Acetylated-PPARγexpression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells

Objective:Polyploid giant cancer cells(PGCCs)with daughter cells express epithelial–mesenchymal transition(EMT)-associated proteins.Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells.In this study,we elucidated the potential for,and underlying mechanism of,adipogenic differentiation of PGCCs with daughter cells(PDCs).Methods:Cobalt chloride was used to induce PGCC formation in HEY(wild-type P53)and MDA-MB-231(mutant P53)cells;these cells were then cultured in adipogenic differentiation medium.Oil red O staining was used to confirm adipogenic differentiation,and the cell cycle was detected with flow cytometry.The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation.Animal xenograft models were used to confirm the adipogenic differentiation of PDCs.Results:PDCs transdifferentiated into functional adipocytes.Two different cell cycle distributions were observed in PDCs after adipogenic differentiation.The expression levels of PPARγ,Ace-PPARγ,and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation.Ace-PPARγand FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown.A485 treatment increased Ace-P53,Ace-PPARγ,and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53.In MDA-MB-231 PDCs,A485 treatment decreased Ace-P53,Ace-PPARγ,and FABP4 expression.Animal experiments also confirmed the adipogenic differentiation of PDCs.Conclusions:Acetylation of P53 and PPARγplays an important role in the adipogenic differentiation of PDCs.

Infratentorial Tuberculoma Mimics Tumor in Immunocompetent Adults: An Analysis of 11 Patients

Backgrounds: Tuberculoma is a granulomatous inflammatory process mimicking a neoplasm, both clinically and radiologically. Although those with an infratentorial origin are rare, this disease is still a diagnostic challenge using conventional workup. However, this disease should not be overlooked because it is essentially curable with proper diagnosis and therapy, usually, a Mycobacterium Tuberculosis (MTB) DNA test is performed. Methods: We retrospectively analyzed the clinical presentations, CSF results, and images of 11 MTB DNA positive and clinically cured cases of infratentorial tuberculoma. Results: Infratentorial tuberculoma usually deteriorated before antituberculosis treatment (ATT). Magnetic resonance imaging showed space-occupying lesions without specific features, 4 within the cerebellum and 7 within the brainstem. Evidence of systemic tuberculosis was found in only 1 case. Clinical manifestations included various combinations of focal signs and symptoms in the brain stem and cerebellum. Cerebrospinal fluid (CSF) findings were also nonspecific. The diagnoses of these cases were based on the positive tests of a nested polymerase chain reaction (N-PCR) assay. Trial therapy with antituberculous drugs resulted in clinical improvement, as documented by MRI in all patients. Conclusions: Infratentorial tuberculoma should be suspected in patients with infratentorial space-occupying lesions who live in geographic areas where tuberculosis is endemic.