Biomedical subjects

M Yoshinouchi

Publications and source records attributed to M Yoshinouchi.

At least 19 recordsLinked to original sources

PubMed2006

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA.

Human cervical cancer is caused by high-risk types of human papillomavirus (HPV) such as HPV16 and HPV18, which possess the E6 and E7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. Silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. However, it remains to be determined whether E6, E7, or both should be silenced to obtain most efficient antitumor activity by an HPV small-interfering RNA (siRNA). Herein, we report two types of siRNAs targeting HPV18 E6, that exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6), designed to target both E6-E7 mRNA and its splicing variant, E6*I-E7 mRNA, efficiently knocked down both E6 and E7 expression. The other (Sp-18E6), designed to specifically target E6-E7 mRNA but not E6*I-E7 mRNA, suppressed E6 to a similar level as Ex-18E6; however, it less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6. Our results suggest that E6-specific suppression may induce more potent anticancer activity than simultaneous E6 and E7 suppression, and that E6-specific targeting is a promising strategy for siRNA-based therapy for HPV-positive cervical cancer.

Animals↗

PubMed2003

Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer.

BACKGROUND: Endoglycosidic heparanase degrades heparan sulfate glycosaminoglycans, and may be important in cancer invasion and metastasis, although its expression in human cervical cancer has not been characterized. MATERIALS AND METHODS: Heparanase association with clinicopathological features related to prognostic significance was examined in patients presenting with invasive cervical cancer. Gene expression of heparanase was assessed by RT-PCR in 10 normal cervix and 92 invasive cervical cancer samples. RESULTS: Heparanase mRNA expression was not detected in any of the normal cervix specimens, but was significantly higher in advanced-stage tumors (P = 0.026). In cases treated with radical hysterectomy and pelvic lymphadenectomy, heparanase mRNA expression was significantly higher in tumors exhibiting lymph-vascular space invasion (P = 0.01). A significant relationship was found between microvessel counts and heparanase mRNA expression (P = 0.035). The disease-free and overall survival rates of patients exhibiting heparanase mRNA expression were significantly lower than those of patients lacking heparanase mRNA expression (P = 0.019 and 0.017, respectively). Furthermore, multivariate analysis showed that heparanase mRNA expression was an independent prognostic factor for both disease-free and overall survival. CONCLUSIONS: These findings provide evidence that heparanase expression can serve as an indicator of aggressive potential and poor prognosis in cervical cancer. Consequently, heparanase inhibitor will be a novel candidate for therapeutic intervention in this disease.

Adult↗

PubMed2001

Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer.

Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis, the process of new lymphatics formation. The present study investigated VEGF-C mRNA expression in invasive cervical cancer tissue. Additionally, the association of VEGF-C mRNA with clinicopathological features was examined. VEGF-C mRNA expression was assessed by reverse transcription-polymerase chain reaction using beta-action as an internal control. 75 patients presenting with invasive cervical cancer were included in the trial. VEGF-C mRNA expression was markedly higher in tumours in which pelvic lymph node metastasis was diagnosed by magnetic resonance (MR) imaging (P = 0.002). 53 patients displaying stage Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. VEGF-C expression was significantly higher in tumours exhibiting deep stromal invasion, pelvic lymph node metastasis and lymph-vascular space involvement (P = 0.016, P = 0.006 and P = 0.036, respectively). Multivariate analysis revealed VEGF-C mRNA expression to be the sole independent factor influencing pelvic lymph node metastasis. Subjects demonstrating VEGF-C mRNA expression displayed significantly poorer prognoses than those lacking VEGF-C mRNA expression (P = 0.049). These findings provide evidence supporting the involvement of VEGF-C expression in the promotion of lymph node metastasis in cervical cancer. Furthermore, examination of VEGF-C expression in biopsy specimens may be beneficial in the prediction of pelvic lymph node metastasis.

Cervix Uteri↗

PubMed2001

Cytocidal effect and DNA damage of nedaplatin: a mathematical model and analysis of experimental data.

PURPOSE: Cell cycle non-specific anticancer agents such as cis-diamminedichloroplatinum(II) are believed to depend linearly on the value of the area under the drug concentration time curve, which is supported by a mathematical model. However, the quantitative non-linear phenomena of both the cytocidal effect and DNA crosslink formation by cisdiammine(glycolato)platinum (nedaplatin) have been shown in vitro. Therefore, we developed a new mathematical model to explain these phenomena. METHODS: We assumed that nedaplatin enters intracellular fluid from medium through simple diffusion to form DNA crosslinks that kill cells. We developed a mathematical model to represent this assumption using differential equations that we then solved using an original computer program. The calculated results were compared with the experimental data. RESULTS: The drug's simple diffusion rate constant, the DNA crosslink formation rate constant, and the crosslink-dependent cell death rate constant in the model were 1.8 x 10(-14) (l h-1), 1.6 x 10(8) (l mol-1/2 h-1), 5.45 x 10(1) (mol-1), respectively. The model fits the experimental results statistically. The model also demonstrated theoretical proof that continuous exposure at a low dose was superior to the short exposure at a high dose seen in published experimental data. CONCLUSIONS: We developed a mathematical model to describe the non-linear pharmacodynamic effect of nedaplatin in vitro. This model may provide a novel drug infusion procedure for cancer patients.

Antineoplastic Agents↗

PubMed2001

Cytocidal effect and DNA damage of nedaplatin in vitro by simulating pharmacokinetic parameters.

PURPOSE: The pharmacodynamic effects of cis-diammine(glycolato)platinum (nedaplatin, 254-S) in vitro have been reported, but the dosage and exposure time in vitro have not always been based on clinical observations of the drug's actions in vivo. Regardless of the actual exposure conditions used, the effect of cell-cycle nonspecific anticancer agents such as nedaplatin is believed to depend on the area under the drug concentration-time curve (AUC). In this study, we evaluated the pharmacodynamics of nedaplatin in vitro, especially in relation to its AUC dependency, in terms of cell survival and DNA crosslinking. METHODS: BG-1 human ovarian cancer cells were treated with various concentrations of nedaplatin to simulate the pharmacokinetics of administration in a clinical setting. The BG-1 cells were exposed to nedaplatin dissolved in medium containing serum using constant concentration conditions, either high (maximum 7.69 mg/l) or low (average 1.33 mg/l). These concentrations were based on doses used in clinical studies. We then adjusted the exposure conditions in vitro to simulate the elimination of the drug from serum in vivo as follows: T1/2 alpha 1.20 h and T1/2 beta 2.70 h. The AUC values were set at 4, 8, 16, 25 and 40 mg.h/l for all exposure conditions. A colony-formation assay for the surviving fraction and an alkaline-elution assay for DNA crosslink measurement were done for the pharmacodynamic evaluation with comparison on the basis of the AUC value. RESULTS: Exposure to a low concentration for a long time was the most effective of the exposure conditions at the same AUC value. The greater the AUC value, the higher the crosslink index under all exposure conditions. This index tended to increase particularly after exposure to the low concentration. The natural logarithm of the surviving fraction (Y') was a linear function of the crosslink index regardless of the drug-exposure condition: ln(Y') = -87.2x + ln(5.79), R2 = 0.89. The threshold cytocidal effect was associated with a crosslink index of 0.02. CONCLUSION: There was a strong correlation between the cytocidal effect of nedaplatin and DNA crosslink formation. The cytocidal effect and DNA crosslinking in vitro depended on the exposure conditions used to define the AUC. Therefore, a new pharmacokinetic-pharmacodynamic model for nedaplatin must be constructed to investigate the most effective administration procedure in vivo.

Antineoplastic Agents↗

PubMed2001

Thrombospondin-1 and -2 messenger RNA expression in normal and neoplastic endometrial tissues: correlation with angiogenesis and prognosis.

The role of thrombospondin (TSP) in tumor angiogenesis and progression remains controversial. The expression of TSP-1 and TSP-2 mRNAs was assessed. Furthermore, TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined. Expression of TSP-1 and TSP-2 were assessed by reverse transcriptase-polymerase chain reaction in 18 normal endometrium and 55 endometrial cancer samples. Microvessel counts were determined by immunostaining for factor VIII-related antigen in endometrial cancer specimens. TSP-1 expression of secretory phase endometrium was markedly higher than that of proliferative phase endometrium (p=0.047). Expression of TSP-1 and TSP-2 was detected in 33 (60.0%) and 15 cases (27.3%), respectively, of 55 endometrial cancer samples. TSP-1 expression was significantly higher in tumors recovered from elderly women (p=0.009). TSP-2 expression was significantly higher in malignancies exhibiting cervical and lymph-vascular space involvement (p=0.029 and p=0.009, respectively). Although not statistically significant, microvessel counts were higher in cases displaying increased TSP-1 expression. The microvessel count in patients with TSP-2 expression was markedly higher than that observed in patients lacking TSP-2 expression (p=0.026). Subjects demonstrating TSP-2 mRNA expression displayed significantly poorer prognosis than those lacking TSP-2 mRNA expression (p=0.016). There was no association between TSP-1 mRNA expression and patient outcome. Our findings provide evidence that elevated TSP expression may be associated with an angiogenic phenotype in endometrial cancer. In addition, TSP-2 expression is a marker for poor prognosis in this disease.

Blood Vessels↗

PubMed2001

[Concurrent chemoradiotherapy for advanced cervical cancer--a pilot study].

Recently, attempts have made to use radiotherapy in combination with chemotherapy in various solid tumors including cervical cancer. Twenty-four patients with locally advanced cervical cancer were treated with concurrent Carboplatin (16-24 mg/m2/day) or Nedaplatin (20 mg/m2/week) and conventional radiotherapy. Of 13 evaluable patients, there were nine complete responders and four partial responders. There was no renal damage or grade 4 hematological toxicity. Gastrointestinal adverse reactions were mild. One patient had grade 3 dermatologic toxicity after delayed radiation therapy. This pilot study suggests that daily Carboplatin or weekly Nedaplatin administered with standard radiation therapy is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer.

Adult↗

PubMed2001

Thrombospondin-1 and -2 messenger RNA expression in invasive cervical cancer: correlation with angiogenesis and prognosis.

PURPOSE: TSP association with clinicopathological features, including microvessel count, regarding prognostic significance was examined in patients presenting with invasive cervical cancer. EXPERIMENTAL DESIGN: Gene expression of TSP-1 and TSP-2 was assessed by reverse transcription-PCR in 10 normal cervix and 78 invasive cervical cancer samples. RESULTS: TSP-1 and TSP-2 mRNA expression was detected in seven (70.0%) of the normal cervical specimens. TSP-2 mRNA expression in normal cervix was significantly higher than that in cases involving cervical cancer (P = 0.032). TSP-1 mRNA expression was significantly lower in tumors characterized by advanced stage (P = 0.047). Fifty-three patients displaying stage Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. Expression of TSP-1 and TSP-2 mRNA was significantly lower in tumors exhibiting parametrial invasion (P = 0.016 and P = 0.049, respectively). Microvessel counts were significantly higher when decreased TSP-1 expression was evident (P = 0.029). The microvessel count in patients lacking TSP-2 mRNA expression was higher than that observed in patients displaying TSP-2 mRNA expression, although it was not statistically significant (P = 0.062). Subjects demonstrating TSP-1 mRNA expression exhibited significantly better prognosis than those lacking TSP-1 mRNA expression (P = 0.0038). Furthermore, TSP-1 mRNA expression was an independent prognostic factor in the multivariate analysis. CONCLUSIONS: These findings provide evidence that TSP-1 expression is of value as a prognostic factor in cervical cancer. The inverse correlation between TSP expression and microvessel count also indicates that decreased TSP expression may be associated with an angiogenic phenotype in this class of neoplasm.

Adult↗

PubMed2000

Down-regulation of the insulin-like growth factor I receptor by antisense RNA can reverse the transformed phenotype of human cervical cancer cell lines.

The insulin-like growth factor I receptor (IGF-IR) plays an essential role in the establishment and maintenance of transformed phenotype, and interference with the IGF-IR pathway by antisense or dominant-negative mutants causes reversal of the transformed phenotype in many rodent and human tumor cell lines. We stably transfected an IGF-IR antisense mRNA expression plasmid into human papillomavirus (HPV)-negative C33a cell line, HPV-16-positive SiHa cell line, and HPV-18-positive HeLa S3 cell line to determine whether the IGF-IR could be a target for cervical cancer cells, especially in the presence of HPV. Approximately 30-80% down-regulation of IGF-IR expression was observed by Western blot in antisense transfected clones. There was a little inhibition in monolayer growth in all cell lines. In C33a cells, wild-type and sense clones formed 92-146 colonies in soft agar after 3 weeks; antisense clones formed <12 colonies. In SiHa cells, wild-type and sense clones formed approximately 60 colonies after 5 weeks; antisense clones formed 0-3 colonies. In HeLa S3 cells, wild-type and sense clones formed 218-291 colonies in soft agar after 2 weeks; antisense clones formed 14-160 colonies. There was a good correlation between IGF-IR down-regulation level and inhibition of transformation in soft agar. Tumorigenesis in nude mice was strongly inhibited in HeLa S3 and SiHa clones transfected with the antisense. These results indicate that down-regulation of IGF-IR by antisense RNA can reverse the transformed phenotype of human cervical cancer cells, even when harboring malignant type HPVs.

Animals↗

PubMed2000

Vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression are implicated in the angiogenesis of endometrial cancer.

Although many angiogenic factors have been described, it is not well defined which factors are expressed in endometrial cancer. The object of this study was to examine mRNA levels of the two angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in endometrial cancer tissues and their association with clinicopathological features including microvessel density. The level of VEGF and PD-ECGF mRNAs was assessed by semi-quantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard in 38 patients with endometrial cancer. Microvessel counts were also assessed by immunostaining for factor VIII-related antigen in the most vascularised area of the specimen. VEGF/beta-actin ratios of non-endometrioid tumours were significantly higher than those of endometrioid tumours (P = 0.013). VEGF/beta-actin ratios of cases with lymph-vascular space involvement were significantly higher than those of cases without lymph-vascular space involvement (P = 0.021). Although it was not statistically significant, PD-ECGF/beta-actin ratios in grade 3 tumours were higher than those in grade 1 and 2 tumours (P = 0.066). The microvessel density was significantly correlated with the level of VEGF and PD-ECGF mRNA expression (P = 0.041 and P < 0.0001, respectively). Our findings provide evidence that the expression of both VEGF and PD-ECGF is involved in the promotion of angiogenesis in endometrial cancer. In addition, VEGF and PD-ECGF might contribute to the aggressive potential of high grade tumours or certain histological subtypes with unfavourable prognosis through the induction of angiogenesis.

Endometrial Neoplasms↗

PubMed2000

Alteration of the CDKN2/p16 gene is not required for HPV-positive uterine cervical cancer cell lines.

To determine whether alterations of the CDKN2/p16 might be involved in HPV-positive cervical cancers, we examined for alterations of this gene and function of the protein p16 to interact with CDK4 in 5 cervical cancer cell lines. No alteration of this gene was detected. Proteins for p16 and CDK4 were normally expressed and function of p16 to interact with CDK4 was not abrogated in these cell lines. These cell lines were human papillomavirus (HPV)-positive and carried wild-type p53. These findings suggest that phosphorylation of pRb by CDK4 is not critical in the carcinogenesis or in the establishment of HPV-positive cervical cancer cell lines, since HPV E6 or E7 viral-transforming proteins inactivate p53 and pRb tumor suppressor protein function, resulting in deregulated progression of the cell cycle.

Cyclin-Dependent Kinase 4↗

PubMed2000

Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer.

We examined gene amplifications of the c-erbB-2 and FGF-3 gene in 48 epithelial ovarian cancers by differential PCR and addressed their association with clinico-pathological features including clinical outcome. Overall, 25.0 and 20.8% of ovarian cancers displayed amplified c-erbB-2 or FGF-3 gene, respectively. Amplification of the c-erbB-2 gene was significantly associated with particular histological cell types, higher histological grade, and low levels of serous CA125. However, there was no correlation between c-erbB-2 gene amplification and patient outcome. No correlation was observed between FGF-3 gene amplification and any clinico-pathological features including overall survival. These findings suggested that c-erbB-2 or FGF-3 gene amplification might be one of the oncogenic events implicated in the development of ovarian cancers, yet is not a useful prognostic marker.

Adult↗

PubMed1999

Serum C-reactive protein as a prognostic factor in patients with epithelial ovarian cancer.

OBJECTIVE: It is well known that the serum level of Interleukin-6 (IL-6) correlates with the level of C-reactive protein (CRP). The purpose of this study is to determine the significance of CRP as a prognostic factor in epithelial ovarian cancer. STUDY DESIGN: The present study is comprised of 120 patients with epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50 mg/l were considered high CRP. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with poor survival. RESULTS: The serum CRP value was significantly associated with the volume of ascites (P = 0.000004). Univariate analysis showed that the FIGO stage, primary tumour diameter, size of residual tumour, histologic grade, volume of ascites and high serum level of CRP were significant prognostic factors. Cox's multivariate proportional hazard model showed that histologic grade was the most important prognostic factor (P = 0.0026). FIGO stage and volume of ascites were also independent factors for 5-year survival (P = 0.0310 and P = 0.0216, respectively). However, the serum CRP value was not an independent prognostic factor. CONCLUSION: CRP is an adverse prognostic factor in univariate analysis, but not in multivariate analysis.

Adenocarcinoma, Clear Cell↗

PubMed1999

Vascular endothelial growth factor is implicated in early invasion in cervical cancer.

The association between the expression of vascular endothelial growth factor (VEGF) and clinicopathological factors has scarcely been examined in cervical cancer. This study examines the level of VEGF messenger RNA (mRNA) expression in invasive cervical cancer and its association with clinicopathological features including microvessel density. The level of VEGF mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using beta-actin as an internal control in 66 patients with stages Ia-IVb invasive cervical cancer. In 42 patients who underwent surgery, the microvessel count was also assessed by immunostaining for factor VIII-related antigen in the most neovascularised area of the specimen. The highest level of VEGF mRNA expression was observed in early invasive cervical cancers. Except for stage IVb, the stage of the disease inversely correlated with the level of VEGF mRNA (P < 0.05). There was no significant difference in the level of VEGF mRNA with respect to histological cell types. 38 patients with stages Ib-IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There was no significant difference in the level of VEGF mRNA with respect to lymph node metastasis, depth of stromal invasion, tumour size, parametrial involvement or vaginal involvement among these patients. A significant relationship was found between the microvessel density and the level of VEGF mRNA (P < 0.01). These findings provide evidence that the expression of VEGF is involved in the promotion of angiogenesis in cervical cancer and plays an important role in early invasion.

Endothelial Growth Factors↗

PubMed1999

Assessment of myometrial invasion at the invasion site of an endometrial carcinoma by ultrasonography along with an intrauterine catheter.

OBJECTIVES: To evaluate by transvaginal ultrasonography (TVU) the thickness of the intact myometrium at the presumed tumor-origin site and to establish criteria for a half myometrial invasion. METHODS: A total of 19 successive patients with endometrial cancer who were treated between January 1, 1997, and January 31, 1998, participated in this study. TVU mode B with and without the use of an intrauterine silicon catheter was performed. RESULTS: Using a catheter, the origin site was correctly detected in 15 cases (79%). The best criterion for half myometrial invasion was a 6-mm thickness of the intact myometrium at the origin site. The sensitivity/specificity/accuracy of TVU with the use of a catheter in cases with the correct estimated origin site, were 1.00/0.67/0.86 for myometrial invasion < 1/2, and 0.67/1.00/0.86 for myometrial invasion > or = 1/2. CONCLUSION: It is of value to use 6-mm as the criterion for the thickness of the intact myometrium at the estimated tumor-origin site in connection with TVU with the use of a catheter for preoperatively assessing half myometrial invasion.

Adult↗

PubMed1999

Analysis by multiplex PCR of the physical status of human papillomavirus type 16 DNA in cervical cancers.

Integration of human papillomavirus (HPV) DNA occurs early in cancer development and is an important event in malignant transformation of cervical cancer. Integration of HPVs preferentially disrupts or deletes the E2 open reading frame, which results in the loss of its expression. The preferential disruption of the E2 gene causes the absence of the E2 gene sequences in the PCR product following integration. Twenty-two carcinomas positive for HPV type 16 (HPV-16) DNA were first tested for the disruption of the E2 gene by PCR. A specific fragment of the E2 gene was not amplified in 10 cases, suggesting integration of HPV DNA into the host genome. Next, multiplex PCR for the HPV E2 and E6 genes was carried out in the remaining 12 cases. Copy numbers of both genes should be equivalent in episomal forms, while the E2 gene copy number will be smaller than that for E6 following the preferential disruption of the E2 gene in concomitant forms. Although relative ratios of HPV E2 to E6 PCR products (E2/E6 ratios) ranged from 1.40 to 2.34 in 10 of 12 cases, multiplex PCR products from 2 cases displayed extremely low ratios of 0.69 and 0.61. Southern blot hybridization with an HPV-16 probe revealed that only in these two cases was both episomal and integrated HPV DNA being carried simultaneously. Thus, multiplex PCR for the E2 and E6 genes of HPV-16 DNA following PCR for the E2 gene can distinguish the pure episomal form from a mixed form of episomal and integrated HPV DNA. Clinical application of this technique will help researchers to understand the implication of the integration of HPV DNA for cervical carcinogenesis and cervical cancer progression.

Base Sequence↗

PubMed1999

Effect of cisplatin on cell death and DNA crosslinking in rat mammary. Adenocarcinoma in vitro.

The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P < 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P < 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P < 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.

Adenocarcinoma↗

PubMed1999

Angiogenesis and platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in cervical cancer.

The object of this study was to clarify the association of platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (dThdPase), separately assessed in cancer cells and in stroma cells, with clinicopathological factors including tumor angiogenesis and prognosis in cervical cancer. The expression of PD-ECGF was evaluated by immunohistochemical staining in 92 patients with stage Ib-II cervical cancer. The microvessel count was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. Microvessel count was significantly higher in tumors with non-squamous cell carcinoma. PD-ECGF expression in cancer cells was significantly higher in tumors with pelvic node metastasis and squamous cell carcinoma. Immunopositivity for PD-ECGF in stroma cells was significantly higher in tumors with large size and deep stromal invasion. The microvessel counts in cases with positive PD-ECGF expression in stroma cells were significantly higher than those in cases with negative PD-ECGF expression in stroma cells (p=0.048). Disease-free survival and overall survival were significantly worse in patients with deep stromal invasion, parametrial involvement, vaginal involvement, lymph-vascular space involvement, pelvic lymph node metastasis and high microvessel count. A multivariate analysis using Cox's proportional hazard model showed that high microvessel count independently predicted disease-free and overall survival. The expression of PD-ECGF in stroma cells may play a crucial role in the promotion of angiogenesis and tumor angiogenesis can be used as a useful prognostic marker for cervical cancer.

Adult↗