Biomedical subjects

JianYu Rao

Publications and source records attributed to JianYu Rao.

6 recordsLinked to original sources

PubMed2003

Analysis of the Na,K-ATPase alpha- and beta-subunit expression profiles of bladder cancer using tissue microarrays.

BACKGROUND: The purpose of this study was to determine the clinical significance of Na,K-ATPase alpha- and beta-subunit expression in a histopathologically well-characterized group of patients representing a wide spectrum of tumor grades and disease stages with transitional cell carcinomas (TCC). METHODS: Na,K-ATPase alpha- and beta-subunit protein expression patterns were analyzed using immunohistochemistry on urothelial cancer tissue microarrays (TMA) of 146 patients diagnosed with urothelial carcinoma. For each subunit, the maximum staining intensity and the percentage of positive cells staining at the maximal intensity were analyzed. RESULTS: Compared with the benign fields, the mean protein expression for both Na,K-ATPase alpha- and beta-subunits were found to be decreased overall in in situ and invasive tumors, as well as in tumor-adjacent dysplastic fields. When Na,K-ATPase alpha- and beta-subunit expression levels were dichotomized into distinct groups, they were both found to be significant predictors of recurrence risk in multivariate logistic regression analysis (P = 0.0062, odds ratio [OR] = 2.6 and P = 0.013, OR = 0.43, for Na,K-ATPase alpha- and beta-subunits, respectively). The authors also found that patients with high alpha- and low beta-subunit expression had a high risk for early recurrence, whereas patients with a low alpha- and high beta-subunit expression had a significantly longer median recurrence-free time (17 months and 125 months, respectively, log rank statistics P = 0.0005). CONCLUSIONS: The results suggested that Na,K-ATPase alpha- and beta-subunit expression levels may be useful predictors of clinical outcomes such as recurrence-free time of bladder cancer patients.

Adult↗

PubMed2003

Immunohistochemical analysis of cyclooxygenase-2 expression in premalignant and malignant esophageal glandular and squamous lesions in Cixian, China.

Increased cyclooxygenase-2 (COX-2) expression has been observed in both squamous cell carcinoma (SCC) and adenocarcinoma (AC) in Western countries, and COX-2 inhibitors have been considered as potential chemopreventive agents for esophageal cancers. Since chemoprevention often targets the premalignant lesions in high-risk population, it is worthwhile to study COX-2 expression in a spectrum of premalignant and malignant lesions obtained from the high-risk populations. In this study, biopsy samples were taken from 240 subjects identified by screening of the high-risk population in Cixian, China, including 27 normal, 29 with squamous hyperplasia, 84 with dysplasia (31 low grade and 53 high grade), 30 with carcinoma in situ, and 70 with invasive carcinoma (60 SCC and 10 AC). For comparison, tissue samples were also collected from He Lon Jiang Province, a low-risk population in China, including 10 patients with invasive SCC, 20 patients with AC, and 17 patients with Barrett's esophagus. The COX-2 protein expression was examined by immunohistochemistry. Using 10% staining as a threshold, 9 of 10 (90%) invasive SCC from low-risk population were COX-2 positive. However, no positive COX-2 staining was seen on normal, hyperplastic, dysplastic, and in situ squamous lesions from the high-risk population, and only 4 of 60 (6%) invasive SCC exhibited positive COX-2 staining. For glandular lesions, 6 of 10 (60%) AC from high-risk area and 15 of 20 (75%) from low-risk area showed positive COX-2 staining, and 12 of 17 (70%) premalignant Barrett's esophagus were also positive. Our findings show that COX-2 expression various in squamous lesions from high- and low-risk areas, but not in glandular lesions. Additional studies are needed to fully explore the mechanisms that are associated with the different COX-2 immunohistochemical staining patterns in esophageal squamous lesions from low- and high-risk populations.

Barrett Esophagus↗

PubMed2003

8q24 amplification in transitional cell carcinoma of bladder.

Genomic amplifications of the long arm of chromosome 8q are frequently detected in a number of tumor types, including neoplasias of the urothelium. DNA level amplification and increased expression of at 8q24 is commonly associated with chromosomal gains in this region. Using a urothelial cancer tissue microarray, the authors investigated the 8q24 amplification on bladder tumors and metastases. High-copy 8q24 amplification was detected in 9% (12 of 131) of primary tumors and 33% (6 of 18) of distant metastases. Additionally, the authors investigated the expression profiles of two frequently used biomarkers, p53 and Ki67, on the same arrays that had been analyzed for the 8q24 amplification. 8q24 amplification was positively correlated with Ki67 protein expression ( < 0.005), whereas a similar correlation with p53 did not reach statistical significance ( = 0.19). The authors conclude that 8q24 amplification occurs in a small subgroup of primary bladder tumors and in a more significant group of distant metastases.

Biomarkers, Tumor↗

PubMed2002

Tissue microarray analysis of cytoskeletal actin-associated biomarkers gelsolin and E-cadherin in urothelial carcinoma.

BACKGROUND: Alterations of expression of the cytoskeletal proteins Gelsolin and E-cadherin have been implicated in urothelial carcinoma tumorigenesis. However, it is not clear how these altered expressions associate with tumor progression, nor is it clear how these protein markers provide prognostic value for urothelial carcinomas. METHODS: Primary urothelial carcinoma tissue microarrays were constructed for 146 patients with urothelial carcinoma. Where available, four replicate tissue samples of invasive tumor, adjacent dysplastic and in situ lesions, and benign tumors were arrayed for each case, resulting in a total of 1208 tissue spots. Immunohistochemical staining for Gelsolin, E-cadherin, p53, and Ki67 (MIB-1) was performed on the arrays. For each marker, the maximum staining intensity (Max), the percentage of positive staining (Pos), and the product of both Max and Pos (MaxPos) were analyzed. RESULTS: Compared with the benign fields, the expression of both cytoskeletal proteins decreased in premalignant and malignant lesions. For Gelsolin, decreased MaxPos was seen in premalignant and preinvasive lesions. However, with an increase in tumor grade and stage, there was a gradual increase in Gelsolin (P < 0.05 for both). E-cadherin expression decreases mainly in high-grade lesions (carcinoma in situ and Grade 3 tumors). Univariate and multivariate analyses showed that Gelsolin Max was a strong independent predictor for the probability of tumor recurrence and for early tumor recurrence in high-grade or high-stage tumors, as well as a strong indicator for tumor progression. CONCLUSIONS: Gelsolin and E-cadherin have distinctive expression patterns. Gelsolin, but not E-cadherin, provides independent prognostic information for high-grade urothelial carcinomas.

Adult↗

PubMed2002

Targeting actin remodeling profiles for the detection and management of urothelial cancers--a perspective for bladder cancer research.

The actin cytoskeleton and numerous proteins associated with its regulation and function constitute over 25% of total proteins in the cell. Growing evidence from this laboratory and others shows that alterations of actin polymerization, or actin remodeling, plays a pivotal role in regulating the morphologic and phenotypic events of a malignant cell. The actin remodeling is the result of activation of oncogenic actin signaling pathways (e.g., Ras and Src), or inactivation of several important actin-binding proteins that have tumor suppressive functions (e.g., Gelsolin, E-Cadherin, etc.). Recently distinctive protein expression patterns of some of these genes in bladder cancer carcinogenic and progressive processes have been observed. Specific actin-pathway antagonists that have growth inhibitory effect on transformed cells, but not normal cells, have been developed. Our overall hypothesis is that actin alterations are progressive and that distinctive actin remodeling profiles are associated with different stages of cancer development and progression. These patterns can be used as markers for cancer early detection and prognostic indication. On the other hand, detection of specific types of actin-signaling pathway alterations also enables a targeted preventive or therapeutic intervention with specific actin signaling pathway blockers, thereby providing an actin-based paradigm for individualized monitoring and intervention of human bladder cancer.

Actins↗

PubMed2002

Protein expression analysis using quantitative fluorescence image analysis on tissue microarray slides.

We have developed a tissue microarray (TMA)-based quantitative fluorescence image analysis (QFIA) method in which protein markers on TMA sections were labeled by immunofluorescence using tyramide signal amplification and a quantitative fluorescence detection system. Using this method, BRCA1 protein expression patterns were studied in the TMA sections of cell lines with known levels of BRCA1 expression and in a small group of human tissue samples obtained from sporadic epithelial ovarian cancers, their corresponding adjacent dysplastic fields, and distant non-tumor areas. We detected distinctive BRCA1 expression patterns in high-grade and low-grade sporadic epithelial ovarian cancers and their associated adjacent dysplastic fields. However, such patterns of expression could not be adequately detected by traditional immunohistochemical staining methods. TMA-QFIA provides a sensitive, automated, and quantitative measurement of protein expression on archived tissue and cell samples and will be a useful tool for protein-level molecular profiling analyses.

BRCA1 Protein↗