Abstract:Background: Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors.Aim: we focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911CMaterial and methods: The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used.Results: We found that: i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391,3.7782) p=0.038], ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215,0,9131) p=0.031] for an individual with at least one A allele at this locus. Conclusions:1. the XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer.2. the NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.
This literature review looks at the epidemiology, clinical manifestations, diagnostics and current medical and surgical management of Clostridium difficile (C. difficile) infection. A literature search of PubMed and Cochrane database regarding C. difficile infection was performed. Information was extracted from 43 published articles from 2000 to the present day which met inclusion criteria. C. difficile is a gram-positive, anaerobic bacillus, which is widely found in the environment, especially in the soil. The occurrence of more resistant strains, which is mainly connected with the wide use of antibiotics, resulted in the rapid spread of the bacteria to different hospital departments. Particularly, elderly patients in surgical wards and intensive care units are at significant risk of developing C. difficile infection, which greatly increases morbidity and mortality. Symptoms of infection with C. difficile vary greatly. At one end of the spectrum, there are asymptomatic carriers, at the other patients with life-threatening toxic megacolon. Metronidazole is considered to be the drug of choice, but recent guidelines recommend Vancomycin. Fulminant colitis and toxic megacolon warrant surgical intervention. The optimal time for surgery is within 48 h of initiating conservative treatment without seeing a response, the development of multiple organ failure or a bowel perforation. A factor that has become increasingly important and relevant is the escalating expense of treatment for patients with C. difficile infection. It is, therefore, highly recommended to consider reviewing all hospital antibiotic policies and clinical guidelines that may contribute to the prevention of the infection.
Many theoretical and experimental models indicate that androgen receptors can play an important role as prognostic factors in breast cancer. The aim of this study was to evaluate the correlations between the presence of androgen receptors on cancer cells and other selected prognostic and predictive factors with established clinical significance in women with breast cancer after radical surgical treatment. 488 adult females were included in the study, who underwent primary radical surgery for breast cancer. 428 patients (87.7%) had Patey's conservative radical mastectomy and 60 (12.3%) Halsted's radical mastectomy. The mean age at operation was 54.3, ranging from 32 to 79. The mean length of hospitalization was 7.2 days for the patients after Patey's mastectomy and 9.8 days for those after Halsted's mastectomy. The androgen receptor is the most frequently detected steroid receptor on breast cancer cells. Therapeutic efficacy of adjuvant hormone therapy was higher in the group of androgen receptor-positive patients than in androgen receptor-negative ones. The prognosis for androgen receptor-positive patients who underwent adjuvant hormone therapy was better than for those androgen receptor-positive patients who did not receive hormone therapy after primary radical surgery for breast cancer. Assessment of androgen receptor levels on cancer cells should become a routine procedure with patients undergoing primary radical surgery for breast cancer, as it seems to be an important predictive factor.
Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with a variety of mucinous tumours of varying biologic behavior. Although appendix or ovaries have usually been implicated as the primary site, cases have been reported in association with neoplastic lesions of other sites. Pseudomyxoma peritonei originating from urachal remnants is a unique entity, reported only 18 times in the English literature thus far. Considering the rarity of the lesion, we report the case of a 50-year-old man surgically treated for pmp associated with a low-grade mucinous urachal neoplasm. Unique aspects of case are the low histologic aggressiveness of the causative lesion (reported only twice worldwide) and the early stage of the disease, with a relatively small amount of intraperitoneal free mucin. Review of the literature about pmp in general and a collation of previously reported cases of pmp originating from the urachus are presented and discussed.
The CpG island methylator phenotype (CIMP), characterized by an exceptionally high frequency of methylation of discrete CpG islands, is observed in 18% to 25% of sporadic colorectal cancers. Another hypermethylation pattern found in colorectal cancers, termed long-range epigenetic silencing, is associated with DNA/histone methylation in three distinct gene clusters at chromosome 2q14.2, showing that DNA hypermethylation can span larger chromosomal domains and lead to the silencing of flanking, unmethylated genes. We investigated whether these two phenotypes are interrelated in colorectal cancers. The CIMP status of 148 sporadic colorectal cancers was determined by methylation-specific PCR. We determined the BRAF V600E mutation by mutant allele -specific PCR amplification. The methylation status of the MLH1 gene and of three CpG islands (EN1, SCTR, and INHBB), corresponding to three distinct clusters along 2q14.2, was determined by methylation-specific PCR. The average number of sites showing methylation in CIMP+ tumors was 2.21, compared with 1.22 for CIMPÀ individuals, and this difference was highly significant (P = 3.6 Â 10 À8, Mann-Whitney test). Moreover, all CIMP+ tumors showed hypermethylation of at least one of these loci, in contrast to CIMPÀ tumors, where 18 (16%) samples remained unmethylated. The mean number of simultaneously hypermethylated CpG islands at 2q14.2 differs significantly between CIMPÀ and CIMP+ tumors, suggesting varying effects of domain silencing in this region. Given that the number of hypermethylated loci at 2q14.2 likely affects the range of silenced flanking genes, high frequency of simultaneous hypermethylation of three CpG islands (EN1, SCTR, and INHBB) may have potential influence on specific characteristics of CIMP+ colorectal cancers. (Mol Cancer Res 2008;6(4):585 -91)
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