Following our results, we concluded that HDR-BRT is a more effective and safer treatment approach for head and neck cancer recurrences than 3D-CRT.
Background and Objective. Many factors are involved in the development of gastric adenocarcinoma. The CpG island methylation of apoptosis and mismatch repair genes by the loss of their function is important in gastric adenocarcinoma. The aim of this study was to determine the methylation frequency of MLH1, MGMT, CASP8, and DAPK in cancerous and adjacent noncancerous stomach tissues, to determine possible associations with the selected clinicopathological characteristics, and to identify possible correlation between the methylation of individual genes. Material and Methods. The methylation status of MLH1, MGMT, DAPK, and CASP8 was investigated in 69 patients with gastric adenocarcinoma by using methylation-specific polymerase chain reaction. The associations between patients’ clinical characteristics and methylation status were assessed. Results. The methylation frequency of the MLH1, DAPK, MGMT, and CASP8 gene promoters in cancerous and adjacent noncancerous tissues was 31.9% and 27.5%; 47.8% and 46.4%; 36.2% and 44.9%; and 5.8% and 5.8%, respectively, but the differences were not significant. There was no significant association between the methylation status of the mentioned genes and clinicopathological characteristics, such as age, sex, tumor type by the Lauren classification, degree of differentiation G, and TNM staging. An inverse correlation between the methylation of the DAPK and MLH1 gene promoters in cancerous and surrounding noncancerous tissues was found. Conclusions. The methylation of the MLH1, MGMT, DAPK, and CASP8 genes was found to occur both in cancerous and noncancerous stomach tissues. These findings provide additional insights into gene methylation patterns in gastric adenocarcinoma.
BackgroundThere is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach.The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites.MethodsSamples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009–2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee.ResultsThe frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4 %, respectively, for MLH1; 22.2, 30.8, and 57.6 %, respectively, for MGMT; and 44.4, 48.7, and 51.5 %, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2–3 compared with N0–1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I–II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, –0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, –0.41; p = 0.01).ConclusionGene promoter methylation depends on the gastric tumor location.
Genes carrying high‐penetrance germline mutations may also be associated with cancer susceptibility through common low‐penetrance genetic variants. To increase the knowledge on genetic pancreatic ductal adenocarcinoma (PDAC) aetiology, the common genetic variability of PDAC familial genes was analysed in our study. We conducted a multiphase study analysing 7745 single nucleotide polymorphisms (SNPs) from 29 genes reported to harbour a high‐penetrance PDAC‐associated mutation in at least one published study. To assess the effect of the SNPs on PDAC risk, a total of 14 666 PDAC cases and 221 897 controls across five different studies were analysed. The T allele of the rs1412832 polymorphism, that is situated in the CDKN2B‐AS1/ANRIL, showed a genome‐wide significant association with increased risk of developing PDAC (OR = 1.11, 95% CI = 1.07‐1.15, P = 5.25 × 10−9). CDKN2B‐AS1/ANRIL is a long noncoding RNA, situated in 9p21.3, and regulates many target genes, among which CDKN2A (p16) that frequently shows deleterious somatic and germline mutations and deregulation in PDAC. Our results strongly support the role of the genetic variability of the 9p21.3 region in PDAC aetiopathogenesis and highlight the importance of secondary analysis as a tool for discovering new risk loci in complex human diseases.
Aim.To compare hMLH1 methylation frequency in stomach antral and body area tissue in chronic atrophic pangastritis patients, and to evaluate possible correlation severity of chronic atrophic gastritis markers.Methods. The study population consisted of 24 participants (with histologically confirmed chronic atrophic pangastritis), who underwent upper endoscopy. Biopsy specimens were taken from the gastric antral and body area. The methylation status of the gene hMlH1 was investigated.Results. Methylation of the CpG island of gene hMLH1 was found in the antral stomach area group 9/24, compared with the body area 2/24. There was a significant difference in gene methylation frequencies in the observed stomach parts (Fisher's exact test, p = 0.04). There was a significant association between gene hMLH1 methylation and the occurrence of severe atrophic gastritis, intestinal metaplasia and the presence of hyperplastic mucosal changes (Fisher's exact test, p < 0.05).Conclusions. hMLH1 gene methylation frequency is higher in the stomach antral tissue compared with the stomach body tissue, and increases with higher level of atrophic gastritis and intestinal metaplasia.
After radical treatment of head and neck cancer about 20-50% of patients are diagnosed with the locoregional recurrence during first two years. The main treatment for recurrent disease is salvage surgery, but in most cases, surgery is not feasible due to the high risk of complications and morbidity, and only 20% of patients are suitable for surgical salvage. Reirradiation is an effective treatment method with acceptable toxicity, but this treatment method is limited to normal tissue tolerance to a total dose. When chemotherapy is administered for recurrence, the response rate is up to 40%, so with the advancement of technical measures, after introduction of intensity-modulated radiotherapy, fractionated stereotactic body radiation therapy, high-dose-rate brachytherapy, proton beam reirradiation, a reirradiation is increasingly more often used for head and neck cancer relapse treatment. In this chapter, we will discuss about reirradiation with curative intent using new different radiation techniques (intensity-modulated radiotherapy (IMRT), stereotactic body radiation therapy (SBRT), high-dose-rate brachytherapy (HDR-BRT) and proton beam reirradiation (PBRT) for previously irradiated head and neck cancer and present recommendations for retreatment of head and neck cancer relapse using reirradiation alone or with systemic chemotherapy/biologic therapy.
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