To investigate the potential effects of resistin-13-peptide on the growth, adhesion, and invasion in human breast carcinoma cells, MDA-MB-231. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and colony-forming assay were used to assess the proliferation effects of resistin-13-peptide. The adhesive ability was investigated by cell adhesion assay, and the invasive potential was assessed using a transwell model. Activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by zymogrophy analysis and western blotting. Tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 were determined by western blotting. In this study, we performed in vivo experiments and determined the effect of resistin-13-peptide on tumor growth and other organs, especially ovaries in a xenograft model using the cell line studied. Resistin-13-peptide inhibited MDA-MB-231 cell growth and colony formation in a dose- and time-dependent manner. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide in a dose-dependent manner. Resistin-13-peptide decreased the gelatinolytic activities of both MMP-2 and MMP-9 and enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA-MB-231 cells. The animal experiments found that the growth of tumors was repressed by resistin-13-peptide, which affected other organs in the same time. Especially, ovaries did not have pathological changes yet. Treatment with resistin-13-peptide is effective in suppressing tumor proliferation, adhesion, and invasion. The possible mechanism is downregulation of MMPs and upregulation of TIMPs.
Bing Pan, Ming-Hui Zhao, Zhong Chen, Lu Lu, Yan Wang, Da-Wei Shi, and Pei-Zhen Han
Jingyuan Ma, Xinyu Huang, Jungong Zhao, Jingyi Lu, Wei Lu, Yuqian Bao, Jian Zhou, and Junfeng Han
Insulin release index (IRI) based on 72-h fasting test has been used for the definitive diagnosis of insulinoma; however, hospitalization and subsequent costs contribute to the disadvantage of IRI. Therefore, a simple and cost-effective screening procedure for the diagnosis of insulinoma for outpatients are crucially needed. Continuous glucose monitoring (CGM) has been widely used for monitoring high level of glucose in diabetic patients. The aim of the study is to determine the potential contribution or implementation of CGM in the screening of the insulinoma. We performed a single-center prospective study with the demographics and laboratory data including 28 patients with the pathological diagnosis of insulinoma and 25 patients with functional hypoglycemia as control group. The analysis showed that areas under the receiver operating characteristic (ROC) curve of coefficient of variation (CV) was 0.914. The CV cutoff point was 19% with the Youden 62.1%, the corresponding sensitivity and specificity were 82.1 and 80%, respectively. In patients with CV greater than the median, more than 60% of insulinomas were located in the head of the pancreas; most Ki-67 values were more than 2% and when compared with the group with CV smaller than the median, the average tumor size was 2.7 times larger. In conclusion, CGM can be used as a valuable tool in not only monitoring high glucose levels in diabetic patients but also identifying the etiology of insulinoma. CV greater than 19% can be highly effective for the screening of insulinoma in outpatients.
Wei Guan, Junhui Hu, Lu Yang, Ping Tan, Zhuang Tang, Brian L West, Gideon Bollag, Hua Xu, and Lily Wu
For men with castration-resistant prostate cancer (CRPC), androgen-deprivation therapy (ADT) often becomes ineffective requiring the addition of docetaxel, a proven effective chemotherapy option. Tumor-associated macrophages (TAMs) are known to provide protumorigenic influences that contribute to treatment failure. In this study, we examined the contribution of TAMs to docetaxel treatment. An increased infiltration of macrophages in CRPC tumors was observed after treatment with docetaxel. Prostate cancer cells treated with docetaxel released more macrophage colony-stimulating factor (M-CSF-1 or CSF-1), IL-10 and other factors, which can recruit and modulate circulating monocytes to promote their protumorigenic functions. Inhibition of CSF-1 receptor kinase signaling with a small molecule antagonist (PLX3397) in CRPC models significantly reduces the infiltration of TAMs and their influences. As such, the addition of PLX3397 to docetaxel treatment resulted in a more durable tumor growth suppression than docetaxel alone. This study reveals a rational strategy to abrogate the influences of TAMs and extend the treatment response to docetaxel in CRPC.
Ssu-Ming Huang, Tzu-Sheng Chen, Chien-Ming Chiu, Leang-Kai Chang, Kuan-Fu Liao, Hsiao-Ming Tan, Wei-Lan Yeh, Gary Ro-Lin Chang, Min-Ying Wang, and Dah-Yuu Lu
Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been shown to affect cancer cell metastasis and invasion. However, the molecular mechanisms underlying GDNF-induced colon cancer cell migration remain unclear. GDNF is found to be positively correlated with malignancy in human colon cancer patients. The migratory activities of two human colon cancer cell lines, HCT116 and SW480, were found to be enhanced in the presence of human GDNF. The expression of vascular endothelial growth factor (VEGF) was also increased in response to GDNF stimulation, along with VEGF mRNA expression and transcriptional activity. The enhancement of GDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Our results also showed that the expression of VEGF receptor 1 (VEGFR1) was increased in response to GDNF stimulation, whereas GDNF-induced cancer cell migration was reduced by a VEGFR inhibitor. The GDNF-induced VEGF expression was regulated by the p38 and PI3K/Akt signaling pathways. Treatment with GDNF increased nuclear hypoxia-inducible factor 1 α (HIF1α) accumulation and its transcriptional activity in a time-dependent manner. Moreover, GDNF increased hypoxia responsive element (HRE)-containing VEGF promoter transcriptional activity but not that of the HRE-deletion VEGF promoter construct. Inhibition of HIF1α by a pharmacological inhibitor or dominant-negative mutant reduced the GDNF-induced migratory activity in human colon cancer cells. These results indicate that GDNF enhances the migration of colon cancer cells by increasing VEGF–VEGFR interaction, which is mainly regulated by the p38, PI3K/Akt, and HIF1α signaling pathways.
Xiao-Hua Jiang, Jie-Li Lu, Bin Cui, Yong-Ju Zhao, Wei-qing Wang, Jian-Min Liu, Wen-Qiang Fang, Ya-Nan Cao, Yan Ge, Chang-xian Zhang, Huguette Casse, Xiao-Ying Li, and Guang Ning
Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterized by the development of tumours of the parathyroid, anterior pituitary and pancreatic islets, etc. Heterozygous germ line mutations of MEN1 gene are responsible for the onset of MEN1. We investigated the probands and 31 family members from eight unrelated Chinese families associated with MEN1 and identified four novel mutations, namely 373_374ins18, 822delT, 259delT and 1092delC, as well as three previously reported mutations, such as 357_360delCTGT, 427_428delTA and R108X (CGA>TGA) of MEN1 gene. Furthermore, we detected a loss of heterozygosity (LOH) at chromosome 11q in the removed tumours, including gastrinoma, insulinoma and parathyroid adenoma from two probands of MEN1 families. RT-PCR and direct sequencing showed that mutant MEN1 transcripts remained in the MEN1-associated endocrine tumours, whereas normal menin proteins could not be detected in those tumours by either immunohistochemistry or immunoblotting. In conclusion, MEN1 heterozygous mutations are associated with LOH and menin absence, which are present in MEN1-associated endocrine tumours.