Correlation Analysis of TAM Subfamily of Receptor Tyrosine Kinases in Ulcerative Colitis / 胃肠病学

Background: TAM receptors (Tyro3, Axl and Mertk), as subfamily of receptor tyrosine kinases, are intracellular negative feedback regulators and play a crucial role in regulating inflammation and immune response. Aims: To study the expressions and clinical value of TAM receptors in serum and intestinal mucosa of patients with ulcerative colitis (UC). Methods: Forty⁃five patients who were initially diagnosed as active UC from June, 2020 to May, 2021 at the First Affiliated Hospital of Kunming Medical University were enrolled prospectively. Fifteen healthy subjects were served as the control group. Eight cases each in moderate UC group and healthy control group were selected randomly for detection of TAM receptors in serum and intestinal mucosa by ELISA, real⁃time PCR and Western blotting. The correlations of serum Tyro3 with routine clinical indicators of UC were analyzed by Pearson correlation coefficient. Furthermore, immunohistochemistry was used to detect the expression level of TAM receptors in intestinal mucosa in all UC patients and the healthy controls. Results: Expressions of Axl and Mertk were not fully consistent in serum and intestinal mucosa in UC patients. While the serum Tyro3 level, as well as the intestinal Tyro3 mRNA and protein expressions were consistently increased in moderate UC patients than in controls (all P<0.05). Serum level of Tyro3 was positively correlated with platelet count and C⁃reactive protein, and negatively correlated with albumin in moderate UC patients (r=0.97, r=0.96, r=-0.86, all P<0.05). Positivity rate of Tyro3 in intestinal mucosa of UC patients was positively correlated with the disease severity (all P<0.05). Conclusions: Tyro3 is closely related to UC and positively correlated with the disease severity. It might be a promising novel molecular marker and therapeutic target of UC.

Cross-talk of GPCRs and RTKs and its effects on oncotherapy / 中国药理学通报

G protein-coupled receptors (GPCRs) are the largest cell surface receptor family, which mediates activities of almost all known cellular response to ligands, including hormones release, neurotransmitters and sensory input.GPCRs can promote development and progression of gastric cancer, colorectal cancer, lung cancer and breast cancer and other tumors.Tyrosine kinase receptors (RTKs) are another important family of membrane receptors, which can regulate cell proliferation, differentiation, migration and survival.Overexpression of RTKs has been found in many cancer cells.Therefore, GPCRs and RTKs are equally important in the clinical treatment of cancer therapeutic.However, GPCRs and RTKs are not independent, and they can use common signal transduction.The present study show that crosstalk between GPCRs and RTKs can facilitate migration of lung epithelial cells, increasing survival of nerve cells and promoting tumor occurrence and development.This article mainly focuses on crosstalk between GPCRs and RTKs and their roles in tumorigenesis and oncotherapy.

The research progress of neuregulin-1/ErbBs signaling in chronic heart failure / 中国药理学通报

Neuregulin-1 (NRG-1) and the ErbBs family of receptor tyrosine kinases are widely expressed in the cardiovascular system.NRG-1/ErbBs signaling plays an essential role in physiology and pathophysiology of the heart,including stabilization of cardiac myocyte structure and function,promotion of cardiac myocyte proliferation and survival,inhibition of cardiac myocyte apoptosis,reduction of myocardial interstitial fibrosis,regulation of energy utilization,and enhancement of angiogenesis and so on.Therefore,NRG-1/ErbBs signaling is involved in the development and treatment of chronic heart failure(CHF).In this review,we bring the growing literature on NRG-1/ErbBs signaling and its significance in cardiovascular development and heart failure.

Fibroblast Growth Factor Receptor 1 Overexpression Is Associated with Poor Survival in Patients with Resected Muscle Invasive Urothelial Carcinoma

PURPOSE: To examine the usefulness of various receptor tyrosine kinase expressions as prognostic markers and therapeutic targets in muscle invasive urothelial cancer (UC) patients. MATERIALS AND METHODS: We retrospectively analyzed the data of 98 patients with muscle invasive UC who underwent radical cystectomy between 2005 and 2010 in Yonsei Cancer Center. Using formalin fixed paraffin embedded tissues of primary tumors, immunohistochemical staining was done for human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 3 (FGFR3). RESULTS: There were 41 (41.8%), 44 (44.9%), and 14 (14.2%) patients who have over-expressed HER2, FGFR1, and FGFR3, respectively. In univariate analysis, significantly shorter median time to recurrence (TTR) (12.9 months vs. 49.0 months; p=0.008) and overall survival (OS) (22.3 months vs. 52.7 months; p=0.006) was found in patients with FGFR1 overexpression. By contrast, there was no difference in TTR or OS according to the HER2 and FGFR3 expression status. FGFR1 remained as a significant prognostic factor for OS with hazard ratio of 2.23 (95% confidence interval: 1.27-3.90, p=0.006) in multivariate analysis. CONCLUSION: Our result showed that FGFR1 expression, but not FGFR3, is an adverse prognostic factor in muscle invasive UC patients after radical cystectomy. FGFR1 might be feasible for prognosis prediction and a potential therapeutic target after thorough validation in muscle invasive UC.

Modulation of potassium channels by receptor tyrosine kinases: Recent progress / 第二军医大学学报

Receptor tyrosine kinase (RTK), a membrane receptor superfamily with intrinsic protein tyrosine kinase activity, has many members and complicated signal transduction pathways. Activation of RTKs can trigger a series of signal transduction pathways and play essential roles in modulating cell growth, proliferation, differentiation and metabolism through influencing gene transcription and expression. Activation of RTK can also rapidly modulate some cellular functions including the modulation of ion channels. Potassium channels play a critical role in stabilization of membrane potential and regulation of cellular excitability. This review highlights the rapid modulation of potassium channels by RTKs and reviews the recent progress in related research.

Nuclear calcium signaling: a cell within a cell

Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.

Advances in anti-tumor therapy targeting the EGFR family of receptor tyrosine kinases / 中国药理学通报

The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases have close connection with the initiation, progression and progn osis of various malignancies. Recently, several approaches such as monoclonal an tibodies, bispecific antibodies, low molecular weight tyrosine kinase inhibitors and gene therapy targeting the EGFR family of receptors for anti-tumor therapy have been developed, some of which are currently undergoing clinical trials. Th ey are generally well tolerated, and have shown encouraging clinical efficacy in a variety of tumor types.

Expression of FGF-R and TGF-R in the Lateral Wall of the Guinea Pig / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The endolymph produced from cochlear lateral wall regulates fluid balance and maintains positive endocochlear potentials. Although many immunohistochemical studies on ion transport enzymes have been reported, their mechanisms are still not completely understood. And there are no reports on the distribution of receptor tyrosine kinases in the cochlear lateral wall of the guinea pig. The purpose of this study is to evaluate the expression of the fibroblast growth factor receptor (FGFR) and transforming growth factor receptor-beta (TGFR-beta, type II) in the lateral wall of the guinea pig cochlea. MATERIALS AND METHODS: We investigated the immunohistochemical localization of the receptor tyrosine kinases (FGFR, TGFR-beta) in the lateral wall of the Preyer's positive, pigmented guinea pig. RESULTS: The results showed that receptor tyrosine kinases were expressed in the cytoplasm of the marginal cells, intermediate cells in the stria vascularis, and type II, III, IV, and V fibrocytes, but not the basal cells and type I fibrocytes, in the lateral wall of the guinea pig. CONCLUSION: The findings suggest that receptor tyrosine kinases are involved in the various ion transports and that they participate in the PLC-IP(3) second messenger system.

Expression of DDR1a in colon carcinoma cells and its relationship with matrix metalloproteinase 2,9 / 重庆医科大学学报

Objective:To investigate the expression of DDR1a and the activities of MMP2,MMP9 in colon carcinoma cells and their mutual relations.Methods:The expression of DDR1a in colon carcinoma cell and human colon smooth muscle cell was detected by Western blot,the activities of MMP2,MMP9 were examined by gelatin zymography analysis.Results:The expression of DDR1a and the activities of MMP2,MMP9 in colon carcinoma cell(LOVO)which has stronger invasive behavior were significant higher(P

Modulation of potassium channels by receptor tyrosine kinases:recent progress / 第二军医大学学报

Receptor tyrosine kinase(RTK),a membrane receptor superfamily with intrinsic protein tyrosine kinase activity,has many members and complicated signal transduction pathways.Activation of RTKs can trigger a series of signal transduction pathways and play essential roles in modulating cell growth,proliferation,differentiation and metabolism through influencing gene transcription and expression.Activation of RTK can also rapidly modulate some cellular functions including the modulation of ion channels.Potassium channels play a critical role in stabilization of membrane potential and regulation of cellular excitability.This review highlights the rapid modulation of potassium channels by RTKs and reviews the recent progress in related research.