OBJECTIVETo study the association of human epidermal growth factor receptor family molecules expression in gastric cancer tissues with the prognosis of patients with gastric cancer.

METHODSClinical data of 161 patients with gastric cancer undergoing gastrectomy in Jiangsu Cancer Hospital between January 2006 and January 2007 were analyzed retrospectively. The expression of HER1, HER2, HER3 and HER4 was detected by immunohistochemistry. Association of the expression of HER family with the prognosis of patients was examined. Kaplan-Meier method was used to analyze the survival.

RESULTSHigh expression rates of HER1, HER2, HER3 and HER4 were 46.0% (74/161), 10.6% (17/161),55.9% (90/161) and 68.3% (110/161) respectively. Univariate analysis revealed that high expression of HER3 was associated with tumor invasion depth, lymph node metastasis, stage, neurovascular invasion, and overall 4-year survival. High expression of HER4 was associated with tumor distant metastasis and stage. High co-expression of HER2 and HER3 was associated with overall 4-year survival (P=0.023). Multivariate analysis revealed that high expression of HER3 and stage were prognostic independent factors.

CONCLUSIONUp-regulated expression of HER3 is associated with the poor prognosis in gastric cancer patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Retrospective Studies ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVE: To explore expression of ErbB3 and ErbB4 genes in laryngeal squamous cell carcinomas and their relation with the biological and clinicopathological parameters. METHOD: Expression of ErbB3 and ErbB4 mRNA in 36 cases of laryngeal carcinomas and normal mucosa of incisal margin, 11 cases of benign proliferative lesions were examined by reverse transcription polymerase chain reaction (RT-PCR). RESULT: In laryngeal carcinomas and benign proliferative lesions, over-expressive positive ratios of ErbB3 were 66.7%, 18.2% respectively (P < 0.01). However, that of ErbB4 were 25.0%, 9.1% respectively (P > 0.05). Differences of expressive level of ErbB3 and ErbB4 were not significant between laryngeal carcinoma and normal mucous of incisal margin (P > 0.05). In addition, expressive level of ErbB3 and ErbB4 were not associated with diversity of clinical pathologic characters (P > 0.05). CONCLUSION ErbB3 and ErbB4 genes play different role in carcinogenesis and development, and relate to the reoccurrence of carcinoma.
Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; genetics ; Receptor, ErbB-3 ; genetics ; metabolism ; Receptor, ErbB-4

Neuregulin 4 (NRG4) is a kind of protein containing epidermal growth factor (EGF)-like domains, mainly expressed and secreted by brown adipocytes. It specifically activates EGF receptor ErbB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) to stimulate cell proliferation, inhibit apoptosis and improve energy metabolism of cells. Increasing evidence has shown that NRG4 plays an important role in epithelial cell-related diseases, cardiovascular diseases, tumors and glycolipid metabolic diseases, and therefore it could be a potential therapeutic target of some diseases.
Animals ; Apoptosis ; Cardiovascular Diseases ; Cell Proliferation ; Energy Metabolism ; Humans ; Metabolic Diseases ; Neoplasms ; Neuregulins ; physiology ; Receptor, ErbB-4 ; physiology ; Signal Transduction

OBJECTIVETo investigate the changes of ErbB receptors mRNA expression in left ventricle of myocardial infarction and its mechanism.

METHODSMyocardial infarction was induced by ligation of the left anterior descending coronary artery in male Sprague Dawley(SD) rats. After 1 month, the rats were sacrificed and mRNA was extracted from the left ventricle. mRNA was also extracted from ventricular myocytes of neonatal SD rats which were cultured under serum deprivation and hypoxia for 5 d. Expression of ErbB receptors mRNA were detected by real-time quantitative PCR.

RESULTThe mRNA expression of ErbB2 and ErbB4 receptors was significantly down-regulated in the left ventricle of myocardial infarction compared with the normal left ventricle; in contrast, there were no changes in mRNA expression of ErbB3. Serum deprivation and hypoxia in vitro caused significant down-regulation of the mRNA expression of ErbB2 and ErbB4 receptors, but the mRNA expression of ErbB3 was not changed.

CONCLUSIONExpression of ErbB2 and ErbB4 receptors mRNA is down-regulated in myocardial infarction, which may results from the hypoxia, deprivation of nutrients and cytokines.

Animals ; Animals, Newborn ; Cells, Cultured ; Down-Regulation ; Glycoproteins ; metabolism ; Heart Ventricles ; metabolism ; Myocardial Infarction ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; Receptor, ErbB-4

OBJECTIVETo study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.

METHODSTAM was used to induce wild-type MCF-7 human breast cancer cell line and establish a tamoxifen-resistant (TAM-R) cell line. RT-PCR, Western blot and immuocytochemical techniques were used to detect and compare mRNA and protein of c-erbB1, cerbB2, c-erbB3, c-erbB4 in wild-type MCF-7 and TAM-R MCF-7 cell lines.

RESULTSCompared with wild-type MCF-7 cells, the mRNA of c-erbB1 increased 6 times (P < 0.05) and the protein 3 times higher (P < 0.05), and the mRNA of c-erbB2 increased 3 times (P < 0.05) and the protein 1.5 times higher (P < 0.05) in TAM-R MCF-7 cells. However, comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. c-erbB4 could not be detected. Under basic conditions, phosphorylated c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased level of phosphorylated MAPK.

CONCLUSIONOur findings demonstrated that the development of TAM-resistance in MCF-7 cells is related with the autocrine release and action of an c-erbB1-specific ligand inducing preferential c-erbB1/c-erbB2 dimerization and downstream activation of the MAPK pathway.

Antineoplastic Agents, Hormonal ; pharmacology ; Blotting, Western ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Immunohistochemistry ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphorylation ; drug effects ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, Epidermal Growth Factor ; biosynthesis ; genetics ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Receptor, ErbB-3 ; biosynthesis ; genetics ; Receptor, ErbB-4 ; Reverse Transcriptase Polymerase Chain Reaction ; Tamoxifen ; pharmacology

OBJECTIVETo investigate the role of miR-520a in regulation ErbB4 expression and the biological behavior of esophageal squamous cell carcinoma (ESCC).

METHODSThe role of miR-520a in regulating the expression of ErbB4 was investigated by Western blotting and luciferase reporter assay system. The effect of miR-520a on the proliferation and invasion of ESCC cells was detected by MTT and Transwell invasion assay, respectively.

RESULTSWestern blotting and luciferase reporter assay revealed that miR-520a down-regulated the expression of ErbB4 in vitro. miR-520a significantly inhibited the proliferation and suppressed the invasion of ESCC cell line Eca109.

CONCLUSIONmiR-520a regulates the expression of ErbB4 and suppresses the proliferation and invasion of ESCC cells in vitro, suggesting its role as a tumor suppressor.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Esophageal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; metabolism ; Receptor, ErbB-4 ; metabolism

OBJECTIVETo study the changes in endogenous neuregulin-1 (Nrg1) expression in the anterior pituitary of female Wistar-Furth rats in different phases of the estrous cycle.

METHODSFemale Wistar-Furth rats during estrous cycles were used. RT-PCR was employed to study the changes in the expression of Nrg1 isoforms and their cognate receptors ErbB-2 and ErbB-4 in the anterior pituitary in different phases of the estrous cycle. Western blotting was used to detect Nrg1 expression at the protein level. Immunofluorescence staining was used to identify hypophyseal cells expressing Nrg1 and observe the localization and distribution of Nrg1 and functional phosphorylation of ErbB-4. The co-expression of Nrg1 and ErbB-4 in the anterior pituitary of Rhesus monkey was also investigated.

RESULTSSome of the Nrg1 isoforms, especially type III Nrg1s, were expressed at a higher level during the estrous cycle I (E1) and estrous cycle II (E2), a result consistent with that of Western blotting for samples of the anterior pituitaries collected at these phases. Immunofluorescence staining identified the gonadotrophs as the main source of Nrg1, and showed an extensive distribution of Nrg1 in the anterior pituitary in E1 and E2 phases accompanied by apparent phosphorylated activation of ErbB-4. Adjacent distribution of Nrg1- and ErbB-4-positive cells was also observed in the anterior pituitary of male Rhesus monkeys.

CONCLUSIONOur results provide evidence for the expression of multiple Nrg1 isoforms and the presence of Nrg1/ErbB-4 signaling in the anterior pituitary of female Wistar-Furth rats. This signaling demonstrates an estrous cycle phase-related pattern. Additionally, Nrg1/ErbB-4-based juxtacrine signaling may exist in the anterior pituitary of male non-human primate.

Animals ; Estrous Cycle ; physiology ; Female ; Macaca mulatta ; Male ; Neuregulin-1 ; metabolism ; Phosphorylation ; Pituitary Gland ; metabolism ; Protein Isoforms ; metabolism ; Rats ; Rats, Inbred WF ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-4

OBJECTIVEThe aim of this study was to explore the expression of erbBs in U937, an acute monocyte leukemia cell line, and their impact on the growth of this cell line.

METHODSExpression of erbBs was detected by RT-PCR and expression of erbB2 at protein level by Western blot. After U937 cells was treated with EKI-785, an irreversible specific inhibitor of erbBs, the growth was assessed by MTT and growth curve, apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit, and signal pathway was detected by Western blot.

RESULTSerbB2-4 were expressed in U937 cell line, but not erbB1. Especially, protein of erbB2 was expressed in this cell line. After treating with EKI-785, the growth of U937 cells was inhibited and early apoptosis was induced. Moreover, the Ras/MAPK and the PI3K/Akt signaling pathways were all blocked.

CONCLUSIONerbBs may play key roles in the development of some leukemia. Therefore, erbBs may become new targets of treatment to leukemia, and EKI-785 has a potency of clinic use to leukemia.

Apoptosis ; drug effects ; Blotting, Western ; Cell Proliferation ; drug effects ; Female ; Humans ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinazolines ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, Epidermal Growth Factor ; biosynthesis ; genetics ; Receptor, ErbB-2 ; antagonists & inhibitors ; biosynthesis ; genetics ; Receptor, ErbB-4 ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; U937 Cells

The introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors has revolutionized the clinical management paradigm of hormone receptor (HR) positive/human epidermal growth factor receptor (HER) 2 negative breast cancer. As of today, CDK 4/6 inhibitors including Palbociclib, Ribociclib, and Abemaciclib have been widely approved by regulatory agencies. Randomized clinical trials demonstrated that CDK 4/6 inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant in the first-, second- or later-line setting for HR positive/HER2 negative locally advanced or metastatic breast cancer led to substantial reduction in the risk of disease progression or death. Adverse effects of treatment were manageable and as or better than expected in terms of patient satisfaction. Considering CDK4/6 inhibitors in combination with endocrine therapy being a novel approach in China clinical practice, the panel developed the consensus comprehensively describing the pharmacology properties, monitoring strategy during treatment and adverse events management, to facilitate greater understanding in Chinese oncologists of a whole new therapeutic class of drug, promote accuracy of clinical decision and help reach the ultimate goal of improving survival and quality of life of the target patient population.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Breast Neoplasms/drug therapy* ; China ; Consensus ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinase 6 ; Humans ; Protein Kinase Inhibitors/therapeutic use* ; Quality of Life ; Receptor, ErbB-2

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have led transformative breakthrough of clinical therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. CDK4/6 inhibitors that have been marketed in China include Ribociclib, Palbociclib, Abemaciclib and Dalpiciclib. For HR-positive HER-2-negative locally advanced and metastatic breast cancer, CDK4/6 inhibitors combined with endocrine therapy have become standard regimen, which can prolong the survival of patients. In the adjuvant treatment stage of early breast cancer, CDK4/6 inhibitors have also achieved positive results and been approved for indications. At present, CDK4/6 inhibitors have been widely used in clinical practice in China. In order to further improve the standardized application of CDK4/6 inhibitors in China, the Breast Cancer Expert Committee of the National Center for Cancer Quality Control and the Professional Committee of Clinical Research of Cancer Drugs of the Chinese Anti-Cancer Association organized the related expert to update the consensus based on the "CDK4/6 inhibitor consensus on clinical application of in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer (2021 edition)" . The updated consensus systematically introduces the pharmacological characteristics, drug monitoring and adverse event management, etc., of CDK4/6 inhibitors to promote the accuracy of clinical decision-making with the ultimate goal to prolong the overall survival of patients and improve the quality of life.
Humans ; Female ; Breast Neoplasms/pathology* ; Quality of Life ; Consensus ; Triple Negative Breast Neoplasms/drug therapy* ; Receptor, ErbB-2/metabolism* ; Protein Kinase Inhibitors ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclin-Dependent Kinase 4/metabolism*