Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGF...Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.展开更多
Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with...Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.展开更多
Background:Vacuum sealing drainage(VSD)and epidermal growth factor(EGF)both play an important role in the treatment of wounds.This study aims to explore the effects of the combination of VSD and EGF on wound healing a...Background:Vacuum sealing drainage(VSD)and epidermal growth factor(EGF)both play an important role in the treatment of wounds.This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.Methods:We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations(0,1,5,10,and 100ng/ml)and different EGF action times(2,10,and 30min).A full-thickness skin defect model was established using male,30-week-old Bama pigs.The experiment included groups as follows:routine dressing change after covering with sterile auxiliary material(Control),continuous negative pressure drainage of the wound(VSD),continuous negative pressure drainage of the wound and injection of EGF 10min followed by removal by continuous lavage(V+E 10min),and continuous negative pressure drainage of the wound and injection of EGF 30min followed by removal by continuous lavage(V+E 30min).The wound healing rate,histological repair effect and collagen deposition were compared among the four groups.Results:An EGF concentration of 10ng/ml and an action time of 10min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells.The drug dispersion effect was better than drug infusion after bolus injection effect,and the contact surface was wider.Compared with other groups,the V+E 10min group promoted wound healing to the greatest extent and obtained the best histological score.Conclusions:A recombinant human epidermal growth factor(rhEGF)concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro.VSD combined with rhEGF kept in place for 10min and then washed,can promote wound healing better than the other treatments in vitro.展开更多
Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was pe...Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was perfor-med on 120 unrelated patients with major depression and 46 control subjects.Blood was collected from all subjects for extraction of genomic DNA.Four single nucleotide polymorphisms(SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Results Mean scores of both score lang and score task,two subtests in WAIS,differed significantly between major depression patients and controls(P<0.0001).Quantitative trait analysis showed that the genetype of rs2250724 was closely associated with score lang and score task in major depression patients.The associations were still significant after 10 000 permutations.Conclusions Although preliminary,our results provide evidence for association between the EGF gene and intelligence in patients with major depression.Genetic variation in the EGF gene may increase the susceptibility of major depression.展开更多
To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was d...To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.展开更多
To evaluate the effects of epidermal growth factor (EGF) on intestinal permeability and bacterial translocation in rats with acute pancreatitis during total parenteral nutrition (TPN). Methods. Thirty- two male Spragu...To evaluate the effects of epidermal growth factor (EGF) on intestinal permeability and bacterial translocation in rats with acute pancreatitis during total parenteral nutrition (TPN). Methods. Thirty- two male Sprague- Dawley rats that underwent injection of 3.5％ sodium taurocholate solution into the pancreatic duct were randomly divided into one of the following two groups: (1) received only TPN (control group) or (2) received TPN with EGF at a dose of 0.2 mg· kg- 1· day- 1 (Egf group). On fifth day of total parenteral nutrition, samples from mesenteric lymph nodes, pancreas, liver and spleen were harvested for cultures. Water, protein and DNA content in jejunal mucosa were determined. D- xylose and fluorescein isothiocyanate (FITC)- dextran were instilled into the lumen of a ligated segament of small intestine. Thirty minutes later, superior mesenteric vein D- xylose and plasma FITC- dextran concentration were measured. Results. Positive cultures in liver and spleen, as well as FITC- dextran concentration in the Egf group were significantly lower than in the control group. Protein and DNA content in jejunal mucosa in the Egf group were significantly higher than in the control group. Conclusion. The results indicate that EGF may prevent increased intestinal permeability and bacterial translocation in rats with acute pancreatitis during TPN.展开更多
The human epidermal growth factor gene was synthesized with DNA synthesizer andby enzymes.Computer assisted to design the gene sequence and the restriction enzyme sites,andto elhninate the repeated and self-complement...The human epidermal growth factor gene was synthesized with DNA synthesizer andby enzymes.Computer assisted to design the gene sequence and the restriction enzyme sites,andto elhninate the repeated and self-complementary sequences.So that multiple doning and gene ex-pression were available for the designed gene sequence.The whole gene was formed by annealing8 chemically synthesized oligodeoxynucleotide fragments,enzymatically filling up the 4 twenty-basespaces and ligating the nicks,and was inserted into EcoR I and HInc Ⅱ sites ofplasmid pUC12.The recombinant plasmid was transformed into E.coli JM103 and 200 whitedones were obtained by X-gal and ampicilin screening.The positive clones were isolated andcharacterized by restriction enzyme analysis and DNA sequencing.展开更多
Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recom...Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recombinant human epidermal growth factors (rh-EGF) on porcine partial-thickness burn wound healing. Healing rates of the burn wounds were quantitated by computer image analysis of the wound Pkotographs. Biopsies were taken for examining the cell DNA cycle by flow cytometry, and for observing the keratinocyte migration and degree of reepithelialization quantitated by anti-keratin antibodies. The results indicated that daily topical application of rh-EGF in suitable concentrations accelerated epithelial healing of partial-thickness burn wounds, and there was also a dose-dependent effect of rh-EGF on healing rates of the partial-thickness burn wounds.展开更多
This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer p...This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.展开更多
基金Supported by National Natural Science Fund of China(31370920)Public Technology Research Program of Zhejiang Province(2014C33157)Medical and Health Research Project of Zhejiang Province(2014KYA225)
文摘Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.
文摘Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.
基金the National Natural Science Foundation of China(81972047,81603008,81572148).
文摘Background:Vacuum sealing drainage(VSD)and epidermal growth factor(EGF)both play an important role in the treatment of wounds.This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.Methods:We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations(0,1,5,10,and 100ng/ml)and different EGF action times(2,10,and 30min).A full-thickness skin defect model was established using male,30-week-old Bama pigs.The experiment included groups as follows:routine dressing change after covering with sterile auxiliary material(Control),continuous negative pressure drainage of the wound(VSD),continuous negative pressure drainage of the wound and injection of EGF 10min followed by removal by continuous lavage(V+E 10min),and continuous negative pressure drainage of the wound and injection of EGF 30min followed by removal by continuous lavage(V+E 30min).The wound healing rate,histological repair effect and collagen deposition were compared among the four groups.Results:An EGF concentration of 10ng/ml and an action time of 10min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells.The drug dispersion effect was better than drug infusion after bolus injection effect,and the contact surface was wider.Compared with other groups,the V+E 10min group promoted wound healing to the greatest extent and obtained the best histological score.Conclusions:A recombinant human epidermal growth factor(rhEGF)concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro.VSD combined with rhEGF kept in place for 10min and then washed,can promote wound healing better than the other treatments in vitro.
基金Supported by National High Technology Research and Development Program of China (863 Program) (2006AA02A407)National Basic Research Program of China (973 Program) (2010CB529603)Beijing Natural Science Foundation (7102109)
文摘Objective To study the association between the epidermal growth factor(EGF) gene and intelligence in patients with major depression.Methods Intelligence measurement using Wechsler Adult Intelligence Scale(WAIS) was perfor-med on 120 unrelated patients with major depression and 46 control subjects.Blood was collected from all subjects for extraction of genomic DNA.Four single nucleotide polymorphisms(SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Results Mean scores of both score lang and score task,two subtests in WAIS,differed significantly between major depression patients and controls(P<0.0001).Quantitative trait analysis showed that the genetype of rs2250724 was closely associated with score lang and score task in major depression patients.The associations were still significant after 10 000 permutations.Conclusions Although preliminary,our results provide evidence for association between the EGF gene and intelligence in patients with major depression.Genetic variation in the EGF gene may increase the susceptibility of major depression.
文摘To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.
文摘To evaluate the effects of epidermal growth factor (EGF) on intestinal permeability and bacterial translocation in rats with acute pancreatitis during total parenteral nutrition (TPN). Methods. Thirty- two male Sprague- Dawley rats that underwent injection of 3.5％ sodium taurocholate solution into the pancreatic duct were randomly divided into one of the following two groups: (1) received only TPN (control group) or (2) received TPN with EGF at a dose of 0.2 mg· kg- 1· day- 1 (Egf group). On fifth day of total parenteral nutrition, samples from mesenteric lymph nodes, pancreas, liver and spleen were harvested for cultures. Water, protein and DNA content in jejunal mucosa were determined. D- xylose and fluorescein isothiocyanate (FITC)- dextran were instilled into the lumen of a ligated segament of small intestine. Thirty minutes later, superior mesenteric vein D- xylose and plasma FITC- dextran concentration were measured. Results. Positive cultures in liver and spleen, as well as FITC- dextran concentration in the Egf group were significantly lower than in the control group. Protein and DNA content in jejunal mucosa in the Egf group were significantly higher than in the control group. Conclusion. The results indicate that EGF may prevent increased intestinal permeability and bacterial translocation in rats with acute pancreatitis during TPN.
文摘The human epidermal growth factor gene was synthesized with DNA synthesizer andby enzymes.Computer assisted to design the gene sequence and the restriction enzyme sites,andto elhninate the repeated and self-complementary sequences.So that multiple doning and gene ex-pression were available for the designed gene sequence.The whole gene was formed by annealing8 chemically synthesized oligodeoxynucleotide fragments,enzymatically filling up the 4 twenty-basespaces and ligating the nicks,and was inserted into EcoR I and HInc Ⅱ sites ofplasmid pUC12.The recombinant plasmid was transformed into E.coli JM103 and 200 whitedones were obtained by X-gal and ampicilin screening.The positive clones were isolated andcharacterized by restriction enzyme analysis and DNA sequencing.
文摘Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recombinant human epidermal growth factors (rh-EGF) on porcine partial-thickness burn wound healing. Healing rates of the burn wounds were quantitated by computer image analysis of the wound Pkotographs. Biopsies were taken for examining the cell DNA cycle by flow cytometry, and for observing the keratinocyte migration and degree of reepithelialization quantitated by anti-keratin antibodies. The results indicated that daily topical application of rh-EGF in suitable concentrations accelerated epithelial healing of partial-thickness burn wounds, and there was also a dose-dependent effect of rh-EGF on healing rates of the partial-thickness burn wounds.
基金supported by the Science and Technology Council,Taiwan,China(NSTC 112-2320-B-039-057 and MOST 111-2320-B-039-067-MY3)the China Medical University,Taiwan,China(CMU112-S-18),awarded to Yuan-Soon Ho+1 种基金the China Medical University,Taiwan,China(CMU112-N-02),awarded to Li-Ching Chenthe Science and Technology Council,Taiwan,China(MOST 110-2320B-039-079)。
文摘This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.
