RESUMO
Purpose: To describe a case of sclerouveitis with exudative retinal detachment in a patient with chronic myelomonocytic leukemia. Observations: An 82-year-old woman with chronic myelomonocytic leukemia (CMML) presented with acute painful right eye redness and decreased visual acuity. Examination revealed right eye anterior and posterior scleritis with exudative retinal detachment, as well as 2+ anterior chamber cell in the right eye and 0.5+ in the left eye. Workup was negative for infectious etiologies and chest imaging revealed no pulmonary nodules. She was treated with prednisolone drops and a tapering course of oral prednisone as she started therapy with ruxolitinib for CMML. Inflammation resolved with treatment, and she remained quiet off steroids while on ruxolitinib. Conclusions and importance: This is the first case report to specifically describe sclerouveitis associated with CMML, despite the known association of this cancer with various inflammatory manifestations. This case demonstrates that CMML may present with scleritis and uveitis, and should be considered as the underlying etiology of inflammatory eye disease in patients with a diagnosis of CMML.
RESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) requires new treatments and targeted approaches to improve survival. The peroxisome proliferator-activated receptor γ (PPARγ) and retinoic X receptor alpha (RXRα) nuclear receptor pathways may be targetable with repurposed Food and Drug Administration (FDA)-approved agents for prevention and treatment. METHODS: Oral cancer and leukoplakia cell lines were treated with the PPARγ agonist (pioglitazone) and RXRα activator (bexarotene). PPARγ activation, cellular proliferation, apoptosis activity and phenotype, including the pharmacodynamic marker, involucrin (IVL), were subsequently analyzed using a reporter gene assay, genomic data, MTT assay and western blot. RESULTS: Microarray analysis of HNSCC tumor versus normal tissue shows IVL expression is significantly increased in normal tissue compared to HNSCC tumors (p < 0.0001). In MSK Leuk1 and CA 9-22 cell lines, pioglitazone increases PPARγ DNA binding activity and IVL promoter activity in a dose dependent manner (p < 0.01 and p < 0.0001). Combination treatment with pioglitazone and bexarotene increases PPARγ DNA binding activity and IVL promoter activity (p < 0.01 and p < 0.0001). MTT analysis shows decreases in cell proliferation when cells are treated with pioglitazone and bexarotene. Decreases in cell proliferation are significant to at least p < 0.05 for all combination versus single agent treatments. Western blot on whole-cell lysate from cells treated with pioglitazone and bexarotene alone or in combination for IVL showed increased protein levels with combination treatment. CONCLUSIONS: Targeting the PPARγ/RXRα heterodimer with pioglitazone and bexarotene was effective in this preclinical project. This was functional in both preneoplastic and oral cancer cell lines. A better understanding of the molecular mechanism on downstream effects on cellular proliferation could potentially have implications clinically, both in oral preneoplasia and possibly head and neck cancer; however, more research needs to be done to explore the potential these medications have in chemoprevention.
