Biomedical subjects

N H Chow

Publications and source records attributed to N H Chow.

68 records · Page 4Linked to original sources

PubMedDate not supplied

Expression of vascular endothelial growth factor in primary superficial bladder cancer.

BACKGROUND: Angiogenesis is of vital importance during the development and progression of solid tumors. This study was performed to test the clinical significance of vascular endothelial growth factor (VEGF) expression in primary superficial bladder cancer. MATERIALS AND METHOD: A cohort of 185 cases of pTa/pT1 transitional cell bladder cancer and six cases of normal urothelium were studied by immunohistochemistry. Expression of VEGF was correlated with biological indicators of bladder cancer and examined for their prognostic value. RESULTS: Variable amounts of VEGF were detected in 35 cases (18.9%), with 17.9% and 20.3% in pTa and pT1 tumors respectively. There was a positive association of VEGF expression with histological grading (p = 0.03). Otherwise, no apparent correlation was observed with remaining biopathological indicators (p > 0.1, respectively). Risk factors in predicting tumor recurrence were multiple tumors at diagnosis and lamina propria invasion (p < 0.05, respectively). Patients with multiple tumors also had a lower survival rate than those with a solitary tumor (p = 0.0008). However, expression of VEGF was not correlated with risk of tumor recurrence or patient survival (p > 0.1). CONCLUSIONS: Expression of VEGF is one of the characteristics of tumor dedifferentiation and may play a role in the development of a subset of superficial bladder cancer. Evaluation of VEGF expression dose not provide independent prognostic information for patients with superficial bladder cancer.

Adult↗

PubMedDate not supplied

The clinical value of p21WAF1/CIP1 expression in superficial bladder cancer.

The clinical value of p21WAF1/CIP1 in superficial bladder cancer remains controversial. To address the question, we examined the expression patterns of p21 and p53 gene products and compared for their significance in a total of 89 cases of superficial (pTa/pT1) bladder cancer. Over-expression of p21 was detected in 32 of 89 (36%) tumors. But, the expression status did not correlate with biological indicators or clinical outcome (p > 0.1, respectively). Factors predicting clinical outcome were multiplicity for tumor recurrence (p = 0.0002) or patient survival (p = 0.03), and the histological grading for disease progression (p = 0.02) or patient survival (p = 0.05). Taking into account the p53 status, a trend approaching better prognosis for p53+p21+ tumors was observed compared with that of p53+p21- bladder cancer (p = 0.08). Our data indicate that evaluation of p21 status does not provide better prognostic information compared with conventional biological indicators of superficial bladder cancer. Maintenance of p21 appears to abrogate the deleterious effects of p53 alterations in the tumorigenesis of human bladder.

Adult↗

PubMedDate not supplied

Expression of nm23-H1 in transitional cell carcinoma of the upper urinary tract.

Transitional cell carcinoma of the upper urinary tract is an uncommon neoplasm. Relatively little information is available regarding the clinical relevance of molecular markers. This study was performed to examine the importance of nm23-H1 gene expression (NM23-H1) in this type of tumors. Immunohistochemical expression of NM23-H1 was analyzed in 90 cases of upper urinary tract cancer, and was compared for its prognostic significance with conventional biological indicators. High expression of NM23-H1 was found in 7 cases (8%), intermediate expression in 32 cases (36%), and low expression in 51 cases (57%). Reduced NM23-H1 (defined as intermediate or low level of expression) was associated with a higher histological grading (p=0.002), invasive tumor growth (p=0. 002), or an increased proliferating cell nuclear antigen labeling index (p=0.004). NM23-H1 tended to inversely relate to later recurrence or long-term survival (p=0.06), but, only tumor staging was found to be significant in predicting clinical outcome (p=0.002). nm23-H1 appears to function as a tumor suppressor for upper urinary tract cancer, however, evaluation of NM23-H1 provides limited prognostic information.

Adult↗

PubMedDate not supplied

Hepatic angiomyolipoma with concomitant hepatocellular carcinomas.

Angiomyolipoma is a rare lipomatous tumor in the liver. Definitive preoperative diagnosis is becoming easier by the use of ultrasonography, computed tomography, and magnetic resonance imaging techniques. Nonsurgical treatment has been advocated for its benign nature. However, recently we encountered one case of hepatic angiomyolipoma with two concomitant hepatocellular carcinomas on a hepatitis B carrier. Although his serum alpha-fetoprotein was normal, under the above impression these lesions were resected. The pathologic findings showed a typical angiomyolipoma and two well-differentiated hepatocellular carcinomas with marked fatty metamorphosis. This is the first report of angiomyolipoma with concomitant hepatocellular carcinomas in the literature. Nonsurgical treatment of angiomyolipoma in an endemic area for hepatocellular carcinoma should proceed with caution because cases of fat-rich minute hepatocellular carcinomas will make the diagnosis difficult.

Angiomyolipoma↗

PubMedDate not supplied

Significance of c-erbB-2 expression in normal and neoplastic epithelium of biliary tract.

There were few, but conflicting, reports dealing with the clinical significance of c-erbB-2 in biliary tract cancer. We evaluated the expression of c-erbB-2 in normal epithelium of bile ducts (n = 46), gallbladder cancer (n = 11), carcinoma of the ampulla of Vater (n = 18), and intrahepatic cholangiocarcinoma (CC) (n = 18). c-erbB-2 protein is present in 63% (29/46) of surface epithelium in large and septal bile ducts, but not in peripheral small ducts. Overexpression of the gene product was found in 27.8% (5/18) of intrahepatic CC, 27.8% (5/18) of carcinoma of the ampulla of Vater, and 63.6% (7/11) of gallbladder cancer. But, there was no c-erbB-2 overexpression in the hyperplasia or atypical hyperplastic bile duct epithelium (p = 0.002). In terms of prognostic implication, expression of c-erbB-2 did not correlate to the histopathological grade (p = 0.60) and tumor stage (p = 0.63). The results indicate that c-erbB-2 protein may play some roles in physiology of normal bile ducts. Overexpression of the gene product occurs in one forth to about two thirds of carcinoma of biliary tract, and may be used as phenotypic marker for neoplastic transformation. However, the gene product may not be important in the aggressive behavior of tumor.

Adult↗

PubMedDate not supplied

Prognostic significance of ferritin expression in colorectal adenocarcinoma.

In recent years, there has been considerable interest in ferritin as an oncofetal protein. However, the clinical significance of ferritin expression in cancer tissues remains unknown. We performed an immunohistochemical study to examine the expression of ferritin in colorectal adenocarcinoma (n = 104). A total of 95 out of 104 (91.3%) colon cancers were positive for ferritin expression. The degree of immunoreactivity has no significant correlation with tumor grade (p = 0.964), size (p = 0.659), serosal invasion (p = 0.331), nodal metastasis (p = 0.955), distant metastasis (p = 0.354) and DNA ploidy status (p = 0.126), but there was a strong association between ferritin expression of tumor cells and stromal mononuclear cell infiltration (p = 0.004). In terms of prognostic significance, multivariate analysis showed that nodal metastasis (p = 0.0123) and distant metastasis (p = 0.0237) were independent poor prognostic factors. However, there was no significant difference in survival between patients with weak and strong ferritin expression in cancer tissues (p = 0.3766). The results indicate that the majority of colorectal adenocarcinomas exhibit ferritin expression. The grade of ferritin expression is strongly associated with stromal mononuclear cell infiltration, but has no significant correlation with any staging parameters or the survival of cancer patients.

Adenocarcinoma↗

PubMedDate not supplied

Expression of c-erbB-2 protein in normal and neoplastic urothelium: lack of adverse prognostic effect in human urinary bladder cancer.

The clinical significance of c-erb B-2 expression in urinary bladder cancer remains controversial. We performed an immunohistochemical study to examine the expression of c-erb B-2 in non-neoplastic urothelium (n = 12) and transitional cell carcinoma of the urinary bladder (n = 82). c-erb B-2 protein was localized in superficial and some intermediate cells of non-neoplastic urothelium. A total of 29 out of 82 (35%) tumors were positive for c-erb B-2 over-expression. There was no significant association of c-erbB-2 expression with tumor grade (p = 0.12), stage (p = 0.93), DNA ploidy status (p = 0.56) and the sex of patients (p = 0.5). Expression of epidermal growth factor receptor and Ki-67 index was available in 33 cases. Both parameters showed no apparent association with c-erbB-2 expression (p = 0.53 and 0.58 respectively). Factors correlated with poor patient survival by univariate analysis were tumor stage (p = 0.0001), tumor grade (p = 0.001), development of second recurrence (p = 0.002) and negative expression of c-erbB-2 (p = 0.017). Important indicators associated with first recurrence were tumor stage (p = 0.028), and c-erbB-2 expression with the risk of second recurrence (p = 0.031). Multivariate survival analysis revealed that tumor stage was among the most important prognostic factors (p = 0.029), followed by tumors without c-erbB-2 expression (p = 0.031) with a median follow-up at 46 months. The age of patients and c-erbB-2 expression were significantly associated with developing second recurrence (p = 0.031 and 0.046 respectively). The results indicate that expression of c-erbB-2 is independent of the stage and grade of bladder cancer. Although c-erbB-2 status can discriminate subpopulations with a high risk of recurrence, evaluation of its expression in paraffin-embedded tumors does not indicate poor prognosis for patients with urinary bladder cancer. To address this discrepancy a better understanding of the regulatory mechanism and physiological properties of c-erbB-2 protein in urothelium is required.

Adult↗

PubMedDate not supplied

Significance of urinary tissue polypeptide specific antigen (TPS) determination in patients with urothelial carcinoma.

Tissue polypeptide specific antigen (TPS) is the M3 epitope of the tissue polypeptide antigen, and a specific epithelial proliferation marker. To examine the benefit of urine TPS (UTPS) measurement in the diagnosis and classification of biological properties of transitional cell carcinoma (TCC), a radioimmunoassay of U-TPS was measured in patients with active TCC (n = 56), at tumor-free status (n = 36), with inflammatory urological disease (n = 44), and age-sex adjusted normal subjects (n = 75). Both neoplastic and inflammatory urological diseases had an increase in U-TPS levels (U/gm creatinine) compared to normal individuals (p = 0.0005), while it normalized in tumor-free condition (p = 0.007). For patients with active TCC, a strong positive association was observed between U-TPS values and both histological grading (p = 0.05) and positive cytology (p = 0.05). U-TPS levels were significantly higher in the presence of nodal or systemic metastasis (p = 0.008 by ANOVA test). Measurement of U-TPS appeared to be an indicator of poor outcome for patients with bladder cancer (p = 0.05 by t test) for a mean follow-up of 26 months. The results indicate that determination of U-TPS can be a supplement in assessing the biological properties of TCC, and may be helpful in identifying patients who need meticulous peri-operative staging survey.

Adult↗

PubMedDate not supplied

Significance of urinary epidermal growth factor and its receptor expression in human bladder cancer.

UNLABELLED: The expression of epidermal growth factor receptor (EGFR) has been suggested to play an important role in the progression of bladder cancer through paracrine stimulation by epidermal growth factor in the urine. However, there is no information regarding the expression of EGFR and urinary ligand measurement in corresponding tumors in patients with bladder cancer. MATERIALS AND METHODS: Paired analysis of urinary levels of epidermal growth factor (U-EGF) and the expression of EGFR was performed on 48 cases of bladder cancer. U-EGF test and EGFR status were correlated with clinicopathologic factors of bladder cancer, and compared for their prognostic value with a mean follow-up of 39.7 months. RESULTS: U-EGF was inversely correlated with the intensity of EGFR expression (p = 0.04); while no substantial relationship was observed with other conventional prognostic indicators (p > 0.1, respectively). Multivariate analysis revealed that factors correlated with the risk of recurrence were EGFR status (p = 0.03) and histological grading (p = 0.05). An important indicator associated with poor patient survival was size of tumor at diagnosis (p = 0.03). DISCUSSION: Although measurement of U-EGF levels did not have any independent prognostic value, our data support the importance of urine EGF/urothelial EGFR interaction in the biological behavior of bladder cancer.

Adult↗

PubMedDate not supplied

Prognostic significance of proliferating cell nuclear antigen expression in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Haphazard cell proliferation is a fundamental biologic defect in cancer. Thus, assessment of the growth fraction provides a valuable index of biological property for human neoplasm. Proliferating cell nuclear antigen (PCNA) expression has been used to estimate the growth fraction of human cancer, and its prognostic value. Information in transitional cell carcinoma (TCC) of the upper urinary tract, however, is very few. MATERIALS AND METHODS: A total of 73 patients with TCC of the upper urinary tract was collected between July 1988 and December 1995 for this study. The labeling index of PCNA immunostaining was correlated with clinicopathologic factors and compared for its prognostic value with a median follow-up of 54 months. RESULTS: The PCNA index was positively associated with histological grading, tumor stage and patient prognosis (P = 0.00, respectively). Multivariate analysis demonstrated that significant factors in relation to patient survival were tumor stage (P = 0.01), followed by PCNA index (P = 0.04) and gender of patients (P = 0.04). Multiple comparison revealed that PCNA index set at 0.30 had prognostic value in terms of patient survival (P = 0.00), and the risk of metachronous bladder recurrence (P = 0.02). CONCLUSION: Our data suggested that assessment of PCNA index may be used as an adjuvant prognostic factor for patients with TCC of the upper urinary tract.

Adult↗

PubMedDate not supplied

Implications of serum basic fibroblast growth factor levels in chronic liver diseases and hepatocellular carcinoma.

Angiogenesis occurs in response to tissue damage, and is of vital importance for tumor growth and metastasis. Basic fibroblast growth factor (bFGF), a well-known angiogenic factor, has been suggested to be a useful diagnostic marker in certain hypervascular tumors. However, the relevance of its detection has not been well evaluated in patients with hepatocellular carcinoma (HCC) and benign chronic liver diseases. In the current study, immunoassay of bFGF was performed on serum samples from 39 patients with HCC, 21 with liver cirrhosis, 22 with chronic hepatitis and 40 normal subjects. The serum bFGF level was significantly increased in patients with liver cirrhosis and HCC when compared with those with chronic hepatitis or normal subjects (all p-values < 0.001). However, no difference was observed between the groups with liver cirrhosis and HCC (p > 0.05). If we set 9.6 pg/ml (mean + 3 standard deviations of bFGF in the control group) as the upper limit of normal serum level of bFGF, elevated bFGF concentrations were noted in 9.1%, 42.9% and 51.3% of patients with chronic hepatitis, liver cirrhosis and HCC respectively. In non-cancer patients, the coexistence of acute illness (p = 0.000) was an independent factor related to the elevation of serum bFGF. On the other hand, a multivariate analysis demonstrated that both advanced stage of cancer (p = 0.026) and coexistence of acute illness (p = 0.000) influence the serum level of bFGF in patients with HCC. We conclude that serum bFGF levels are significantly higher in patients with HCC and are positively correlated with advanced tumor stage. Nevertheless, elevation of serum bFGF may also be observed in a significant number of patients with liver cirrhosis. Therefore, measurement of serum bFGF alone cannot be satisfactory as a tumor marker for diagnosis of HCC. In addition, it is important to point out that coexistence of acute illness may be a crucial confounding factor in the diagnosis or monitoring of any cancer by the estimation of serum bFGF.

Adult↗

PubMedDate not supplied

Urinary excretion of transforming growth factor-alpha in patients with transitional cell carcinoma.

This study was performed to examine the involvement of transforming growth factor-alpha (TGF-alpha) in urothelial tumorigenesis. TGF-alpha urine levels were measured in patients with urothelial carcinoma (n = 68), patients who were tumor-free (n = 58), patients with non-neoplastic inflammatory disease (n = 20), and normal controls (n = 39). Both inflammatory and neoplastic urologic diseases had elevated TGF-alpha urine levels (169.5 ng/gm and 116.7 ng/gm, respectively) as compared to normal controls (39.1 ng/gm) (P = 0.0001). For patients with active cancer, TGF-alpha levels were positively associated with histologic grading (P = 0.009), nodular shape, expression of epidermal growth factor receptor in primary tumor (P = 0.03, respectively). But, there was no important relationship with staging classification, number and size of tumor (P > 0.1, respectively). TGF-alpha urine levels did not correlate with the serum content (n = 26; P > 0.5), or the immunohistochemical expression of TGF-alpha (n = 60) in corresponding tumor (P < 0.05, 0.1). Significant factors in predicting patient survival were clinical staging, nodular shape and size of tumor (P < 0.05, respectively). Our data implies that interaction of urinary TGF-alpha/urothelial epidermal growth factor receptor may play a positive role in the carcinogenesis of human urothelium.

Adult↗

PubMedDate not supplied

Modulating the antitumor immunity of MBT-2 murine bladder tumor bearing mice by postoperative administration of interferon-alpha.

This study was conducted mainly to investigate the effect of interferon-alpha (IFN-alpha) on the antitumor immunity of a tumor bearing host (TBH) when postoperatively administrated with or without lethally irradiated autologous tumor cells. Using the C3H/He-MBT-2 murine bladder tumor model, a status of postoperative residual tumor was mimicked by rechallenging tumor cells 24 hours after resecting the day-17 tumor. Using immunohistochemical analysis we demonstrated that after treating with lethally irradiated MBT-2 tumor cells (IRMBT-2) + IL-2 cells of CD4+, CD8+, CD44+ and CD11b+ phenotypes prominently infiltrate the subcutaneous local injection sites. In contrast, only scanty immune responding cells could be seen locally if treated with IRMBT-2 + IFN-alpha 2b, albeit in the presence of interleukin-2 (IL-2). However, the spleens of D17TBM treated with IRMBT-2 + IFN-alpha 2b contained the highest percentage of CD44+ memory T cells and cells of the CD11b+ phenotype; moreover, their natural killer (NK), lymphokine activated killer (LAK) and cytotoxic T lymphocytes (CTL) activities were significantly augmented. The results of in vivo tumor rechallenge revealed that administration of IFN-alpha, either alone or combined with IRMBT-2, could both effectively suppress the outgrowth of perioperative rechallenged tumor cells as well as prolong the survival of TBH. We conclude that despite the presence of autologous tumor vaccine, postoperative administration of IFN-alpha can further enhance the antitumor immunity of TBH and therefore can be an effective adjuvant therapy to improve the therapeutic results of surgery on a tumor bearing host.

Animals↗

PubMedDate not supplied

The expression of p53 and bcl-2 in superficial bladder transitional cell carcinoma and its role in the outcome of postoperative intravesical chemotherapy.

BACKGROUND: We evaluated whether p53 and bcl-2 expression has any predictive value on the outcome of postoperative adjuvant intravesical chemotherapy for superficial bladder transitional cell carcinoma (TCC). MATERIALS AND METHODS: Immunostaining for p53 and bcl-2 was performed on paraffin-embedded tumor tissues obtained from 100 patients with superficial bladder TCC. 56 had solitary and 44 had multiple tumors; 36 were grade I, 53 grade II and 11 grade III; 50 were stage pTa and 50 stage pT1. They all received transurethral resection (TUR) and weekly intravesical instillation chemotherapy with either Thiotepa (70 patients) or Epirubicin (30 patients) for consecutive 8 doses postoperatively. RESULTS: Overall, 7 (7%) tumors were p53+ and 12 (12%) tumors were bcl-2+. Of these, only one tumor was combined p53+ and bcl-2+. The status of tumor p53 and bcl-2 positivity was found to be not significantly correlated with either tumor grade or stage. After adjuvant intravesical chemotherapy, tumor recurrence is significantly correlated with tumor multifocality (p = 0.0002) but not with tumor grade and stage. Compared with p53- or bcl-2- tumors, patients with p53+ or bcl-2+ tumors do not show a higher tumor recurrence rate. The number of recurrence-free patients was also not significantly different in p53+ versus p53- tumors, bcl-2+ versus bcl-2- tumors. Six (6%) patients eventually developed disease progression, and none stained positively for either p53 or bcl-2. CONCLUSIONS: We conclude that in superficial bladder TCC the status of tumor p53 and bcl-2 expression is not correlated with stage and grade. Their expression, either alone or combined, has no predictive role on the outcome of post-TUR intravesical chemotherapy on tumor recurrence.

Administration, Intravesical↗