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Effect of various factors on the induction of liver tumors in animals by quinoline.

Tumorigenic effect of a diet containing quinoline on the liver of various animals and the synergistic or antagonistic effect by other chemicals on quinoline hepatocarcinogenesis in rats were examined. It was concluded that 4,4'-diaminodiphenylmethane (0.1%) and 3-methylcholanthrene (0.0067%) had a significant inhibitory effect on liver carcinogenesis due to quinoline in rats, but 1-naphthyl isothiocyanate (0.06%) and p-hydroxypropiophenone (1.0%) had no inhibitory effect in the present observations. Transmission electron-microscopic study demonstrated the fine structure of vascular tumors induced by quinoline. On the other hand, it was found that quinoline induced liver tumors in both sexes of mice and rats but not in hamsters or guinea pigs. Male rats were more susceptible than females to the tumorigenic action of quinoline, and mice showed the least susceptibility. Histological changes in the liver of rats or mice induced by quinoline were clasified as hemangioendotheliomas or hemangiosarcomas and hepatocellular carcinomas. Several rats treated with quinoline had hemangiosarcomatous metastatic foci in the lung.

1-Naphthylisothiocyanate↗

The induction of liver tumors by 239Pu citrate or 239PuO2 particles in the Chinese hamster.

The influence of radiation dose distribution on the frequency of 239Pu-induced liver tumors was evaluated in the Chinese hamster. Different concentrations of 239Pu citrate 239PuO2 particles of known sizes were injected intravenously via the jugular vein. About 60% of the injected 239Pu citrate was deposited in the liver and 40% in the bone. The 239Pu citrate was rather uniformly distributed throughout the liver parenchyma. Injected plutonium oxide particles were taken up by the reticuloendothelial system with 90% of the body burden deposited in the liver. The 239PuO2 particles were localized in the Kupffer cells and produced nonuniform dose distributions that were dependent on particle size. There was an activity- and dose-dependent increase in the incidence of total liver parenchymal cell tumors following injection with either plutonium particles or citrate. For animals that received 14.0-, 2.7-, 0.3-, and 0.04-Gy dose to liver from 239Pu citrate the cumulative tumor incidence was 39, 32, 5, and 0%, respectively. Animals that were injected with the 0.24 micron 239PuO2 particles had doses of 42.0, 7.2, and 0.8 Gy to the liver and tumor incidences of 34, 26, and 5%, respectively. Plutonium citrate also produced hemangiosarcomas of the liver and tumors in bone and bone marrow. The latent period for liver tumor appearance in animals exposed to 239Pu citrate or 239PuO2 particles increased as the injected activity decreased. For animals injected with a similar total activity (7.4 Bq/g), the lifetime cumulative liver tumor incidence was similar for animals exposed to either 239Pu citrate (32%) or 239PuO2 (26%). There was little effect of particle size on liver tumor incidence. These data indicate that, in Chinese hamster liver, local radiation dose distribution is less important in altering tumor incidence than injected activity or average dose. However, the more uniform irradiation from 239Pu citrate administration was more effective in cancer production than the nonuniform irradiation from 239PuO2 particles.

Alpha Particles↗

Curious manifestations in cavernous hemangioma of the liver.

We report a cavernous hemangioma of the liver with some curious findings. Angiography showed a hypervascular lesion and the arterioportal shunt which commonly is regarded as a pathognomonic sign of malignancy. Laparoscopy showed a well-defined, reddish-purple elevated lesion with a central umbilication. As the patient was a painter and dealing with vinyl chloride monomer, we suspected the possibility of hemangiosarcoma. The lesion proved to be a cavernous hemangioma with central fibrous replacement probably in consequence of thrombosis of some cavernous spaces.

Angiography↗

Primary urethral tumors in dogs.

In a review of cases of neoplasia in dogs seen at The Animal Medical Center during a 6-year period, 20 cases of primary urethral tumors were found. The majority of these cases were in older dogs (av abe, 10.4 years) and females (18/20). The most common clinical signs were hematuria and stranguria. Nineteen of the 20 tumors were diagnosed clinically, and the most consistent and useful diagnostic method was pneumocystography-cystography, with voiding urethrography. Of the 5 tumor types (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma, hemangiosarcoma, and embryonic rhabdomyosarcoma), squamous cell carcinoma was the most common (12/20). Metastasis occurred in 6 of the 20 dogs. Because of metastasis to regional lymph nodes and diffuse extent of the tumor in the urethra in many of the dogs, a caudal abdominal approach for surgical excision is recommended if treatment is attempted.

Animals↗

Splenic fibrosis and sarcomas in F344 rats fed diets containing aniline hydrochloride, p-chloroaniline, azobenzene, o-toluidine hydrochloride, 4,4'-sulfonyldianiline, or D & C red No. 9.

In six carcinogenicity bioassays, male and female F344 rats were fed diets containing aniline hydrochloride (CAS: 142-04-1; hydrochloride benzenamide), p-chloroaniline (CAS: 106-47-8), azobenzene (CAS: 103-33-3), o-toluidine hydrochloride (CAS: 636-21-5), dapsone (CAS: 80-08-0; 4,4'-sulfonyldianiline), or D & C red No. 9 [CAS: D85500000; 5-chloro-2-[2-hydroxy-1-naphthalenyl)azo)-4-methylbenzenesulfon ic acid, barium salt]. The rats, from 6 weeks to 2 years old, were given the compounds at two dose levels, the estimated maximum tolerated dose and one-half that dose. In all six bioassays, dose-dependent incidences of splenic sarcomas and fibrosis were seen, with the highest incidences in male rats. Fibrosis occurred in the splenic parenchyma and/or the capsule. Fatty infiltration also was seen in the spleen. Sarcomas appeared to arise in the splenic red pulp or splenic capsule, usually in association with areas of parenchymal and capsular fibrosis and pigmentation. Larger tumors metastasized to the peritoneal cavity and abdominal organs. In some rats there was marked osseous metaplasia when the primary tumor metastasized to peritoneal surfaces. Other, less common, splenic neoplasms included hemangiosarcoma and hemangiopericytoma. Some rats had such extensive peritoneal involvement that the site of origin of their sarcoma was difficult to determine.

Aniline Compounds↗

Comparison of nitrosocimetidine with nitrosomethylnitroguanidine in chronic feeding tests in rats.

N-Nitrosocimetidine, a nitroso derivative of the drug cimetidine, was given to groups of 20 male and 20 female rats in drinking water at a concentration of 0.5 mM for more than 2 years. The life span of the rats was not decreased compared with untreated control animals, and there was no significant increase in incidence of any tumor that could be attributed to the treatment. In comparison, 45% or more of 20 male rats treated with the analogous nitrosoguanidine, N-nitroso-N-methyl-N'-nitroguanidine, at an equimolar concentration in drinking water developed neoplasms of the glandular stomach. There was some shortening of life span in these animals. An additional group of 20 male rats was given an identical treatment with N-nitroso-N-methyl-N'-nitroguanidine in water, but prepared fresh on alternate days, rather than once a week, to minimize decomposition. These animals died more rapidly than did the previous group and had a higher incidence of neoplasms of the glandular stomach. The neoplasms seen in this organ were usually adenomas or adenocarcinomas, but there were a few hemangiosarcomas and neurosarcomas. There is a possibility that nitrosocimetidine could be formed by interaction of cimetidine with nitrite in the stomach, but the carcinogenic risk arising would be very small based on the negative result of this study.

Animals↗

[Intraosseous osteolytic lesions. Diagnostic, differential diagnosis and therapy (author's transl)].

Any pathological damage occurring in a bone will produce either an osteolytic or osteosclerotic lesion which can be seen in the macroscopic specimen as well as in the roentgenogram. Various bone lesions may lead to local destructions of the bone. An osteoma or osteoplastic osteosarcoma produces an osteosclerotic lesion showing a dense mass in the roentgenogram; a chondroblastoma or an osteoclastoma, on the other had, induces an osteolytic focal lesion. This paper presents examples of different osteolytic lesions of the humerus. An osteolytic lesion seen in the roentgenogram may be either produced by an underlying non-ossifying fibroma of the bone, by fibrous dysplasia, osteomyelitis or Ewing's sarcoma. Differential diagnostic considerations based on the radiological picture include eosinophilic bone granuloma, juvenile or aneurysmal bone cyst, multiple myeloma or bone metastases. Serious differential diagnostic problems may be involved in case of osteolytic lesions occurring in the humerus. Cases of this type involving complications have been reported and include the presence of an teleangiectatic osteosarcoma as well as that of a hemangiosarcoma of the bone.

Bone Cysts↗

DNA damage in liver, kidney, bone marrow, and spleen of rats and mice treated with commercial and purified aniline as determined by alkaline elution assay and sister chromatid exchange induction.

Aniline of unknown purity has been reported to induce spleen hemangiosarcoma in rats. Aniline has been found to be negative in terms of mutagenicity in both bacteria and yeasts. We have found that both commercial (already rather pure) and repurified aniline are clearly positive to a similar extent in inducing DNA damage in vivo in liver and kidney of rats. Both the commercial and repurified product are also clearly positive in induction of sister chromatid exchanges in vivo in male Swiss mice bone marrow cells. Liver, kidney, and bone marrow DNA damage was absent in male Swiss mice.

Aniline Compounds↗

A survey of feeding N-nitrosodimethylamine (NDMA) to domestic animals over an 18 year period.

Sodium nitrite and formalin have been used as preservatives in the fish meal industry in Norway since 1953. In 1957, fur farms suffered losses of mink due to a new, malignant liver disease. Experimental feeding of herring meal to cows and sheep resulted in the death of some of the animals. Further studies showed that amines (TMAO) normally present in fish, can react with sodium nitrite used as preservative, or nitrogen oxides from the combustion of fuel oils used during processing, to produce the toxic agent, NDMA. Mink and fox may consume considerable amounts of fish meal in their diets. If the fish meal contains sufficient NDMA, the incidence of liver failure or tumours can be quite high. Long-term exposure to as little as 0.1 mg NDMA/kg b.w./day in the diet of mink, cows and sheep can produce fibro-occlusive changes in the hepatic vessels. These lesions can later cause capillary ectasies-like changes in cows, which are similar in appearance to hemangiomas seen in mink. The mink liver hemangiomas develop into hemangiosarcomas. We currently consider capillary ectasies-like changes in cows exposed to NDMA to represent pre-cancerous lesions.

Animal Feed↗

Report on carcinogenesis bioassay of 1,2-dichloroethane (EDC).

In a carcinogenesis bioassay of the halogenated solvent 1,2-dichloroethane (ethylene dichloride, or EDC), oral administration of the compound produced cancers in rats and mice. In male rats, dosage with EDC caused forestomach cancers, hemangiosarcomas (vascularized cancers) of multiple organs, and subcutaneous fibromas (cancers beneath the skin). Female rats exposed to EDC developed mammary (breast) cancers--in some high-dose animals as early as the 20th week of the study. The chemical also caused breast cancers as well as uterine cancers in female mice, and respiratory tract cancers in both male and female mice.

Animals↗

Biologic and morphologic characteristics of hepatocellular lesions in BALB/c female mice fed 2-acetylaminofluorene.

2-Acetylsaminofluorene (2-AAF) induced foci of hepatocellular alterations, hepatocellular adenomas, and hepatocellular carcinomas in BALB/c female mice. The incidence of basophilic cell foci decreased with high dose levels of 2-AAF, and the incidence of hepatocellular adenomas decreased with both high dose levels and length of administration of 2-AAF. The results suggest that the hepatocellular foci of cellular alteration may give rise to the hepatocellular adenomas which in turn may give rise to hepatocellular carcinomas. The study also suggests that both hepatocellular adenomas and carcinomas may develop de novo. Hepatocellular carcinomas rarely metastasized before 18 months, and the less differentiated hepatocellular carcinomas were more likely to metastasize. 2-AAF did not alter the incidence of spontaneous hemangiosarcomas.

2-Acetylaminofluorene↗

[Review of the misdiagnosed cases focusing on the quality control of histopathological diagnosis].

A serious problem for every pathologist is how to avoid making errors in histopathological diagnosis. Five cases which I misdiagnosed or nearly did were reviewed, and the ways to avoid making errors were discussed. The first case was clinically a gastric carcinoma. In the biopsy of gastric mucosa, I took a lymphoepithelial lesion for poorly differentiated adenocarcinoma. In the surgical specimen, the histological diagnosis was malignant lymphoma. The second case was a tumor of cecum. Clinically cecal cancer was suspected and operated due to the complication of invagination. Histological examination of cecal tumor revealed marked lymphocytic infiltration with plasma cells. The immunohistochemistry showed a mixed pattern of B- and T-lymphocytes with monoclonal proliferation of plasma cells (IgA, Kappa). Because an inflammatory polyp could not be ruled out, it was offered to consultation. The diagnosis was malignant lymphoma, lymphoplasmacytoid type. The third case was a neck tumor. Although histological diagnosis at first was undifferentiated carcinoma, immunohistochemically tumor cells were unexpectedly negative for epithelial membrane antigen and positive for creatine kinase-mm. Finally it was diagnosed as rhabdomyosarcoma. The fourth case was a struma nodosa. In the frozen section, it was diagnosed as follicular adenoma. However, in the permanent section, the diagnosis was corrected to papillary carcinoma, follicular type, because many intranuclear inclusions were clearly observed. The last case was a finger tumor. Since hemangiosarcoma could not be histologically ruled out, it was offered to consultation. The diagnosis was intravascular papillary endothelial hyperplasia. In conclusion, I emphasize the importance of consultation in order to avoid making errors in histopathological diagnosis.

Adult↗

Primary liver tumors among Danish patients exposed to Thorotrast.

The potential carcinogenic effects of internally deposited alpha-particle-emitting nuclides, notably plutonium, in the liver in humans are unknown but are of concern in relation to exposures from the nuclear industry. However, patients injected with the radiographic contrast medium Thorotrast are chronically exposed to alpha-particle radiation from 232ThO2 in the liver. Among 1003 patients injected with Thorotrast, 584 of whom were alive 15 years after the injection and 40 at the end of follow-up, a total of 127 liver cancers were diagnosed, 45 of which were hepatocellular carcinomas, 41 cholangiocarcinomas and 33 hemangiosarcomas. The median time from injection to diagnosis was 35 years (range 18-48) and the cumulative frequency was 55.4% after 48 years. In univariate and multivariate analyses, the cumulative frequency of liver cancer was best described as a function of the estimated mean cumulative alpha-particle radiation dose to the liver 15 years ago, being independent of age, gender and volume of injected Thorotrast. This may be interpreted to mean that the liver cancer rate is not related to the dose rate and that the period from malignant transformation to diagnosis of cancer is 15 years. The risk of liver carcinogenesis induced by alpha-particle radiation, assuming 15 years from induction to diagnosis, was estimated to be 712 cases/10(4) persons per gray. This value is considerably higher than estimated earlier.

Adolescent↗

Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene.

Polyoma virus middle T-transformed murine endothelioma cell lines provide a useful model for studying vascular lesions such as hemangiomas, hemangiosarcomas, and Kaposi's sarcoma and tumor-associated angiogenesis. In vivo they produce fast-growing, hemorrhaging, cavernous blood-filled hemangiomas, mainly formed by recruited host endothelial cells, suggesting an angiogenesis-like process underlying the lesion. The molecular mechanism(s) responsible for the recruitment of host endothelial cells by endothelioma cells has not yet been identified. We found that five different cultured endothelioma cell lines produced a soluble factor, named endothelioma-derived motility factor (EDMF) that stimulates chemotaxis (motility induced by a gradient of soluble attractant), haptotaxis (motility in response to substrate-bound attractant), and chemoinvasion (migration through a layer of reconstituted basement membrane, Matrigel) of normal human, bovine, and murine endothelial cells. The inhibitory effect of actinomycin D and of enzymatic treatment on its activity proved that EDMF is a protein. EDMF binds to heparin, since its activity was inhibited by heparin, and it was retained on a heparin-Sepharose column. Its molecular weight, as assessed by Sephacryl S-200 gel filtration, ranges from 40,000-65,000. Although in many aspects EDMF is similar to vascular permeability factor-vascular endothelial growth factor, this was not detected in endothelioma cell supernatants, as assessed by enzyme-linked immunosorbent assay, thus indicating that EDMF might be related to, but is not identical with, vascular permeability factor. Our findings support the notion that recruitment of host endothelial cells by endothelioma cells in vivo might be mediated by a still unidentified, soluble factor that stimulates and directs endothelial cell migration.

Animals↗

[Continuous intra-arterial infusion therapy via the occiptial artery for head and neck tumors: second choice treatment].

We report three cases in which continuous intra-arterial infusion therapy via the occipital artery was combined with radiotherapy for head and neck tumors. An angiographic catheter was inserted into the feeding artery of the tumor retrogradely via the occipital artery under fluoroscopic guidance. Patients treated were maxillary sinus cancer, tongue cancer and hemangiosarcoma. No complications occurred due to this procedure in any of the three patients. This procedure was considered very useful when the approach from the superficial temporal artery was not possible due to prior treatment.

Adult↗

[Adrenal hemangioma: review of the literature].

Hemangiomas are rarely encountered in the adrenal gland. Only 48 surgical cases of adrenal hemangioma have been reported, with four additional cases not surgically treated. Literature has been reviewed, including Japanese, which had not been done up to now. One additional case removed surgically is presented herein. The only 4 cases of hemangiosarcoma reported in the literature are included, although no relation has been described between benign and malignant vascular tumors. Comment includes definition, classification, clinical aspects, diagnostic procedures, complications and treatment.

Adrenal Gland Neoplasms↗

Pericardiectomy in dogs: 22 cases (1978-1994).

OBJECTIVE: To determine long-term outcome of dogs with neoplastic and nonneoplastic pericardial disease that undergo pericardiectomy. DESIGN: Retrospective study. ANIMALS: 22 dogs. PROCEDURE: Dogs that underwent pericardiectomy and in which the diagnosis had been confirmed histologically were included. Data collected from each record included signalment, history, clinical signs, results of diagnostic evaluations, operative management, postoperative complications, histologic diagnosis, and outcome. Dogs were grouped on the basis of underlying cause of pericardial disease (neoplastic vs nonneoplastic), and survival times were determined by means of Kaplan-Meier analyses. RESULTS: 9 dogs had neoplastic pericardial disease (chemodectoma, 4; hemangiosarcoma, 2; malignant mesothelioma, 2; lymphoblastic lymphoma, 1). Thirteen dogs had nonneoplastic pericardial disease (benign idiopathic pericarditis, 10; lymphocytic plasmacytic pericarditis, 2; osseous metaplasia of unknown cause, 1). Thoracic radiography and echocardiography were the most specific methods for diagnosis of pericardial effusion. Pleural effusion was the most common postoperative complication (8/22 dogs). Prevalence of postoperative complications was not associated with underlying cause of pericardial disease, surgical approach, or surgical procedure (subtotal vs total pericardiectomy). Median survival time of dogs with neoplastic disease (52 days) was significantly shorter than median survival time of dogs with nonneoplastic disease (792 days). Dogs that developed pleural effusion > 30 days after pericardiectomy had a poor prognosis for survival. CLINICAL IMPLICATIONS: Radiography and echocardiography are useful for diagnosis of pericardial effusion in dogs. Dogs with neoplastic pericardial disease have a significantly shorter survival time than do dogs with nonneoplastic pericardial disease.

Animals↗