Angiogenesis has a pivotal role in the growth and metastasis of pancreatic neuroendocrine tumors (PNETs). Apatinib inhibits angiogenesis as a highly selective KDR inhibitor and has been used to treat advanced gastric cancer and malignancies in clinical settings. However, the efficacy of apatinib in PNETs remains unclear. The aim of this study was to compare the antitumor efficacy of apatinib with that of the standard PNET drug sunitinib in our subcutaneous and liver metastasis models of insulinoma and non-functional PNET. Our results revealed that apatinib had a generally comparable or even superior antitumor effect to that of sunitinib on primary PNET, and it inhibited angiogenesis without directly causing tumor cell cytotoxicity. Apatinib inhibited the tumor in a dose-dependent manner, and the high dose was well tolerated in mice. We also found that the apatinib efficacy in liver metastasis models was cell-type (disease) selective. Although apatinib efficiently inhibited INR1G9-represented non-functional PNET liver metastasis, it led to the emergence of a hypoxic area in the INS-1-represented insulinoma and promoted liver metastasis. Our study demonstrated that apatinib has promise for clinical applications in certain malignant PNETs, and the application of anti-angiogenesis drugs to benign insulinomas may require careful consideration.
Shan Wu, Jianjun Zhou, Jing Guo, Zhan Hua, Jianchen Li, and Zai Wang
Yuan Zhou, ShengNan Wang, Jing Wu, JianJun Dong, and Lin Liao
Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Many patients with MODY2 in Asia have delayed timely treatment because they did not receive the correct diagnosis. This study aims to analyze the clinical characteristics and GCK mutations in Asian MODY2.
We have collected 110 Asian patients with MODY2 from the PubMed, Embase, Medline, Web of Science, CNKI, and Wanfang with the following search terms: ‘maturity-onset diabetes of the young’ OR ‘MODY’ OR ‘maturity-onset diabetes of the young type 2’ OR ‘MODY2’ OR ‘GCK-DM’ OR ‘GCK-MODY’. Both mutations of GCK and clinical characteristics of MODY2 were analyzed.
There were 96 different mutations that occurred in coding regions and non-coding regions. Exon 5 and 7 were the most common location in coding regions and missense was the primary mutation type. The proportion of probands younger than 25 was 81.8%, and 81.4% of the probands had family history of hyperglycaemia. Ninety percent and 93% of Asian MODY2 probands exhibited mild elevation in FPG (5.4–8.3 mmol/L) and HbA1c (5.6–7.6%), respectively.
In most Asian patients, MODY2 occurred due to GCK mutation in coding regions, and exon 5 and 7 were the most common locations. FPG, HbA1c, and familial diabetes were important reference indicators for diagnosing MODY2. Altogether, the study indicates that for the young onset of diabetes with mild elevated blood glucose and HbA1c and family history of hyperglycaemia, molecular genetic testing is suggested in order to differentiate MODY2 from other types of diabetes earlier.