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Zhenhe Suo

Publications and source records attributed to Zhenhe Suo.

At least 19 recordsLinked to original sources
PubMed2006

Activation of EDTA-resistant gelatinases in malignant human tumors.

Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion.

Animals↗
PubMed2006

Subcellular localization pattern of protoporphyrin IX is an important determinant for its photodynamic efficiency of human carcinoma and normal cell lines.

Photodynamic therapy (PDT) is a combination of light with a lesion-localizing photosensitizer or its precursor to destroy the lesion tissue. PDT has recently become an established modality for several malignant and non-malignant conditions, but it can be further improved through a better understanding of the determinants affecting its therapeutic efficiency. In the present investigation, protoporphyrin IX (PpIX), an efficient photosensitizer either endogenously induced by 5-aminolevulinic acid (ALA) or exogenously administered, was used to correlate its subcellular localization pattern with photodynamic efficiency of human oesophageal carcinoma (KYSE-450, KYSE-70) and normal (Het-1A) cell lines. By means of fluorescence microscopy ALA-induced PpIX was initially localized in the mitochondria, whereas exogenous PpIX was mainly distributed in cell membranes. At a similar amount of cellular PpIX PDT with ALA was significantly more efficient than photodynamic treatment with exogenous PpIX at killing all the 3 cell lines. Measurements of mitochondrial membrane potential and intracellular ATP content, and electron microscopy showed that the mitochondria were initially targeted by ALA-PDT, consistent with intracellular localization pattern of ALA-induced endogenous PpIX. This indicates that subcellular localization pattern of PpIX is an important determinant for its PDT efficiency in the 3 cell lines. Our finding suggests that future new photosensitizers with mitochondrially localizing properties may be designed for effective PDT.

Adenosine Triphosphate↗
PubMed2006

The prognostic impact of EphB2/B4 expression on patients with advanced ovarian carcinoma.

OBJECTIVES: To analyze expressions of the EphB2 and EphB4 receptors in ovarian carcinomas and explore their clinicopathological correlations and prognostic value. METHODS: 115 patients with advanced ovarian carcinoma FIGO IIB to IV were involved. RT-PCR and immunohistochemistry were used to examine the expressions of EphB2/B4 receptor mRNA and protein. Correlations between protein expression and clinicopathological factors were also analyzed. RESULTS: Ovarian carcinoma patients with age elder than 60 years had higher EphB2 expression than younger patients. Expression of EphB2 and EphB4 protein did not significantly correlate with any other clinical variables, including FIGO stage, residual tumor, histological type and differentiation grade. No significant correlation between mRNA and protein expression level for both of these receptors was seen. It was found that patients with strong immunostaining for EphB2 (P = 0.03) or EphB4 (P = 0.003) receptors had poorer survival, and patients with strong immunostaining for EphB4 receptor showed poorer response to chemotherapy (P = 0.036). CONCLUSIONS: These studies suggest that EphB2 and B4 receptors are of prognostic value and EphB4 receptor may be an independent predictor of chemotherapy response in ovarian cancer patients.

Adult↗
PubMed2006

Induction of hypoxia-inducible factor-1alpha overexpression by cobalt chloride enhances cellular resistance to photodynamic therapy.

Although photodynamic therapy (PDT) has been approved by regulatory agencies worldwide for the treatment of several oncologic and non-oncologic conditions, PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption limits the efficacy of this modality. This may largely be due to hypoxia-mediated angiogenesis via hypoxia-inducible factor-1alpha (HIF-1alpha), a major transcription factor involved in angiogenesis, hematopoiesis and anaerobic energy metabolism. We hypothesized that hypoxia-induced HIF-1alpha overexpression may also lead to tumor cells resistant to PDT by favouring tumor cell proliferation. Human esophageal normal Het-1A and tumor KYSE-70 and KYSE-450 cell lines were used in the present study. High-expression of HIF-1alpha induced in vitro by cobalt chloride (CoCl(2))-mediated chemical hypoxia mimic was clearly seen in the Het-1A cell line. In addition, cells treated with CoCl(2) were more resistant to 5-aminolevulinic acid (ALA)-mediated PDT than those without CoCl(2) treatment. The photosensitivity of the cells to ALA-PDT decreased with increasing HIF-1alpha expression by enhancing CoCl(2) concentrations. Moreover, transfection of the cells with anti-HIF-1alpha short interfering RNA (siRNA) knocked down the HIF-1alpha expression and restored the photosensitivity of the cells to ALA-PDT. However, the induction of HIF-1alpha expression by CoCl(2) was not indicated in both KYSE-70 and KYSE-450 cell lines, and no difference in cell survival was found after ALA-PDT in the presence and absence of CoCl(2). We thus conclude that high-expression of HIF-1alpha induced by CoCl(2) plays an important role in the resistance of the Het-1A cells to ALA-PDT. The present finding suggests that hypoxia-induced HIF-1alpha overexpression attenuates PDT efficacy through probably not only angiogenesis, but also cellular resistance to the modality. PDT in combination with anti-HIF-1alpha treatment may thus enhance the PDT efficacy.

Aminolevulinic Acid↗
PubMed2006

Chromosome 2q24.2 is lost in sporadic but not in BRCA1-associated ovarian carcinomas.

AIMS: Comparison between BRCA1-associated and sporadic ovarian carcinomas is a potential method to identify candidate modifier gene/s involved in the carcinogenic pathway of either or both groups. A previous study identified a significant difference in the frequency of copy number gain at 2q24-q32 by comparing BRCA1-associated and sporadic ovarian tumour specimens using comparative genomic hybridisation (CGH). The present study aimed to investigate the reported allelic imbalance at 2q24-32 by amplification of several microsatellite markers at the region by quantitative microsatellite analysis (QuMA) using Taqman at the same region identified as a site of allelic imbalance. METHODS: The copy number of the genomic region in 2q24-32 was established in 21 BRCA1-associated ovarian carcinomas and 14 sporadic cases using quantitative microsatellite polymerase chain reaction (PCR). Statistical analysis was performed using permutation test analysis. RESULTS: A significant loss at D2S156 marker (2q24.2) (p = 0.026) compared with the other three markers at 2q24-32 was found in the sporadic cohort but not in the BRCA1-associated group (p = 0.385). CONCLUSIONS: Our data do not support the association between copy number gain at 2q24-32 and BRCA1 mutation status in ovarian cancers reported previously. The novel finding of the present study was significant loss at 2q24.2 in sporadic ovarian cancers.

Adenocarcinoma↗
PubMed2005

The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas.

OBJECTIVES: To examine the expressions of the protein and mRNA of EPHA2 and EphrinA-1 in epithelial ovarian carcinomas/ovarian cancer cell lines and explore their prognostic value. METHODS: To validate the immunohistochemical method, two ovarian cancer cell lines (OVCAR3 and SKOV3) were examined with RT-PCR, Western blot, and immunohistochemistry for EphA2 and EphrinA-1 expressions. Tumors from 118 patients with advanced epithelial ovarian cancer were then evaluated for EPHA2 and Ephrin A-1 protein expression, and frozen tissues from 30 cases were used for laser capture microdissection (LCM) assistant RT-PCR RNA analysis. RESULTS: 11 (9.3%), 67 (56.8%), 26 (22.0%), and 14 (11.9%) tumors demonstrated negative, weak, moderate, and strong EphA2 protein expressions, respectively, while 3 (2.5%), 67 (56.8%), 32 (27.1%), and 16 (13.8%) tumors were negative, weak, moderate, and strong for Ephrin A-1 protein expression, respectively. Variable amount of mRNA expression was observed in the 30 tumors analyzed by the method of LCM assistant RT-PCR. There was a trend for association between higher levels of either EphA2 or Ephrin A-1 expression and higher histological grade (P = 0.05 for both factors). No significant correlation between the expressions of EphA2 or Ephrin A-1 and age, histological type, and FIGO stage was observed. Patients with higher levels of EphA2 protein expressions had significantly shorter survival. Cox multivariate analyses revealed that residual tumor after surgery, histological type, and EphA2 protein expression were of independent prognostic significance. CONCLUSIONS: High level of EphA2 protein expression is significantly associated with a shorter patient survival and EphA2 receptor is a valuable prognostic marker for ovarian carcinoma.

Adult↗
PubMed2004

Prognostic significance of dysadherin expression in cervical squamous cell carcinoma.

The protein and mRNA expression of dysadherin was studied in a series of squamous cell cervical carcinomas, and their clinicopathological associations and prognostic value were explored. Immunohistochemistry was used to assess protein expression of dysadherin in 206 patients with squamous cell cervical carcinoma, FIGO stage Ia-IVb. Frozen tissues from 20 cases in which the tumors showed variable dysadherin protein expression were used for laser capture microdissection (LCM) and processed for RTPCR detection of dysadherin mRNA. Immunohistochemically, all the dysadherin-positive staining was membranous. Positive cell membranous dysadherinpositive staining was often observed at the edge of tumor nests, although strong immunoreactivity throughout whole tumor nests was also seen in some tumors. Basal cells of the normal cervical epithelia were positive for dysadherin while its expression in the squamous cell cervical carcinomas was variable. Among the 206 tumors, 23 (11.2%) were negative, 53 (25.7%) were scored 1+, 54 (26.2%) were scored 2+ and 76 (36.9%) were scored 3+. In the 20 tumors analyzed, mRNA expression of dysadherin basically corresponded to its protein expression. No significant correlation between expression of dysadherin and age, FIGO stage or lymph node status was observed. Higher level of dysadherin expression, however, was significantly associated with shorter overall survival (p=0.04). We conclude that there is dysadherin protein expression in basal and parabasal cells of normal cervical epithelia, and higher level of dysadherin protein expression in squamous cell cervical carcinoma is predictive of a shorter overall survival, indicating that dysadherin may be a valuable prognostic marker in cervical carcinoma.

Adult↗
PubMed2004

Expression of Ephb2 and Ephb4 in breast carcinoma.

Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, play key roles in diverse biological processes. Eph receptors comprise the largest family of receptor tyrosine kinases consisting of eight EphA receptors (with five corresponding ephrinA ligands) and six EphB receptors (with three corresponding transmembrane ephrinB ligands). Originally identified as neuronal pathfinding molecules, EphB receptors and ephrinB ligands are later proved to be crucial regulators of vasculogenesis and embryogenesis. More studies indicate that Eph receptors are involved in angiogenesis and tumorigenesis. This study aimed to investigate the expression of EphB2 and EphB4 in breast carcinomas. Semiquantitative RT-PCR and immunohistochemistry were used to examine the expression patterns of EphB2 and EphB4. Clinicopathological and survival correlations were statistically analyzed in a series of 94 breast carcinomas, 9 normal specimens and 4 breast carcinoma cell lines. 1(1%), 16(17%), 29(31%), 48(51%) of the 94 tumors were negative, weak, moderate and strong EphB2 protein expression, respectively. 6(6%), 27(29%), 28(30%), 33(35%) of the tumors were negative, weak, moderate and strong EphB4 expression, respectively. Both EphB2 and EphB4 RTPCR products could be detected in all specimens. Increased EphB2 protein expression was negatively associated with overall survival, and there was a trend that increased EphB2 protein expression was correlated with shorter disease free survival, while EphB4 protein expression was associated with histological grade and stage. EphB4 membrane staining was increased with S phase fraction and associated with DNA aneuploidy. These findings indicate that both EphB2 and EphB4 are involved in the development of breast cancer and that both molecules could be potential predictive markers.

Aneuploidy↗
PubMed2004

Prognostic value of EphA2 and EphrinA-1 in squamous cell cervical carcinoma.

OBJECTIVES: To analyze the expressions of the protein and mRNA of EphA2 and EphrinA-1 in squamous cell cervical carcinomas and explore their prognostic value in cervical carcinoma. METHODS: Immunohistochemistry was used to assess the protein expressions of EphA2 and EphrinA-1 in 206 patients with squamous cervical carcinoma FIGO stage Ia-IVb. Frozen tissues from 20 cases in which the tumors showed variable EphA2 and EphrinA-1protein expressions were used for laser capture microdissection (LCM). About 50 cancer cells in each frozen section were captured with the LCM method and processed for RT-PCR detection of EphA2 and EphrinA-1 mRNA. RESULTS: Among the 206 squamous cervical carcinomas, 23 (11.2%) showed negative, 94(45.6%) weakly positive, 72 (35.0%) moderately positive, and 17 (8.3%) strongly positive for EphA2 immunostaining. For EphrinA-1 protein expression, 17 tumors (8.3%) showed negative, 95 (46.1%) weakly positive, 71(34.5%) moderately positive, and 23 (11.2%) strongly positive. EphA2 and EphrinA-1 often colocalized in the same tumor areas and vascular endothelial cells. Variable amount of mRNA expressions of EphA2 and EphrinA-1 were observed in the 20 tumors analyzed. There was no significant correlation between the overexpressions of EphA2/EphrinA-1 and age and FIGO stage. High level of EphA2 was significantly associated with overall survival in univariate and multivariate analysis. Moderate to high EphrinA-1 protein expression was significantly associated with overall survival in multivariate analysis. The combined high level of expression of EhpA2 and moderate to high level of expression of EphrinA-1 was a strong predictor of overall survival. CONCLUSIONS: High levels of EphA2 together with moderate to high level of EphrinA-1 protein expressions in squamous cervical carcinoma were predictive for a shorter overall survival and these proteins may be valuable prognostic markers.

Adult↗
PubMed2004

Real-time PCR quantification of c-erbB-2 gene is an alternative for FISH in the clinical management of breast carcinoma patients.

Evaluation of gene amplification and protein expression of the c-erbB-2/neu in breast carcinomas has been an important task in breast cancer management. Although immunohistochemistry is widely applied, fluorescence in situ hybridization (FISH) technology shows its advantage in discriminating tumors in an objective manner. More recently, development of LightCycler technology permits evaluation of gene amplification with a small volume of DNA run in a 20 microL glass capillary. In this study, a series of 87 breast carcinomas were chosen for evaluation of c-erbB-2/neu gene amplification detected by both LightCycler technology and FISH. Real-time polymerase chain reaction (PCR) was performed in LightCycler capillaries with 10 ng sample DNA. By using LightCycler Relative Quantification Software version 1 (LightCycler, Roche, Mannheim, Germany), the amount of c-erbB-2 DNA was calculated as a ratio of c-erbB-2/reference gene quantity in a sample, and then the ratio was divided by the ratio of c-erbB-2 gene/reference gene quantities of a calibrator DNA (a standard DNA provided in the kit), which was run with each sample reaction in parallel. Dual-color FISH was performed on sections of the formalin-fixed, paraffin-embedded tissue array samples using the DAKO HER2 FISH pharmDX kit (DAKO A/S, Glostrup, Danmark) according to the manufacturer's instructions. Furthermore, immunohistochemistry was performed in parallel, with both the NCL-CB11 and HercepTest antibodies. Both the FISH technology and the LightCycler-PCR identified a similar percentage of tumors with c-erbB-2 gene amplification in our present study, 16% (14/87) and 15% (13/87), respectively, whereas immunohistochemistry demonstrated 32% and 34% c-erbB-2 overexpression with the NCL-CB11 and HercepTest antibodies, respectively. In addition, FISH and PCR were highly correlated in detecting tumors mainly with 3+++ c-erbB-2 protein expression by immunohistochemistry, indicating that LightCycler real-time quantification of c-erbB-2 gene may be an alternative to FISH in breast cancer clinical application.

Biomarkers, Tumor↗
PubMed2003

Electron microscopy in diagnosis of spindle cell tumors.

One of the major diagnostic challenges in routine surgical pathology is the group of spindle cell tumors. An extensive list of differential diagnoses is often relevant, and the need for an accurate diagnosis for treatment of the patients is evident. Although immunohistochemistry is a routine adjunct tool in most pathological laboratories, and molecular techniques are rapidly integrated, identification of ultrastructural features is still of great importance. For some tumor diagnoses, electron microscopy is more straightforward and timesaving than use of other methods, such as immunohistochemistry and molecular analyses. However, spindle cell lesions often require the use of all special techniques available. In this article, we discuss the role of electron microscopy in diagnosis of spindle cell tumors and focus upon some more recently described entities.

Carcinoma↗
PubMed2002

EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival.

One hundred patients with breast carcinoma followed for 7-11 years were included in the present study of EGFR family members, using immunohistochemistry and RT-PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, lymph node status, S-phase fraction, and stage were confirmed to be significantly associated with both disease-free and cancer-specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance.

Adult↗
PubMed2002

The expression of EGFR family ligands in breast carcinomas.

Expression of EGF, HB-EGF, TGF-alpha, HRG-alpha, HRG-beta1, and HRG-beta3 in 100 frozen breast carcinoma materials was immunohistochemically studied. Among these tumors, 67% were positive for EGF, 53% for HB-EGF, 57% for TGF-alpha, 60% for HRG-alpha, 53% for HRG-beta1, and 63% for HRG-beta3 in the neoplastic epithelial cells. No significant associations between expression of the growth factors and clinicopathological features like tumor size, histologic grade, node status, ploidy, ER status, and c-erbB-4 expression were observed, with the exceptions that significant relations were present between EGF expression and tumor size (p = 0.01) and between HRG-beta3 expression and node status (p = 0.02). The expressions of these growth factors showed no association with cancer-specific survival by the Kaplan Meier analysis.

Adult↗
PubMedDate not supplied

Type 1 protein tyrosine kinases in breast carcinoma: a review.

One of the most studied onco-gene families in breast tumors is the type 1 protein tyrosine kinase family, which consists of EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. Overexpression of c-erbB-2 protein/mRNA in breast carcinomas is consistently associated with poor prognosis, while EGFR overexpression has been confirmed to have a synergistic clinical effect on the c-erbB-2 influence. The expression pattern of c-erbB-4 in breast carcinomas is special. Unlike other type 1 protein tyrosine kinases, expression of c-erbB-4 protein/mRNA is reduced in carcinomas compared with that in normal breast epithelia, and its expression has also been associated with a better clinical outcome, indicating the need for c-erbB-4 analysis when clinical therapeutic application of EGFR and c-erbB-2 anitbodies is considered. In addition, studies of the adaptor proteins in breast carcinomas are highly indicated in order to clarify the mechanisms behind the dysregulated expression of such receptors in breast carcinomas.

Biomarkers, Tumor↗
PubMedDate not supplied

5'-CpG island methylation of the FHIT gene is associated with reduced protein expression and higher clinical stage in cervical carcinomas.

Aberrant transcription of the FHIT gene has been observed in many solid tumors, suggesting that 5'-CpG island methylation of the FHIT gene is involved in tumor development. The authors investigated the status of the 5'-CpG island methylation of the FHIT gene and protein expression in a series of 40 cervical carcinomas and 10 normal cervical epithelial samples, and correlated the data with clinicopathological findings. Methylation-specific PCR was applied to detect the incidence of the 5'-CpG island methylation, and immunohistochemistry was used for FHIT protein staining. 5'-CpG island methylation of the FHIT gene was detected in 40% (16/40) of the cervical cancer samples and in none of normal cervical epithelial specimens. Furthermore, the 5'-CpG island methylation was positively associated with clinical stage (p=.002). All the normal cervical epithelial samples (10/10) and 90% (36/40) of the cervical carcinomas were positive when the unmethylated primer pair was applied. Of the 16 cervical carcinomas with 5'-CpG island methylation of the FHIT gene by PCR, 15 showed reduced FHIT protein expression. This study suggests that 5'-CpG island methylation plays an important role in inactivation of the FHIT gene in cervical cancer.

Acid Anhydride Hydrolases↗
PubMedDate not supplied

Papillary serous carcinoma of the ovary: an ultrastructural and immunohistochemical study.

Twenty-four patients with ovarian serous papillary carcinoma were enrolled in the present ultrastructural and immunohistochemical study. Immunohistochemistry was used to examine the status of proliferation activity with antibodies against Ki67 and BM28, and the status of EGFR family members with antibodies against EGFR, c-erbB-2, and c-erbB-4. Ultrastructurally, poorly differentiated tumors often revealed solid sheets of tumor cells with variable desmosomes, cell connection complexies, and microvilli. No mature cilia, which are often present in benign and borderline ovarian epithelial tumors, were seen in these 24 carcinomas. However, two poorly differentiated tumors demonstrated oligocilia. In addition, numerous secondary lysosomes and bizzare intracytoplasmic pseudocavities were more often present in the poorly differentiated tumors. Immunohistochemically, strong expressions of BM28 and Ki67 in more than 50% of the tumor cells were found in 12/15 (80%) and 11/15 (73%) of the poorly differentiated tumors, respectively, compared with 3/9 (33%) and 1/9 (11%) of the moderately differentiated tumors, respectively. Higher levels of EGFR and c-erbB-2 expressions were more often observed in the poorly differentiated tumors, compared with that in the moderately differentiated tumors. In conclusion, oligocilium, numerous secondary lysosomes, and bizarre intracytoplasmic inclusions are more often seen in poorly differentiated ovarian serous carcinomas. Poorly differentiated ovarian serous carcinomas express higher levels of Ki67, BM28, EGFR, and c-erbB-2 proteins.

Biomarkers, Tumor↗
PubMedDate not supplied

Malignant mesothelioma.

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Diagnosis, Differential↗