A 7-year-old, spayed female, domestic short hair cat showed signs of a 2-week history of chronic anorexia, depression, and severe weight loss. Upon physical examination, pyrexia, mild gingivitis, and pale mucus membranes were noted. Laboratory analysis revealed normocytic normochromic non-regenerative anemia, severe thrombocytopenia, and hypergammaglobulinemia. Serum protein electrophoresis revealed the presence of elevated alpha-2 fraction within the globulin concentration. Based on history, clinical signs, and laboratory results, systemic viral infection was strongly suspected. Reverse transcriptase polymerase chain reaction identified the presence of feline immunodeficiency virus (FIV) in the serum. Furthermore, gene sequencing revealed the virus as FIV subtype A. Treatment with anti-retroviral agents, including azidothymidine (AZT) and recombinant human interferon-alpha, was continued for 4 weeks. However, the patient's clinical condition deteriorated, resulting in death 1 month after initiation of treatment due to progressive renal failure. Necropsy and histopathology revealed hepatic and renal necrosis with hyper-cellular bone marrow mainly comprised of myeloid precursor cells. This case report is the first to describe phylogenetic subtyping, anti-retroviral combination treatment, and clinical outcomes in an FIV-infected cat in Korea. In addition, this report suggests that treatment should be initiated during the early phase of infection that could be effective for the virus.
Anemia ; Animals ; Anorexia ; Anti-Retroviral Agents ; Bone Marrow ; Cats* ; Child ; Depression ; Electrophoresis ; Female ; Fever ; Gingivitis ; Hair ; Humans ; Hypergammaglobulinemia ; Immunodeficiency Virus, Feline* ; Interferon-alpha* ; Korea ; Membranes ; Mucus ; Necrosis ; Physical Examination ; Renal Insufficiency ; Reverse Transcriptase Polymerase Chain Reaction ; Thrombocytopenia ; Weight Loss ; Zidovudine*

Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods: The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results: Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion: The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment.