Epigenetic changes involved in cancer development, unlike genetic changes, are reversible. DNA methyltransferase and histone deacetylase inhibitors show antiproliferative effects in vitro, through tumor suppressor reactivation and induction of apoptosis. Such inhibitors have shown activity in the treatment of hematologic disorders but there is little data concerning their effectiveness in treatment of solid tumors. FHIT, WWOX and other tumor suppressor genes are frequently epigenetically inactivated in lung cancers. Lung cancer cell clones carrying conditional FHIT or WWOX transgenes showed significant suppression of xenograft tumor growth after induction of expression of the FHIT or WWOX transgene, suggesting that treatments to restore endogenous Fhit and Wwox expression in lung cancers would result in decreased tumorigenicity. H1299 lung cancer cells, lacking Fhit, Wwox, p16 INK4a and Rassf1a expression due to epigenetic modifications, were used to assess efficacy of epigenetically targeted protocols in suppressing growth of lung tumors, by injection of 5-aza-2-deoxycytidine (AZA) and trichostatin A (TSA) in nude mice with established H1299 tumors. High doses of intraperitoneal AZA/TSA suppressed growth of small tumors but did not affect large tumors (200 mm 3 ); lower AZA doses, administered intraperitoneally or intratumorally, suppressed growth of small tumors without apparent toxicity. Responding tumors showed restoration of Fhit, Wwox, p16 INKa , Rassf1a expression, low mitotic activity, high apoptotic fraction and activation of caspase 3. These preclinical studies show the therapeutic potential of restoration of tumor suppressor expression through epigenetic modulation and the promise of re-expressed tumor suppressors as markers and effectors of the responses. ' 2006 Wiley-Liss, Inc.Key words: DNA methylation; tumor suppressor genes; 5-aza-2-deoxycytidine Lung cancer is the leading cause of cancer death in the western hemisphere for men and women, eclipsing the combined mortalities from breast, colon and prostate cancers. Genomic aberrations involving chromosome 3p are the most frequent and earliest genetic events in lung carcinogenesis. 1,2 In particular, the FHIT gene, spanning the human common fragile site, FRA3B, at chromosome 3p14.2, and the RASSF1A gene at 3p21 are frequently silenced in lung cancer and show hallmarks of tumor suppressor genes. 3 FHIT is altered in many other types of cancers, including breast, head and neck, cervical, bladder, esophageal, gastric, pancreatic and renal cancer and alterations occur in very early stages of preneoplasia in some organs. Fhit loss is associated with progression and outcome in cancers of various organs. 4 Similarly, the WWOX gene at FRA16D is frequently silenced in lung cancers, and has recently been shown to suppress growth of lung cancer cells in nude mice. [5][6][7] The RASSF1A promoter region is hypermethylated in a large fraction of lung and other cancers 8,9 and methylation of the RASSF1A regulatory region has been proposed as a biomarker of lung ca...

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An otherwise healthy 29-year-old woman presented with a complaint of odynophagia of several months' duration. On examination, she was found to have a broadly based, yellow, exophytic lesion on the right lateral pharyngeal wall. Findings on biopsy were consistent with amyloidosis. Th e patient underwent tonsillectomy with resection of the oropharyngeal lesion. Final pathology established a diagnosis of nodular non-AL-type amyloidosis. Localized amyloidosis of the oropharynx is exceptionally rare. Additionally, most cases of localized amyloidosis are of the AL type, not the AA (i.e., non-AL) type seen in this patient.