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PubMed1995

Immunohistochemical distribution pattern of intermediate filament proteins in 50 feline neoplasms.

Twenty-eight epithelial and 22 nonepithelial feline tumors were studied immunohistochemically. Epithelial tumors were 10 squamous cell carcinomas, two basal cell tumors, two sebaceous gland carcinomas, three apocrine gland carcinomas, three thyroid papillary carcinomas, one thyroid solid carcinoma, one renal clear cell carcinoma, one renal papillary carcinoma, one endometrial carcinoma, and four lung bronchioloalveolar carcinomas. Nonepithelial tumors were 10 fibrosarcomas, one liposarcoma, one leiomyosarcoma, one rhabdomyosarcoma, one hemangiosarcoma, two mast cell tumors, one osteosarcoma, three melanomas, and two lymphomas. Commercially available antibodies directed against high- and low-molecular-weight keratins (keratin, RCK-102, NCL-5D3), vimentin, desmin, glial fibrillary acidic protein (GFAP), and neurofilament intermediate filament (IF) proteins were used in the avidin-biotin-peroxidase complex technique on formalin-fixed, paraffin-embedded tumor tissue samples. All epithelial tumors except the endometrial carcinoma expressed some type of keratin protein. Squamous cell carcinomas expressed high-molecular-weight keratins exclusively. Coexpression of high- and low-molecular-weight keratins was observed in one basal cell tumor, sebaceous and apocrine adenocarcinomas, and thyroid, renal, and lung carcinomas. In addition to keratins, vimentin immunoreactivity was found in all basal cell tumors, all sebaceous gland, thyroid papillary, renal, and lung adenocarcinomas, and one of the apocrine gland adenocarcinomas. Immunoreactivity with GFAP antibody was found in one basal cell tumor and one sebaceous gland adenocarcinoma. The endometrial carcinoma did not react with any of the antibodies applied. Nonepithelial tumors analyzed expressed either vimentin (fibrosarcomas, liposarcoma, haemangiosarcoma, mast cell tumors, osteosarcomas, melanomas) or vimentin and desmin (leiomyosarcoma, rhabdomyosarcoma, one fibrosarcoma) IF proteins exclusively. Lymphomas did not react with any of the antibodies employed. These findings indicate that IF proteins antibodies can be included in diagnostic panels of antibodies for immunocharacterization of feline tumors. In addition, they can be used as a basis for the diagnoses of poorly differentiated or undifferentiated feline neoplasms.

Animals↗
PubMed1996

Lymphangiosarcoma in a young dog.

Lymphangiosarcoma was diagnosed from biopsy material obtained from an 8-week-old puppy with a progressively enlarging subcutaneous inguinal swelling. Histologically, the tumor was composed of endothelial cells immediately adjacent to large collagen bundles. Tumor cells formed irregular vascular channels which extended along the connective tissue investments of small vessels and nerves of the subcutis and deep dermis. Similar neoplastic tissue extensively infiltrated an inguinal lymph node. Neoplastic cells were immunohistochemically stained for factor 8-related antigen and were weakly positive when compared with several hemangiomas and hemangiosarcomas. Transmission electron microscopy revealed numerous micropinocytotic vesicles and a continuous basal lamina. The puppy was euthanatized at 8 months of age due to severe septic polyarthritis. Lymphangiosarcoma was documented at the site of the original tumor as well as in the axillary lymph node at necropsy.

Animals↗
PubMed1991

Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industry--Part II: Carcinogenicity, mutagenicity, and developmental toxicity of 1,3-butadiene.

1,3-butadiene (BD) is present in synthetic rubber and motor fuels (gasoline). BD is shown to cause lymphocytic lymphomas, heart hemangiosarcomas, lung alveolar bronchiolar cancers, forestomach-squamous cell cancers, harderian gland neoplasms, preputial gland adenoma or carcinoma, liver-hepatocellular cancers, mammary gland acinar cell carcinomas, ovary-glanulosa cell carcinoma, brain cancers, pancreas adenoma and carcinoma, testis-Leydig cell tumors, thyroid follicular adenoma and carcinoma, and zymbal gland carcinoma in rodents and to date no exposure level has been established at which this chemical does not cause cancers. In humans BD causes increase in lymphomas, leukemias, and other cancers of hematopoietic systems and organs. BD is also a potent alkylating agent, directly toxic to developing embryos and damages progeny after parental exposure.

Animals↗
PubMed1999

Intrapericardial neoplasia in dogs.

A retrospective study was conducted from 1,919 necropsies of dogs, and 52 cases were selected on the basis of primary or metastatic neoplasia in the pericardium, the heart base, or the myocardium. Primary intrapericardial neoplasms were more frequent than intrapericardial metastases. Hemangiosarcomas were the most frequent primary neoplasms, followed by chemodectomas. Lymphomas were the most frequent metastatic neoplasms, followed by fibrosarcomas and rhabdomyosarcomas. Other neoplasms, either primary or metastatic, occurred rarely.

Animals↗
PubMed2006

Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV.

BACKGROUND: Jaagsiekte sheep retrovirus (JSRV) causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env) protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6) vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. RESULTS: We have generated mouse monoclonal antibodies (Mab) against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV), a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. CONCLUSION: Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is unnecessary to invoke a role for insertional mutagenesis, gene activation, viral replication, or expression of other viral gene products in sheep lung tumorigenesis, although these processes may play a role in other clinically less important sequelae of JSRV infection such as metastasis observed with variable frequency in sheep.

Adenocarcinoma↗
PubMed1991

Radiation carcinogenesis in dogs irradiated during prenatal and postnatal development.

To evaluate the lifetime hazards of ionizing radiation exposure, 1680 beagles received whole-body, 60-Cobalt gamma exposures or sham-exposures during development. Eight groups of 120 dogs each received mean doses of 16 or 83 cGy at 8 (preimplantation), 28 (embryonic), or 55 (late fetal) days postcoitus (dpc), or 2 (neonatal) days postpartum (dpp). One group of 120 dogs received 83 cGy at 70 dpp (juvenile), and one group of 240 dogs received 83 cGy at 365 dpp (young adult). Sham-irradiations were delivered to 360 controls. Sexes were equally represented. Young dogs, up to 4 years of age, had an increase in benign and malignant neoplasms after irradiation in the perinatal period at 55 dpc or 2 dpp. Among these, 4 fatal cancers were observed. No malignancies occurred in comparably-aged controls. The increase in both fatal neoplasms and all neoplasms in the perinatally-exposed groups were statistically significant. Over the full lifetime, dogs irradiated in the perinatal period also had the strongest evidence for an increased risk for fatal malignancies of all types. Though not as strong, there was a trend for increased risk for fatal cancer in dogs irradiated at all other ages. The risk of fatal malignancy after irradiation was greater in females than in males. Dogs exposed at 55 dpc had a significant increase in lymphoid neoplasia and dogs exposed at 8 and 55 dpc had increased risk for hemangiosarcoma. There was no evidence for an increased risk for mammary carcinoma in irradiated females. Dogs exposed as juveniles at 70 dpp had a significant increase in all benign and malignant thyroid neoplasms, including fatal thyroid carcinoma.

Aging↗
PubMed1980

Carcinogenicity and toxicity of methoxychlor.

Methoxychlor is carcinogenic for the liver of C3H and BALB/c mice and Osborne-Mendel rats, and possibly for the liver of dogs. Methoxychlor is also carcinogenic for the testis of BALB/c male mice, bone of B6C3F1 female mice, and the ovary of Osborne-Mendel female rats. The incidences of carcinomas of the liver were increased in C3H male mice and BALB/c male and female mice fed methoxychlor. There also was an increase in malignant neoplasms at all sites in BALB/c male and female mice. C3H and BALB/c male mice were more susceptible to the carcinogenic effects of methoxychlor than were female mice. BALB/c mice were more susceptible than C3H mice. Osborne-Mendel male and female rats developed significant incidences of carcinomas of the liver. The incidence of sarcomas of the spleen and abdomen, mostly hemangiosarcomas, was increased in male rats. Neoplasms of the pituitary, adrenals, and mammary gland were also increased in methoxychlor-treated female rats. Miniature swine given methoxychlor developed chronic renal disease in relatively short periods of time. There also was hyperplasia of the mammary gland and uterus, suggesting an estrogen-like effect on those organs. Methoxychlor applied to the skin of rabbits caused a dose-related atrophy of the testes, as well as chronic renal disease. Atrophy of the testes and chronic renal disease could not be evaluated in mice and rats because of insufficient data.

Animals↗
PubMed1984

Radionuclide injury to the lung.

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed.

Adenocarcinoma↗
PubMed1990

Neoplastic and potentially prenoeplastic changes in the upper respiratory tract of rats and mice.

The National Toxicology Program (NTP) database was examined for tumor incidences and chemicals producing tumors in the nasal cavity, larynx, or trachea. Slides from appropriate studies were then examined in an attempt to unify terminology and make comparisons between induced and spontaneous tumors and hyperplastic or preneoplastic lesions produced in the upper respiratory system. An attempt was also made to compare the species affected, route of administration, and tumor types produced by different chemicals. The results are not meant to be all inclusive of the NTP database but to be representative of observed trends. General conclusions that emerged from this review were that rats are much more susceptible to epithelial tumors of the nasal cavity than mice; that only mice have been reported to have chemically induced hemangiomas and hemangiosarcomas of the nasal cavity; that tumors of the olfactory epithelium and squamous cell tumors of the respiratory epithelium are almost uniformly malignant and invasive, while other tumors of the respiratory epithelium are typically less invasive; that most chemically induced tumors of the olfactory region, either mesenchymal or epithelial, do not require an inhalation route of exposure but appear to occur by systemic targeting of this region; and that a uniform nomenclature for tumors of the nasal cavity is needed.

Animals↗
PubMed1985

Relationships between DNA adduct formation and carcinogenesis.

An impressive array of evidence has been obtained during the past decade establishing correlations between specific DNA adducts and carcinogenesis. Many of the studies utilized organ specific differences in carcinogenesis to establish the correlations. More recently, we have investigated similar relationships between target and nontarget cell populations within the liver. Chronic exposure to methylating hepatocarcinogens predominantly induces hemangiosarcomas, whereas exposure to ethylating agents causes hepatocellular carcinomas. This cell specificity in carcinogenesis correlates well with the presence of promutagenic DNA adducts. In the case of methylating agents, the nonparenchymal cells accumulate O6-methylguanine whereas the hepatocytes do not. Exposure to ethylating agents leads to accumulation of O4-ethyldeoxythymidine, but not O6-ethyldeoxyguanosine in hepatocytes. These differences reflect the ability of the two cell populations to repair O6-alkylguanine and the extent of purine and pyrimidine alkylation with methylating and ethylating agents. Hepatocytes of rats exposed to diethylnitrosamine for 28 days have four to five times more promutagenic DNA adducts (O6-alkyldeoxyguanosine and O4-alkyldeoxythymidine) than hepatocytes of rats exposed to nearly equimolar doses of dimethylhydrazine. Both O6-methylguanine and O4-methyldeoxythymidine are rapidly repaired by rat hepatocytes, while only O6-ethyldeoxyguanosine is rapidly repaired. Studies comparing the relationship between the induction of gamma-glutamyl transpeptidase-positive foci, hepatocellular carcinoma and promutagenic lesions such as O4-ethyldeoxythymidine will be useful in understanding associations between the molecular dosimetry of DNA adducts, initiation, and progression of hepatocarcinogenesis.

Alkylating Agents↗
PubMed2004

The incidence of disseminated intravascular coagulation in dogs with malignant tumor.

The incidence of DIC in 208 dogs with a malignant tumor was evaluated. The incidence of DIC was 9.6% in dogs with a malignant tumor which was a solid tumor in all. In 164 dogs with a malignant solid tumor, the incidence of DIC was 12.2%. The incidence of DIC in dogs with hemangiosarcoma, mammary gland carcinoma and adenocarcinoma of the lung was significantly higher than that in dogs with other malignant tumors. These results suggested that special care in looking for DIC should be taken in dogs with a malignant solid tumor.

Animals↗
PubMed2005

Metastatic tumors to the adrenal glands in domestic animals.

Although metastases to the adrenals are common in humans, they have not been thoroughly studied in animals. The purpose of this retrospective study was to document the types of malignant tumors that metastasize to canine, feline, equine, and bovine adrenals, and the rate at which they do so. The average rate of adrenal involvement in metastatic cancer was 112/534 (21.0%) in dogs, 12/81 (14.8%) in cats, 18/67 (26.9%) in horses, and 5/16 (31.3%) in cattle. In dogs, 26 different tumor types metastasized to the adrenals. Pulmonary, mammary, prostatic, gastric, and pancreatic carcinomas, and melanoma had the highest rates of metastasis to the adrenal glands in dogs. Hemangiosarcoma and melanoma had high rates of adrenal involvement in horses. In cats and cattle, relevant data were only available for lymphoma. Adrenal metastases usually occurred in the late stages of the disease. One dog had developed Addison's disease (hypoadrenocorticism) secondary to lymphoma. Metastatic lesions represented 126/472 (26.7%) of canine, 12/20 (60.0%) of feline, 21/80 (26.3%) of equine, and 5/9 (55.5%) of bovine adrenal neoplasms. This study shows that adrenal glands should be thoroughly examined during both clinical work-up and postmortems when disseminated neoplasia is suspected.

Adrenal Gland Neoplasms↗
PubMed2005

Cutaneous angiomatosis in a young dog.

A 1-year-old, spayed, female, mixed-breed dog had two reddish-purple cutaneous lesions, one on the right dorsal antebrachium and the other on the right shoulder. The lesions consisted of approximately 13 x 3 cm and 15 x 10 cm, irregular, patchy regions of 0.5-3.0 cm, circular, sometimes raised, reddish-purple swellings resembling ecchymoses. The lesion on the antebrachium had been noticed since the dog was adopted at 6 months of age and appeared to have increased in size over an 11-week period, at which time skin punch biopsy revealed an infiltrative pattern of well-differentiated blood vessels leading to an interpretation that the lesion was a well-differentiated hemangiosarcoma. The second lesion was revealed when the dog had its fur shaved in that area during surgical preparation to excise the antebrachial lesion. No other skin lesions were found on the dog. Microscopically, there was a widely disseminated and infiltrative-like pattern of benign-appearing small blood vessels, which were throughout the superficial and deep dermis and subcutis. Although the disseminated nature suggested malignancy, the histologic appearance of well-differentiated small blood vessels and nonprogressive clinical features indicate that the lesions were benign. The dog has been followed for 6 years and to date has no evidence of progression of the antebrachial lesion or shoulder lesion. To the authors' knowledge, this is the first report of a congenital angiomatosis-like lesion in a young dog, with extensive involvement of the forelimb.

Angiomatosis↗
PubMed2003

MR imaging for evaluation of lesions of the cranial vault: a pictorial essay.

PURPOSE: A variety of diseases affect the calvaria. They may be identified clinically as palpable masses or incidentally in radiologic examinations. There are many diagnostic possibilities, including congenital, neoplastic, inflammatory and traumatic lesions. The purpose of this study is to illustrate the main calvarial lesions through MR imaging, their signal intensity and extension to neighboring sites. METHOD: A retrospective analysis of 81 cases, from November 1996 to July 2001, was conducted. The examinations were performed on a 1.5 T equipment and each one of the cases was pathologically proven. RESULTS: The results were: dermoid cysts [4 cases (5%)], epidermoid cysts [2 cases (2.5%)], cephalocele [14 cases (17.5%)], sinus pericranii [3 cases (3.7%)], leptomeningeal cysts [4 cases (5%)], Langerhans cell histiocytosis [10 cases (12.5%)], lipoma [4 cases (5%)], fibrous dysplasia [13 cases (16.2%)], osteoma [8 cases (10%)], hemangioma [1 case (1.2%)], meningioma [3 cases (3.7%)], chondrosarcoma [5 cases (6.2%)], hemangiosarcoma [1 case (1.2%)], multiple myeloma [3 cases (3.7%)], sarcomatous transformation of Paget disease [1 case (1.3%)], and metastasis [5 cases (6.2%)]. CONCLUSION: MRI identifies bone marrow abnormalities and invasion of adjacent tissues at an early stage. Therefore, it is an essential method when it commes to properly evaluating calvarial lesions.

Abnormalities, Multiple↗
PubMedDate not supplied

Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: a pilot study.

Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).

Amputation, Surgical↗
PubMedDate not supplied

Vascular endothelial growth factor concentrations in body cavity effusions in dogs.

Vascular endothelial growth factor (VEGF) has potent angiogenic, mitogenic, and vascular permeability enhancing properties specific for endothelial cells. VEGF is present in high concentrations in inflammatory and neoplastic body cavity effusions and has been implicated in the pathogenesis of neoplastic and inflammatory effusion formation. In this study, VEGF was quantitated by solid-phase enzyme-linked immunoadsorbent assay (ELISA) in samples of pericardial, pleural, and peritoneal effusions (N = 38) from dogs (N = 35) with neoplastic and non-neoplastic diseases. VEGF was detected in 37 of 38 effusions (median, 754; range, 18-3,669 pg/mL) and was present in much higher concentrations than in previously established normal concentrations for canine plasma (median, < 1 pg/mL; range, < 1-18 pg/mL) or in those previously noted in the plasma of dogs with hemangiosarcoma (HSA; median, 17 pg/mL; range, < 1-67 pg/mL). In 4 dogs with HSA, the concurrent plasma VEGF concentration was much lower than in the abdominal effusion (P = .029). No significant correlation was demonstrated between VEGF effusion concentration and effusion total protein content or nucleated cell count. Mean VEGF concentrations were significantly higher in pericardial (median, 3,533; range, 709-3,669 pg/mL) and pleural effusions (median, 3,144; range, 0-3,663 pg/mL) compared to peritoneal effusions (median, 288; range, 18-2,607 pg/mL; P < .05). There was no marked difference demonstrated between effusions associated with malignant and nonmalignant diseases. Further studies are necessary to elucidate the role of VEGF in body cavity effusion formation in dogs.

Animals↗
PubMed2001

Twenty-six-week carcinogenicity study of sulfamethoxazole in CB6F1-Tg-rasH2 mice.

Sulfamethoxazole (SMX), a hormone-mediated rodent-specific nongenotoxic carcinogen, was administered to CB6F1 mice carrying a human prototype c-Ha-ras gene (Tg-rasH2) at doses of 0, 25, 100 or 400 mg/kg/day and to the wild-type mice at a dose of 400 mg/kg/day in feed for 26 weeks to evaluate the carcinogenicity and to validate the Tg-rasH2 model. N-Methyl-N-nitrosourea was administered at an intraperitoneal dose of 75 mg/kg to Tg-rasH2 as a positive control and the experimental system was confirmed to be valid. Histopathological examination revealed adenomas of the lung and Harderian gland and hemangiosarcoma of the spleen at low frequencies in the Tg-rasH2 treated with SMX; however, no statistically significant differences were observed either in the onset or prevalence rates of these neoplasms compared with that in the control group. Between the wild-type mice and Tg-rasH2, the onset rate and prevalence of the neoplasms were not significantly different, but the neoplasms tended to be more frequent in Tg-rasH2 mice showing a sensitivity to tumorigenicity. Follicular epithelial cell hyperplasia was observed in the thyroid gland in the groups of Tg-rasH2 given 100 mg/kg SMX or more, but no neoplastic lesion was observed. SMX was judged to be negative for carcinogenic potential in Tg-rasH2 in the present study.

Animals↗
PubMed1978

Angiographic diagnosis of benign and malignant splenic tumors.

Fifteen cases of benign and malignant nodular splenic tumors, including six cysts, one hamartoma, two hemangiosarcomas, five reticulum cell sarcomas, and one Hodgkin's disease, are presented with their arteriographic manifestations. The value of splenic arteriography is emphasized, since it may provide rather specific information in the diagnosis of benign and malignant nodular splenic tumors. Differential diagnostic considerations are also discussed.

Adolescent↗