Biomedical subjects

Nan-Haw Chow

Publications and source records attributed to Nan-Haw Chow.

At least 19 recordsLinked to original sources

PubMed2006

Collaboration of RON and epidermal growth factor receptor in human bladder carcinogenesis.

PURPOSE: Collaboration of heterologous receptor tyrosine kinases has emerged as an important paradigm in tumor progression. We recently proved that RON has an important role in human bladder carcinogenesis. Since epidermal growth factor receptor has been suggested to cross-talk with RON, we examined the significance of epidermal growth factor receptor in modulating RON associated tumorigenesis. MATERIALS AND METHODS: The biological significance of collaboration between RON and epidermal growth factor receptor was examined in the TSGH8301, J82 and JR bladder cancer cell lines with different expression status. Immunoprecipitation and immunoblotting assays were done to investigate the interaction of RON with epidermal growth factor receptor in relation to epidermal growth factor receptor kinase inhibitor treatment. Time lapse wound healing monitoring and Transwelltrade mark assay were used for cell migration analysis and the effect on cell transformation was analyzed with foci formation assay. Finally, a bladder cancer cohort of 78 patients was studied for clinical significance by immunohistochemistry. RESULTS: Epidermal growth factor receptor was directly associated with RON, irrespective of ligand stimulation. The siRNA experiment and epidermal growth factor receptor kinase inhibitors efficiently inhibited RON related biological effects, including mitogenesis, migration, anti-apoptosis and neoplastic transformation. Co-expression of RON/epidermal growth factor receptor was found in 26 of 78 patients (33.3%) with bladder cancer. It was significantly associated with tumor invasion (p < 0.05), the risk of local recurrence (p = 0.0003) and decreased patient survival (p = 0.04). Important indicators for patient survival were co-expression of RON and epidermal growth factor receptor (p = 0.001) and tumor staging (p = 0.05). CONCLUSIONS: Cross-talk between epidermal growth factor receptor and RON exists in vivo. Thus, it should be considered in treatment planning for patients with bladder cancer.

Carcinoma, Transitional Cell↗

PubMed2005

The significance of prohibitin and c-Met/hepatocyte growth factor receptor in the progression of cervical adenocarcinoma.

To examine the importance of prohibitin 1 and c-Met/hepatocyte growth factor receptor (HGFR) expression in human cervical adenocarcinomas, 85 patients (69 with invasive adenocarcinoma [ACA] and 16 with adenocarcinoma in situ [AIS]) were studied using immunohistochemistry. High prohibitin 1 expression was found in 51 (73.9%) of the 69 ACAs and 11 (68.7%) of the 16 AIS lesions. Prohibitin 1 overexpression was significantly higher in ACA and AIS than in adjacent nonneoplastic glandular epithelium (P < .001 for both comparisons). Prohibitin 1 expression was also positively related to tumor size (P = .019) or parametrial involvement (P = .027) in ACA. c-Met was expressed in 21 ACAs (30.4%) and was positively correlated with the Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics) stage classification (P = .007) or nodal metastasis (P = .047). Nodal metastasis (P = .028) and c-Met expression (P = .022) were independent predictors for the overall survival of patients in multivariate analysis using the Cox regression method. Prohibitin 1 activation seems to be an early event, whereas c-Met overexpression may be important for the progression of cervical adenocarcinomas. Evaluation of c-Met expression status may identify a subset of patients with cervical adenocarcinoma who require more intensive treatment.

Adenocarcinoma↗

PubMed2005

Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients.

PURPOSE: RON and MET belong to a subfamily of tyrosine kinase receptors. They both can induce invasive growth, including migration, cell dissociation, and matrix invasion. Cross-linking experiments show that RON and MET form a noncovalent complex on the cell surface and cooperate in intracellular signaling. We wanted to examine the clinical significance of RON and MET expression patterns in node-negative breast cancer. EXPERIMENTAL DESIGN: We studied the protein expressions of RON and MET in five breast cancer cell lines and a homogeneous cohort of 103 T(1-2)N(0)M(0) breast carcinoma patients, including 52 patients with distant metastases and 51 patients with no evidence of disease after at least a 10-year follow-up. RESULTS: Both HCC1937 and MDA-MB-231 cancer cell lines co-overexpressed RON and MET. The MCF-7 cell line did not express RON or MET. In multiple logistic regression analysis, RON expression (odds ratio, 2.6; P = 0.05) and MET expression (odds ratio, 4.7; P = 0.009) were independent predictors of distant relapse. RON+/MET+ and RON-/MET+ tumors resulted in a large risk increase for 10-year disease-free survival after adjusting for tumor size, histologic grade, estrogen receptor, bcl-2, HER-2/neu, and p53 status by multivariate Cox analysis (risk ratio, 5.3; P = 0.001 and risk ratio, 3.76; P = 0.005). The 10-year disease-free survival was 79.3% in patients with RON-/MET- tumors, was only 11.8% in patients with RON+/MET+ tumors, and was 43.9% and 55.6% in patients with RON-/MET+ and RON+/MET- tumors. CONCLUSIONS: Co-expression of RON and MET seems to signify an aggressive phenotype in node-negative breast cancer patients.

Adult↗

PubMed2005

Frequency and clinicopathologic correlates of ErbB1, ErbB2, and ErbB3 immunoreactivity in urothelial tumors of upper urinary tract.

OBJECTIVES: To investigate the frequency and clinicopathologic correlates of ErbB1, ErbB2, and ErbB3 receptor expression in patients with upper urothelial carcinoma. METHODS: Immunohistochemical staining for ErbB1, ErbB2, and ErbB3 was done with serial sections from archival specimens of 94 patients who underwent nephroureterectomy plus bladder cuff resection for urothelial carcinoma of the renal pelvis and ureter (median follow-up 40 months, range 1 to 177). The correlates between ErbB receptor expression and clinical outcome in terms of recurrence, progression, disease-free survival, and overall survival were analyzed by Kaplan-Meier plots, with the log-rank test and Cox proportional hazards model. RESULTS: ErbB1, ErbB2, and ErbB3 expression was present in 9 (9.5%), 13 (13.8%), and 26 (27.7%) tumors, respectively. Thirty-seven patients (39.4 %) had at least one receptor expressed and eight (8.5%) had coexpression of two or three receptors. ErbB2 expression was significantly associated with tumor invasiveness (P = 0.03), and ErbB1 and ErbB3 expression was not. The incidence of subsequent tumor recurrence in the urinary bladder correlated significantly with ureteral tumor involvement and ErbB2 expression (P = 0.04 and P = 0.04, respectively). On univariate and multivariate analyses, tumor staging and ErbB2 expression were independent predictors of disease progression (P = 0.01 and P = 0.01, respectively), disease-free survival (P = 0.02 and P = 0.002, respectively), and overall survival (P = 0.01 and P = 0.02, respectively). CONCLUSIONS: ErbB2 expression predicts for disease progression and disease-related survival in upper urothelial carcinoma.

ErbB Receptors↗

PubMed2005

Mini chamber system for long-term maintenance and observation of cultured cells.

We constructed a mini chamber system that was able to maintain cell culture on a microscope for long periods. It is a modified closed system with medium perfusion and CO2 circulation. The closed CO2 circulation and ample air inside the chamber distinguish it from other closed systems. Using different cell lines, the system was shown to be able to support long-term, time-lapse recording. After 229 hours of time-lapse recording, A2058 cells (a melanoma cell line) became overconfluent but still multiplied. Many CAD cells (a murine neuron-like cell line) still moved their cell bodies and kept their neurite-like processes after 28 days of recording. The entire healing process of a scratch-wounded 124 (a bladder cancer cell line) monolayer can be monitored. Such a modified closed system should find many applications in developmental biology, cell biology, and cancer biology where long-term, time-lapse recording is required or when the health of cells is important.

Bioreactors↗

PubMed2004

The novel targets for anti-angiogenesis of genistein on human cancer cells.

Genistein has been reported to be a natural chemopreventive in several types of human cancer. In our prior study, soy isoflavones were shown to induce cell cycle arrest and apoptosis of bladder cancer cells in the range of human urine excretion. This study was designed to identify the novel molecular basis underlying anti-angiogenic activities of soy isoflavones. An immortalized E6 and five human bladder cancer cell lines were studied by immunoassay, flow cytometry, functional activity, reverse transcription-polymerase chain reaction, immunoblotting, and transwell co-culture in vitro. The efficacy of soy isoflavones on angiogenesis inhibition in vivo was examined by nude mice xenograft and chick chorioallantoic membrane bioassay. Factors analyzed included angiogenic factors, matrix-degrading enzymes, and angiogenesis inhibitors. Genistein was the most potent inhibitor of angiogenesis in vitro and in vivo among the isoflavone compounds tested. It may also account for most of the reduced microvessel density of xenografts observed and the suppressed endothelial migration by soy isoflavones. Genistein exhibited a dose-dependent inhibition of expression/excretion of vascular endothelial growth factor165, platelet-derived growth factor, tissue factor, urokinase plasminogen activator, and matrix metalloprotease-2 and 9, respectively. On the other hand, there was an up-regulation of angiogenesis inhibitors-plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1. In addition, a differential inhibitory effect between immortalized uroepithelial cells and most cancer cell lines was also observed. Altogether, we discovered that tissue factor, endostatin, and angiostatin are novel molecular targets of genistein. The current investigation provides further evidence in support of soy-based foods as natural dietary inhibitors of tumor angiogenesis.

Angiogenesis Inhibitors↗

PubMed2004

Allelic loss of 14q32 in the pathogenesis of gastrointestinal and ampullary malignancies: mapping of the target region to a 17 cM interval.

PURPOSE: The genetic basis for gastrointestinal and ampullary carcinomas remains uncertain. This study was performed to pinpoint novel chromosomal region involved in the tumorigenesis of gastrointestinal tract. METHODS: We screened the allelic status on 16 chromosomal arms in a patient with synchronous ampullary carcinoma and gastric cancer, but who had no family history of familial cancer syndrome. The significance of the shared 14q deletion was examined on clinical cohorts of sporadic gastric (n=12) and ampullary (n=10) carcinoma, respectively. Then, high-density allelotype mapping was performed on 14q32 by using 23 microsatellite markers for the synchronous tumors. RESULTS: The synchronous gastric and ampullary carcinomas had no frameshift mutations in the APC, MSH2, MSH3, and MSH6 genes. Among the microsatellite markers screened, only D14S267 showed identical loss in the synchronous tumors. The same allelic loss was also detected in one of ampullary carcinomas (10%) and two of gastric cancers (16.7%). Fine mapping of 14q determined a minimally deleted region between D14S65 and D14S1010 (17 centiMorgans) for the synchronous tumors. CONCLUSIONS: This study illustrates a paradigm using molecular genetic approach in identifying chromosome 14q32 that may harbor a tumor suppressor gene involved in the pathogenesis of a subset of gastrointestinal and ampullary malignancies.

Aged↗

PubMed2004

Genistein arrests hepatoma cells at G2/M phase: involvement of ATM activation and upregulation of p21waf1/cip1 and Wee1.

Genistein, a soy isoflavone, has a wide range of biological actions that suggest it may be of use in cancer prevention. We have recently reported that it arrests hepatoma cells at G2/M phase and inhibits Cdc2 kinase activity. In the present study, we examined the signaling pathway by which genistein modulates Cdc2 kinase activity in HepG2 cells and leads to G2/M arrest, and found that it caused an increase in both Cdc2 phosphorylation and expression of the Cdc2-active kinase, Wee1. Genistein also enhanced the expression of the cell cycle inhibitor, p21waf1/cip1, which interacts with Cdc2. Furthermore, phosphorylation/inactivation of Cdc25C phosphatase, which dephosphorylates/activates Cdc2, was increased. Genistein enhanced the activity of the checkpoint kinase, Chk2, which phosphorylates/inactivates Cdc25C, induced accumulation of p53, and activated the ataxia-telangiectasia-mutated (ATM) gene. Caffeine, an ATM kinase inhibitor, inhibited these effects of genistein on Chk2, p53, and p21waf1/cip1. These findings suggest that the effect of genistein on G2/M arrest in HepG2 cells is partly due to ATM-dependent Chk2 activation, an increase in Cdc2 phosphorylation/inactivation as a result of induction of Wee1 expression, and a decrease in Cdc2 activity as a result of induction of p21waf1/cip1 expression.

Antineoplastic Agents↗

PubMed2004

Characteristics of hepatocellular carcinoma in a high arsenicism area in Taiwan: a case-control study.

Arsenic contamination of drinking water is noticeably linked to the occurrence of skin, bladder, lung cancers, and hepatocellular carcinoma (HCC). Blackfoot disease (BFD) caused by arsenicosis is endemic in southwestern Taiwan, where artesian well water contains high concentrations of arsenic, and mortality from HCC shows a dose-response increase by concentration of arsenic in the well water. This case-control study was conducted to examine the clinical characteristics of HCC patients of BFD-endemic area. A total of 65 HCC cases (54 men and 11 women) were recruited from the BFD-endemic areas. The clinicopathological features were compared with 130 age- and sex-matched HCC control patients from non-BFD-endemic areas. Characteristics analyzed included hepatitis viral infection status, hepatitis activity, liver function, histological findings, computed tomography scan characteristics, and patient survival. No differences were observed between HCC patients or their tumors, from study and control areas.

Aged↗

PubMed2003

Stable-isotope dimethyl labeling for quantitative proteomics.

In this paper, we report a novel, stable-isotope labeling strategy for quantitative proteomics that uses a simple reagent, formaldehyde, to globally label the N-terminus and epsilon-amino group of Lys through reductive amination. This labeling strategy produces peaks differing by 28 mass units for each derivatized site relative to its nonderivatized counterpart and 4 mass units for each derivatized isotopic pair. This labeling reaction is fast (less than 5 min) and complete without any detectable byproducts based on the analysis of MALDI and LC/ESI-MS/MS spectra of both derivatized and nonderivatized peptide standards and tryptic peptides of hemoglobin molecules. The intensity of the a(1) and y(n-1) ions produced, which were not detectable from most of the nonderivatized fragments, was substantially enhanced upon labeling. We further tested the method based on the analysis of an isotopic pair of peptide standards and a pair of defined protein mixtures with known H/D ratios. Using LC/MS for quantification and LC/MS/MS for peptide sequencing, the results show a negligible isotopic effect, a good mass resolution between the isotopic pair, and a good correlation between the experimental and theoretical data (errors 0-4%). The relative standard deviation of H/D values calculated from peptides deduced from the same protein are less than 13%. The applicability of the method for quantitative protein profiling was also explored by analyzing changes in nuclear protein abundance in an immortalized E7 cell with and without arsenic treatment.

Amination↗

PubMed2003

Identifying the factors and signal pathways necessary for anchorage-independent growth of Ha-ras oncogene-transformed NIH/3T3 cells.

Ha-ras(Val 12) overexpression was positively correlated with colony formation by NIH/3T3 derivative "2-12" cells harboring an inducible Ha-ras(Val 12) transgene. The ras-farnesylation inhibitor, Lovastatin, completely suppressed colony formation at higher dosages. However, Ha-ras oncogene overexpression alone could not stimulate colony formation under serum-deprived conditions, suggesting that ras is required but not sufficient for supporting colony formation. Substituting cow colostrum (AC-2) for serum did not result in colony formation from 2-12 cells in soft agar, suggesting the colostrum lacked or contained insufficient amounts of factors that stimulate colony formation. Supplementation of AC-2-containing medium with growth factors, such as insulin-like growth factor-1 (IGF-1), partially restored the capability of anchorage-independent cell growth induced by Ha-ras overexpression. Consistently, antibodies specific for IGF-1 receptors only partially blocked colony formation from 2-12 cells. The data indicate that multiple factors, including IGF-1, are required for Ha-ras-dependent colony formation. Signal transduction studies revealed that, under Ha-ras overexpression conditions, IGF-1 utilizes phosphatidyl inositol 3-kinase and NF-kappaB to transduce colony formation-related signaling.

3T3 Cells↗

PubMed2003

The value of color flow Doppler ultrasonography of the superior thyroid artery in the surgical management of Graves disease.

HYPOTHESIS: The factors affecting blood flow within the hypervascular thyroid gland and the effect of vascularization on the preparation for thyroidectomy as treatment for Graves disease can be documented. DESIGN: Blood flow through the superior thyroid arteries of patients with Graves disease, maintained in a euthyroid status, was measured by color flow Doppler ultrasonography. The microvessel density was assessed immunohistochemically using the level of expression of factor VIII in tissue sections. Both the thyroid gland's weight and blood loss volume were measured during the operation. SETTING: Tertiary care teaching hospital. PATIENTS: Fifty-two patients with Graves disease undergoing thyroidectomy. RESULTS: The blood flow rate was significantly correlated with thyroid weight (P<.01), thyroid microvessel density (P<.001), and histopathologic microscopic pattern (P<.001). The relation between these factors could be expressed as follows: Blood flow (mL/min) = [[0.0158 + 0.00136] x (weight (g) x microvessel density)](1/2) (R2 = 0.64, P<.001). Diffuse microfollicular hyperplastic thyroid tissue had a significantly higher blood flow and vascular density than tissue having an inactive colloid pattern (P<.01). Ten patients having a blood loss exceeding 200 mL during thyroidectomy showed a higher preoperative blood flow rate and microvessel density (P<.01). Of 8 patients whose blood flow was more than 0.15 L/min, 6 (75%) had blood loss in excess of 200 mL during surgery. CONCLUSIONS: The blood flow of the superior thyroid artery is positively related to intrathyroid microvessel density, glandular weight, and histopathologic microscopic pattern. Preoperative color flow Doppler ultrasonography may help in identifying patients with Graves disease who are liable to bleed intraoperatively during thyroidectomy.

Adult↗

PubMed2003

Clinical significance of allelotype profiling for urothelial carcinoma.

OBJECTIVES: To perform a global loss of heterozygosity (LOH) analysis on a cohort of urothelial carcinoma to investigate the clinical implication of specific chromosomal loss. Allelic deletions detected as LOH have been used to study the markers for carcinogenesis. METHODS: We examined the allelic loss on 14 chromosomal regions in a total of 71 cases of urothelial carcinoma. The results were analyzed in relation to biologic indicators of urothelial carcinoma and the clinical outcome with a mean follow-up of 101 months. RESULTS: The incidence of LOH in order of frequency was 9p (54.9%), 9q (49.3%), 13q (40.8%), 14q (40.8%), 10q (39.4%), 17p (39.4%), 8p (38.0%), 21q (36.6%), 11p (31.0%), 18q (23.9%), 4q (21.1%), 3p (16.9%), 6q (14.1%), and 1q (8.5%). Positive association with one of the indicators was observed in 3p, 9p, 9q, 10q, 14q, and 18q. The chromosomes that correlated with two biologic indicators were 4q, 6q, 11p, 17p, and 21q. Univariate analysis found that patients having combined 9p and 14q deleted tumors had particularly poor long-term survival compared with those with other patterns of chromosomal alterations (P = 0.01). In the multivariate model, nonpapillary tumors had a greater risk of recurrence, and stage classification was the only important indicator in predicting patient survival (P = 0.04). CONCLUSIONS: LOH assessment does not provide independent prognostic value compared with stage classification. However, chromosomes 4q, 6q, 9p, 11p, 14q, 17p, and 21q may harbor important tumor suppressor genes involved in the progression of urothelial carcinogenesis.

Adult↗

PubMed2003

Effects of soy isoflavones on apoptosis induction and G2-M arrest in human hepatoma cells involvement of caspase-3 activation, Bcl-2 and Bcl-XL downregulation, and Cdc2 kinase activity.

Genistein, biochanin-A, and daidzein, the predominant soy isoflavones, have been reported to lower the risk of cancer, but it is not known whether they protect against human hepatoma cancer. This study was designed to investigate their effects on cell growth, the cell cycle, and apoptosis induction in the human hepatoma cell lines, HepG2, Hep3B, Huh7, PLC, and HA22T. Genistein, biochanin-A, and daidzein inhibited growth of all five lines in a dose-dependent manner. DNA fragmentation studies and the TUNEL assay demonstrated that isoflavones caused tumor cell death by induction of apoptosis. Activation of caspase-3 and cleavage of the caspase-3 substrate, poly(ADP-ribose)polymerase, was seen in hepatoma cells after 24 hours' exposure to isoflavones. In addition, isoflavone cytotoxicity correlated with downregulation of Bcl-2 and Bcl-XL expression. Synergistic effects of the three isoflavones were observed on cell growth inhibition, apoptosis induction, and anti-apoptotic protein expression. Flow cytometry showed that genistein, but not biochanin-A or daidzein, induced progressive and sustained accumulation of hepatoma cancer cells in the G2/M phase as a result of inhibition of Cdc2 kinase activity. Coapplication of caffeine prevented this cell cycle arrest, but not apoptosis, showing that cell cycle arrest was not necessary for apoptosis. Furthermore, the isoflavones combination also had a significant tumor-suppressive effect in nude mice. These results suggest that isoflavones might be promising agents for the treatment of human hepatoma.

Animals↗

PubMed2002

Serum tissue polypeptide specific antigen as a noninvasive prognostic indicator for early recurrence of hepatocellular carcinoma after curative resection.

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is a useful cell proliferation marker in diagnosing and monitoring patients with a variety of malignancies. The objective of this study was to determine the usefulness of serum TPS as a noninvasive prognostic factor for early recurrence of hepatocellular carcinoma (HCC) after patients undergo curative resection. METHODS: Serum TPS levels were measured by monoclonal TPS immunoradiometric assay in 54 patients shortly before they underwent curative resection for HCC. The recurrence time was correlated with the TPS level and with other prognostic factors using the log-rank test in univariate analysis and a Cox regression in multivariate analysis. Receiver operating characteristic analysis was performed to examine the power of the various prognostic factors to distinguish between patients with recurrent tumors and patients who were disease free. RESULTS: Patients who had higher levels of TPS (>or= 150 U/L) had earlier recurrences compared with patients who had lower levels of TPS (< 150 U/L; P = 0.016) in univariate analysis. Tumor size, the number of tumors, portal vein invasion, and the resection margins also were associated significantly with the time to tumor recurrence (P = 0.015, P = 0.004, P = 0.003, and P = 0.003, respectively). Serum alpha-fetoprotein was not a significant risk factor for tumor recurrence. In multivariate analysis, the TPS level, tumor size, and resection margins were independent prognostic factors (P = 0.025, P = 0.018, and P = 0.016, respectively). The inclusion of TPS in addition to tumor size and resection margins increased the rate of corrective prediction from 0.72 to 0.80. CONCLUSIONS: The current study demonstrated that the preoperative serum TPS level was a significant factor in predicting early recurrence of HCC after curative resection. Patients with high serum TPS levels warrant more aggressive treatment and close follow-up after they undergo tumor resection.

Adult↗

PubMed2002

Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation.

PURPOSE: The c-met proto-oncogene encodes a receptor tyrosine kinase (Met) and has been shown to play a role in oncogenesis. Given that high titers of hepatocyte growth factor, the specific ligand for Met, are excreted in the urine and tend to reflect disease activity of bladder cancer, we performed this study to examine the clinical significance of Met in human bladder cancer. MATERIALS AND METHODS: We studied the mRNA expression and genomic alteration of c-met in five bladder cancer cell lines. Significance of Met overexpression was then compared with p53 nuclear accumulation (TP53) in primary bladder cancer (n = 142 patients). RESULTS: Expression of c-met mRNA tended to positively correlate with differentiation of cancer cell lines in the absence of point mutation. High expression of Met was found in seven cases (4.9%), low expression in 32 cases (22.5%), and negative expression in 103 cases (72.5%). Expression of Met was positively associated with histologic grade, stage classification, tumor size, and nodular tumor growth (P <.05, respectively); however, it was not related to TP53 status. Factors that predicted disease progression were tumor stage, Met status, and TP53 accumulation (P <.05, respectively). Indicators for poor long-term survival were invasive cancer, multiple tumors, and Met overexpression (P =.0006,.01, and.04, respectively). CONCLUSION: The c-met proto-oncogene plays a more important role in the progression of bladder carcinogenesis than p53. Evaluation of Met expression could identify a subset of bladder cancer patients who may require a more intensive treatment strategy.

Adult↗

PubMedDate not supplied

The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer.

The purpose of the study was to investigate the prognostic value and clinicopathological correlate of tumor p53, p16 and Rb protein expression in patients with locally advanced urinary bladder cancer. Sixty-five patients (44 men and 21 women; 40 to 84 yrs old) with locally advanced urinary bladder cancer (21 pT2, 27pT3, 17pT4) undergoing radical cystectomy and bilateral pelvic lymph node dissection were followed up for 2 to 116 months (mean +/- SD: 30.02 +/- 6.46 months). Immunohistochemical staining for p53, Rb and p16 proteins were performed on surgically obtained, formalin fixed and paraffin embedded tissue sections. Thirty of the tumors (46.2%) were p53+, 52 of the tumors (80%) were p16- and 41 (63%) were Rb-. Only 5 of the tumors (7.7%) had normal expression of all three proteins. The tumor expression status of p53 could not be correlated with p16 (P = 1.000) or Rb (P = 1.000). Only a marginal inverse relationship was found between the expression of p16 and Rb (P = 0.056). Higher grade tumors had significantly lower percentage of p16 abnormality (P = 0.05), while higher grade (not higher stage) tumors had higher percentage of Rb abnormality (P = 0.0245). Univariate analysis showed that tumor expression of Rb or p16, alone or combined, had no predictive value on progression-free and disease-specific survival. It did, however, show a significant correlation between progression-free survival and tumor p53 and LN status (P = 0.032 and P = 0.0304) and a significant correlation between tumor stage disease-specific survival (P = 0.042). Multivariate analysis showed tumor stage and nodal status to be two significant independent indicators for progression-free survival (P = 0.0038 and P = 0.0049) and disease-specific survival (P = 0.0066 and P = 0.0484). It was also noteworthy that, after receiving postoperative adjuvant systemic M-VEC chemotherapy, patients with node-positive p53-normal tumors had significantly better progression-free and disease-specific survivals than those with node-positive p53-abnormal tumors (P = 0.036 and P = 0.0479, respectively). This study has found tumor expression of p53, p16 and Rb proteins in locally advanced bladder cancer to be frequently abnormal. Although multivariate analysis showed tumor stage and nodal status to be the only two statistically significant parameters, p53 may also serve as an additional prognostic predictor of the outcome of postoperative adjuvant systemic chemotherapy in patients with regional lymph node tumor involvement. Such patients with p53-normal tumors experienced significantly better progression-free and disease-specific survivals than those with p53-abnormal tumors.

Adult↗

PubMedDate not supplied

Immunohistochemical microvessel count is not a reliable prognostic predictor in colorectal carcinoma.

BACKGROUND/AIMS: Immunohistochemical microvessel count for angiogenesis is associated with the growth and metastasis of various solid tumors, but its role in colorectal carcinoma remains controversial. This study aimed to determine its role in predicting the relapse and survival of colorectal carcinomas after curative surgery. METHODOLOGY: Representative paraffin-embedded sections of invasive colorectal cancers from 104 patients were studied by immunohistochemical staining using polyclonal anti-factor VIII antibody. Two investigators examined the microvessel count in the hot spot area of tumor using a 400x field in a blind fashion. RESULTS: There was no correlation between microvessel count and tumor size, location of carcinoma, tumor cell differentiation and nodal status. The microvessel count appeared to be lower among advanced-stage cancers as compared with early-stage cancers (pN0 vs. pN1+ pN2: 56 +/- 25. vs. 50 +/- 20; Dukes A + B vs. C + D: 56 +/- 25 vs. 49 +/- 18). In node-negative patients, the value of microvessel count greater than or equal to 75 seemed to correlate with longer disease-free survival and overall survival. CONCLUSIONS: Based on these results, immunohistochemical microvessel count seemed to decrease as colorectal cancer progressed and was not a reliable prognostic predictor in colorectal carcinoma.

Adult↗