Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.

Progressive telomere shortening is thought to be important in hematologic neoplasia, TRF shortening has been observed [17][18][19] the regulation of cellular senescence and that the upregulation and in some instances an enhancement of telomerase actior reactivation of telomerase activity may be a critical if not rate vity. [19][20][21] In myelodysplastic syndrome, reduction of TRF is 4.53 ± ± ± 0.72 kb vs 6.13 ± ± ± 1.68 kb; P = 0.0005). All samples chronic and blastic phase of CML.obtained from CML in the chronic phase (n = 33) had detectable telomerase activity above background, regardless of age. In the blast phase (n = 21), a significant increase of telomerase activity was detected compared to that in the chronic phase Materials and methods(33.84 ± ± ± 37.86% vs 6.08 ± ± ± 3.21; P = 0.016). Among patients in the blastic phase, 50% of patients had moderate to high telomerase Patients and samples activity (Ͼ10 relative value), and the remaining patients had telomerase activity higher than that in the normal peripheral blood cells. No significant differences in hematologic findings, durWe studied 54 samples obtained from 41 patients with Philaation of chronic phase or blast phase, and telomere length in delphia translocation-positive CML (aged 14 to 77 years old).the blastic phase were noted between these two groups separThirty-three samples were obtained in the chronic phase and ated by telomerase activity. CML patients with moderate to high 21 were from the blastic phase; 13 patients were subsequently telomerase activity had a high frequency of additional cytoganalyzed at both chronic phase and blastic phase. We basienetic changes (P = 0.01).cally used bone marrow samples, but some samples were

Adenocarcinoma (ADC) is the most frequent histological type of lung cancer and comprises the majority of lung cancers in nonsmokers. Thus, genetic factors responsible for ADC susceptibility need to be determined to establish efficient ways of preventing the disease. The OGG1 gene, encoding a glycosylase for 8-hydroxyguanine, an oxidatively damaged promutagenic base, has the polymorphism Ser326Cys, and OGG1-326Cys protein was indicated to have a lower ability to prevent mutagenesis than the OGG1-326Ser protein. Case-control studies to date suggest that the OGG1-326Cys allele is associated with a higher risk for several types of cancers, including overall lung cancer. However, the contribution of this polymorphism to lung ADC risk is unclear. In the present study, the OGG1-Ser326Cys polymorphism was assessed for association with lung ADC risk using a case-control study of a Japanese population consisting of 1097 cases and 394 controls. Odds ratios (OR) of the 326Cys allele carriers increased in a dose-dependent manner with allele number (P for the trend test = 0.04). The OR of homozygotes for the 326Cys allele was increased significantly when homozygotes for the 326Ser allele were used as a reference (OR = (1) ADC, SQC and SCC are three major histological types of lung cancer. It is known that the development of SQC and SCC is strongly associated with smoking, whereas that of ADC is less associated compared with the other two types, indicating that carcinogenic processes are different between ADC and SQC and SCC.1(1) Recently, ADC has become the most frequent histological type of lung cancer, and it comprises the majority of lung cancers in non-smokers.(2) Thus, genetic factors, as well as environmental factors, responsible for the susceptibility of ADC in each individual need to be determined to establish efficient ways of preventing the disease. The OGG1 gene encodes a protein with DNA glycosylase and AP lyase activities that remove 8OHG, an oxidatively damaged promutagenic base, from double-stranded DNA.(3,4) We previously found a SNP at codon 326 associated with the amino acid change Ser326Cys.(5) The lower ability of OGG1-326Cys protein than OGG1-326Ser protein to prevent mutagenesis by 8OHG has been shown by both in vitro (5,6) and in vivo (7) studies. It was also demonstrated that homozygotes for the OGG1-326Cys allele have a lower capacity to repair 8OHG than others.(8) Frequencies of the OGG1-326Cys allele are different among populations, and the frequency is higher in Asians (i.e. >40%) than in Caucasians (i.e. <20%).(9) As reviewed by Weiss et al.(10) several case-control (association) studies have been undertaken on several populations, including Caucasians and Asians, and the OGG1-326Cys allele encoding the less active OGG1 protein was reported to be associated with the risk of a variety of human cancers such as esophageal, prostate, orolaryngeal and nasopharyngeal cancers. Case-control studies have also been undertaken on the association of this SNP with lung cancer risk. (9,(11)(12)(13)(14)(15)(16) ...