Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8⁺ T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

Yuan, Chun-Hui,Yang, Xue-Qin,Zhu, Cheng-Liang,Liu, Shao-Ping,Wang, Bi-Cheng,Wang, Fu-Bing Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive $CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively. $CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of $CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of $CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of $CD8^+$ T cells. Furthermore, in vivo neutralization of $CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating $CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy.

Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

Wang, Chun-Hua,Shyu, Rong-Yaun,Wu, Chang-Chieh,Chen, Mao-Liang,Lee, Ming-Cheng,Lin, Yi-Yin,Wang, Lu-Kai,Jiang, Shun-Yuan,Tsai, Fu-Ming Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.6

The tazarotene-induced gene 1 (TIG1) protein is a retinoidinducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

Chun-Hua Wang,Rong-Yaun Shyu,Chang-Chieh Wu,Mao-Liang Chen,Ming-Cheng Lee,Yi-Yin Lin,Lu-Kai Wang,Shun-Yuan Jiang,Fu-Ming Tsai 한국분자세포생물학회 2018 Molecules and cells Vol.41 No.6

The tazarotene-induced gene 1 (TIG1) protein is a retinoid-inducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

Recent Progress in HER2 Associated Breast Cancer

Wang, Wei-Jia,Lei, Yuan-Yuan,Mei, Jin-Hong,Wang, Chun-Liang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Breast cancer is the most common cancer worldwide among women and the second most common cancer. Approximately 15-23% of breast cancers over-express human epidermal growth factor receptor2 (HER2), a 185-kDa transmembrane tyrosine kinase, which is mainly found at the cell surface of tumor cells. HER2-positive breast cancer, featuring amplification of HER2/neu and negative expression of ER and PR, has the three following characteristics: rapid tumor growth, lower survival rate, and better response to adjuvant therapies. Clinically, it is notable for its role in a pathogenesis that is associated with increased disease recurrence and acts as a worse prognosis. At the same time, it represents a good target for anti-cancer immunotherapy despite the prevalence of drug resistance. New treatments are a major topic of research, and a brighter future can be expected. This review discusses the role of HER2 in breast cancer, therapeutic modalities available and prognostic factors.

Three-dimensional cone beam computed tomography analysis of temporomandibular joint response to the Twin-block functional appliance

Yuan-yuan Jiang,Lian Sun,Hua Wang,Chun-yang Zhao,Wei-Bing Zhang 대한치과교정학회 2020 대한치과교정학회지 Vol.50 No.2

Objective: To propose a three-dimensional (3D) method for evaluating temporomandibular joint (TMJ) changes during Twin-block treatment. Methods: Seventeen patients with Class II division 1 malocclusion treated using Twinblock and nine untreated patients with a similar malocclusion were included in this research. We collected their cone beam computed tomography (CBCT) data from before and 8 months after treatment. Segmentations were constructed using ITK-SNAP. Condylar volume and superficial area were measured using 3D Slicer.The 3D landmarks were identified on CBCT images by using Dolphin software to assess the condylar positional relationship. 3D models of the mandible and glenoid fossa of the patients were constructed and registered via voxel-based superimposition using 3D Slicer. Thereafter, skeletal changes could be visualized using 3DMeshMetric in any direction of the superimposition on a color-coded map. All the superimpositions were measured using the same scale on the distance color-coded map, in which red color represents overgrowth and blue color represents resorption. Results: Significant differences were observed in condylar volume, superficial area, and condylar position in bothgroups after 8 months. Compared with the control group (CG), the Twin-block group exhibited more obvious condyle-fossa modifications and joint positional changes. Moreover, on the color-coded map, more obvious condyle-fossa modifications could be observed in the posterior and superior directions in the Twin-block group than in the CG. Conclusions: We successfully established a 3D method for measuring and evaluating TMJ changes caused by Twin-block treatment. The treatment produced a larger condylar size and caused condylar positional changes. [Korean J Orthod 2020;50(2):86-97]

First-Principles Study of the Influence of Zirconium on the Diffusion of Uranium Defects in Uranium Dioxide

Huan Wang,Yu Zou,Zhong Zhang,Kai-Yuan Wang,Huan An,Chang-Yong Zhan,Jun Wang,Jian-Chun Wu 한국물리학회 2019 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.74 No.8

The migration properties of uranium vacancies and interstitials in zirconium-doped uranium dioxide are studied by using density functional theory (DFT) and the climbing-image nudge elastic band (CI-NEB) method. The strong correlations among uranium $5f$ electrons were described by using a spherically averaged Hubbard parameter. In the model, the zirconium atoms are introduced by replacing the uranium atoms at the nearest and the next nearest neighbor sites along the diffusion path of uranium defects. The doping with zirconium obviously reduces the migration barriers for defects in uranium dioxide. The effect of doping with zirconium on the diffusion of uranium defects decreases with increasing distance between the zirconium dopant and the uranium defects. Further, we investigated the lattice distortion and the electron transfer associated with the migration of uranium defects, and we analyzed the physical origin of the reduction in the migration barriers caused by zirconium doping.

Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

Lei, Yuan-Yuan,Wang, Wei-Jia,Mei, Jin-Hong,Wang, Chun-Liang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.20

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

Chemical and Pharmacological Studies of Saponins with a Focus on American Ginseng

Yuan, Chun-Su,Wang, Chong-Zhi,Wicks, Sheila M.,Qi, Lian-Wen The Korean Society of Ginseng 2010 Journal of Ginseng Research Vol.34 No.3

Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L.) are the two most recognized ginseng botanicals. It is believed that the ginseng saponins called ginsenosides are the major active constituents in both ginsengs. Although American ginseng is not as extensively studied as Asian ginseng, it is one of the best selling herbs in the US, and has garnered increasing attention from scientists in recent years. In this article, after a brief introduction of the distribution and cultivation of American ginseng, we discuss chemical analysis of saponins from these two ginsengs, i.e., their similarities and differences. Subsequently, we review pharmacological effects of the saponins, including the effects on the cardiovascular system, immune system, and central nervous system as well as the anti-diabetes and anti-cancer effects. These investigations were mainly derived from American ginseng studies. We also discuss evidence suggesting that chemical modifications of ginseng saponins would be a valuable approach to develop novel compounds in drug discovery.

Phenotypes and Prognostic Factors of Syringomyelia in Single-Center Patients With Chiari I Malformation: Moniliform Type as a Special Configuration

Chunli Lu,Longbing Ma,Chenghua Yuan,Lei Cheng,Xinyu Wang,Wanru Duan,Kai Wang,Zan Chen,Hao Wu,Gao Zeng,Fengzeng Jian 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

Objective: The specific association between morphometric characteristics of the syrinx and the prognosis of Chiari malformation type I (CM-I) with syringomyelia following surgical procedure seems to have not been fully elaborated. This study focused on the preoperative clinical and radiologic parameters in CM-I patients with syringomyelia to find out the relationship between the patients’ clinical status and the phenotypes of the syrinx with surgical outcome. Methods: A continuous series of pediatric and adult patients with CM-I and syringomyelia from a prospectively maintained database in a single center were included, and we explored the related factors affecting the prognosis following decompression surgery through retrospective analysis of clinical presentations, imaging characteristics, and the morphological features of syringomyelia, to provide a clinical reference for the treatment of syringomyelia. Results: There were 28 pediatric patients (13.8%), and 174 adults (86.2%) included in our study. The average Chicago Chiari Outcome Scale score was 14.56 ± 1.78. The overall prognosis after surgery was good in our series, among them 152 cases (75.25%) with a favorable prognosis, and syrinx was resolved effectively in 172 cases (85.15%). According to the univariate and multivariate analyses, the preoperative symptom duration, observation time, and with/without moniliform type were independent factors affecting the prognosis in adults. The most obvious difference between moniliform type and nonmoniliform type lies in the preoperative symptom duration, ventral subarachnoid space at the foramen magnum, and with/without straightened cervical physio-curve. Conclusion: Timely decompression surgery could achieve a better outcome in CM-I patients with syringomyelia. Moniliform syringomyelia may suggest a relatively better prognosis.

Chemical and Pharmacological Studies of Saponins with a Focus on American Ginseng

Chun-Su Yuan,Chong-Zhi Wang,Sheila M. Wicks,Lian-Wen Qi 고려인삼학회 2010 Journal of Ginseng Research Vol.34 No.3

Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius L.) are the two most recognized ginseng botanicals. It is believed that the ginseng saponins called ginsenosides are the major active constituents in both ginsengs. Although American ginseng is not as extensively studied as Asian ginseng, it is one of the best selling herbs in the US, and has garnered increasing attention from scientists in recent years. In this article, after a brief introduction of the distribution and cultivation of American ginseng, we discuss chemical analysis of saponins from these two ginsengs, i.e., their similarities and differences. Subsequently, we review pharmacological effects of the saponins, including the effects on the cardiovascular system, immune system, and central nervous system as well as the anti-diabetes and anti-cancer effects. These investigations were mainly derived from American ginseng studies. We also discuss evidence suggesting that chemical modifications of ginseng saponins would be a valuable approach to develop novel compounds in drug discovery.