Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma

Abstract

Objective To elucidate the safety of adalimumab for rheumatoid arthritis (RA) patients with renal insufficiency, including those with end‐stage renal disease undergoing hemodialysis. Methods Sixty‐five RA patients, including 2 patients undergoing hemodialysis, treated with adalimumab in our hospital from December 1, 2008 to June 30, 2011 were retrospectively analyzed. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated from the Cockcroft‐Gault formula at the start and end of followup after adalimumab treatment. The proportion of the patients who discontinued or switched adalimumab treatment and the change of the eGFR were compared between patients with (n = 39) and without (n = 26) renal insufficiency, defined as an eGFR <60 ml/minute/1.73 m2. Results There was no significant difference between the 2 groups in the proportion of the patients who discontinued or switched adalimumab treatment (51.3% versus 50.0%; P = 0.53). The mean ± SD changes of eGFR were from 41.6 ± 13.3 to 43.4 ± 17.9 ml/minute/1.73 m2 in patients with renal insufficiency and from 83.6 ± 17.5 to 83.0 ± 16.8 ml/minute/1.73 m2 in patients without renal insufficiency, and the differences in each group were not statistically significant (P = 0.92 and P = 0.78, respectively). No severe infections or other severe adverse events were observed in either group during adalimumab treatment. Conclusion Our data indicate that adalimumab does not worsen renal function and has no serious adverse events even for RA patients with renal insufficiency, including those undergoing hemodialysis, and suggest that it could be a potential therapeutic option for them.

Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors

“…IGSF4 gene, a novel immunoglobulin (Ig)‐like intercellular adhesion molecule located on chromosome 11q23, was first characterized as a tumor suppressor of non‐small‐cell lung cancer. Methylation of the gene was found to be associated with poor survival in non‐small‐cell lung carcinoma 30. In accordance with prior research, univariate survival analysis in this study demonstrated that progression‐free survival was found to be significantly shorter for patients with IGSF4 methylation compared to those without IGSF4 methylation.…”

Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma

“…No evidence for hypermethylation of the CADM1 promoter region in neuroblastoma To investigate whether hypermethylation of the CADM1 promoter is involved in regulating CADM1 expression levels in neuroblastoma, eight CpG sites located in the promoter region that have been demonstrated to be methylated in several tumours (Fukami et al, 2003;Steenbergen et al, 2004;Kikuchi et al, 2006) were tested for methylation by bisulphite sequencing. Hypermethylation was defined as methylation of a CADM1 is a tumour suppressor gene in neuroblastoma S Nowacki et al specific CpG site in >50% of the clones sequenced.…”

“…Therefore, the molecular mechanism underlying transcriptional repression in these cases is unlikely to be hypermethylation. Although we cannot rule out the possibility that hypermethylation of a distinct set of CpG sites in the promoter region might have occurred as described for cervical cancer (Li et al, 2005), the eight CpG sites chosen for our analysis have been considered to be representative for global hypermethylation in several studies (Fukami et al, 2003;Steenbergen et al, 2004;Kikuchi et al, 2006). Nevertheless, hypermethylation can be indicative, but is not necessarily involved in downregulation of CADM1 expression as suggested from previous analysis of two prostate cancer cell lines (Fukuhara et al, 2002).…”

“…One might therefore suggest that this tumour suppressor requires a critical transcript level to prevent aggressive behaviour of malignant cells in solid tumours resulting in progressive and advanced cancer. Promoter hypermethylation of CADM1 has been observed in many malignancies (Fukami et al, 2003;Li et al, 2005;Ehrlich et al, 2006;Kikuchi et al, 2006;Worsham et al, 2006) and has thus been suggested to represent the most common molecular mechanism responsible for gene silencing of CADM1 in human cancers. In contrast to these reports, we could not detect any associations of CADM1 expression level with the methylation status of the CADM1 promoter region in a set of 18 primary neuroblastomas.…”

“…Loss of CADM1 expression has been described in many malignancies, including liver, pancreatic, breast, brain and prostate cancers, particularly in those showing invasion or metastasis (Kuramochi et al, 2001;Fukuhara et al, 2002;Jansen et al, 2002;Houshmandi et al, 2006;Heller et al, 2007). Promoter hypermethylation was reported to account for downregulation of CADM1 in several human cancers (Murakami, 2005;Ehrlich et al, 2006;Kikuchi et al, 2006;Worsham et al, 2006). Moreover, high expression levels of CADM1 from a recombinant adenovirus vector were shown to inhibit cell proliferation and to induce apoptosis in the non-small cell lung cancer cell line A549 (Mao et al, 2004).…”