Craniofacial Dysostosis ; Humans ; Receptors, Fibroblast Growth Factor

No abstract available.
Colon* ; Liver* ; Platelet-Derived Growth Factor* ; Receptors, Platelet-Derived Growth Factor*

BACKGROUND: Several reports have demonstrated that TGFalpha and EGF are mitogenic for keratinocytes. Whenther its expression on epithelial tumors is a marker of malignancy or signifies an important step in the development of neoplasia is poorly understood. EGF receptors are also present in normal epidermis and epithelial tumors but their physiological roles are not yet understood. OBJECTIVE: Our purpose was to examine the staining patterns of TGFalpha, EGF and EGF receptors on the npithelial tumors of the skin, and to investigate kinetics of expression of EGF receptors. METHODS: We performed immunoperoxidase staining(ABC technique) with monoclonal anti-TGFalpha antibody, polyclonal anti-EGF antibody and polyclonal anti-EGF receptor antibody on the formalinfixed, paraffin-embedded tissue specimens of benign, premalignant and malignant skin tumors. RESULTS: The density of the expression of TGFalpha and EGF was not correlated with the degree of the malignancy of the epithelial tumors and is neither constant in any kind of the tumors. However the infiltrative type of basal cell carcinoma(BCC) is stronger that its solid type on the expression of TGFalpha and EGF. All benign tumors demonstrated a diffuse pattern within tumor lobules. pression of TGFalpha and EGF. All benign tumors demonstrated a diffuse pattern within tumor lobules. Focal TGFalpha immunostaining was seen in three of 10 squamous cell carcinomas(SCC) and four of 10 BCCs. TGFalpha immunostaining was absent from the outermost one to two layers of tumor lobules of all keratoacanthomas. The specimens which increased the expression of TGFalpha and EGF tended to decrease the expression of EGF receptor. CONCLUSION: These data suggest that the density of immunohistochemical expression of TGFalpha and EGF may be not dependent on the differentiation of tumor cells, and the pattern of immunohistochemical expression of TGFalpha can differentiate SCC from benign tumors such as keratoacanthoma. FGF receptor may be occupied by both of TGFalpha and EGF. With the receptors being occupied, a down regulation of the receptors may occur which results in decreased EGF receptor expression.
Down-Regulation ; Epidermal Growth Factor* ; Epidermis ; Keratinocytes ; Keratoacanthoma ; Kinetics ; Receptor, Epidermal Growth Factor* ; Receptors, Fibroblast Growth Factor ; Skin* ; Transforming Growth Factor alpha*

BACKGROUND/AIMS: The aim of study was to investigate the expression of TGF-beta, TGF-RII and VEGF determined by immunohistochemical analysis with a comparison of the clinicopathological parameters such as tumor size, grade of dysplasia, lymph node metastasis and Dukes' stage in colorectal adenomas and adenocarcinomas, by use of a tissue microarray method. METHODS: The expression of TGF-beta1, TGF-betaRII, and VEGF was determined by immunohistochemistry in 20 adenomas and 40 adenocarcinomas. Tissue microarrays consisting of 2 mm cores from corresponding blocks were constructed and stained. RESULTS: In adenomas, the staining intensity of TGF-beta, TGF-betaRII and VEGF was increased in a high-grade dysplasia group of patients as compared a with low-grade dysplasia group of patients, respectively. The staining intensity of TGF-betaRII was significantly increased in a high-grade dysplasia group of patients than a low-grade dysplasia group of patients (p =0.021). For the adenocarcinomas, the expression and staining intensity of TGF-beta1, TGF-betaRII and VEGF were increased as compared with the adenomas (p<0.001). However, no significant correlation was observed between the staining intensity of TGF-beta, TGF-betaRII and VEGF and the clinicopathological parameters. CONCLUSIONS: The increased expression of TGF-beta1, TGF-betaRII and VEGF in colorectal adenocarcinoma suggests a role for these proteins in colorectal carcinogenesis. Loss of the growth-inhibitory effect of TGF-beta may commence in the early stage of colorectal carcinogenesis.
Adenocarcinoma* ; Adenoma* ; Carcinogenesis ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Receptors, Transforming Growth Factor beta* ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1* ; Vascular Endothelial Growth Factor A*

To understand the expression of hoth TGF-beta l and II ligands and the receptors, artificial fracture was made on rat femur. Fracture callus and epiphyseul plate were stained immunohistochemically on 3rd. 7th, 14th, 21st, 42nd and 56th day after trauma. Polyclonal antibody was used to stain TGF-beta I and II ligands and receptors. At epiphyseal plate, both ligand and receptor were expressed from each cell in proliferating and maturing zone. But there was no difference between type I and II except expression time. TGF-beta II ligand and receptor were expressed earlier: they were expressed mostly by the cells at the zone of proliferating cartilage but TGF-beta1 ligand and receptor were expressed mostly hy the cells at zone of maturing cartilage. At fracture site, TGF-beta expression was observed from 3rd day after trauma and it reached its maximum intensity at 2 weeks. It decreased thereafter and disappeared at 6 weeks after trauma. In enchondral ossification area, TGF-beta expressing cells were scattered throughout the enchondral mass. In intramembranous ossification area, the ligands and receptors were expressed from the osteohlasts just heneath the periosteum. ln summary, TGF-beta ligands and receptors were expressed at epiphyseal plate and fracture callus. There was no difference between TGF-beta 1 and 2 expres.ion except the appearance time at epiphyseal plate. We could not draw any conclusion about ligand and rcceptor mechanism with this immunohistochemical staining.
Animals ; Bony Callus* ; Cartilage ; Femur ; Growth Plate* ; Ligands* ; Periosteum ; Rats ; Receptors, Artificial ; Transforming Growth Factor beta ; Transforming Growth Factor beta1

PURPOSE: The objective of this study was to characterize transdifferentiated lens epithelial cells analyzed by reverse transcription-polymerase chain reaction (RT-PCR) for the expression of mRNAs encoding growth factors, growth factor receptors and pathologic extracellular matrix proteins and by Western blot analysis for the proteins encoded by these mRNAs. Moreover, after antioxidants treatment, such as Nacetyl cysteine (NAC), we observed the effect on changes in the expression of growth factors, growth factor receptors and extracellular matrix proteins. METHODS: TGF-beta treated rat lens cultured with medium 199 (Sigma Co. St. Louis, MO) was subject to RT-PCR and Western blot analysis to assess expression of mRNAs and proteins encoded by these mRNAs. RESULTS: The expression of mRNAs for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta receptor, epidermal growth factor (EGF), epidermal growth factor receptor, fibroblast growth factor (FGF), fibroblast growth factor receptor and connective tissue growth factor (CTGF) were increased. The levels of type I collagen, fibronectin, and alpha-smooth muscle actin (SMA) mRNAs were also increased. However, the expression of growth factors, receptors, extracellular matrix were decreased by antioxidant, such as NAC. CONCLUSIONS: The enhanced expression of growth factors, growth factor receptors and extracellular matrix in present the molecular mechanism underlying pathogenesis of cataracts. And the suppression of growth factors and growth factor receptors with treatment of antioxidants, such as NAC, suggests the possibility of using drugs in the prevention or treatment of cataracts.
Actins ; Animals ; Antioxidants ; Blotting, Western ; Cataract ; Collagen Type I ; Connective Tissue Growth Factor ; Cysteine ; Epidermal Growth Factor ; Epithelial Cells ; Extracellular Matrix Proteins ; Extracellular Matrix* ; Fibroblast Growth Factors ; Fibronectins ; Intercellular Signaling Peptides and Proteins ; Rats* ; Receptor, Epidermal Growth Factor ; Receptors, Fibroblast Growth Factor ; Receptors, Growth Factor ; Receptors, Transforming Growth Factor beta ; RNA, Messenger ; Transforming Growth Factor beta

PURPOSE: The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). MATERIALS AND METHODS: A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). RESULTS: In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. CONCLUSION: High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.
Adenoids* ; Carcinoma, Adenoid Cystic* ; Disease-Free Survival ; Fibroblast Growth Factor 2 ; Humans ; Immunohistochemistry ; Medical Records ; Multivariate Analysis ; Nasal Cavity ; Prognosis ; Proto-Oncogenes ; Receptors, Fibroblast Growth Factor ; Receptors, Platelet-Derived Growth Factor ; Risk Factors ; Vascular Endothelial Growth Factor A*

BACKGROUND: Although it is well known that transforming growth factor beta (TGF-beta) may induce catagen change of hair follicles and inhibit hair growth, it is still unclear which subtype of TGF-beta and its specified receptor might be expressed in human hair follicles of androgenetic alopecia (AGA) patients. OBJECTIVE: To delineate precise expression of TGF-beta subtype in human hair follicles of androgenetic alopecia patients. METHODS: Immunohistochemical studies were performed on paraffin sections of human hair follicles by applying type 1, 2, and 3 TGF-beta antibodies and type I and II receptor antibodies. We ascertained the expression of TGF-beta subtype in hair follicles of androgenetic alopecia patients. We also compared the expression pattern of each type of TGF-beta receptor. We evaluated the change of TGF-beta expression of hair follicles in the catagen phase. RESULTS: TGF-beta1 was well-expressed in the outer area of the inner root sheath (IRS) or dermal connective sheath area. TGF-beta2 was commonly expressed in the inner 1/2 of the outer root sheath (ORS). TGF-beta3 was expressed in the hair cortex, IRS, and cuticle in normal hair follicles obtained from both the vertex and occipital area. On the contrary, in specimens from AGA, the enhanced expression of type 2 TGF-beta or type II receptor was observed in the vertex area (bald) compared to the occipital area (non bald). When the expression patterns of TGF-beta 1, 2, and 3 were compared between anagen and catagen phases, TGF-beta2 and 3 were positively expressed in the epithelial strands and secondary hair germs in the catagen phase. The immunoreactivities of TGF-beta 1 and 2 were intensified in the ORS areas of the catagen phase. CONCLUSION: The expression of type 1, 2 TGF-beta and type I and II receptors in follicular epithelial cells might be related to catagen induction and development of androgenetic alopecia of human hair in vivo.
Alopecia ; Antibodies ; Epithelial Cells ; Hair Follicle* ; Hair* ; Humans* ; Paraffin ; Receptors, Transforming Growth Factor beta ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.
Chungcheongnam-do ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Lymphangiogenesis ; Models, Animal ; Neoplasm Metastasis ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor D ; Vascular Endothelial Growth Factor Receptor-3

growth factor(EGF) and activation of its receptor(EGFR) are associated with progressive growth of SCCHN. Vascular endothelial growth factor(VEGF) signaling molecules are related with neoangiogenesis and vascular metastasis of SCC. In this study, we determined the therapeutic effect of AEE788(Novartis Pharma AG, Basel, Switzerland), which is a dual inhibitor of EGFR/ErbB2 and VEGFR tyrosine kinases, on human oral SCC. At first, we screened the expression of EGFR, c-ErbB2(HER-2) and VEGFR-2 in a series of human oral SCC cell lines. And then we evaluated the effects of AEE788 on the phosphorylation of EGFR and VEGFR-2 in a oral SCC cell line expressing EGFR/HER-2 and VEGFR-2. We also evaluated the effects of AEE788 alone, or with paclitaxel(Taxol) on the oral SCC cell growth and apoptosis. As a result, all oral SCC cells expressed EGFR and VEGFR-2. Treatment of oral SCC cells with AEE788 led to dose-dependent inhibition of EGFR and VEGFR-2 phosphorylation, growth inhibition, and induction of apoptosis. Moreover, AEE788 sensitizes the cells to paclitaxel-mediated toxicity and apoptosis. These data mean EGFR and VEGFR-2 can be reliable targets for molecular therapy of oral SCC, and therefore warrant clinical use of EGFR/VEGFR inhibition in the treatment of patients with recurrent or metastatic oral SCC.]]>
Apoptosis ; Carcinoma, Squamous Cell ; Cell Line ; Epidermal Growth Factor ; Head ; Humans ; Neoplasm Metastasis ; Phosphorylation ; Phosphotransferases ; Receptor, Epidermal Growth Factor ; Receptors, Vascular Endothelial Growth Factor ; Survival Rate ; Tyrosine ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2