mycophenolic-acid and Ovarian-Neoplasms

Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory muscle diseases which remain a therapeutic challenge. The association between DM and malignancy is relatively well established while this relationship is weaker with PM. The clinical management and research for an occult malignancy as well as the follow-up of patients with DM or PM is a matter of debate. Herein we report a case of DM who, despite an extensive clinical, radiological and biological work-up developed an occult ovarian cancer 12 months after the initial diagnosis. This case report was used as support to review the actual expert recommendations for the search of an occult malignancy in presence of DM or PM.

Topics: Adenocarcinoma; Aged; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Cyclosporins; Dermatologic Agents; Dermatomyositis; Diagnosis, Differential; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Ovarian Neoplasms; Polymyositis; Prednisone; Risk Factors; Time Factors

The effects of the differentiation-inducing agents sodium butyrate (NaOBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine nucleotide metabolism, was studied in an ovarian carcinoma cell line (GZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and DMSO moderately decelerated purine synthesis de novo, but MA accelerated it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. NaOBt and DMSO did not affect the cellular nucleotide content, but MA caused a 73% decrease in GTP content and about a 50% increase in the cellular content of UTP. The following alterations in cellular enzyme activity were observed 72 h following exposure: NaOBt decreased the activity of hypoxanthine-guanine phosphoribosyltransferase and increased the activity of IMP and of AMP 5'-nucleotidases, DMSO increased the activity of IMP 5'-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line studied, the differentiation process induced by NaOBt and DMSO may be associated with a general shift in the direction of purine metabolism from anabolism to catabolism, whereas that induced by MA is associated with a specific decrease in the production of GTP.

Topics: Butyrates; Butyric Acid; Cell Differentiation; Cell Division; Dimethyl Sulfoxide; Female; Guanosine Triphosphate; Humans; IMP Dehydrogenase; Mycophenolic Acid; Ovarian Neoplasms; Purine Nucleotides; Tumor Cells, Cultured