ObjectiveTo summarize the correlation between human epidermal growth factor receptor 2 (HER2) gene expression and the efficacy of targeted therapy for patients with HER2-positive breast cancer, and to summarize the new progress in the study of HER2 gene copy number. MethodThe relevant literatures on researches of targeted therapy effectiveness for patients with HER2-positive breast cancer were retrieved and reviewed. ResultsHER2 gene copy number and HER2/centromere on chromosome 17 (CEP17) ratio were related to the prognosis of patients with HER2-positive breast cancer, and circulating tumor DNA sequencing was expected to be a predictive indicator of targeted therapy effectiveness. ConclusionHigher copy number of HER2 gene might be associated with a better prognosis of HER2-positive breast cancer, and HER2/CEP17 ratio and circulating tumour DNA are of some significances in evaluating treatment response of trastuzumab for patients with HER2-positive breast cancer.
OBJECTIVE: To investigate the efficiency of recombinant human epidermal growth factor (rhEGF) on burn wound healing and to explore the effective density of the ointments. METHODS: A total of 120 cases of burn in superficial II degree and profound II degree were randomly divided into 2 groups. In the first group of 15 cases of superficial II degree, the wounds were treated by rhEGF ointments of different density, 0.5 microgram/g, 10 micrograms/g and 50 micrograms/g, to screen out the effective density. And in the other 105 cases of the second group, optimal density of the ointments based on the result of the first group were employed to treat the burn wound in superficial II degree and profound II degree, with the self-corresponding wounds of the same degree as control, to study the efficiency of rhEGF on wound healing, according to the wound healing time, and adverse reaction of the ointment. RESULTS: In the first group, the average healing time of superficial II wound treated by ointments of 10 micrograms/g and 50 micrograms/g significantly shortened when compared with that treated by ointments of 0.5 microgram/g(P lt; 0.01), but there was no obvious difference between the cases treated by ointments of 10 micrograms/g and 50 micrograms/g. In the second group, the healing time of superficial II wound treated by ointments of 10 micrograms/g was (8.39 +/- 2.25) days, (9.52 +/- 2.56) days in the control (P lt; 0.01); and healing time of profound II burn treated by ointments of 10 micrograms/g was (16.80 +/- 2.99) days, (18.27 +/- 3.17) days in the control (P lt; 0.01). And healing rates of burn wound at different periods were higher than those of the control. CONCLUSION: The above results indicate that rhEGF ointments can enhance burn wound healing significantly, and the ointment of 10 micrograms/g is a good choice for clinical application.
ObjectiveTo analyze the clinicopathologic characteristics and prognosis of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with different expression status of estrogen receptor (ER). MethodsThe patients with HER2-negative breast cancer met the inclusion and exclusion criteria and were treated in the Affiliated Hospital of Southwest Medical University from January 1, 2017 to December 31, 2019 were retrospectively collected, and then were assigned into 3 groups according to the ER expression status: ER-negative (ER expression positive rate <1%) group, ER-low expression (ER expression positive rate 1%–10%) group, and ER expression positive rate >10% group. The differences of clinicopathologic characteristics, therapy, and prognosis among the 3 groups were compared. And the risk factors affecting recurrence and metastasis of patients with ER-low expression were analyzed by Cox proportional hazards regression model. ResultsA total of 610 patients with HER2-negative breast cancer were included in this study, including 130 patients in the ER-negative group, 48 patients in the ER-low expression group, and 432 patients in the ER expression positive rate >10% group. The Bonferroni method was used to correct the test level after pairwise comparison, it was found that the histological grade was later (P<0.001, P=0.023) and the Ki-67 expression was higher (P<0.001, P=0.023) in the ER-negative group and ER-low expression group as compared with the ER expression positive rate >10% group; The proportion of the patients receiving chemotherapy in the ER-negative group was higher than that of the ER expression positive rate >10% group (χ2=10.310, P=0.001), while which had no statistical difference between the ER-low expression group and the ER-negative group or the ER expression positive rate >10% group (Fisher exact probability method, P=1.000; χ2= 3.585, P=0.058); The proportion of patients receiving endocrine therapy in the ER-low expression group was higher than that in the ER-negative group (χ2=36.333, P<0.001) and lower than the ER expression positive rate >10% group (χ2=246.996, P<0.001). The difference in disease-free survival (DFS) curves among 3 groups was statistically significant (χ2=46.805, P<0.001); There were no statistical differences in the overall survival (OS) curve and DFS curve between the ER-negative group and the ER-low expression group (Two stage test, P=0.786; χ2=1.141, P=0.286), and which in the ER expression positive rate >10% group were significantly better than thoses in the ER-negative group (χ2=10.137, P=0.001; χ2=39.344, P<0.001) and the ER-low expression group (χ2=4.075, P=0.044; χ2=31.911, P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that N1 and N2 [N0 as reference: RR (95%CI)=7.740 (1.939, 30.897), P=0.004; RR (95%CI)=9.513 (1.990, 45.478), P=0.005) and T3 [T1 as reference: RR (95%CI)=27.357 (2.188, 342.041), P=0.010] increased the probabilities of recurrence and metastasis HER2-negative breast cancer patients with ER-low expression. ConclusionsAccording to results of this study, patients with HER2-negative breast cancer showed certain differences in histological grade and Ki-67 expression among patients with three different ER expression status, but no statistical difference is found between ER-low expression and ER-negative breast cancer, and the prognoses of both are worse than that of ER expression positive rate >10% breast cancer patients. Lymph node metastasis and larger tumor are risk factors affecting recurrence and metastasis in ER-low expression breast cancer patients.
ObjectiveTo investigate the most appropriate culture time with the action of EGF in colon cancer stem cells enrichment by suspension culture.MethodsDLD-1 cells were cultured in serum-free medium containing 20 ng/mL EGF to generate spheroid cells. The time gradient was set to 10 d, 20 d, 30 d and 40 d, the cell proportion of CD133+, CD44+ and CD133+CD44+ were confirmed by flow cytometery. The ability of self-renewal was detected by the sphere forming assay and the limited dilution assay, and the in vitro tumorigenicity of the cells was detected by the colony formation assay.ResultsIn the 30 d group, the proportion of CD133+ and CD133+ CD44+ cells were significantly higher than those in the other groups (allP<0.05), the CD44+ cell was higher than that in the 20 d group (P<0.05), but there was no significant difference with the other two groups (P>0.05). The results of the limited dilution assay and the colony formation assay, the number of spheres in the 30 d or 40 d group was the highest among the 4 groups, and there was no statistical difference between the 30 d group and 40 d group (P>0.05), with statistically significant difference between the 30 d, 10 d and 20 d groups (all P<0.05). The results of the sphere forming assay and the self-renewal ability of 30 d group was significantly higher compared with other groups (all P< 0.05).ConclusionThe cancer stem cells could be enriched more efficiently by suspension culture using 20 ng/mL EGF for 30 days.
Objective To investigate the clinicopathological characteristics of HER2 protein expression in different degrees in human epidermal growth factor receptor 2 (HER2) negative breast cancer and the factors related to the efficacy of neoadjuvant chemotherapy in breast cancer with low HER2 expression. Methods The clinicopathological data of 161 patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in the Department of Breast Surgery, Affiliated Hospital of Southwest Medical University from March 2019 to March 2022 were retrospectively collected. The difference of clinical and pathological characteristics of patients with different levels of HER2 protein expression were analyzed, and the factors influencing the pathological complete remission (pCR) rate of breast cancer patients with low HER2 expression after neoadjuvant chemotherapy with unconditional logistic regression model were analyzed. Results Among 161 HER2 negative breast cancer patients, 108 cases were low HER2 expression, accounting for 67.1%. Compared with those with zero expression of HER2 [immunohistochemistry (IHC) 0], the patients with low HER2 expression had higher axillary lymph node metastasis rate (P=0.048), lower histological grade (P=0.006), and higher proportion of positive hormone receptor expression (P<0.001). There was no significant difference in pCR rate among the HER2 IHC 0, IHC 1+ and IHC 2+ / in situ hybridization (ISH)– (P=0.099) , and the pCR rate of low expression of HER2 was lower than that of zero expression of HER2 in the general population and Luminal subgroup, and the difference was statistically significant (P<0.05). There was no significant difference in triple negative breast cancer subgroup (P=0.814). The logistic regression analysis showed that age, histological grade and estrogen receptor expression status were independent influencing factors for pCR rate after neoadjuvant chemotherapy with low HER2 expression (P<0.05). Conclusions Different degrees of HER2 protein expressions in patients with HER2-negative breast cancer have unique clinicopathological characteristics. The pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer is lower than that in patients with zero HER2-expression breast cancer. Age, histological grade and estrogen receptor expression status are independent factors influencing the pCR rate of neoadjuvant chemotherapy in patients with low HER2-expression breast cancer.
Objective To explore the effect of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and the combination of bFGF and EGF in the neural differentiation of human bone marrow mesenchymal stem cells (hBMSCs), and the role of Wnt/β-catenin signaling pathway in this process. MethodsThe identified 4th-generation hBMSCs were divided into five groups according to different induction conditions, namely control group (group A), EGF induction group (group B), bFGF induction group (group C), EGF and bFGF combined induction group (group D), and EGF, bFGF, and Dickkopf-related protein 1 (DKK-1) combined induction group (group E). After 7 days of continuous induction, the cell morphology was observed by inverted fluorescence phase contrast microscopy, levels of genes that were related to neural cells [Nestin, neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP-2), and glial fibrillary acidic protein (GFAP)] and key components of the Wnt/β-catenin signaling pathway (β-catenin and Cyclin D1) were detected by RT-PCR, and the levels of proteins that were related to neural cells (Nestin and GFAP) as well as genes that were involved in Wnt/β-catenin signaling pathway [β-catenin, phosphorylation β-catenin (P-β-catenin), Cytoplasmic β-catenin, and Nuclear β-catenin] were explored by cellular immunofluorescence staining and Western blot. ResultsWhen compared to groups A and B, the typical neuro-like cell changes were observed in groups C-E, and most obviously in group D. RT-PCR showed that the relative expressions of Nestin, NSE, and MAP-2 genes in groups C-E, the relative expressions of GFAP gene in groups D and E, the relative expression of NSE gene in group B, the relative expressions of β-catenin gene in groups C and D, and the relative expressions of Cyclin D1 gene in groups B-D significantly increased when compared with group A (P<0.05). Compared with group E, the relative expressions of Nestin, NSE, MAP-2, GFAP, β-catenin, and CyclinD1 genes significantly increased in group D (P<0.05); compared with group C, the relative expression of Nestin gene in group D significantly decreased (P<0.05), while NSE, MAP-2, and GFAP genes significantly increased (P<0.05). The cellular immunofluorescence staining showed that the ratio of NSE- and GFAP-positive cells significantly increased in groups C-E than in group A, in group D than in groups C and E (P<0.05). Western blot assay showed that the relative expression of NSE protein was significantly higher in groups C and D than in group A and in group D than in groups C and E (P<0.05). In addition, the relative expression of GFAP protein was significantly higher in groups C-E than in group A and in group D than in group E (P<0.05). Besides, the relative expressions of β-catenin, Cytoplasmic β-catenin, Nuclear β-catenin, and the ratio of Nuclear β-catenin to Cytoplasmic β-catenin were significantly higher in groups C and D than in group A and in group D than in group E (P<0.05), whereas the relative expression of P-β-catenin protein was significantly lower in groups C and D than in group A and in group D than in group E (P<0.05). Conclusion Different from EGF, bFGF can induce neural differentiation of hBMSCs. In addition, EGF can enhance the hBMSCs neural differentiation of bFGF, while the Wnt/β-catenin signaling pathway may play a positive regulatory role in these processes.
Objective To investigate the effect of topical external administration of recombinant human epidermal growth factor (rhEGF) when controll ing blood sugar on expression of epidermal growth factor receptor (EGFR) and EGFR mRNA of wound in diabetes mell itus (DM) combined with scald. Methods A total of 136 male Wistar rats weighing (188.57 ± 6.59) g were randamly divided into 4 groups (groups A, B, C, and D, n=34). The rats was made DM model by intraperitoneal injected 60 mg/kg streptozocin in groups A, B, and C; rats were injected buffer alone in group D as control group. After 8 weeks, the rats of 4 groups were placed in 80℃ hot water for 6 seconds for preparation of the back deep II degree scald model. In group A, the blood sugar level was controlled at the level of group D 1 week before scald model; within 24 hours after models preparation, rhEGF was sprayed on wound at 150 U/cm2 . In group B, the rats were given the same treatment as group A except not controll ing blood sugar. In group C, the blood sugar was controlled as group A and wound was suture fixation with 1% silver sulfadiazine cream at 24 hours after the model. In group D, the same treatment as group A was given after injury. The heal ing rate of the wound was detected at 3, 7, 11, 15, and 21 days after injury; the EGFR mRNA expression was determined by mRNA hybridization in situ, and the EGFR protein expression was deterimined by immunohistochemistry and Western blot at 1, 3, 5, 7, 11, 15, and 21 days. Results? All the rats survived at the end of experiment. There was no significant difference in the heal ing rate of the wound among the 4 groups at 3 days (P gt; 0.05). The heal ing rate of the wound was significantly higher in groups A and D than in groups B and C (P lt; 0.05) at 7, 11, 15, and 21 days. The expession of EGFR mRNA in 4 groups was observed by hybridization in situ, which mainly distributed in the dermal fibroblasts, capillary endothel ial cells and remnants of skin and wound edge epithel ium of the subsidiary; the expessions reached the peak at 5 days in group A, at 7 days in groups B and C, and at 11 days in group D; and the peak level was significantly higher in groups A and D than in groups B and C (P lt; 0.05). Immunohistochemistry and Western blot showed that the expession of EGFR protein was observed in 4 groups and reached the peak level at 7 days in groups A and B, and at 11 days in groups C and D; showing significant difference between groups B, C and groups A, D (P lt; 0.05). Conclusion External appl ication of rhEGF when controll ing blood sugar can accelerate obviously the wound heal ing in DM combined with scald. After controll ing blood sugar, external appl ication of rhEGF can boost obviously the expressions of EGFR mRNA, EGFR, and the extending process of signal conduction.
OBJECTIVE To observe the effect of recombinant human epidermal growth factor (rhEGF) on healing of chronic ulcer wound. METHODS From January 1999 to January 2001, twenty-six patients with chronic wounds were adopted in this study. Among them, there were 17 males and 9 females, aged from 12 to 61 years. The area of the chronic wound varied from 3 cm x 3 cm to 5 cm x 8 cm and the disease course was 7 to 16 days. These patients were treated with rhEGF in the way of sprinkling locally (400 U/10 cm2). Another 26 patients with chronic wounds were adopted as the control group and were treated with 0.9% saline in the same way. The healing time of wounds and the local and systemic reactions of patients were observed. RESULTS The healing time of chronic wounds was shorter obviously to about 7 days with rhEGF than that of the control group and there was significant difference between the two groups(P lt; 0.01). CONCLUSION rhEGF can obviously promote the healing of chronic ulcer wound.
ObjectiveTo systematically evaluate the correlation of amplification of human epidermal growth factor receptor 2 (HER2) with the clinicopathological characteristics and prognosis of colorectal cancer patients.MethodsPubMed, EMbase, Cochrane Library, Chinese Biomedical Literature Database (CBM), Wanfang, and other databases were searched, and cohort studies focused on the relationship between HER2 amplification and clinicopathological characteristics and prognosis of colorectal cancer patients were included. The retrieval time limit was from October 2020, and RevMan 5.4 software was used for meta-analysis.ResultsA total of 9 studies (11 cohorts) were included for meta-analysis of 7 209 patients with colorectal cancer. Results of the meta-analysis showed that HER2 amplification was not associated with overall survival [HR=1.10, 95%CI (0.98, 1.24), P=0.11]. HER2 amplification was not correlated with gender [OR=0.98, 95%C1 (0.74, 1.31), P=0.90] and tumor differentiation [OR=0.80, 95%C1 (0.49, 1.32), P=0.39], but correlated with the tumor location [OR=1.85, 95%C1 (1.01, 3.37), P=0.04], RAS wild-type gene [OR=6.36, 95%C1 (3.41, 11.87), P<0.000 01], TNM stage [OR=0.45, 95%C1 (0.32, 0.64), P<0.000 01], lymph node metastasis [OR=1.54, 95%C1 (1.12, 2.13), P=0.008], and the depth of tumor invasion [OR=0.17, 95%C1 (0.05, 0.55), P=0.003].ConclusionCurrent evidence shows that HER2 amplification is not associated with OS in patients with colorectal cancer, but associated with tumor infiltration, lymph node metastasis, TNM stage, tumor site, and RAS genotype.
ObjectiveTo evaluate the effect of heparin binding epidermal growth factor-like growth factor (HB-EGF) on liver regeneration after partial orthotopic liver transplantation. MethodsFourty SD rats were used to establish the model of partial orthotopic liver transplantation with ameliorated two-cuff technique. Then all the rats were divided into 2 groups: experiment group and control group. Twenty rats of experiment group were administered 500 μg/kg HBEGF via vena caudalis immediately after operation twice a day, while the same volume of saline was administered to the rats in control group. Five rats in each group were selected randomly and killed at the 6th hour, day 2, 4 and 7 after operation, respectively. The serum levels of albumin (Alb) and alanine aminotransferase (ALT) in the blood sample were detected. Every liver was removed and weighed. The expression of Ki67 was detected by using immunohistochemistry assay. The regeneration activity of hepatocytes was evaluated by flow cytometry. ResultsThe wet weights of liver in experiment group were all significantly higher than that in control group at the 6th hour, day 2 and 4 after transplantation (P＜0.05). The serum levels of ALT were significantly lower in experiment group than those in control group at the 6th hour, day 2， 4, 7 after operation (P＜0.05), while the levels of Alb were significantly higher on day 4 and 7. The proliferating index and Ki-67 labeling index of graft in experiment group were higher than those in control group on day 2 and 4 after transplantation （2 d: P＜0.01; 4 d: P＜0.05）. ConclusionHBEGF could promote the regeneration of rat hepatocytes after partial liver transplantation.