Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou, Guang-Xi,Li, Xiao-Yu,Zhang, Qi,Zhao, Kun,Zhang, Cui-Ping,Xue, Chang-Hu,Yang, Kun,Tian, Zi-Bin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1, YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

Superluminescent diode integrated with monitor photodiode

Zhou Shuai,Liu Kun,Li Peng,Pang Fu-Bin,Zhang Jing,Kong Xiang-Ping,Duan Li-Hua,Zhang Chang-Chun 한국물리학회 2023 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.82 No.2

Ridge-waveguide superluminescent diodes with integrated rear-side monitoring photodiode have been fabricated. When electrical isolation trench is not etched to active layer, the leakage current of monitoring photodiode is determined by the resistance between active region electrode and monitoring photodiode electrode, i.e. the resistance multiplied by the leakage current approximately equals to 0.8 V. In order to reduce the leakage current of monitoring photodiode, the electrical isolation trench must be etched into substrate layer. In addition, the electrical isolation trench has to be far enough away from the active region so that the superluminescent diode could achieve small spectral ripple.

MiRNA-15a Mediates Cell Cycle Arrest and Potentiates Apoptosis in Breast Cancer Cells by Targeting Synuclein-γ

Li, Ping,Xie, Xiao-Bing,Chen, Qian,Pang, Guo-Lian,Luo, Wan,Tu, Jian-Cheng,Zheng, Fang,Liu, Song-Mei,Han, Lu,Zhang, Jian-Kun,Luo, Xian-Yong,Zhou, Xin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: Recent studies have indicated that microRNA-15a (miR-15a) is dysregulated in breast cancer (BC). We aimed to evaluate the expression of miR-15a in BC tissues and corresponding para-carcinoma tissues. We also focused on effects of miR-15a on cellular behavior of MDA-MB-231 and expression of its target gene synuclein-${\gamma}$ (SNCG). Materials and Methods: The expression levels of miR-15a were analysed in BC formalin fixed paraffin embedded (FFPE) tissues by microarray and quantitative real-time PCR. CCK-8 assays, cell cycle and apoptosis assays were used to explore the potential functions of miR-15a in MDA-MB-231 human BC cells. A luciferase reporter assay confirmed direct targets. Results: Downregulation of miR-15a was detected in most primary BCs. Ectopic expression of miR-15a promoted proliferation and suppressed apoptosis in vivo. Further studies indicated that miR-15a may directly interact with the 3'-untranslated region (3'-UTR) of SNCG mRNA, downregulating its mRNA and protein expression levels. SNCG expression was negatively correlated with miR-15a expression. Conclusions: MiR-15a has a critical role in mediating cell cycle arrest and promoting cell apoptosis of BC, probably by directly targeting SNCG. Thus, it may be involved in development and progression of BC.

The role of Pin1 in the development and treatment of cancer

민상현,Xiao Zhen Zhou,Kun Ping Lu 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.12

Protein phosphorylation and post-phosphorylationevents regulate many cellular signaling pathways. Peptidyl-prolyl isomerase (Pin1) is the only peptidyl-prolylcis/trans isomerase that interacts with numerous oncogenicor tumor suppressive phosphorylated proteins, causesconformational changes in target proteins, and eventuallyregulates the activities of such proteins. These alterationsin activity play a pivotal role in tumorigenesis. Since Pin1is overexpressed and/or activated in various types of cancers,and the dysregulation of proline-directed phosphorylationcontributes to tumorigenesis, Pin1 represents anattractive target for cancer therapy. This review willdescribe the role of Pin1 in cancer and the current status ofPin1 inhibitor development.

New Evidence for the Involvement of the EGF Receptor Pathway in Hair Follicle Morphogenesis in uncv Mice

Jing Zhang,Xiao Kun Teng,Li Zhen Si,Ping Tong Zhou,Xiang Yin Kong,Lan Dian Hu 한국유전학회 2008 Genes & Genomics Vol.30 No.4

Hair follicle (HF) morphogenesis depends upon a delicate balance between cell proliferation and apoptosis, both of which are known to be controlled by a number of signal pathways. In this study, we utilize the uncv homozygous mouse to investigate the underlying mechanisms giving rise to the relevant phenotypes. In so doing, we have detected changes in the EGFR, Akt and MAPK signaling pathways. Our results show that the expression patterns of active Akt, MAPK and EGFR are altered with regard to localization in the outer root sheath (ORS) of the wild type mouse and in the follicular bulbs of the uncv homozygous mouse. These data suggest that EGFR signaling may play different roles in different cellular locations. Further, ectopic EGFR signaling in the follicular bulbs of the uncv homozygous mouse may lead to catagen (entrance into the apoptosis phase). Moreover, when the EGFR ligand was overexpressed in the uncv heterozygous mouse, aggravation of HF disordered development ensued. Together, these results demonstrate that EGFR participates in a functionally compartmentalized signaling network that controls follicular development homeostasis.

Continuous DC-CIK Infusions Restore CD8⁺ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

Zhao, Yan-Jie,Jiang, Ni,Song, Qing-Kun,Wu, Jiang-Ping,Song, Yu-Guang,Zhang, Hong-Mei,Chen, Feng,Zhou, Lei,Wang, Xiao-Li,Zhou, Xin-Na,Yang, Hua-Bing,Ren, Jun,Lyerly, Herbert Kim Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

Wang, Hua-Qian,Li, Dong-Li,Lu, Yu-Jing,Cui, Xiao-Xing,Zhou, Xiao-Fen,Lin, Wei-Ping,Conney, Allan H.,Zhang, Kun,Du, Zhi-Yun,Zheng, Xi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-${\kappa}B$, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.

Biomechanical Evaluation of 2 Endoscopic Spine Surgery Methods for Treating Lumbar Disc Herniation: A Finite Element Study

Yang Zou,Shuo Ji,Hui Wen Yang,Tao Ma,Yue Kun Fang,Zhi Cheng Wang,Miao Miao Liu,Ping Hui Zhou,Zheng Qi Bao,Chang Chun Zhang,Yu Chen Ye 대한척추신경외과학회 2024 Neurospine Vol.21 No.1

Objective: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion: In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota–HIF1a/PTBP1 pathway

Xuan Lihui,Xu Zheng,Luo Jinhua,Yin Wang,Yan Yuhui,Qu Can,Xie Zuozhong,Skonieczna Magdalena,Zhou Ping-Kun,Huang Ruixue 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut–lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50–100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial–mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.