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The Contribution of Pets to Human and Veterinary Medicine
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Toceranib (SU11654) is a receptor tyrosine kinase (RTK) inhibitor that is used to treat canine mast cell tumors. Toceranib phosphate was approved by the FDA for animal use in 2009, under the tradename Palladia™ (Zoetis, Parsippany, NJ). Sunitinib (SU11248) is a receptor tyrosine kinase inhibitor closely related to SU11654 that is used to treat renal cell carcinoma in people as well as specific types of gastrointestinal cancer. Sunitinib was approved by the FDA in 2006 as Sutent®. These two molecules are structural cousins. Pharmaceutical company Sugen conducted the original research on both of these molecules and became interested in targeting KIT receptor tyrosine kinases found in certain human cancers (gastrointestinal stromal tumors, small lung cancers, acute myeloid leukemia) during the late 1990s. At that time, the company became aware of the role of KIT mutations in canine mast cell tumors (a common cancer type found in dogs). A small clinical trial was performed in canine patients with mast cell tumors and results were promising, thereby providing useful proof of concept data to encourage translational research in humans. Furthermore, SU11654 demonstrated pharmacokinetic (PK) properties comparable to SU11248 in dogs. In fact, Sutent does not have a high therapeutic index and the PK properties seen in dogs are much better approximations of human PK properties than that seen in murine models. The fact that some of the same mutations identified in human gastrointestinal stroma tumors were present in canine mast cell tumors made this research especially informative.
Immunoregulatory Factors Secreted by Human or Murine Placenta or Gestational Tumors
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
When dealing with EPF, it should be pointed out that immunosuppressive materials have been traced by Clark and associates21 who coined the term embryo-associated suppressor factor (EASF). This material inhibits T-cell proliferation after PHA stimulation and the growth of P815 mast cell tumor line. Its molecular weight62 is 7500 Da on high-performance liquid chromatography (HPLC; TSK G 2000). Reports have been published that there might be an almost perfect correlation between successful implantation and production of EASF.22 Similar materials have been traced in swine (40 kDa), boars, etc.
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).
Hypnotherapy in Treatment of Mastocytosis: A Prospective Study
Published in International Journal of Clinical and Experimental Hypnosis, 2021
Frédérique Retornaz, Michel Grino, Audrey Vanhaudenhuyse, Laurent Chiche, Chloé Stavris, Myriam Bennani, Marie Elisabeth Faymonville, Anouk Alitta
Currently there is no curative treatment for mastocytosis. Two treatment options are available. The first, symptomatic, aims to prevent and limit the degranulation of mast cells (long-term antihistamines, sodium cromoglycate, anti-leukotriene and food avoidance regimens) and/or its consequences (analgesics, antidepressants, antispasmodics, antidiarrhea). The second, targeted, aims to control mast cell tumor proliferation, especially in its aggressive form. Chemotherapy (cladribine) or targeted therapies (midostaurine, masitinib, and other molecules under development) are used (Rossignol et al., 2019). Despite these treatments, many patients remain highly disabled by the symptoms of this disease, which are difficult to control (Hermine et al., 2008).
Protein kinase inhibitors for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Vincent Chau, Ravi A. Madan, Jeanny B. Aragon-Ching
Masitinib (AB1010) is a selective TKI, targeting mainly wildtype and mutated C-KIT receptor (C-KITR), platelet-derived growth factor receptor α/β (PDGFRα/β), lymphocyte-specific kinase (LCK), LCK/YES-related protein (LYN), fibroblast growth factor receptor 3 (FGFR3), and focal adhesion kinase (FAK) [22]. Masitinib was initially approved for the treatment of canine mast cell tumors [23]. Masitinib is being investigated in a variety of malignancies, including prostate cancer, given that it can inhibit c-KITR. Preclinical studies show that C-KIT expression is increased during clinical prostate cancer progression and may play a role in intraosseous expansion [24].
High intensity focused ultrasound for the treatment of solid tumors: a pilot study in canine cancer patients
Published in International Journal of Hyperthermia, 2022
Jennifer Carroll, Sheryl Coutermarsh-Ott, Shawna L. Klahn, Joanne Tuohy, Sabrina L. Barry, Irving C. Allen, Alayna N. Hay, Jeffrey Ruth, Nick Dervisis
Twenty dogs were enrolled in the study, with 12 males and 8 females. Of the males and females, all but 1 from each group were castrated or spayed. The median age at presentation was 10.5 years (range:7–13yrs). The study population included a mixture of purebred and mixed breed dogs. The mean weight was 28.02 kg (±12.6). The tumors were located over the distal extremities in 15/20 dogs, the trunk in 3/20 dogs, the ventral cervical region in 1/20 dogs, and the tail base in 1/20 dogs. Tumor histologies represented in this study were: 15 soft tissue sarcomas, 1 osteosarcoma, 3 mast cell tumors, and 1 thyroid carcinoma (Table 2).