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A Histopathologic Classification of Chemical-Induced Injury of the Liver
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
John M. Cullen, Boris H. Ruebner
Continuous or repetitive liver injury causes chronic liver injury associated with fibrosis and, if continued long enough, may lead to cirrhosis (Figure 8) (Cameron and Karunaratne, 1936). A variety of chemicals administered in this fashion may have this effect, particularly chlorinated hydrocarbons such as carbon tetrachloride, PCBs, dinitrobenzene, and trinitrotoluene (Bridge et al., 1942; Himsworth, 1947; Klatskin, 1975; Miller 1920) (Table 2-3). Pyrrolizidine alkaloids can also cause this type of response as do nitrosamines, dibutyltin salts, and excessive vitamin A (Klatskin, 1975; Rouiller, 1964; Zimmerman, 1969; Barnes and Magee, 1958; Barnes and Stoner, 1961). A particularly interesting group is that including inorganic arsenicals (Franklin et al., 1950; Weir, 1930), vinyl chloride (Plaa, 1980), and thorotast. While all these compounds produce fibrosis if given chronically, the resulting lesion in this group of compounds appears to be a more diffuse fibrosis, which has been termed hepatoportal sclerosis. Although cirrhotic nodules usually do not develop, these patients often have portal hypertension. Hemangiosarcoma is a late complication.
Hematopoietic System
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Kristin Henson, Tanasa Osborne, Gregory S. Travlos
Primary neoplasms of the bone marrow are considered rare in F344 rats (MacKenzie and Eustis 1990). Additionally, there are no reported incidences of primary bone marrow neoplasia, including multicentric tumors, in the NTP database (Travlos 2006b). Histiocytic sarcomas were reported to be a primary bone marrow neoplasm in Donryu rats with an approximate incidence of 4.5 percent and possibly a primary bone marrow neoplasm in F344 rats with an approximate incidence of 1.5 percent (Ogasawara et al. 1993; Travlos 2006b). A review of neoplasms identified in Crl:CD-1 mice noted that lymphoma was the most common cause of death in carcinogenicity studies; however, no neoplasms were specifically identified as originating in the bone marrow (Bradley and Petersen-Jones 2011). In the NTP database, bone marrow hemangiosarcoma was reported with an incidence of approximately 1 percent for male and 0.5 percent for female B6C3F1 mice (Travlos 2006b). Benign and malignant mast cell tumors were reported in bone marrow, also from B6C3F1 mice, with an incidence of 0.04 percent and 0.24 percent, respectively, and with an incidence of 0.04 percent for malignant mast cell tumors in the females (Travlos 2006b).
Canine and Feline Nasal and Paranasal Neoplasm: Morphology and Origin
Published in Gerd Reznik, Sherman F. Stinson, Nasal Tumors in Animals and Man, 2017
In the beagle dog, exposure to various beta-emitting radionucleides has produced squamous cell carcinoma in varying incidences with different radionucleides. Adenocarcinoma was not produced and hemangiosarcoma was rarely produced.90 In contrast, spontaneously occurring sinonasal neoplasms in the dog have a predominance of adenocarcinoma, as is seen in the present and previous studies.1–4 From the preceding paragraphs, it can be concluded that there is a species variation in the incidence of spontaneously occurring sinonasal neoplasms of different histomorphologic features. Environmental factors such as exposure to different carcinogens may induce a change in incidence in the spontaneous morphologic types. Experimental manipulation with carcinogens not only produces species variation and is related to the mode and dosage of administration, but may produce a change in the incidence of histologic types that is seen spontaneously in the respective animal species. It is obvious that by extrapolating from natural and experimental models and from investigation into environmental factors as cause or promoting factors in carcinogenesis, a comparative histomorphologic understanding between the species is essential and cannot be ignored.
Tolerability of long-term temperature controlled whole-body thermal treatment in advanced cancer-bearing dogs
Published in International Journal of Hyperthermia, 2022
B. Wylleman, L. Brancato, I. Gorbaslieva, E. van Zwol, M. G. M. C. Mori da Cunha, J. Benoit, D. Tierny, P. Vueghs, J. Van den Bossche, O. Rudenko, M. Janicot, J. Bogers
Taken together, our findings show that the HyperTherm-mediated WBTT and procedures can be safely used for the treatment of canine patients with advanced malignancies. The principal gains compared to previously used techniques [19], are 1) the safety that arises from automatization of the procedure, which is based on continuous thermometry and consequently 2) the duration at which we can incubate the patient. As observed during previous and ongoing preclinical work, this duration of incubation at 41.5 °C is a decisive factor in order to obtain the anti-cancer effect of thermal treatment (unpublished data). Our positive preliminary clinical benefit results tend to support a genuine therapeutic potential for long-term WBTT which needs to be confirmed on a larger canine patient population with spontaneous advanced tumors. In a follow-up study (which is currently being initiated), we will investigate in-depth the mode of action (vascular changes, immune response, effect on metastases and DNA damage repair) and clinical efficacy of WBTT in a specific patient population (head and neck tumors and resected hemangiosarcoma). Nevertheless, combined with previously reported safety and tolerability results in minipigs [27], these results greatly contribute to the support of ongoing clinical evaluation of WBTT in advanced cancer human patients.
Predictive modeling for cancer drug discovery using canine models
Published in Expert Opinion on Drug Discovery, 2020
Michael D. Lucroy, Mark A. Suckow
Canine hemangiosarcoma (HSA) is an aggressive, ultimately fatal, cancer arising from multipotential bone marrow-derived stem cells that arrest their differentiation at the hemangioblast or angioblast stage [60]. The spleen is the most common site of HSA in the dog, although liver, heart, skeletal muscle may also be sites of origin [61,62]. After splenectomy, or wide surgical excision at other sites, survival is short with death typically due to widespread metastasis often resulting in significant hemorrhage [61,63–67]. Angiosarcoma is a rare, aggressive cancer of people with similarly poor outcomes and few effective treatment options [68].
Experimental studies on the biological effects of chronic low dose-rate radiation exposure in mice: overview of the studies at the Institute for Environmental Sciences
Published in International Journal of Radiation Biology, 2018
Ignacia Braga-Tanaka, Satoshi Tanaka, Atsushi Kohda, Daisaku Takai, Shingo Nakamura, Tetsuya Ono, Kimio Tanaka, Jun-ichiro Komura
Table 3 shows the influence of chronic low dose-rate gamma ray exposure on the incidence rates of neoplasms, lethal and nonlethal, compared to the nonirradiated controls. Increased incidence rates for Harderian gland neoplasms [adenoma (2.9-fold increase in males; 5.2-fold increase in females) and adenocarcinoma (2.4-fold increase in males; 2.6-fold increase in females)] in mice exposed to 20 mGy/day were attributed to radiation exposure (p < .01, Peto’s trend test). Hepatocellular adenoma incidence rates in male mice were significantly increased at all dose-rates (1.5-fold increase at 20 mGy/day) and is the only neoplasm that was significantly increased at 0.05 mGy/day. From the 20 mGy/day group, only females showed significantly increased hepatocellular adenoma incidence rate (2.2-fold increase) (p < .01). Although the incidence rates for hepatocellular adenoma does not appear to increase with dose in the males, significant Peto’s trend tests (p < .01) in both sexes indicate that the increases are radiation dose-related. Despite very low incidence rates, significant increases in hepatoblastoma (1 mGy/day) and myeloid leukemia (20 mGy/day) in males were attributed to radiation exposure and were radiation dose-dependent (p < .01 Peto’s trend test). Incidence rate for hemangiosarcoma was significantly increased (2.2-fold) only in females, although trend tests show that the increased incidence were radiation dose-dependent in both sexes (p < .01, Peto’s trend test). Bronchiolo-alveolar neoplasms of the lungs, adenoma (2.1-fold) and carcinoma (2.9-fold), were significantly increased only in females and were radiation dose dependent for adenomas in females and carcinomas in both sexes. Other neoplasms with significantly increased incidence rates in irradiated females that were dose dependent were ovarian neoplasms (11.8 ∼ 37.5-fold) and subcapsular cell adenomas of the adrenal (9.7-fold), suggesting that female hormones play a role as well.