ABSTRACT
Renal cell carcinoma (RCC) is relatively resistant to chemotherapy and radiotherapy. Clear cell RCC (ccRCC) accounts for the majority of RCC, which have mutations or epigenetic silencing of the von Hippel-Lindau (VHL) gene. VHL-positive Caki-2 cells are killed by an endogenous anticancer substance, 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2). The MTT reduction assay reflecting mitochondrial succinate dehydrogenase activity was employed for assessment of cell viability. We confirmed anticancer activities of camptothecin (topoisomerase I inhibitor), etoposide (topoisomerase II inhibitor), doxorubicin (topoisomerase II inhibitor) in VHL-positive Caki-2 cells. Combination of topoisomerase inhibitors with 15d-PGJ2 exhibited the synergistic effect in VHL-positive Caki-2 cells. However, 15d-PGJ2 did not increase cytotoxicities of topoisomerase inhibitors on VHL-negative 786-O cells. In addition, the 15d-PGJ2-enhanced antitumor activity of topoisomerase inhibitors was detected in neither VHL-positive nor VHL-negative RCC4 cells. Our finding indicated that 15d-PGJ2 enhanced the antitumor activity of topoisomerase inhibitors independently of VHL.
ABSTRACT
Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics.
Subject(s)
Antipsychotic Agents/adverse effects , Hypoglycemia/etiology , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Bipolar Disorder/blood , Bipolar Disorder/complications , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Depressive Disorder, Major/blood , Depressive Disorder, Major/complications , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Diagnostic Errors , Female , Humans , Hypoglycemia/blood , Hypoglycemia/diagnosis , Middle Aged , Quetiapine Fumarate/adverse effects , Quetiapine Fumarate/therapeutic useABSTRACT
Phospholipase B (PLB) from the asporogenous yeast Candida utilis was purified to homogeneity from a culture broth. The apparent molecular mass was 90-110 kDa by SDS-PAGE. The enzyme had two pH optima, one acidic (pH 3.0) and the other alkaline (pH 7.5). At acidic pH the enzyme hydrolyzed all phospholipids tested without metal ions. On the other hand, the PLB showed substrate specificity and required metal ions for alkaline activity. The cDNA sequence of the PLB was analyzed by a combination of several PCR procedures. The PLB encoded a protein consisting of 643 amino acids. The amino acid sequence contained a lipase consensus sequence (GxSxG) and catalytic arginine and aspartic acid motifs which were identified as the catalytic triad in the PLB from Kluyveromyces lactis, suggesting that the catalytic mechanism of the PLB is similar to that of cytosolic phospholipase A(2) (cPLA(2)), found in mammalian tissues.