High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'.

Abstract: Many tumors readily convert l-glutamine to α-ketoglutarate. This conversion is almost invariably described as involving deamidation of l-glutamine to l-glutamate followed by a transaminase (or dehydrogenase) reaction. However, mammalian tissues possess another pathway for conversion of l-glutamine to α-ketoglutarate, namely the glutaminase II pathway: l-Glutamine is transaminated to α-ketoglutaramate, which is then deamidated to α-ketoglutarate by ω-amidase. Here we show that glutamine transaminase and ω-amidase specific activities are high in normal rat prostate. Immunohistochemical analyses revealed that glutamine transaminase K (GTK) and ω-amidase are present in normal and cancerous human prostate and that expression of these enzymes increases in parallel with aggressiveness of the cancer cells. Our findings suggest that the glutaminase II pathway is important in providing anaplerotic carbon to the tricarboxylic acid (TCA) cycle, closing the methionine salvage pathway, and in the provision of citrate carbon in normal and cancerous prostate. Finally, our data also suggest that selective inhibitors of GTK and/or ω-amidase may be clinically important for treatment of prostate cancer. In conclusion, the demonstration of a prominent glutaminase II pathway in prostate cancer cells and increased expression of the pathway with increasing aggressiveness of tumor cells provides a new perspective on 'glutamine addiction' in cancers.

A rare case of lung carcinoma with mucoepidermoid histopathology: a case report and review of the literature.

Mucoepidermoid carcinoma of the lung is exceedingly rare. Our case involves a 58-year-old male who presented with shortness of breath, dysphagia, and weight loss. He denied ever smoking. Chest x-ray revealed trapped lung, and CT demonstrated a right bronchial mass. Diagnosis of lung carcinoma was made by bronchoscopic FNA biopsy. EGFR mutation was negative. Staging workup demonstrated evidence of advanced disease. Performance status was good, and it was decided to start chemotherapy and radiation for palliation. Lung carcinomas often present as an obstructing hilar mass. There are different histological grades that affect progression and survival. Though uncommon, metastatic spread has been previously reported. Studies have investigated the possible role of tyrosine kinase inhibitors in both EGFR-mutated and non-mutated cases. Unfortunately, there has been little consensus as to which therapies are most beneficial.