Democracy and Nation Formation: National Identity Change and Dual Identity in Taiwan, 1991-2011

Using the data collected from various national poll surveys conducted after the transition to democracy in the late 1980's, this study analyzes the trend of national identity change among the general populace in Taiwan. Counter to the popular view that the nascent Taiwanese national identity rose at the cost of the orthodox Chinese national identity, this study argues that most people in fact upheld dual identity in the first two decades following the democratic transition. They acquired a new Taiwanese national identity without forsaking the old Chinese identity. In analyzing the phenomenon of dual identity, this dissertation challenges the conventional view that national identities are mutually exclusive. It also shows that the trajectories of the two national identities are different processes, having occurred during different historical stages and in different international environments. They were also the results of different political forces. In explaining the rise of Taiwanese national identity, this study focuses on the factors of state and politics, rather than history and ethnicity. It is contended that the new national identity is largely engendered by democratic institutions and political participation. It thus was able to co-exist with existing Chinese national identity. This dissertation then explains the decline of Chinese national identity not with the rise of Taiwanese identity, but with the rise of China. The dominance of the People's Republic of China (PRC) in the international community along with its staunch One China Principle has removed the important component of the Republic of China (ROC) from the Chinese national identity in Taiwan. Chinese unification no longer means the fulfillment of self-rule but to be ruled by another state (the PRC). People who have identified with the ROC no longer opt for a unified great China and hence forgo their Chinese national identity

SiMMap: a web server for inferring site-moiety map to recognize interaction preferences between protein pockets and compound moieties

The protein–ligand interacting mechanism is essential to biological processes and drug discovery. The SiMMap server statistically derives site-moiety map with several anchors, which describe the relationship between the moiety preferences and physico-chemical properties of the binding site, from the interaction profiles between query target protein and its docked (or co-crystallized) compounds. Each anchor includes three basic elements: a binding pocket with conserved interacting residues, the moiety composition of query compounds and pocket–moiety interaction type (electrostatic, hydrogen bonding or van der Waals). We provide initial validation of the site-moiety map on three targets, thymidine kinase, and estrogen receptors of antagonists and agonists. Experimental results show that an anchor is often a hot spot and the site-moiety map can help to assemble potential leads by optimal steric, hydrogen bonding and electronic moieties. When a compound highly agrees with anchors of site-moiety map, this compound often activates or inhibits the target protein. We believe that the site-moiety map is useful for drug discovery and understanding biological mechanisms. The SiMMap web server is available at http://simfam.life.nctu.edu.tw/

Smoking, Green Tea Consumption, Genetic Polymorphisms in the Insulin-Like Growth Factors and Lung Cancer Risk

Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR) = 13.16, 95% confidence interval (CI) = 2.96–58.51). Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA)19/(CA)19 and (CA)19/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01–0.44) compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

FAK Regulates VEGFR2 Expression and Promotes Angiogenesis in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) remains a significant clinical challenge because of its high vascularity and metastatic and recurrent rates. Tumor angiogenesis is considered an important mediator in the regulation of tumor cell survival and metastasis in TNBC. Angiogenesis is induced by the binding of vascular endothelial growth factor to vascular endothelial growth factor receptor 2 (VEGFR2). Focal adhesion kinase (FAK) plays an important role in regulating various cell functions in normal and cancer cells. Previous studies have focused on investigating the function of endothelial FAK in tumor cell angiogenesis. However, the association between tumor FAK and VEGFR2 in tumor angiogenesis and the possible mechanisms of this remain unclear. In this study, we used a public database and human specimens to examine the association between FAK and VEGFR2. At the same time, we verified the association between FAK and VEGFR2 through several experimental methods, such as quantitative real-time polymerase chain reaction, Western blotting, and next-generation sequencing. In addition, we used the endothelial cell model, zebrafish, and xenograft animal models to investigate the role of FAK in TNBC angiogenesis. We found that FAK and VEGFR2 were positively correlated in patients with TNBC. VEGFR2 and several other angiogenesis-related genes were regulated by FAK. In addition, FAK regulated VEGFR2 and VEGF protein expression in TNBC cells. Functional assays showed that FAK knockdown inhibited endothelial tube formation and zebrafish angiogenesis. An animal model showed that FAK inhibitors could suppress tumor growth and tumor vascular formation. FAK promotes angiogenesis in TNBC cells by regulating VEGFR2 expression. Therefore, targeting FAK could be another antiangiogenic strategy for TNBC treatment

Combination of FAK inhibitor and cytokine-induced killer cell therapy: An alternative therapeutic strategy for patients with triple-negative breast cancer

Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC

Association between green tea consumption and smoking status with lung cancer risk.

<p>Data were matched by age and gender, calculated by multiple conditional logistic regression and adjusted for exposure to fume of cooking, and family history of lung cancer.</p>1<p>P<0.01,</p>2<p>P = 0.04; P value was adjusted by multiple testing (bonferroni correction).</p

Genotype frequencies of <i>IGF1</i> (CA)_n repeat, <i>IGF2</i> 820 and <i>IGFBP3</i> -202 among cases and controls.

<p>Data were matched by age and gender, calculated by conditional logistic regression.</p>1<p>Data were calculated by two-sided χ² test.</p>2<p>The probability of the χ² test for Hardy-Weinberg equilibrium in control group.</p

Frequency distribution of specific characteristics by case and control status.

<p>Data were matched by age and gender, calculated by conditional logistic regression.</p>1<p>Two-sided χ² test or Fisher's exact test for discrete variables and paired <i>t</i>-test for continuous variables.</p

The joint effect of cumulative smoking dose with <i>IGF1</i> (CA)_n repeat, <i>IGF2</i> 820, <i>IGFBP3</i> -202 genotypes for lung cancer risk.

<p>Data were matched by age and gender, calculated by multiple conditional logistic regression and adjusted for green tea consumption, exposure to fume of cooking, and family history of lung cancer.</p>1<p>P<0.01,</p>2<p>P = 0.08,</p>3<p>P = 0.03; P value was adjusted by multiple testing (bonferroni correction).</p