Significance Of Pigment Epithelium-derived Factor Research Articles

Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in colorectal adenoma and cancer.

The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment. To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC. In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant. The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002). It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.

The expression changes and clinical significance of PEDF in bladder mucosa and bladder cancer

Objectives To investigate the expression changes and clinical significance of pigment epithelium derived factor(PEDF) in bladder mucosa and bladder cancer. Methods Bladder cancer tissue and tissue adjacent to carcinoma from patients in our hospital diagnosed with bladder cancer were collected, mRNA expression level of PEDF and protein levels in different clinical stages of bladder cancer tissue were tested by using RT-PCR, Western Blot and immunohistochemistry. The relevant expression level of VEGF 、MMP-2、MMP-9 and MMP-12 were also analyzed by IHC. The relevance between PEDF and different physiological parameters was analyzed by collecting clinical data. Results mRNA level, protein expression level of PEDF in bladder cancer tissues were significantly lower than normal tissue. Correlation analysis showed that the positive rate of PEDF significantly associated with clinical stages, lymph node metastasis of bladder cancer (P 0.05). Conclusions There may be some relativity between PEDF expression differences and development of bladder cancer. Key words: Urinary Bladder Neoplasms; Vascular Endothelial Growth Factor A

Prognostic Significance of Pigment Epithelium-Derived Factor Expression in Patients with Non-Small-Cell-Lung Cancer

The aims of this study were to examine prognostic significance of pigment epithelium-derived factor (PEDF) in patients with stage IA-IIIB non-small cell lung cancer (NSCLC). Using immunohistochemistry and multivariate analysis, we set out to investigate whether PEDF expression could provide prognostic information in NSCLC in a cohort of 69 patients who had undergone radical resection for NSCLC. The correlation between PEDF and the clinical pathological features of stage I-III NSCLC after radical surgery were analyzed as well as influence on long term survival. No correlation between PEDF intensity, PEDF area or PEDF area index and clinic opathologic parameters was seen. PEDF values showed a slight correlation to the tumor stage. There was a significant negative correlation (T = -0.288, p = 0.002) between pathologic T-stage and median PEDF area and vice versa a positive correlation (T = 0.227, p = 0.016) with median PEDF intensity. We could not detect any correlation between PEDF and long term survival. For PEDF analysis, there was only a slight correlation between expression and T-stage of the tumor.

Abstract 5097: PEDF inhibits bone metastases formation, prolongs survival and enhances the antitumor efficacy of low-dose chemotherapy in castration-refractory prostate cancer.

Abstract Background: The development of metronomic/low dose administration of conventional chemotherapeutic drugs has shown great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (DTX) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with DTX (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1-PEDF or -control cells into the left lobe of the dorsal prostate of anesthetized mice. For bone metastases, CL1-PEDF or -control cells were injected into the proximal region of the tibia. Results: We showed that PEDF expression inhibits the proliferation and induces the differentiation of CPRC cells in vitro, and decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In vivo, PEDF expression inhibits the formation of bone metastases and bone destruction, and prolongs significantly (P=0.01; 95% confidence interval) the median survival of CL1 tumor-bearing mice (53±0.001 days versus 57±1). Furthermore, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established s.c. tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1) and prolongs significantly the survival of tumor-bearing mice undergoing low dose chemotherapy. Conclusions: These data reinforce the significance of PEDF as a potent target for the treatment of CRPC. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose chemotherapies. Citation Format: Thomas Nelius, Jennifer Hirsch, Stephanie Filleur. PEDF inhibits bone metastases formation, prolongs survival and enhances the antitumor efficacy of low-dose chemotherapy in castration-refractory prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5097. doi:10.1158/1538-7445.AM2013-5097 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

793 PIGMENT EPITHELIUM-DERIVED FACTOR INHIBITS BONE METASTASES FORMATION, PROLONGS SURVIVAL AND ENHANCES THE IN VIVO ANTITUMOR ACTIVITIES OF LOW-DOSE CHEMOTHERAPY IN CASTRATION-REFRACTORY PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: The development of metronomic/low dose administration of conventional chemotherapeutic drugs has shown great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (DTX) and cyclophosphamide (CTX) chemotherapies in vivo. METHODS: PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with DTX (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1-PEDF or -control cells into the left lobe of the dorsal prostate of anesthetized mice. For bone metastases, CL1-PEDF or -control cells were injected into the proximal region of the tibia. RESULTS: We showed that PEDF expression inhibits the proliferation and induces the differentiation of CPRC cells in vitro, and decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In vivo, PEDF expression inhibits the formation of bone metastases and bone destruction, and prolongs significantly (P 0.01; 95% confidence interval) the median survival of CL1 tumorbearing mice (53 0.001 days versus 57 1). Furthermore, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established s.c. tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1) and prolongs significantly the survival of tumor-bearing mice undergoing low dose chemotherapy. CONCLUSIONS: These data reinforce the significance of PEDF as a potent target for the treatment of CRPC. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose chemotherapies.

Effect of PEDF on the in vivo antitumor activities of low-dose chemotherapy in CRPC.

173 Background: The development of metronomic/low dose administration of conventional chemotherapeutic drugs has shown great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (DTX) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with DTX (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1-PEDF or -control cells into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF expression inhibits the proliferation and induces the differentiation of CPRC cells in vitro, and decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In the survival study, PEDF expression prolongs significantly (P=0.01; 95% confidence interval) the median survival of CL1 tumor-bearing mice (53±0.001 days versus 57±1). Furthermore, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established s.c. tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1) and prolongs significantly the survival of tumor-bearing mice undergoing low dose chemotherapy. Conclusions: These data reinforce the significance of PEDF as a potent target for the treatment of CRPC. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose chemotherapies.

Effect of PEDF on survival and in vivo antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer.

e15103 Background: The development of metronomic/low-dose treatment with conventional chemotherapeutic drugs has recently shown promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is downregulated in prostate cancer. Previously we demonstrated that overexpression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validate PEDF anti-tumor properties in highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxic effects of low-dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human PC3 and CL1 cell lines were genetically modified to stably express fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and for proliferation by growth curves and clone formation in Matrigel. PEDF anti-tumor effects were assessed on established SC xenografts in mice treated with Doc (5mg/kg IP every 4 days, 1mg/kg IP daily for 10 days, 0.5mg/kg IP every other day), CTX (10-20mg/kg in drinking water) or placebo. Survival studies were performed by injecting CL1 cells that express PEDF or control into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits proliferation and induces differentiation of all CPRC cells tested in vitro. Similarly, PEDF expression decreases by 85% and 70% the development of SC PC3 and CL1 tumors, respectively. In the survival study, we found that PEDF expression prolongs significantly (p=0.01; 95% confidence interval) median survival of CL1 tumor-bearing mice (53±0.001 days versus 57±1). Most importantly, we demonstrated that PEDF enhances the cytotoxic effects of low-dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1). Conclusions: This data reinforces the significance of PEDF as a potential new target when treating advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low-dose Doc and CTX chemotherapies.

Abstract 3717: Pigment epithelium-derived factor prolongs survival and enhances the in vivo antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer

Abstract Background: The development of metronomic/low-dose administration of conventional chemotherapeutic drugs has recently shown great promise in the treatment of castration-refractory prostate cancer (CRPC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which has been shown to be down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF could enhance the cytotoxic effects of low-dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human CRPC PC3 and CL1 cell lines were genetically modified to stably co-express the fluorescent DsRed Express protein with PEDF. Resulting cell lines were characterized in vitro for PEDF expression by Western blot and for proliferation by growth curves and clone formation in Matrigel. PEDF anti-tumor effects were assessed on established subcutaneous xenografts in mice treated with Doc (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg ip every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells, pre-mixed with 50nM hr-PEDF or carrier control, into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits the proliferation and induces the differentiation of all CRPC cells tested in vitro. Similarly, PEDF expression decreases the development of subcutaneous PC3 and CL1 tumors in immune-compromised mice by 85% and 70%, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxic effects of low-dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for both PC3 and CL1). Conclusions: This data reinforces the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low-dose Doc and CTX chemotherapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3717. doi:1538-7445.AM2012-3717

780 PIGMENT EPITHELIUM-DERIVED FACTOR PROLONGS SURVIVAL AND ENHANCES THE IN VIVO ANTI-TUMOR ACTIVITIES OF LOW-DOSE CHEMOTHERAPY IN CASTRATION-REFRACTORY PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: The development of metronomic/low dosing of conventional chemotherapeutic drugs have recently showed great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which has been shown to be down-regulated in prostate cancer. We have previously demonstrated that the overexpression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF antitumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF could enhance the cytotoxicity effects of low dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. METHODS: Human CRPC PC3 and CL1 cell lines were genetically modified to stably co-express the fluorescent DsRed Express protein with PEDF. Resulting cell lines were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with Doc (5mg/kg ip every 4 days, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells, pre-mixed with 50nM hrPEDF or carrier control, into the left lobe of the dorsal prostate of anesthetized mice. RESULTS: We showed that PEDF inhibits the proliferation and induces the differentiation of all CPRC cells tested in vitro. Similarly, PEDF expression decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors in immuno-compromised mice, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for both PC3 and CL1). CONCLUSIONS: These data reinforce the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose Doc and CTX chemotherapies.

Effect of PEDF on survival and the in vivo antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer.

237 Background: The development of metronomic/low dose of conventional chemotherapeutic drugs have recently showed great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with Doc (5mg/kg ip every 4 dy, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells with 50nM hrPEDF or carrier control into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits the proliferation and induces the differentiation of all CPRC cells tested in vitro. Similarly, PEDF expression decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1). Conclusions: These data reinforce the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose Doc and CTX chemotherapies.

Inhibition and significance of pigment epithelium-derived factor in the development and metastasis of prostate cancer

To study the inhibition and significance of pigment epithelium-derived factor (PEDF) in the development and metastasis of prostate cancer. The expression of PEDF was examined in the normal prostate tissue, benign prostatic hyperplasia, prostate cancer tissue and prostate cancer cell lines, PC-3 and Lncap by immunohistochemical SP method and Western blot. In combination with clinical data, statistical analysis was performed to evaluate the relation of the expression level of PEDF in prostate cancer and the relationship between different histological grades of prostate cancer. In normal prostate tissue and benign prostate tissue, the expression of PEDF were elevated and it was far higher than the prostate cancer and prostate cancer cell line. The expression of PEDF and the pathological grade of prostate cancer were related to the differentiated carcinoma of prostate tissue, and the expression level of PEDF in poorly differentiated carcinoma below the highly differentiated carcinoma of prostate cancer. In metastatic prostate cancer, the expression of PEDF was lower than that of prostate cancer without metastasis (12% vs 43.1%). The expression of PEDF and the incidence of prostate cancer have a negative correlation. The lower grade of prostate cancer cells, the less the tissue expression of PEDF and the higher tendency of invasion and metastasis.

Prognostic Role of Pigment Epithelium-Derived Factor in Clear Cell Renal Cell Carcinoma

Aims: The purpose of this study was to investigate the prognostic significance of pigment epithelium-derived factor (PEDF) in human clear cell renal cell carcinoma (CCRCC) tissues. Patients and Methods: We investigated the expression of PEDF and its correlation with clinicopathological features in 203 patients who underwent radical nephrectomy for CCRCC. Expression of PEDF and CD34-positive vessels (microvessel density, MVD) in tumor samples was examined by immunohistochemistry. The relationship between PEDF expression and clinicopathologic features including tumor diameter, MVD, and survival was evaluated by univariate and multivariate analyses. Results: Of 203 patients, 116 cases (57.1%) were positive for PEDF. A significant association was found between PEDF expression and high MVD (p = 0.012). PEDF expression was inversely correlated with grade (p = 0.004) and pT stage (p = 0.001). Multivariate analysis using the Cox regression model indicated that PEDF expression was an independent favorable prognostic factor (risk ratio, 4.105; p = 0.001). However, no significant correlation was found between PEDF expression and age, gender, tumor diameter or lymph node invasion. Conclusion: Our findings suggest that PEDF may be a favorable prognostic indicator in patients with CCRCC.

In vitro and in vivo biological activity of PEDF against a range of tumors

Background: Pigment epithelium-derived factor (PEDF) is an emerging anti-cancer agent that targets both tumor tissue and its supporting vasculature. These direct and indirect effects of PEDF have been examined in vitro and in vivo for a range of malignancies. Objective: This review seeks to present PEDF as a potential anti-cancer agent with applications across multiple malignancies. We refer closely to experimental methodology whilst still highlighting the clinical significance of PEDF in cancer, drawing on biological findings in vitro and in vivo. Methods: A Pubmed database search was performed limiting the scope of this discussion paper mainly to PEDF's biological role in cancer, specifically lung, breast, prostatic, ovarian and pancreatic carcinomas, melanoma, glioma and osteosarcoma. Conclusions: The biological roles of PEDF are diverse and multidimensional. As an anti-cancer agent, PEDF has great potential as a focused anti-neoplastic therapy against a variety of tumor types.

Change and significance of serum pigment epithelium-derived factor in type 2 diabetic nephropathy

To investigate the change of pigment epithelium-derived factor (PEDF) in type 2 diabetic nephropathy, and to explore the significance of PEDF in the development of diabetic nephropathy. ELISA was used to detect the serum PEDF and immunoturbidimetry was used to measure the urinary albumin excretion (UAE) in 49 healthy controls and 132 type 2 diabetic patients, including 48 with normal urinary albumin excretion rate (NA group), 50 with microalbuminuria (MA group), and 34 with overt diabetic nephropathy (PR group). HbA1c, triglyceride (TG), total cholesterol, high density lipoprotein cholesterol (HDL-c), and highly sensitive C-reactive protein (hs-CRP) were simultaneously determined. The serum PEDF levels of the NA, MA, and PR groups were (3.7 +/- 2.2) mg/L, (4.7 +/- 2.9) mg/L, and (5.7 +/- 2.8) mg/L respectively, all significantly higher than that of the control group (2.7 +/- 1.3) mg/L. P < 0.05, 0.01, and 0.01 respectively). The serum PEDF levels of the MA and PR groups were significantly higher than that of the NA group (both P < 0.01), and that of the PR group was significantly higher than that of the MA group (P < 0.05). Correlation analysis demonstrated that serum PEDF level was positively correlated with HbA1c (r = 0.198, P < 0.01), FPG (r = 0.231, P < 0.01), TG (r = 0.302, P < 0.01), hs-CRP (r = 0.214, P < 0.01), and urinary albumin excretion rate (UAER) (r = 0.169, P < 0.05), significantly, but negatively correlated with HDL-c (r = -0.237, P < 0.01). Stepwise multiple linear regression analysis showed that TG (beta = 0.314, P < 0.01), hs-CRP (beta = 0.260, P < 0.01), and UAER (beta = 0.148, P < 0.05) were significant independent determinants for serum PEDF. Serum PEDF level significantly increases in type 2 diabetic patients, and the magnitude of PEDF is related to the severity of diabetic nephropathy. TG, hs-CR and UAER are significant independent determinant for serum PEDF. The increase of PEDF may involve in the development of diabetic nephropathy.