Growth Factor Receptor
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2022 ◽  
Vol 42 (2) ◽  
pp. 141-149
Author(s):  
Saeam Shin ◽  
Hye In Woo ◽  
Jong-Won Kim ◽  
Yoonjung Kim M.D. ◽  
Kyung-A Lee

2021 ◽  
Vol 62 (1) ◽  
pp. 201-208
Author(s):  
Mirela Marcela Nichita ◽  
◽  
Călin Giurcăneanu ◽  
Mara Mădălina Mihai ◽  
Mihaela Ghigulescu ◽  
...  

2021 ◽  
Author(s):  
Kento Fukano ◽  
Mizuki Oshima ◽  
Senko Tsukuda ◽  
Hideki Aizaki ◽  
Mio Ohki ◽  
...  

Sodium taurocholate cotransporting polypeptide (NTCP) is a receptor that is essential for hepatitis B virus (HBV) entry into the host cell. A number of HBV entry inhibitors targeting NTCP have been reported to date; these inhibitors have facilitated a mechanistic analysis of the viral entry process. However, the mechanism of HBV internalization into host cells after interaction of virus with NTCP remains largely unknown. Recently, we reported that troglitazone, a thiazolidinedione derivative, specifically inhibits both HBV internalization and NTCP oligomerization, resulting in inhibition of HBV infection. Here, using troglitazone as a chemical probe to investigate entry process, the contribution of NTCP oligomerization to HBV internalization was evaluated. Using surface plasmon resonance and transporter kinetics, we found that troglitazone directly interacts with NTCP and non-competitively interferes with NTCP-mediated bile acid uptake, suggesting that troglitazone allosterically binds to NTCP, rather than to the bile acid-binding pocket. Additionally, alanine scanning mutagenesis showed that a mutation at phenylalanine 274 of NTCP (F274A) caused a loss of HBV susceptibility and disrupted both the oligomerization of NTCP and HBV internalization without affecting viral attachment to the cell surface. An inhibitor of the interaction between NTCP and epidermal growth factor receptor (EGFR), another host cofactor essential for HBV internalization, impeded NTCP oligomerization. Meanwhile, co-immunoprecipitation analysis revealed that neither troglitazone nor the F274A mutation in NTCP affect the NTCP-EGFR interaction. These findings suggest that NTCP oligomerization is initiated downstream of the NTCP-EGFR interaction, and then triggers HBV internalization. This study provides significant insight into the HBV entry mechanisms. Importance Hepatitis B virus (HBV) infection is mediated by a specific interaction with sodium taurocholate cotransporting polypeptide (NTCP), a viral entry receptor. Although the virus-receptor interactions are believed to trigger viral internalization into host cells, the exact molecular mechanisms of HBV internalization are not understood. In this study, we revealed the mode of action whereby troglitazone, a specific inhibitor of HBV internalization, impedes NTCP oligomerization, and identified NTCP phenylalanine 274 as a residue essential for this oligomerization. We further analyzed the association between NTCP oligomerization and HBV internalization, a process that is mediated by epidermal growth factor receptor (EGFR), another essential host cofactor for HBV internalization. Our study provides critical information on the mechanism of HBV entry, and suggests that oligomerization of the viral receptor serves as an attractive target for drug discovery.


2021 ◽  
pp. 107815522110422
Author(s):  
Hiroshi Sugimoto ◽  
Satoshi Matsumoto ◽  
Yukio Tsuji ◽  
Keisuke Sugimoto

Introduction Osimertinib is a tyrosine kinase inhibitor that targets the epidermal growth factor receptor. Elevated serum creatine kinase level is an uncommon adverse event associated with osimertinib treatment for lung cancer. Case Report We report a previously healthy 56-year-old woman who developed elevated serum creatine kinase levels during osimertinib monotherapy for epidermal growth factor receptor mutation-positive lung adenocarcinoma. Management & Outcome During treatment, she experienced leg cramps and her serum creatine kinase levels increased, peaking at 989 U/l. Further investigation revealed no evidence of cardiotoxicity or myositis; thus, osimertinib-induced myopathy was assumed to be the cause of her elevated serum creatine kinase levels. We successfully managed both lung cancer and osimertinib-induced myopathy using 1-week pauses of osimertinib therapy without dose reduction. Discussion Short-term suspension of osimertinib without dose reduction may be a reasonable option for osimertinib-induced myopathy.


Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1573
Author(s):  
Chun-Ting Lin ◽  
Ting-Hao Chen ◽  
Chen-Cheng Yang ◽  
Kuei-Hau Luo ◽  
Tzu-Hua Chen ◽  
...  

The results of many studies indicate that cadmium (Cd) exposure is harmful to humans, with the proximal tubule of the kidney being the main target of Cd accumulation and toxicity. Studies have also shown that Cd has the effect of activating the pathway of epidermal growth factor receptor (EGFR) signaling and cell growth. The EGFR is a family of transmembrane receptors, which are widely expressed in the human kidney. The aim of this study was to investigate the kidney function estimated glomerular filtration rate (eGFR), and its relationship with plasma Cd level and EGFR gene polymorphism. Using data from Academia Sinica Taiwan biobank, 489 subjects aged 30–70 years were analyzed. The demographic characteristics was determined from questionnaires, and biological sampling of urine and blood was determined from physical examination. Kidney function was assessed by the eGFR with CKD-EPI formula. Plasma Cd (ug/L) was measured by inductively coupled plasma mass spectrometry. A total of 97 single-nucleotide polymorphisms (SNPs) were identified in the EGFR on the Taiwan biobank chip, however 4 SNPs did not pass the quality control. Multiple regression analyses were performed to achieve the study aim. The mean (±SD) plasma Cd level of the study subjects was 0.02 (±0.008) ug/L. After adjusting for confounding variables, rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA types had higher eGFR (4.89 mL/min/1.73 m2 (p = 0.035), 5.54 mL/min/1.73 m2 (p = 0.03), 4.96 mL/min/1.73 m2 (p = 0.048) and 5.16 mL/min/1.73 m2 (p = 0.048), respectively). Plasma cadmium and rs845555 had an interactive effect on eGFR. In conclusion, EGFR polymorphisms could be modifiers of Cd kidney toxicity, in which rs13244925 AA, rs6948867 AA, rs35891645 TT and rs6593214 AA may be protective, and Cd interacting with rs845555 may affect kidney function.


The Breast ◽  
2021 ◽  
Vol 59 ◽  
pp. S49
Author(s):  
Hope S. Rugo ◽  
Fabrice André ◽  
Yeon Hee Park ◽  
Pamela Drullinsky ◽  
Sibylle Loibl ◽  
...  

2021 ◽  
pp. 174547
Author(s):  
Jun-Hei Chang ◽  
Chen-Chuan Cheng ◽  
Yen-Yu Lu ◽  
Cheng-Chih Chung ◽  
Yung-Hsin Yeh ◽  
...  

2021 ◽  
Vol Volume 14 ◽  
pp. 1291-1302
Author(s):  
Ji Eun Park ◽  
Mi Jeong Hong ◽  
Shin Yup Lee ◽  
Jang Hyuck Lee ◽  
Jin Eun Choi ◽  
...  

2021 ◽  
Vol 157 (8) ◽  
pp. 401-402
Author(s):  
Borja Arias-Peso ◽  
Álvaro Tello Fernández ◽  
Mohamed Bakkali el Bakkali

Author(s):  
Aprajita ◽  
Dr. Rinu Sharma

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