Vascular endothelial growth factor (VEGF) exerts its biological functions by its specific VEGF receptors (VEGFRs), which includes VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1 and neuropilin-2. These VEGF receptors not only distribute in endothelial cells, but also in epidermal keratinocytes. VEGFRs may play a significant role in pathogenesis of the epidermal neoplasm and the VEGF-VEGFR signaling pathway may be a novel therapy target for neoplasm derived from epidermis.
Animals ; Epidermis ; metabolism ; Humans ; Neoplasms ; metabolism ; Neuropilins ; genetics ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; genetics ; metabolism

Vascular endothelial growth factor (VEGF) exerts its biological functions by its specific VEGF receptors (VEGFR), which includes VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1, and neuropilin-2. These VEGFR distributes in endothelial cells, and are also expressed in normal skin, inflammatory skin diseases, and skin cancers. The VEGF-VEGFR signaling pathway may be a new key target in the management of the skin diseases.
Animals ; Humans ; Receptors, Vascular Endothelial Growth Factor ; biosynthesis ; Signal Transduction ; Skin Diseases ; metabolism ; Vascular Endothelial Growth Factor A ; physiology

Cadherins ; metabolism ; Female ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells ; metabolism ; Receptor, Notch1 ; metabolism ; Receptors, CXCR4 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor C ; metabolism

The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.
Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Bevacizumab ; Humans ; Lymphangiogenesis ; Neoplasms ; drug therapy ; metabolism ; Neovascularization, Pathologic ; metabolism ; Placenta Growth Factor ; Pregnancy Proteins ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; classification ; metabolism ; Vascular Endothelial Growth Factor B ; metabolism ; Vascular Endothelial Growth Factor C ; metabolism ; Vascular Endothelial Growth Factor D ; metabolism

OBJECTIVETo study the expression of vascular endothelial growth factor (VEGF) and its receptors, the fms-like tyrosine-1 (flt-1) and kinase insert domain-containing receptor (KDR) in endometrial carcinoma and investigate the functions of VEGF and its receptors for endometrial carcinoma angiogenesis and its relation to the grade of tumor.

METHODSImmunocytochemistry and in situ hybridization technique were used to measure the level of VEGF, flt-1, KDR protein and mRNA in endometrial carcinoma tissue from 23 patients and endometrial samples from 6 normal menopausal women. A few endometrial carcinoma samples were homogenized for Western blot analysis. The blood vessel density was estimated by counting blood vessels stained with endothelial marker VIII factor.

RESULTSThe VEGF and its receptors were widely expressed in the cytoplasm of endothelial cells and tumor cells of endometrial carcinoma. The level of VEGF protein in endothelial cells and endometrial cancer cells of grade II and III tumor tissues was higher than that in grade I and normal menopausal endometrium (P < 0.05). VEGF mRNA did not show higher expression with the increase of tumor grade but its expression in normal tissue was lower than that in cancer (P < 0.05). The expression of flt-1 protein and mRNA in endothelial cells got higher in III than in grade II and I (P < 0.05), but invariable in cancer cells (P > 0.05), flt-1 expression in cancer was higher than that in normal menopausal endometrium either in endothelial cells or in cancer cells (P < 0.05). The expression of KDR protein in endothelial and cancer cell was high but did not alter with the increase of tumor grade (P > 0.05), the level of its mRNA was higher in cancer than that in normal tissue (P < 0.05). The microvascular density in grade III (48 +/- 12) was higher than that in grade II (26 +/- 16), grade I (27 +/- 14) and normal menopausal tissue (26 +/- 11, P < 0.05).

CONCLUSIONSThe expression pattern of VEGF, flt-1 and KDR protein and mRNA increased with the increase of tumor grade in endometrial carcinoma indicates that VEGF and its receptors contribute to the neovascularization of tumors and is one of the factors that relate to rapid tumor growth of endometrial carcinoma.

Endometrial Neoplasms ; metabolism ; physiopathology ; Endothelial Growth Factors ; genetics ; metabolism ; Extracellular Matrix Proteins ; metabolism ; Female ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Lymphokines ; genetics ; metabolism ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Vascular Endothelial Growth Factors

OBJECTIVETo investigate the correlation between the expression of the kinase insert domain-containing receptor (KDR) and the histological grade of prostate adenocarcinoma.

METHODSForty-eight samples of prostate adenocarcinoma tissues and 20 samples of benign prostatic hypertrophy (BPH) tissues were studied by LsAB immunohistochemical staining.

RESULTSThe positive expression rate of KDR was 73% in prostate adenocarcinoma and 30% in BPH. The expression of KDR was stronger in prostate adenocarcinoma, and there was no relationship between staining intensity and the histological grade of carcinoma.

CONCLUSIONKDR, expressed more highly in prostate adenocarcinoma, promises to be a new target in the treatment of prostate adenocarcinoma.

Adenocarcinoma ; metabolism ; Humans ; Male ; Prostatic Hyperplasia ; metabolism ; Prostatic Neoplasms ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis

OBJECTIVETo investigate the significance of beta-adrenergic receptor 2 (beta2-AR) and vascular endothelial growth factor-2 (VEGFR-2) in the occurrence and development of infantile hemangioma through detecting the expression of beta2-AR and VEGFR-2 in the different stages of infantile hemangiomas.

METHODSAccording to the Mulliken's classification standard, we classified the specimens as proliferating group (32 cases), involuting group (17 cases) and involuted group (11 cases). Normal skin tissue surrounding the hemangioma from 7 cases were chosen as control group. The expression of beta2-AR and VEGFR-2 was detected by immunohistochemical technique in proliferating hemangioma, involuting hemangioma, involuted hemangioma. The mean optical density was measured by image analysis system (Image Pro Plus 6.0) and SPSS 16.0 software was applied for statistical analysis.

RESULTSThe expression of beta2-AR and VEGFR-2 was strongly positive in proliferating hemangioma, while positive in involuting hemangioma and weakly positive in the involuted stage. The mean optical density of each phase was 0.064 751 2 +/- 0.012 747, 0.031 6017 +/- 0.006 848,0.011 869 8 +/- 0.039 349 for beta2-AR, and 0.068 940 9 +/- 0.029 274, 0.028 445 5 +/- 0.006 396, 0.011 184 1 +/- 0.004 198 for VEGFR-2. The differences between different stages had a statistically significance (P < 0.05). Correlation analysis on the mean optical density between beta2-AR and VEGFR-2 had a statistically significance (P < 0. 05).

CONCLUSIONSBeta2-AR and VEGFR-2 may be involved in the occurrence and development of infantile hemangioma.

Child ; Child, Preschool ; Female ; Hemangioma ; metabolism ; Humans ; Infant ; Male ; Receptors, Adrenergic, beta-2 ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; metabolism

OBJECTIVETo examine the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1, VEGFR2) in transdifferentiated human proximal tubular epithelial (HK-2) cell induced by transforming growth factor beta1 (TGFbeta1).

METHODSThe transdifferentiation of HK-2 cells was detected by evaluation of expression of alpha-SMA by cytoimmunochemistry and RT-PCR. The VEGF mRNA was evaluated with RT-PCR. The secreted VEGF in the culture media was measured with ELISA. The cellular VEGF, VEGFR1, and VEGFR2 were measured with Western blot.

RESULTSThe immunostain of alpha-SMA were positive in HK-2 cell induced by TGFbeta1 at the concentration of 5 and 8 ng/ml for 72 h. The expression of alpha-SMA mRNA was induced by TGFbeta1 in concentration- and time-dependent manners. The expressions of mRNA and protein of VEGF were upregulated by TGFbeta1 at the concentration of 0.1 and 1 ng/ml for 72 h and at the concentration of 8 ng/ml for 12 h and 24 h when compared with the control. But expressions of mRNA and protein of VEGF were downregulated by TGFbeta1 at the concentration of 3, 5, and 8 ng/ml for 72 h and at the concentration of 8 ng/ml for 36, 48, and 72 h, respectively. Meanwhile, Protein levels of VEGFR1 and VEGFR2 were upregulated by TGFbeta1 in concentration- and time- dependent manners.

CONCLUSIONSIncreased expression of VEGFR1 and VEGFR2 and two-phase change in VEGF expression occurred in the process of tubular epithelial transdifferentiation induced by TGFbeta1. Reduced expression of VEGF may contribute to tubular epithelial transdifferentiation in a vicious circle.

Cell Differentiation ; Epithelial Cells ; cytology ; Humans ; Kidney Tubules, Proximal ; cytology ; RNA, Messenger ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Transforming Growth Factor beta ; pharmacology ; Transforming Growth Factor beta1 ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo study the expression of vascular endothelial cell growth factor (VEGF) and its receptor FLT-1, FLK-1 mRNA in breast cancer tissues and their correlation with clinicopathological factors.

METHODSThe expression of VEGF and and its receptor FLT-1, FLK-1 mRNA were analyzed by reverse transcription - polymerase chain reaction (RT-PCR) in the specimens from 47 patients with breast cancer and 11 patients with benign breast disease.

RESULTSVEGF121, 165 mRNA were all detected in malignant and benign breast tissues, with higher level, (0.420 +/- 0.133 and 0.291 +/- 0.094 respectively) in breast cancer tissues than in benign breast tissues, [0.196 +/- 0.067 (P = 0.000) and 0.206 +/- 0.058 (P = 0.001) respectively]. VEGF121 mRNA expression was stronger than VEGF165 mRNA expression (P = 0.000) in breast cancer tissues, whereas there is no significant difference in benign breast tissues (P = 0.666). FLT-1, FLK-1 mRNA were expressed in 18 of 47 (38.3%) and 12 of 47 (25.5%) breast cancer tissues respectively, but not in benign breast tissues. Moreover, no correlation was observed between the expression of VEGF121, VEGF165, FLT-1, FLK-1 mRNA in breast cancer tissues and patients' age, tumor size, lymph node metastasis, tumor stages, estrogen or progesterone receptor status.

CONCLUSIONThe expression of VEGF and its receptor FLT-1, FLK-1 mRNA were up-regulated in breast cancer tissues, suggesting its important role in angiogenesis of breast cancer.

Breast Neoplasms ; metabolism ; pathology ; Female ; Humans ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; genetics ; metabolism

OBJECTIVETo investigate the pathohistological characteristics of the prostate tissues in patients who receive a second TURP and to evaluate their clinical significance.

METHODSWe collected surgical specimens from 50 cases of TURP (the control group) and another 50 cases of re-TURP (the re-TURP group), detected the expressions of CD34, vascular endothelial growth factor (VEGF) and androgen receptor (AR) in the prostate tissues by immunohistochemistry (S-P), and determined microvessel density (MVD) and the expressions of VEGF and AR. We performed statistical analyses on the results obtained from the specimens of the control group as well as from those of the first and second operations of the re-TURP group.

RESULTSVEGF and AR expressed in all the specimens. The expressions of VEGF and AR and MVD were significantly higher in the re-TURP group than in the controls (P < 0.05), but showed no significant differences between the first and second operations in the re-TURP group (P > 0.05). Positive correlations were found between the expressions of AR and VEGF, VEGF and MVD, and AR and MVD (r = 0.650, 0.705 and 0.525, P < 0.05).

CONCLUSIONIncreased AR, VEGF and MVD in the prostatic tissues may be one of the important causes of recurrence of BPH after TURP, and could be considered as the risk factors for postoperative recurrence and targeted indicators for preventive measures.

Humans ; Male ; Prostatic Hyperplasia ; metabolism ; pathology ; surgery ; Receptors, Androgen ; metabolism ; Reoperation ; Transurethral Resection of Prostate ; Vascular Endothelial Growth Factor A ; metabolism