Gene expression pattern associated with radiotherapy sensitivity in cervical cancer.

UNLABELLED: The objective of the present preliminary study was to determine if a difference in the pattern of gene expression exists between tumors that were subsequently found to be sensitive to radiotherapy and tumors found to be resistant to radiotherapy. PATIENTS AND METHODS: A total of 16 patients with invasive squamous cell carcinoma of the uterine cervix were included in this study. All patients were treated with standardized radiotherapy alone. Ten of the tumors were clinically radiosensitive and six were radioresistant. Total RNA, extracted from tumor specimens obtained prior to treatment, was hybridized onto an oligonucleotide microarray with probe sets complementary to over 20,000 transcripts. The genes were first subjected to a statistical filter to identify genes with statistically significant differential expression levels between those that were radiosensitive and those that were radioresistant. A back-propagation neural network was then constructed to model the differences so that patterns could be easily identified. RESULTS: Although a number of genes were found to express differentially between radiosensitive and radioresistant tumors; the 10 most discriminating genes were used to construct the model. Using the expressions from these 10 genes, we found that neural networks constructed from random subsets of the whole data were capable of predicting radiotherapy responses in the remaining subset, which appears stable within the dataset. DISCUSSION: This study shows that such an approach has the potential to differentiate tumor radiosensitivity, although confirmation of such a pattern using other larger independent datasets is necessary before firm conclusions can be drawn.

Compliance with a pelvic muscle exercise program as a causal predictor of urinary stress incontinence amongst Chinese women.

AIM: To determine the importance and contribution of compliance in a pelvic muscle exercise program as a factor in reducing the severity of urinary stress incontinence amongst Chinese women. METHODS: Two hundred fourteen women presenting with urinary stress incontinence who agreed to undertake a program of pelvic muscle exercises were recruited into the study. Incontinence (wetting episodes), pelvic muscle strength, exercises compliance, correctness of pelvic muscle exercise technique, duration of stress incontinence, and previous history of pelvic surgery were recorded on four occasions: baseline (first clinic session) and second to fourth clinic sessions. Demographic data were also collected at baseline. Stepwise multiple regression analyses were used to determine the relative importance of compliance to exercise regime in predicting the severity of incontinence. Path analysis was used to provide a summary description of the influence of compliance on the outcomes over the four visits. RESULTS: The pelvic muscle training program appears to be able to reduce the overall urinary incontinence episodes by 85.2% and achieved a 73.1% increase in pelvic muscle strength. Although the number of wetting episodes in any visit are causally linked to that recorded in previous visit, those who were more compliant had a greater reduction. Age, mode of delivery, menopausal status, history of pelvic surgery, and duration of incontinence did not appear to contribute significantly to predicting incontinence. CONCLUSION: Compliance with pelvic muscle exercises significantly contributed to a reduction in urinary stress incontinence.

Customizing fetal biometric charts.

OBJECTIVE: To study the effects of maternal and pregnancy characteristics on fetal biometric size using longitudinal ultrasound measurements and to construct customized models for fetal biometric size charts. METHODS: A cohort of 533 healthy pregnant women with normal singleton pregnancies were recruited for regular ultrasound examination for fetal biometry between 24 and 40 weeks' gestation. Multilevel modeling was used to construct models of fetal head size, femur length and abdominal circumference. Variables of maternal and pregnancy characteristics including booking weight and height, age, parity and fetal sex were included in the construction of the customized fetal biometric size charts. RESULTS: Increased fetal head size and abdominal circumference were significantly associated with extremes of maternal age. Maternal height had a statistically significant influence on biparietal diameter. Maternal booking weight had an influence on fetal abdominal circumference and femur length. Fetal sex was found to have a statistically significant influence on the final regression models of biparietal diameter, head circumference and femur length. Parity had an influence on fetal head circumference and abdominal circumference. CONCLUSIONS: Maternal and pregnancy characteristics have a significant influence on in-utero fetal biometry. We produced models to construct customized fetal biometric size charts. Further validation studies are necessary to evaluate the clinical usefulness of such customized fetal biometric size charts.

Clinical and pathologic significance of microsatellite instability in endometrial cancer.

Microsatellite instability (MSI) is identified as electrophoretic shifts in allele sizes of microsatellite DNA sequences. It is characteristic of a subset of sporadic colorectal tumors as well as hereditary nonpolyposis colorectal cancer (HNPCC). The cells that display MSI are thought to be susceptible to increased mutability. MSI has been detected in a wide variety of human tumors, but the influence of this form of genetic instability on disease initiation and progression remains unclear. Using a polymerase chain reaction (PCR)-based method we screened 50 sporadic primary endometrial carcinomas to characterize the prevalence of MSI in these tumors and analyze the correlation of MSI with clinicopathologic parameters in this malignancy. Fifteen cases (30%) displayed low frequency of MSI (MSI-L) showing MSI at one locus in 5 loci examined. Two cases (4%) showed high frequency of MSI (MSI-H) having MSI at 2 or more loci. Taking MSI-L and MSI-H cases together as MSI-positive, statistical analysis of patient age, tumor grade, and stage failed to disclose significant differences or trends between cases with MSI-positive and MSI-negative (P > 0.05). No significant relationship was observed between patients with MSI and without MSI (P > 0.05), however, the MSI exhibited only in those cases without evidence of disease at the 24th month after treatment. The difference is statistically significant when compared with patients who are alive with disease or died of disease (P < 0.01). However, the overall survival curves were not statistically different. We conclude that MSI is present in a subgroup of endometrial cancer.