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Background and purpose: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is of advantage in treating non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, their clinical effects vary individually. This study aimed to evaluate whether the EGFR ligand, plasma transforming growth factor α (TGF-α), could act as a predictor for the EGFR-TKI treatment e?ciency in NSCLC patients with EGFR mutations and the association between TGF-α and prognosis in these patients. Methods: Seventy-five NSCLC patients with EGFR gene positive mutation were included in the current study from May 2012 to Jul. 2014 in Ruikang Hospital A?liated to Guangxi University of Chinese Medicine. Plasma TGF-α was measured using enzyme-linked immunosorbent assay (ELISA) in all of the patients before EGFR-TKI treatment. The radiographic evaluation was performed 2 months after the therapy. The association between TGF-α and clinical outcome and its prediction e?ciency were determined, followed by the further analysis of the association between TGF-α and overall survival (OS) as well as progression-free survival (PFS). Results: After EGFR-TKI treatment, there were 20 patients with partial response (PR), 25 with stable disease (SD) and 30 with progression disease (PD) in all 75 NSCLC patients harboring EGFR positive mutation. The disease control (DC) rate reached 60%. Patients in PD group presented statistically significant higher plasma TGF-αthan patients in the DC group (P<0.01). Multivariate COX model indicated that smoking status, lymph node metastasis and plasma TGF-α levels were independent risk factors for prognosis in these patients. The ROC analysis revealed that baseline plasma TGF-α showed good prediction e?ciency [area under the curve (AUC)=0.926] and the cut-off point of TGF-α was 16.75 pg/mL. Higher level of TGF-α (≥16.75 pg/mL) was associated with smoking history, clinical stage, lymph node metastasis and clinical outcome of the patients (P<0.05). In comparison to patients with low TGF-α, the patients with high TGF-α concentration presented significantly reduced median OS and PFS (log-rank P<0.05). Conclusion: Higher plasma TGF-α (≥16.75 pg/mL) had a predictive role in EGFR-TKI resistance and poor prognosis.
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AIM:To explore the effects of transforming growth factor-α( TGF-α) in the monoclonal formation , proliferation, migration and adhesiveness of human endothelial progenitor cells ( EPCs).METHODS: The isolated and cultured EPCs were treated with various concentrations of TGF-α(final concentrations of 1, 5, 10μg/L, respectively).At the same time, the PBS control and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) group (10μg/L TGF-αplus 1∶1 000 EGFR-TKI) were set.The effects of TGF-αon monoclonal formation , proliferation, migration and adhesiveness of EPCs were determined by clone formation experiment , thiazolyl blue tetrazolium bromide (MTT), EdU, Transwell and adhesion assays , respectively.The expression of epithelial growth receptor (EGFR) and vascular endothelial growth factor ( VEGF) were measured by Western blotting .RESULTS:Different concentrations of TGF-αall significantly induced the monoclonal formation , proliferation, migration and adhesiveness of EPCs (P<0.01), which were inhibited by EGFR-TKI.The results of Western blotting showed that TGF-αalso induced the expression of EGFR and VEGF with a cer-tain concentration effect ( P<0.01) .CONCLUSION:By combining with EGFR induced the expression of VEGF , TGF-αsignificantly promotes the related cell function of monoclonal formation , proliferation, migration, adhesiveness in EPCs.
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BACKGROUND:Cerebral vascular malformations are the leading cause of hemorrhagic apoplexy in young adults, and the rupture and bleeding of malformed vessels may cause severe neurological dysfunction. The mechanism of cerebral vascular malformations remains unclear. Modern molecular biology studies have shown that, angiogenic growth factors are abnormal y expressed in cerebral vascular malformations. OBJECTIVE:To evaluate differences in the expression of angiogenic growth factors in cerebral vascular malformations, and discuss the possible relationship between cerebral vascular malformations and angiogenic growth factors. METHODS:Fifty patients with cerebral vascular malformations and fifty patients with intracerebral hemorrhage were included in this study. The expressions of angiogenic growth factor (vascular endothelial growth factor and transforming growth factor-α) in the cerebral vascular malformation specimens and the normal superficial temporal artery specimens were detected with immunohistochemical staining. RESULTS AND CONCLUSION:In the normal superficial temporal artery of intracerebral hemorrhage patients, no expression of vascular endothelial growth factor and transforming growth factor-αwas found;in the vascular malformations, they were highly expressed (P<0.05). Compared with normal blood vessels, vascular endothelial growth factor and transforming growth factor-αexpression was significantly increased in patients with cerebral vascular malformations.
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BACKGROUND:Vascular endothelial growth factor and transforming growth factor play a crucial role in embryonic development, wound healing, inflammation, cancer, ischemic hypoxia and other physiological and pathological processes, and participate in the development and progression of brain damage. OBJECTIVE: To evaluate the differences in the expression of vascular endothelial growth factor and transforming growth factor-α during the early phase of cerebral aneurysm formation in rats. METHODS:Twenty-eight healthy Sprague-Dawley rats were randomized into three groups. Sham operation group (n=8): the left carotid artery bifurcation and bilateral renal artery were only exposed, without ligation, and rats were kiled that day. 15 days group (n=10) and 30 days group (n=10): the left common carotid artery, internal carotid artery, external carotid artery and bilateral renal artery were ligated, to establish aneurysm model, and rats were kiled at 15 and 30 days, respectively. The bilateral sides of the anterior cerebral artery/olfactory artery bifurcations were harvested and observed under light microscopy for pathological changes. Immunohistological staining was performed to detect the expression of vascular endothelial growth factor and transforming growth factor-α. RESULTS AND CONCLUSION:The results showed that, no aneurysm formed in the sham operation group and 15 days group. In the 30 days group, one saccular aneurysm and five early aneurysm-like changes were found in the right anterior cerebral artery/olfactory artery bifurcations. In the sham operation group and 15 days group, no vascular endothelial growth factor was expressed. In the 30 days group, the positive rate of vascular endothelial growth factor was up to 80%, indicating that vascular endothelial growth factor is possibly involved in the formation of aneurysm. Transforming growth factor-α expression in the sham operation group and 15 days group was more apparent than that in the 30 days group, indicating that transforming growth factor-α is damaged or secretion is reduced in this process, which was possibly related to the formation of aneurysm.
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Objective To explore the clinical significance of changes of plasma Endothelim-1(ET-1)and serum Transforming Growth Factor-α(TGF-α),Transforming Growth Factorβ1(TGF-β1)levels in patients with liver cirrhosis. Methods The plasma ET-1 and serum TGF-α,TGF-β1 levels were determined in 66 patients with liver cirrhosis by RIA or ELISA,among which 30 cases had abdominal fluid while the other 36 cases had not In addition,35 healthy individuals were enrolled into the study as control. Results The plasma ET-1 levels were significantly lower in the patients group than control(P ＜0.01),while the serum TGF-α and TGF-β1 levels were significantly higher in the patients than those in control(P ＜ 0.01). In cases with abdominal fluid the plasma ET-1 levels were particularly high and had significantly negative correlation with serum TGF-α and TGF-β1 levels(r = -0. 4782,-0. 5014 respectively,P ＜ 0. 01). Conclusions The plasma ET-1,serum TGF-α and TGF-β1 levels were closely related to the diseases process of liver cirrhosis and had good clinical application values in diagnosis and prognosis.
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Objective Nonsyndromic cleft lip with or without cleft palate(NSCL/P)is a common craniofacial birth defect which results in lifelong medical and social consequences.Although Asians have the highest birth prevalence of oral-facial clefts,the majority of gene mapping studies of cleft lip with or without cleft palate(CL/P)have been in European or Ameriean Caucasians.Therefore,the obiective of this study was to evaluate association between transforming growth factor alpha(TGF-α)gene BamH Ⅰ polymorphism and NSCL/P in Chinese.Methods 107 patients with NSCL/P and 136 healthy controls were examined for TGF-α/BamH Ⅰ genotypes.TGF-α/BamH Ⅰ typing was carried out by digesting the locus specific polymerase chain reaction amplified products with alleles specific BamH Ⅰ restriction enzyme(PCR-RELP).Resuits A1 allele frequency was 0.06 and A2 allele frequency was 0.94 in the controls.A1 allele frequency was 0.14 and A2 allele frequency was 0.86 in patients with NSCL/P(x2=8.27,df=1,P＜0.05).A1 allele frequency was 0.17 and A2 allele frequency was 0.83 in the bilateral cleft lip with or without cleft palate.A1 allele frequency was 0.13 and A2 allele frequency was 0.87 in the unilateral cleft lip with or without cleft palate(x2=0.36,df=1,P＞0.05).There was no statistically significant between the case with family history and the case without family history(x2=0.34,df=1,P＞0.05).Conclusions The above data demonstrate that there is evidence for the association of TGF-α polymorphism with development of NSCL/P in Chinese.
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AIM: To testify the special cytotoxicity of TGFa-SAP on proliferating vascular smooth muscle cells and endothelial cells. METHODS: Conjugation of saporin to TGFα was accomplished after derivatization of saporin and TGFα with N-succinimidyl-3 (2-pyridyldithio) proprionate. Cytotoxicity assays were measured by cell count. The studies of influence of TGFα-SAP on values of thymidine and leucine incorporation into SMCs and ECs were measured by 3H-thymidine uptake and 3H-leucine uptake, respectively. RESULTS: Cytotoxicity assays testified TGFα-SAP conjugate could inhibit remarkably proliferation of SMCs in culture. The values of thymidine of TGFα-SAP group (1 × 10-9 mol·L-1 and 1 × 10-7 mol·L-1) in comparison significantly decreased to 60.9% and 56.0% of the control group respectively, suggesting that cellular DNA synthesis obviously decreased as TGFα-SAP was added. But saporin did not affect cellular DNA synthesis at higher level. The rate of 3H-leucine incorporation of TGFα-SAP group significantly decreased to 47.3% of the control group, suggesting that SMCs protein synthesis obviously decreased as TGFα-SAP was added. But TGFαSAP at the same level did not affect DNA synthesis and protein synthesis of ECs compared with the control group. CONCLUSION: TGFα-SAP possesses the more effective cytotoxicity than saporin and the more specific citotoxicity on proliferating vascular smooth muscle cells than on proliferating endothelial cells.
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Objective:To assess the possible role of expression of TGFα and EGFR in nasal polyps and its re-lationship with PCNA labeling index. Method: Specimens from 20 patients of nasal polyps were studied with im-munohistochemical technique. Result: The expression of TGFα,EGFR and PCNA were increased in the epitheli-um, gland cells and inflammatory cells of nasal polyps. There was a close correlation between the intensities ofTGFα,EGFR and PCNA. Conclusion: TGFα may play a key role in epithelial cell proliferation in nasal polyps.
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The distribution of transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) in developing mouse embryos of gestational age 8 to 15 days was immunohistochemically (ABC method) studied to investigate the differential expression of these growth factors. Paraffin embedded sections were immunostained with antibodies for TGF-α and EGF. Staining of TGF-α was observed in several organs derived from endoderm, mesoderm and ectoderm in 9-day-old mouse embryos, such as in the heart, optic pit, head mesenchyme, neural tube and primitive gut, and the staining became more intense in 10 to 15-day-old mouse embryos. The staining of EGF was seen in the heart and primitive gut derived from mesoderm and ectoderm respectively, in 9-day-old mouse embryos, but it was observed in other organs as well in 10 to 15-day-old embryos although the intensity was weaker. In the development of heart, immunoreactivity for TGF-α was more intense than EGF, which suggests more active involvement of TGF-α. In the lung, TGF-α staining was observed both in the bronchus and lung bud, whereas EGF staining was seen only the bronchus. In the nervous system, TGF-α was expressed more extensively and more intensively than EGF. In the developing skeletal system, TGF-α staining was stronger and the expression was observed at earlier stage compared with EGF. These results indicate that the activity of TGF-α is more potent than EGF in the development of mouse embryo in general, especially, in the development of mouse heart, nervous system, mesenchyme and skeletal system.
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Animals , Mice , Antibodies , Bronchi , Ectoderm , Embryonic Structures , Endoderm , Epidermal Growth Factor , Gastrula , Gestational Age , Head , Heart , Intercellular Signaling Peptides and Proteins , Lung , Mesoderm , Nervous System , Neural Tube , ParaffinABSTRACT
BACKGROUND: Factors that regulate hair matrix cell division within the hair follicles and control hair growth cycle have been poorly understood untill now. One of the main.causes seems to be lack of good in vitro models. OBJECTIVE: This study was performed to investigate the hair growth promoting potencies of several agents including individual components of keratinocyte growth media. METHODS: Several agents such as epidermal growth factor, insulin, bovine pituitary extract which were contained in keratinocyte growth media as well as minoxidil and transforming growth factor-α were added to the isolated anagen hair follicles. Measuring the length of hair follicle, thymidine and leucine uptake were used for hair growth parameter. RESULTS: Isolated anagen hair follicles in keratinocyte growth media showed a significant increase in length over 48 hours. [Methyl-³H] thymidine and [U-¹⁴Cl leucine uptake were sustained at basal state as well as over 48 hours and [methyl-³H] thymidine uptake increased in the matrix cells under autoradiography. Insulin with a concentration above 0.5µg/ml and transforming growth factor-α with a concentration above 10ng/ml showed a promoting effect on hair growth. However, other agents did not promote hair growth at all. CONCLUSION: Our in vitro model resembles the in vivo status of hair growth for a limited period of time and we think that normal human hair organ culture may be a useful model for developing hair growth promoting agents in vitro.