparing surgery.

OBJECTIVES: To assess the degree to which limb-sparing surgery is implemented in patients with soft-tissue sarcoma, and its outcome. DESIGN AND SETTING: A detailed review of 40 patients who were all tertiary referrals to one surgeon, and general review of all 215 patients with sarcoma treated in South Australia between 1986 and 1992. INTERVENTIONS: Conservation of the limb by wide resection or marginal resection of soft tissue, combined when necessary with radiotherapy. Amputation was used when limb conservation failed or was not possible. MAIN OUTCOME MEASURES: Median survival time after treatment. RESULTS: Limb-sparing treatment was successful in 37 of the group of 40 patients. Thirty-two patients received adjuvant radiotherapy, and 19 received chemotherapy. Median survival time was 35 months. Review of all 215 patients with sarcoma revealed a higher initial amputation rate and a lower use of combined treatment methods than in our series. Twenty-six patients (65%) were initially incorrectly diagnosed before referral, resulting in a median delay in treatment of 16 weeks. CONCLUSIONS: The concept of limb-sparing surgery is well established, but is not yet as widely practised for limb sarcomas as it could be. Delay in diagnosis is a significant problem.

Adolescent↗
PubMed1990

Sarcomas in three generations of a family with neurofibromatosis.

The development of sarcomas in three generations of a family with neurofibromatosis (NF) is described. A 7-month-old boy developed a prostatic rhabdomyosarcoma. Family history revealed that his maternal grandmother had died of a malignant peripheral nerve sheath tumor at age 37 years and had been affected with neurofibromatosis. His mother (aged 36 years) has also developed a malignant peripheral nerve sheath tumor and NF has been confirmed in both mother and son. This family illustrates a cluster of sarcomas associated with NF and shows the importance of thorough investigation of reported family illnesses.

Adult↗
PubMed1963

MALIGNANCY IN SCARS, CHRONIC ULCERS, AND SINUSES.

A collection of 44 cases of malignancy in scars, chronic ulcers, and sinuses, included the following predisposing lesions: a 20-year-old sinus from ischial bursitis, a 23-year-old bed sore, a congenital gumma about 50 years old, three burn scars (average age of scar 56 years), 11 sinuses from chronic osteomyelitis, and 27 chronic ulcers of the leg. The osteomyelitis cases included two rapidly fatal sarcomas, one in a sinus present for 16 years, the other in a 20-year-old sinus. The remaining tumours in this group were squamous carcinomas that developed in sinuses with an average duration of 37 years. In the cases of varicose ulcer, the ulcer had been present on the average for 21 years before the onset of malignancy. One patient in this group, with an ulcer not known to be more than five years old, developed a sarcoma that was fatal in six months. The biopsy diagnosis was difficult in 17 cases, including one of the cases of sarcoma. The difficulty was greatest in cases of osteomyelitis. The conditions discussed are now known as ;Marjolin's ulcer'. In the present series, the degree of malignancy in tumours arising in scars may be low but the malignancy of tumours arising in chronic ulcers and sinuses may be high.

Burns↗
PubMed1992

[The findings of color Doppler sonography in breast tumors].

UNLABELLED: 72 histologically confirmed tumours of the breast--37 carcinomas and 35 benign tumours--for which mammograms were also available were examined by colour Doppler sonography. Vascularisation of benign processes showed at most 2 vessels (with the exception of 3 sarcoma phylloides and one proliferative mastopathy). Vascularisation clearly in excess of benign processes was observed in only 15 of the 37 carcinomas. In 33 of the carcinomas there was no doubt concerning the diagnosis preoperatively, in the remaining 4 the high vascularity was taken as an indication for surgery. CONCLUSION: In rare cases colour Doppler sonography can provide additional information in the presence of 'vascular' tumours. It is not possible to differentiate between poorly vascularised carcinomas and benign tumours.

Adult↗
PubMed1975

Plasma membrane alteration associated with malignant transformation in culture.

The intramembrane organization of the plasma membranes of nonmalignant cells in culture has been compared by freeze-fracturing with that of virally-transformed malignant cells. No dramatic differences are present in the distribution of intramembrane particles in the plasma membranes of these cells when the cells are examined without fixation or with mild fixation (glutaraldehyde treatment) prior to freezing. However, a redistribution of intramembrane particles into aggregates occurs in the membranes of nontransformed cells after treatment with glycerol. The aggregation of particles is extensive in normal chick embryo fibroblasts, and less extensive in mouse 3T3 cells. The glycerol-induced particle redistribution is not inhibited at 4 degrees, but it is inhibited by pretreatment with 2.5% glutaraldehyde. A significant number of the cells remain viable after the glycerol treatment, and the process is reversible. Particle aggregation does not appear to be related to either growth rate or cell density. Transformed Rous sarcoma virus/chick embryo fibroblasts and simian virus 40/3T3 cells have few particle aggregates after glycerol treatment. The plasma membranes of chick embryo fibroblasts transformed with a mutant of Rous sarcoma virus (TS-68) that is temperature sensitive for transformation, have few particle aggregates when grown at the permissive temperature (37 degrees). Extremely prominent particle aggregates are present in the plasma membranes of cells grown at the nonpermissive temperature (41 degrees). These observations indicate that there is an alteration in the plasma membrane associated with viral transformation which is related to a glycerol-sensitive mechanism that controls the distribution of intramembrane particles.

Animals↗
PubMed1998

[Thoracoscopic diagnosis and therapy of lung metastases].

INTRODUCTION: The purpose of this study was to evaluate the impact of thoracoscopy on staging and therapy of peripheral pulmonary nodules in patients with a cancer history. PATIENTS AND METHODS: Videothoracoscopy (VATS) was performed in patients presenting peripheral pulmonary nodules (< 3cm) in CT-scan. 65 patients (63%) presented less than 3 nodules and 39 patients (37%) had multiple lesions in the lungs. History revealed a primary gastro-intestinal cancer in 35 patients (34%), a sarcoma in 26 patients (25%), breast cancer in 13 patients (13%) and miscellaneous primary cancer in 22 patients (21%). VATS was performed under general anesthesia using a standard equipment (Olympus). Double lumen endotracheal intubation was carried out. Thoracoscopic pulmonary resection was accomplished with endoscopic stapler (Autosuture Multi-Fire Endo GIA 30). The specimens were removed in a retrieval bag and a tube was inserted into the thoracic cavity. RESULTS: In 24 patients (23%) conversion to thoracotomy was performed, because of adhesions (n = 12), technical reasons (n = 8), no tumor detectable (n = 4). Thoracoscopic wedge resection for coin lesions was performed in 61 of the 80 patients (76%). Three patients underwent decortication and in 16 patients biopsy was sufficient for therapeutical considerations. Additional informations in comparison to conventional diagnostic were found in 39 patients (49%). The treatment regimen altered in 32 patients (40%). CONCLUSIONS: In this study VATS proved to be a sensitive technique for staging of pulmonary coin lesions. Additional informations were achieved in 49% and therapeutic strategy was changed in 40% of the patients due to the distant spread of malignancy or detection of benign lesions obtained by thoracoscopic staging.

Adult↗