Ribosomal proteins are encoded by a gene family, members of which are overexpressed in human cancers. Many of them have been found, using oligonucleotide microarray hybridization, to be differentially expressed in the faeces of patients with various stages of col-orectal cancer (CRC). The gene encoding ribosomal protein L19 (RPL19), a prognostic marker for human prostate cancer, is differentially expressed in CRC patients. Measurement of faecal RPL19 mRNA might improve prognostic prediction for CRC patients. Using quantitative real-time reverse transcription PCR, levels of RPL19 mRNA were detected in samples of colonic tissues from 44 CRC patients, in the faeces of 54 CRC patients and 15 controls, and in 11 colonic cell lines. Seven of 24 patients with late-stage CRC (Dukes' stages C and D) expressed over 2-fold more RPL19 in colonic tumour tissues than in corresponding normal tissues (P= 0.038). The mean faecal RPL19 mRNA levels of late-staged patients were higher than those of controls (P= 0.003) and early-staged patients (P= 0.008). Patients with both high serum levels of carcinoembryonic antigen (CEA; >5 ng/mL) and high-faecal RPL19 mRNA (≥0.0069) had higher risk (odds ratio, 8.0; P= 0.015) and lower overall 48-month survival (33.8 ± 13.7%, P= 0.013). Oligonucleotide microarray hybridization analysis of faecal molecules identified gene transcripts differentially present in faeces. In conclusion, faecal RPL19 expression is associated with advanced tumour stages and addictive to serum CEA in predicting prognosis of CRC patients.
Most LAM avulsions and EAS defects seem to be caused by the first vaginal birth. Subsequent vaginal deliveries after the first were unlikely to cause further LAM trauma.
Relatively low doses of space radiation have been correlated with an increased incidence and earlier appearance of cataracts in space travelers. The lens is a radiosensitive organ of the body with a very obvious late end point of radiation damage--cataract. However, many molecular changes occur in the lens soon after radiation exposure and long before the appearance of an opacification. The goal of our research is to elucidate early mechanisms associated with particle radiation-induced cataractogenesis, with the ultimate goal of developing countermeasures. Normal, cultured non-immortalized human lens cells were grown on matrix-coated plastic tissue culture vessels and irradiated with particle beams at Lawrence Berkeley National Lab (LBNL) or at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab. Samples were harvested at different times after radiation exposure. Using a focused genetic approach, total RNA and protein extracts from control and irradiated samples were processed and probed for the expression of genes associated with extracellular matrix (ECM) proteases. Matrix metalloproteinases (MMPs) have previously been studied in adult postmortem human lenses, in post-cataract intraocular lens (IOL) surgery capsular bags and with immortalized human lens cell cultures. Significant differences exist in the expression pattern with these various model systems. We have evidence for the cell stage-specific expression of MMP family of genes during lens fiber differentiation, and for radiation-induced alterations in the misregulation of MMP expression. Our data indicate that radiation exposure may lead to differences in the expression of radiation stress responses, which may impact selective ECM remodeling and cell differentiation.
BackgroundLevator ani muscle (LAM) and anal sphincter injuries are common after vaginal birth and are associated with pelvic organ prolapse and anal incontinence.AimsOur objective was to investigate long‐term association between delivery mode, LAM avulsion and obstetric anal sphincter injuries (OASIS) in women at least 20 years after their first birth.MethodsAll women recruited at ‘index birth’ of the Dunedin (New Zealand) arm of ProLong (PROlapse and incontinence LONG‐term research) Study, were invited to have translabial and transperineal ultrasound assessment of LAM and anal sphincters. Post‐processing analysis of imaging data was performed blinded against delivery data. Statistical analysis was performed using the χ2 test and results are expressed as odds ratios (OR).ResultsOf the initial 1250 participants, 196 women returned for examination. Mean age was 50.8 years with a mean body mass index of 27.6 and median parity was three. They were seen on average 23 years after their first delivery. Four data sets were unavailable and one declined ultrasound assessment, leaving 191 for analysis. LAM avulsion was diagnosed in 29 (15.2%), and 24 women (12.6%) had significant anal sphincter defect. LAM avulsion was associated with forceps delivery (OR 2.45, 95% CI 1.04–5.80, P = 0.041). Forceps conveyed a greater risk of OASIS (21%) compared to a spontaneous vaginal delivery (11%) but did not reach statistical significance.ConclusionsForceps delivery is associated with long‐term injurious effect on pelvic floor structures. Discussions of the long‐term negative impact of pelvic floor structures and their functions are necessary to achieve an informed consent toward an operative vaginal delivery.
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