Biomedical subjects

David Chia

Publications and source records attributed to David Chia.

8 recordsLinked to original sources

PubMed2006

Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis.

Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and a known mediator of glucocorticoid-regulated inflammatory responses. Using a combined multiple high-throughput approach, we recently identified a reduced expression of ANXA1 in human breast cancer. The finding was confirmed at the gene level by quantitative reverse transcription-polymerase chain reaction and at the protein level by immunohistochemical staining of normal, benign, and malignant breast tissues. In this study, we constructed and used a high-density human breast cancer tissue microarray to characterize the expressional pattern of ANXA1 according to histopathologies. The tissue microarray contains 1,158 informative breast tissue cores of different histologies including normal tissues, hyperplasia, in situ and invasive tumors, and lymph node metastases. Our results showed that there was a significant decrease in glandular expression of ANXA1 in ductal carcinoma in situ and invasive ductal carcinoma compared with either normal breast tissue or hyperplasia (P < .0001). Moreover, in benign breast tissue, myoepithelial cells showed strong expression of ANXA1. There was a decrease of ANXA1 expression in myoepithelial cells in ductal carcinoma in situ lesions compared with the same cell population in either normal or hyperplastic lesions. These results suggest that suppressed ANXA1 expression in breast tissue is correlated with breast cancer development and progression.

Annexin A1↗

PubMed2006

Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial.

OBJECTIVES: Prostate volume correlates both with prostate-specific antigen (PSA) values and with the presence of benign prostatic hyperplasia (BPH). Here we examine the relationship between prostate volume and PSA level in a large, geographically diverse sample of men undergoing prostate cancer screening. METHODS: We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated by DRE performed by trained examiners at the PLCO sites. Linear and logistic regression was used to assess the effect of prostate volume and age on PSA levels. Regression coefficients were adjusted for the effect of prostate volume measurement error. RESULTS: Prostate volume estimated by DRE showed considerable measurement error. Averaging volume over screening visits and accounting for examiner bias greatly reduced this error. Linear regression analysis showed a slope of 0.030/cm3 of log PSA on prostate volume when correcting for measurement error (95% confidence interval [CI], 0.029 to 0.031). Age was independently associated with (log) PSA, with a slope of 0.022 per year. Logistic regression analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm3 increase in prostate volume. The correlation of log PSA and prostate volume was 0.37. Prostate volume was not correlated with body mass index and showed weak correlation (r = 0.14) with age. CONCLUSIONS: Prostate volume and age are independently associated with increased PSA levels in a population of men undergoing screening.

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PubMed2006

Prostate specific antigen changes as related to the initial prostate specific antigen: data from the prostate, lung, colorectal and ovarian cancer screening trial.

PURPOSE: Annual screening with PSA, although of unproven benefit, is currently used for prostate cancer early detection. A large fraction of screened men have low (less than 2 ng/ml) initial PSA. The yield over time of positive PSA screens (ie more than 4 ng/ml) in these men has not been well characterized in large cohorts in the United States. MATERIALS AND METHODS: Men in the screening arm of the PLCO received baseline PSA and annual tests for 5 years. 30,495 of these men had baseline PSA 4 ng/ml or less. We estimated the cumulative probability of converting to PSA greater than 4 at years 1 through 5 as a function of baseline PSA. RESULTS: Among men with baseline PSA less than 1 ng/ml, 1.5% converted by year 5 (95% CI 1.2-1.7). Among men with baseline PSA of 1.0 to 1.99 ng/ml, 1.2% (95% CI 0.9-1.3) and 7.4% (95% CI 6.8-8.1) converted by year 1 and 5, respectively. A total of 33.5% and 79% of men with initial PSA of 2.0 to 2.99 and 3.0 to 4.0, respectively, converted by year 5. Of men with baseline PSA less than 1 ng/ml converting to PSA more than 4 ng/ml, 8% were diagnosed with cancer within 2 years of conversion. About 10% of men with baseline PSA less than 1 ng/ml and negative baseline DRE had a positive DRE within 3 years. CONCLUSIONS: For men choosing PSA screening, screening every 5 years for baseline PSA less than 1 ng/ml and every 2 years for PSA 1 to 2 ng/ml could result in a 50% reduction in PSA tests and in less than 1.5% of men missing earlier positive screens, but with an unknown effect on prostate cancer mortality.

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PubMed2005

Prostate Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of a randomized trial.

BACKGROUND: The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. METHODS: A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. RESULTS: Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. CONCLUSION: The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.

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PubMed2005

Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses.

To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p<0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology.

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PubMed2005

Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial.

OBJECTIVE: Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial. STUDY DESIGN: This was a randomized controlled trial of screening versus usual care. Baseline screening results are reported. RESULTS: Of 39,115 women randomized to receive screening, 28,816 received at least 1 test. Abnormal TVU was found in 1338 (4.7%), and abnormal CA-125 in 402 (1.4%). Twenty-nine neoplasms were identified (26 ovarian, 2 fallopian, and 1 primary peritoneal neoplasm). Nine were tumors of low malignant potential and 20 were invasive. The positive predictive value for invasive cancer was 3.7% for an abnormal CA-125, 1.0% for an abnormal TVU, and 23.5% if both tests were abnormal. CONCLUSION: The effect of screening on ovarian cancer mortality in the PLCO cohort has yet to be evaluated and will require longer follow-up. Screening identified both early- and late-stage neoplasms, and the predictive value of both tests was relatively low.

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PubMed2005

Expression of transcription factor Yin Yang 1 in prostate cancer.

The transcription repressor Yin Yang 1 (YY1) is expressed in several human cancer cell lines and its expression correlates with resistance to immune-mediated apoptosis. This study used tissue microarrays to investigate the expression and localization of YY1 in 1364 representative tissue samples from 246 hormone naive prostate cancer patients who underwent radical prostatectomy. Staining intensity and frequency measures for both YY1 nuclear and cytoplasmic expression were higher in neoplastic tissues and in PIN samples compared to matched benign cells (p < 0.0001 for all comparisons). Expression of YY1 is predominantly elevated in early malignancy (PIN), as well as in tumors of intermediate to high morphologic grade (Gleason's grade 3-5). Using multivariate Cox proportional hazards analysis, we observed that low nuclear YY1 staining is an independent predictor of a shorter time to recurrence (p = 0.012). Based on these results, we hypothesize that YY1 may play a role in prostate cancer development; however, decreased YY1 may give metastatic cells a survival advantage. These results may also implicate YY1 as a useful diagnostic and prognostic marker.

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PubMed2003

COX-2-dependent stabilization of survivin in non-small cell lung cancer.

Elevated tumor cyclooxygenase 2 (COX-2) expression is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. The mechanism(s) by which COX-2 exerts its cytoprotective effects are not completely understood but may be due to an imbalance of pro- and anti-apoptotic gene expression. To analyze COX-2-dependent gene expression and apoptosis, we created cell lines constitutively expressing COX-2 cDNA in sense and antisense orientations. Whereas COX-2 sense cells have significantly heightened resistance to radiation and drug-induced apoptosis, COX-2 antisense cells are highly sensitive to apoptosis induction. We found that the expression of the anti-apoptotic protein survivin correlated positively with COX-2 expression. A COX-2-dependent modulation of survivin ubiquitination led to its stabilization in COX-2 overexpressing cells, and this effect was replicated by exogenous PGE2 treatment of parental tumor cells. In contrast to previous studies in other cell types, in nonsmall cell lung cancer cells survivin was expressed in a cell cycle-independent manner. When established in SCID mice in vivo, COX-2 antisense-derived tumors had significantly decreased survivin levels while COX-2 sense-derived tumors demonstrated elevated levels compared with controls. In accord with these findings, survivin and COX-2 were frequently upregulated and co-expressed in human lung cancers in situ.

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