Browsing by Author "Chen, Po-Ming"

Now showing 1 - 3 of 3

Bioinspired Engineering of a Bacterium-Like Metal-Organic Framework for Cancer Immunotherapy
(1970-01-01)
Chen, Po-Ming
;
Pan, Wen-Yu
;
Miao, Yang-Bao
;
Liu, Yu-Miao
;
Luo, Po-Kai
Bacteria-mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium-like metal-organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side-effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2-aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium-like MOFs under exposure to an near-infrared laser and the immune checkpoint blockade of systemically administered alpha PD-1 is evaluated in tumor-bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis.
MicroRNA-30a increases tight junction protein expression to suppress the epithelial-mesenchymal transition and metastasis by targeting Slug in breast cancer
(2016-03-29)
Chang, Chia-Wei
;
Yu, Jyh-Cherng
;
Hsieh, Yi-Hsien
;
Yao, Chung-Chin
;
Chao, Jui-I
The epithelial-to-mesenchymal (EMT) transition is a prerequisite for conferring metastatic potential during tumor progression. microRNA-30a (miR-30a) expression was significantly lower in aggressive breast cancer cell lines compared with non-invasive breast cancer and non-malignant mammary epithelial cell lines. In contrast, miR-30a overexpression reversed the mesenchymal appearance of cancer cells to result in a cobblestone-like epithelial phenotype. We identified Slug, one of the master regulators of EMT, as a target of miR-30a using in silico prediction. Reporter assays indicated that miR-30a could bind to the 3'-untranslted region of Slug mRNA. Furthermore, we linked miR-30a to increased expression of claudins, a family of tight junction transmembrane proteins. An interaction between Slug and E-box in the claudin promoter sequences was reduced upon miR-30a overexpression, further leading to reduction of filopodia formation and decreased invasiveness/metastasis capabilities of breast cancer cells. Consistently, delivery of miR-30a in xenografted mice decreased tumor invasion and migration. In patients with breast cancer, a significantly elevated risk of the miR-30a(low)/CLDN2(low)/FSCNhigh genotype was observed, linking to a phenotypic manifestation of larger tumor size, lymph node metastasis, and advanced tumor stage among patients. In conclusion, the miR-30a/Slug axis inhibits mesenchymal tumor development by interfering with metastatic cancer cell programming and may be a potential target for therapy in breast cancer.
The APE1 Asp/Asp Genotype and the Combination of APE1 Asp/Asp and hOGG1-Cys Variants Are Associated With Increased p53 Mutation in Non-Small Cell Lung Cancer
(2012-11-01)
Lin, Chun-Hsuan
;
Chen, Po-Ming
;
Cheng, Ya-Wen
;
Chen, Chih-Yi
;
Yuan, Chiun-Jye
Background: The hOGG1 Ser326Cys polymorphism is associated with lung cancer risk, but there are limited data regarding an association between the APE1 Asp148Glu polymorphism and lung cancer. Biological evidence shows that the hOGG1-Cys allele results in less DNA repair activity; however, this is not associated with p53 mutation in lung cancer. Therefore, we investigated whether an interaction between 110001 and APE1 is associated with the frequency of p53 mutation in lung cancer. Methods: We studied 217 Taiwanese adults with primary lung cancer. DNA polymorphisms of hOGG1 and APE1 were determined by polymerase chain reaction (PCR)-based restriction fragment length polymorphism. Mutations in p53 exons 5-8 were detected by direct sequencing. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE I in lung cancer. Results: As expected, no association between hOGG1 polymorphism and p53 mutation was observed in this population. However, a higher risk of p53 mutation was found in participants with the APE I Asp/Asp genotype than in those with the APE1-Glu allele (OR, 2.15; 95% CI, 1.19-3.87; P = 0.011). The risk of p53 mutation was also higher in participants with APEI Asp/Asp plus hOGG1-Cys than in those with APE1-Glu plus hOGG1 Ser/Ser (OR, 3.72; 95% Cl, 1.33-10.40; P = 0.012). Conclusions: These results suggest that the APE I Asp/Asp genotype and the combination of the APE I Asp/Asp and hOGG1-Cys variants are associated with increased risk of p53 mutation in non small cell lung cancer.