A retrospective study of 18 cases of adenoid cystic cancer at a tertiary care centre in Delhi.

Context: Adenoid cystic carcinoma (ACC) is a rare neoplasm that usually arises from the salivary, lacrimal, or other exocrine glands. It is characteristically locally infiltrative in nature and has a tendency toward local recurrence, high propensity for perineural invasion, and prolonged clinical course. Aim: To analyze the presentation and natural history of cases of adenoid cystic tumors of salivary glands in our institution; and to compare with the existing literature. Design and Setting: Retrospective study at the Department of Radiotherapy. Materials and Methods: Data on 18 patients of ACC of the salivary glands treated between 2004 and 2008 were reviewed with respect to clinical presentation, stage, and histology. Results: There were 8 cases of major salivary gland tumors (47%), of which 2 were in the submandibular and 6 were involving the parotid. Ten patients (53%) had minor salivary gland involvement. Two patients had metastasis at the time of presentation. All patients underwent surgery. Radiotherapy was delivered to 16 patients and chemotherapy to 6 patients (concurrent, n = 3 and adjuvant, n = 3) and no adjuvant therapy was given to 2 patients. All patients were alive at a median follow-up of 3 years. No patient developed local or distant failure during the study duration. Conclusion: ACC has locally aggressive behavior. Radiotherapy adjuvant to surgery improves local control in locally advanced disease. Longer follow-up is mandatory in view of incidence of late metastasis.

HBx protein modulates PI3K/Akt pathway to overcome genotoxic stress-induced destabilization of cyclin D1 and arrest of cell cycle.

Growth arrest represents an innate barrier to carcinogenesis. DNA damage and replicational stress are known to induce growth arrest and apoptotic death to avert genomic instability and consequently carcinogenesis. In this study, working on the genotoxic stress induced by hydroxyurea and methylmethanesulfone, we observed a growth arrest at G1/S-phase that was mediated by destabilization of cyclin D1. The growth arrest was independent of the stability of cdc25A and preceded transcriptional up-regulation of p21(waf1). Cyclin D1 destabilization involved its phosphorylation by GSK-3beta at threonine-286, since overexpression of the kinase-dead mutant of GSK-3beta or cyclin D1T(286A) Inutant conferred stability to cyclin D1. Further, overexpression of cyclin D1(T286A) also helped in bypassing G1/S phase growth arrest. We also observed a rapid inactivation of Akt/PKB kinase in the presence of hydroxyurea. Enforced expression of the constitutively active Akt or viral oncoprotein HBx (Hepatitis B virus X protein) was sufficient to overcome growth arrest, independent of ATR signaling and stabilized cyclin D1. Thus, the present work not only establishes cyclin D1 to be a novel mediator of genotoxic stress signaling, but also explains how a deregulated mitogenic signaling or a viral oncoprotein can help bypass growth arrest.