1,705 results
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2. Author Correction: MiR218 Modulates Wnt Signaling in Mouse Cardiac Stem Cells by Promoting Proliferation and Inhibiting Differentiation through a Positive Feedback Loop.
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Wang, Yongshun, Liu, Jingjin, Cui, Jinjin, Sun, Meng, Du, Wenjuan, Chen, Tao, Ming, Xing, Zhang, Lulu, Tian, Jiangtian, Li, Ji, Yin, Li, Liu, Fang, Pu, Zhongyue, Lv, Bo, Hou, Jingbo, and Yu, Bo
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MICRORNA ,STEM cells ,CELL proliferation - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Cell proliferation effect of deep-penetrating microcavity tandem NIR OLEDs with therapeutic trend analysis.
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Park, Yongjin, Choi, Hye-Ryung, Jeon, Yongmin, Kim, Hyuncheol, Shin, Jung Won, Huh, Chang-Hun, Park, Kyoung-Chan, and Choi, Kyung-Cheol
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ORGANIC light emitting diodes ,CELL proliferation ,TREND analysis ,CYTOCHROME oxidase ,LIGHT emitting diodes ,FIBROBLASTS - Abstract
Long wavelengths that can deeply penetrate into human skin are required to maximize therapeutic effects. Hence, various studies on near-infrared organic light-emitting diodes (NIR OLEDs) have been conducted, and they have been applied in numerous fields. This paper presents a microcavity tandem NIR OLED with narrow full-width half-maximum (FWHM) (34 nm), high radiant emittance (> 5 mW/cm
2 ) and external quantum efficiency (EQE) (19.17%). Only a few papers have reported on biomedical applications using the entire wavelength range of the visible and NIR regions. In particular, no biomedical application studies have been reported in the full wavelength region using OLEDs. Therefore, it is worth researching the therapeutic effects of using OLED, a next-generation light source, and analyzing trends for cell proliferation effects. Cell proliferation effects were observed in certain wavelength regions when B, G, R, and NIR OLEDs were used to irradiate human fibroblasts. The results of an in-vitro experiment indicated that the overall tendency of wavelengths is similar to that of the cytochrome c oxidase absorption spectrum of human fibroblasts. This is the first paper to report trends in the cell proliferation effects in all wavelength regions using OLEDs. [ABSTRACT FROM AUTHOR]- Published
- 2022
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4. Chemical alternative for cell identification and cross-contamination detection.
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Msalbi, Dhouha, Elloumi-Mseddi, Jihene, Hakim, Bochra, Sahli, Emna, and Aifa, Sami
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CELL cycle ,CELL proliferation ,CELL lines ,CELL culture ,CANCER cells - Abstract
Misidentification of human cell lines has previously led to confusing results during cell culture experiments. Although several enzymatic as well as molecular analysis approaches have been developed for cell-line authentication, these methods remain costly. In the present paper, we describe a simple chemical alternative based on known compound cell cytotoxicity. In addition to cisplatin, a pool of eight tamoxifen derivative compounds was used to compare the cytotoxic effects on three different breast cancer cell lines: MCF-7, T47D and MDA-MB-231. Our results show that four out of the eight cytotoxic-related compounds allowed to distinguish the different cell lines based on their IC
50 (the half maximal inhibitory concentration) values which are cell type dependent. The remaining chemicals, particularly the most cytotoxic P15, showed close IC50 values for all the cell lines. Interestingly, flow cytometry experiments have identified notable differences among the three cell lines treated with P15. T47D and MDA-MB231 cells were blocked in SubG1 phase and S phase, respectively, while no significant change in cell cycle profile was noticed for MCF-7 cells. Differences were also noted at the level of caspase-3 activity and cell proliferation in P15-treated cells. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. Traveling wave behavior in a two-phase flow model of tumor growth.
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Mansour, Mahmoud Bakheet A.
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TUMOR growth ,MATHEMATICAL models ,CELL motility ,CELL proliferation ,DYNAMICS - Abstract
Tumor growth which undergoes complex bio-mechanical processes has been a significant focus for mathematical modeling, with particular interest in its dynamic behavior. In this paper, we consider a two-phase flow model for describing the dynamics of tumor growth. The model accounts for aggregate cell movement and mechanical interactions between tumor cells as well as cell proliferation. In suitable limits, by using the dynamical systems theory approach, tumor growth in this mechanical model is shown to occur in the form of traveling waves that can propagate either forward or backward, depending on the values of the parameters. Our results, in particular, the wave profiles of tumor cell density are more realistic and explain those obtained in a recently developed simple, experiment-based, model for studying non-spatial dynamics of tumor cells. [ABSTRACT FROM AUTHOR]
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- 2010
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6. Author Correction: Enhancing Cell Proliferation and Osteogenic Differentiation of MC3T3-E1 Pre-osteoblasts by BMP-2 Delivery in Graphene Oxide-Incorporated PLGA/HA Biodegradable Microcarriers.
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Fu, Chuan, Yang, Xiaoyu, Tan, Shulian, and Song, Liangsong
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CELL proliferation ,OSTEOBLASTS - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2020
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7. Author Correction: ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner.
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Suk, Fat-Moon, Chang, Chi-Ching, Lin, Ren-Jye, Lin, Shyr-Yi, Liu, Shih-Chen, Jau, Chia-Feng, and Liang, Yu-Chih
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CELL proliferation ,CYCLINS - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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8. STAT5-dependent regulation of CDC25A by miR-16 controls proliferation and differentiation in FLT3-ITD acute myeloid leukemia.
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Sueur, Gabrielle, Boutet, Alison, Gotanègre, Mathilde, Mansat-De Mas, Véronique, Besson, Arnaud, Manenti, Stéphane, and Bertoli, Sarah
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CELL proliferation ,ACUTE myeloid leukemia ,CELL differentiation ,MESSENGER RNA ,GENE expression - Abstract
We recently identified the CDC25A phosphatase as a key actor in proliferation and differentiation in acute myeloid leukemia expressing the FLT3-ITD mutation. In this paper we demonstrate that CDC25A level is controlled by a complex STAT5/miR-16 transcription and translation pathway working downstream of this receptor. First, we established by CHIP analysis that STAT5 is directly involved in FLT3-ITD-dependent CDC25A gene transcription. In addition, we determined that miR-16 expression is repressed by FLT3-ITD activity, and that STAT5 participates in this repression. In accordance with these results, miR-16 expression was significantly reduced in a panel of AML primary samples carrying the FLT3-ITD mutation when compared with FLT3wt cells. The expression of a miR-16 mimic reduced CDC25A protein and mRNA levels, and RNA interference-mediated down modulation of miR-16 restored CDC25A expression in response to FLT3-ITD inhibition. Finally, decreasing miR-16 expression partially restored the proliferation of cells treated with the FLT3 inhibitor AC220, while the expression of miR-16 mimic stopped this proliferation and induced monocytic differentiation of AML cells. In summary, we identified a FLT3-ITD/STAT5/miR-16/CDC25A axis essential for AML cell proliferation and differentiation. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications.
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Naseri, Rozita, Navabi, Seyed Jafar, Samimi, Zeinab, Mishra, Abhay Prakash, Nigam, Manisha, Chandra, Harish, Olatunde, Ahmed, Tijjani, Habibu, Morais-Urano, Raquel P., and Farzaei, Mohammad Hosein
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DIABETES complications ,CELL proliferation ,CELLULAR signal transduction ,DIABETES ,GLYCOPROTEINS ,GLYCOSYLATION - Abstract
Objectives: Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. Methods: All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. Results: Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. Conclusions: The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. Cell patterning via optimized dielectrophoretic force within hexagonal electrodes in vitro for skin tissue engineering.
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Huan, Zhijie, Ma, Weicheng, Xu, Min, Zhong, Zhixiong, Li, Xiangpeng, and Zhu, Zhenhong
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CELL aggregation ,TISSUE engineering ,LASER beam cutting ,SKIN regeneration ,ELECTRODES - Abstract
Tissue reconstruction through in vitro cell seeding is a popular method for tissue engineering. In this paper, we proposed a thin-layer structure consisting of multiple hexagons for the regeneration of skin tissue. Cells could be seeded and cultured within the structure via dielectrophoresis (DEP) actively. A thin layer of the structure was fabricated with biocompatible medical-grade stainless steel via precise laser cutting. The fabricated layers were stacked together to form a 3D electrode pair, which could be used to generate a 3D electric field. Thus, the suspended cells within the structure could be patterned via DEP manipulation. The input voltage was examined and optimized to ensure cell viability and patterning efficiency during the DEP manipulation process. As soon as we applied the optimized voltage, human foreskin fibroblast (HFF) cells could be attracted along the edge of the electrodes, forming hexagonal cellular patterns. After that, a single layer of the patterned cells was further cultured in an incubator for 7 days and observed under a microscope. The obtained images showed that the seeded cells could proliferate and fill in the hexagonal wells, which could be used for further skin tissue regeneration. As shown in the experimental results, this structure could be used for active cell seeding and proliferation for the development of skin tissue engineering. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. 3D Bioprinted GelMA Based Models for the Study of Trophoblast Cell Invasion.
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Ding, Houzhu, Illsley, Nicholas P., and Chang, Robert C.
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BIOPRINTING ,TROPHOBLAST ,CELL lines ,EPIDERMAL growth factor ,CELL proliferation ,CELL migration - Abstract
Bioprinting is an emerging and promising technique for fabricating 3D cell-laden constructs for various biomedical applications. In this paper, we employed 3D bioprinted GelMA-based models to investigate the trophoblast cell invasion phenomenon, enabling studies of key placental functions. Initially, a set of optimized material and process parameters including GelMA concentration, UV crosslinking time and printing configuration were identified by systematic, parametric study. Following this, a multiple-ring model (2D multi-ring model) was tested with the HTR-8/SVneo trophoblast cell line to measure cell movement under the influence of EGF (chemoattractant) gradients. In the multi-ring model, the cell front used as a cell invasion indicator moves at a rate of 85 ± 33 µm/day with an EGF gradient of 16 µM. However, the rate was dramatically reduced to 13 ± 5 µm/day, when the multi-ring model was covered with a GelMA layer to constrain cells within the 3D environment (3D multi-ring model). Due to the geometric and the functional limitations of multi-ring model, a multi-strip model (2D multi-strip model) was developed to investigate cell movement in the presence and absence of the EGF chemoattractant. The results show that in the absence of an overlying cell-free layer of GelMA, movement of the cell front shows no significant differences between control and EGF-stimulated rates, due to the combination of migration and proliferation at high cell density (6 × 10
6 cells/ml) near the GelMA surface. When the model was covered by a layer of GelMA (3D multi-strip model) and migration was excluded, EGF-stimulated cells showed an invasion rate of 21 ± 3 µm/day compared to the rate for unstimulated cells, of 5 ± 4 µm/day. The novel features described in this report advance the use of the 3D bioprinted placental model as a practical tool for not only measurement of trophoblast invasion but also the interaction of invading cells with other tissue elements. [ABSTRACT FROM AUTHOR]- Published
- 2019
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12. C5a promotes migration, proliferation, and vessel formation in endothelial cells
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Kunihiro Yamaoka, Koichi Oshita, Norifumi Sawamukai, Mikiko Tokunaga, Sonosuke Yukawa, Shigeru Iwata, Kazuyoshi Saito, Ryuji Kurihara, Kenji Chiba, Shohei Shimajiri, and Yoshiya Tanaka
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C5a ,Endothelium ,Angiogenesis ,Immunology ,Complement C5a ,chemical and pharmacologic phenomena ,Inflammatory diseases ,Biology ,Cell Line ,Neovascularization ,Vasculogenesis ,Endothelial cell ,Cell Movement ,medicine ,Animals ,Humans ,Complement Activation ,Activated complement ,Cell Proliferation ,Pharmacology ,Neovascularization, Pathologic ,Cell growth ,Cell Cycle ,Endothelial Cells ,hemic and immune systems ,Cell biology ,Complement system ,Original Research Paper ,Endothelial stem cell ,medicine.anatomical_structure ,cardiovascular system ,Endothelium, Vascular ,medicine.symptom - Abstract
Objectives The goal of this paper is to investigate the effects of activated complement C5a on vascular endothelium during vessel formation. Methods A human microvascular endothelial cell line (HMEC-1) derived from post-capillary venules in skin was used to measure DNA synthesis, proliferation and cell-cycle progression. In vitro ring-shaped formation by the cells was assessed by using type I collagen gel matrix and a cell-migration assay using the Chemotaxicell chamber. A Matrigel plug assay was performed to confirm the effect of C5a in vivo. Results C5a progressed the cell cycle of HMEC-1 into G2/M phases, and induced DNA synthesis and proliferation in a dose-dependent manner. C5a efficiently induced migration and ring-shaped structure formation both in vitro and in vivo. Furthermore, a C5a receptor antagonist (W-54011) suppressed all HMEC-1 activities including proliferation and migration. Conclusions Proliferation, migration, and ring-shaped formation by HMEC-1 cells was induced by C5a. The actions were efficiently inhibited by a specific antagonist against C5a. Our results implicated C5a in vessel formation and as a potent target for management of inflammatory diseases.
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13. The regenerative potential of Pax3/Pax7 on skeletal muscle injury.
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Azhar, Muhamad, Wardhani, Bantari Wisynu Kusuma, and Renesteen, Editha
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SKELETAL muscle injuries ,WORK-related injuries ,STEM cells ,INHIBITION of cellular proliferation ,CELL proliferation ,MUSCLE injuries - Abstract
Background : Skeletal muscle mishaps are the most well-known incidents in society, especially among athletes and the military population. From the various urgency, this accident needs to be cured more quickly. However, the current treatment still has some shortcomings and is less effective. In this case, Paired box 3 and Paired box 7 (Pax3/Pax7) proteins that induce stem cells could potentially be an alternative treatment for skeletal muscle injuries. This paper aimed to analyse the potential treatment of Pax3/Pax7 proteins inducing the stem cell for skeletal muscle injuries. We did a narrative review by gathering several scientific journals from several leading platforms like PubMed and Scopus. As common accidents, skeletal muscle disease could be due to workplace and non-workplace causes. The highest risk occurs in the athlete and military environment. The treatment of current skeletal muscle injuries is protection, rest, ice, compression, and elevation (PRICE), non-steroidal anti-inflammatory drugs (NSAIDs), and mechanical stimulation. However, it is considered less effective, especially in NSAIDs, inhibiting myogenic cell proliferation. The current finding indicates that the stem cells have markers known as Pax3/Pax7. The role of both markers in muscle injury, Pax3/Pax7, as transcription factors will induce cell division by H3K4 methylation mechanisms and chromatin modifications that stimulate gene activation. Conclusion: Regulation by Pax3/Pax7 factors that affect stem cells and stem cell proliferation is one of the alternative treatments. This regulation can accelerate the healing of injury victims, especially injuries to the skeletal muscles. Finally, after being compared, Pax3/Pax7 induces stem cells to have the potential to be one of the skeletal muscle injury treatments. Keywords: Pax3 and Pax7, Pax3/Pax7, Skeletal muscle, Athlete, Stem cells, Cell proliferation, Injuries. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Dual therapeutic targeting of MYC and JUNB transcriptional programs for enhanced anti-myeloma activity.
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Lind, Judith, Aksoy, Osman, Prchal-Murphy, Michaela, Fan, Fengjuan, Fulciniti, Mariateresa, Stoiber, Dagmar, Bakiri, Latifa, Wagner, Erwin F., Zwickl-Traxler, Elisabeth, Sattler, Martin, Kollmann, Karoline, Vallet, Sonia, and Podar, Klaus
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GENETIC transcription regulation ,BONE marrow ,MULTIPLE myeloma ,CELL proliferation ,TRANSCRIPTION factors ,BORTEZOMIB - Abstract
Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells via targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel proteolysis targeting chimera (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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15. WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer.
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Fan, Hao, Hu, Xuefei, Cao, Fuao, Zhou, Leqi, Wen, Rongbo, Shen, Hao, Fu, Yating, Zhu, Xiaoming, Jia, Hang, Liu, Zixuan, Wang, Guimin, Yu, Guanyu, Chang, Wenjun, and Zhang, Wei
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COLORECTAL cancer ,PROTEIN-tyrosine phosphatase ,PHOSPHOPROTEIN phosphatases ,CELL proliferation ,TUMOR growth - Abstract
Protein tyrosine phosphatase SHP2 activates RAS signaling, which is a novel target for colorectal cancer (CRC) therapy. However, SHP2 inhibitor monotherapy is ineffective for metastatic CRC and a combination therapy is required. In this study, we aimed to improve the antitumor efficacy of SHP2 inhibition and try to explore the resistance mechanism of SHP2 inhibitor. Results showed that WWP1 promoted the proliferation of CRC cells. Genetic or pharmacological inhibition of WWP1 enhanced the effect of SHP2 inhibitor in suppressing tumor growth in vitro and in vivo. WWP1 may mediate feedback reactivation of AKT signaling following SHP2 inhibition. Furthermore, nomogram models constructed with IHC expression of WWP1 and SHP2 greatly improved the accuracy of prognosis prediction for patients with CRC. Our findings indicate that WWP1 inhibitor I3C can synergize with SHP2 inhibitor and is expected to be a new strategy for clinical trials in treating advanced CRC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma.
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Liu, Chenghao, Zhuo, Yicheng, Yang, Xiaofeng, Yang, Chen, Shu, Min, Hou, Bowen, Hou, Jun, Chen, Xueling, Wang, Lianghai, and Wu, Xiangwei
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GENE expression ,SOMATOMEDIN A ,HEPATOCELLULAR carcinoma ,CELL proliferation ,RNA-binding proteins ,CIRCULAR RNA - Abstract
RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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17. Identification of an H-Ras nanocluster disrupting peptide.
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Steffen, Candy Laura, Manoharan, Ganesh babu, Pavic, Karolina, Yeste-Vázquez, Alejandro, Knuuttila, Matias, Arora, Neha, Zhou, Yong, Härmä, Harri, Gaigneaux, Anthoula, Grossmann, Tom N., and Abankwa, Daniel Kwaku
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RAS proteins ,PEPTIDES ,DRUG target ,CELL survival ,CELL proliferation - Abstract
Hyperactive Ras signalling is found in most cancers. Ras proteins are only active in membrane nanoclusters, which are therefore potential drug targets. We previously showed that the nanocluster scaffold galectin-1 (Gal1) enhances H-Ras nanoclustering via direct interaction with the Ras binding domain (RBD) of Raf. Here, we establish that the B-Raf preference of Gal1 emerges from the divergence of the Raf RBDs at their proposed Gal1-binding interface. We then identify the L5UR peptide, which disrupts this interaction by binding with low micromolar affinity to the B- and C-Raf-RBDs. Its 23-mer core fragment is sufficient to interfere with H-Ras nanoclustering, modulate Ras-signalling and moderately reduce cell viability. These latter two phenotypic effects may also emerge from the ability of L5UR to broadly engage with several RBD- and RA-domain containing Ras interactors. The L5UR-peptide core fragment is a starting point for the development of more specific reagents against Ras-nanoclustering and -interactors. The 23mer L5URcore peptide is identified, which binds with low micromolar affinity to Ras-binding domains, notably of Raf proteins, thus disrupting their galectin1-interaction, H-Ras-nanoclustering, -signalling and more broadly cell proliferation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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18. Heat shock protein 70 is associated with duration of cell proliferation in early pod development of soybean.
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Tanaka, Seiya, Ariyoshi, Yuri, Taniguchi, Takatoshi, Nakagawa, Andressa C. S., Hamaoka, Norimitsu, Iwaya-Inoue, Mari, Suriyasak, Chetphilin, and Ishibashi, Yushi
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HEAT shock proteins ,CELL proliferation ,SOYBEAN ,CROP yields ,GENETIC transcription regulation ,GENE families - Abstract
Pod is an important organ for seed production in soybean. Pod size varies among soybean cultivars, but the mechanism is largely unknown. Here we reveal one of the factors for pod size regulation. We investigate pod size differences between two cultivars. The longer pod of 'Tachinagaha' is due to more cell number than in the short pod of 'Iyodaizu'. POD SIZE OF SOYBEAN 8 (GmPSS8), a member of the heat shock protein 70 (HSP70) family, is identified as a candidate gene for determining pod length in a major QTL for pod length. Expression of GmPSS8 in pods is higher in 'Tachinagaha' than 'Iyodaizu' and is highest in early pod development. The difference in expression is the result of an in/del polymorphism which includes an enhancer motif. Treatment with an HSP70 inhibitor reduces pod length and cell number in the pod. Additionally, shorter pods in Arabidopsis hsp70-1/-4 double mutant are rescued by overexpression of GmPSS8. Our results identify GmPSS8 as a target gene for pod length, which regulates cell number during early pod development through regulation of transcription in soybean. Our findings provide the mechanisms of pod development and suggest possible strategies enhancing yield potential in soybean. The pod is a crucial organ for soybean seed production. One of the HSP70 family genes is associated with pod size regulation mediated by duration of cell proliferation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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19. Novel fabrication of macromolecular multi-functional hydrogel encapsulated with HUCB-derived mesenchymal stem cells to effective regeneration of cardiac repair after acute myocardial infarction.
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Xue, Jun and Gao, Yu Ping
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MYOCARDIAL infarction ,MESENCHYMAL stem cells ,CARDIAC regeneration ,HYDROGELS ,CORD blood - Abstract
Acute myocardial infarction (AMI) has been treated via injectable hydrogels and biomaterial patches invented using tissue engineering advancements over the past decade. Yet the curative potential of injectable hydrogels and stem cells is limited. Here, we propose the development of an injectable and conductive hydrogel composed of oxidised macromolecular hyaluronic acid and chitosan-grafted aniline tetramer polymeric components. In an attempt to enhance the therapeutic potential of AMI therapy, mesenchymal stem cells derived from human umbilical cord blood (HUCB-MSC) have been integrated into the formulation of a conductive hydrogel. For reliable connection to the beating hearts, the hydrogel exhibited suitable adhesive properties. Hydrogel's potent biocompatibility was determined by in vitro investigations of cell viability and proliferation of NRCMs and H9C2 cardiomyocytes. After myocardial injection, longer HUCB-MSCs survival length, cardiac functioning, and histology in SD rat myocardium were demonstrated, greatly associated by up-regulation and downregulation of cardiac-related relative gene expressions of angiogenic factors and inflammatory factors, respectively. The injectable hydrogel that contained HUCB-MSCs substantially enhanced the therapeutic benefits, indicating a potentially beneficial therapeutic approach to AMI therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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20. Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice.
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Wu, Szu-Hsien Sam, Kim, Somi, Lee, Heetak, Lee, Ji-Hyun, Park, So-Yeon, Bakonyi, Réka, Teriyapirom, Isaree, Hallay, Natalia, Pilat-Carotta, Sandra, Theussl, Hans-Christian, Kim, Jihoon, Lee, Joo-Hyeon, Simons, Benjamin D., Kim, Jong Kyoung, Colozza, Gabriele, and Koo, Bon-Kyoung
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KNOCKOUT mice ,GENETIC models ,CELL proliferation ,CELL populations ,FLUORESCENT proteins ,STEM cells ,P16 gene - Abstract
Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected. We now report Red2Flpe-SCON: a mosaic knockout system that uses multicolor reporters to label both mutant and wild-type cells. We develop the Red2Flpe mouse line for red clone-specific Flpe expression, as well as the FRT-based SCON (Short Conditional IntrON) method to facilitate tunable conditional mosaic knockouts in mice. We use the Red2Flpe-SCON method to study Sox2 mutant clonal analysis in the esophageal epithelium of adult mice which reveal that the stem cell gene, Sox2, is less essential for adult stem cell maintenance itself, but rather for stem cell proliferation and differentiation. Inducible genetic mosaics can provide information about cellular lineages that are otherwise difficult to obtain. Here the authors report a mosaic knockout system called Red2Flpe-SCON, which allows lineage tracing of wild-type and mutant cells using a multicolour fluorescent reporter in mice. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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21. Zedoarondiol inhibits human bronchial smooth muscle cell proliferation through the CAV-1/PDGF signalling pathway.
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Lyu, Yinglan, Feng, Wandi, Song, Jingze, Wang, Chunguo, Fu, Yu, Zhao, Baosheng, and Meng, Yanyan
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SMOOTH muscle ,CELLULAR signal transduction ,MUSCLE cells ,CELL proliferation ,PROTEOMICS ,PLATELET-derived growth factor - Abstract
Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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22. Purification and identification of intestinal mucosal cell proliferation-promoting peptides from Crassostrea hongkongensis.
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Pan, Jianyu, Wan, Peng, Chen, Deke, Chen, Hua, Chen, Xin, Sun, Huili, and Cai, Bingna
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CRASSOSTREA ,CELL proliferation ,MUCOUS membranes ,CANCER chemotherapy ,FUNCTIONAL foods - Abstract
Oyster peptides, together with polysaccharides, were found to protect the intestinal mucosal barrier against the harmful effects of 5-FU chemotherapy on rats in our previous study. However, whether oyster (Crassostrea hongkongensis) peptide can promote intestinal epithelia cell proliferation and migration alone is unknown. In this paper, oyster tissue was hydrolyzed using pepsin, trypsin, papain, bromelain, neutrase, flavorzyme, and alcalase protease. Among the hydrolysates that produced by trypsin showed the highest promoting effect on intestinal epithelia cell (IEC-6) proliferation and was fractionated into three molecular weight ultra-filtrates of > 10, 10-5, and < 5 kDa. The 10-5 kDa ultra-filtrate showed the highest promoting effect on cell proliferation, at 146.16 ± 6.56% (0.16 mg/ml), and was subjected to further purification. Two oyster peptides (F3-1 and F3-2) were purified from the 5-10 kDa ultra-filtrate by SEC and RP-HPLC. Their molecular mass and amino acid sequences were identified as VAPEEHPVLL (MW, 1102.5872 Da) and SYELPDGQVITIGNER (MW, 1789.9247 Da) by MALDI-TOF-MS/MS. Peptides F3-1 and F3-2 exhibited 150.81 ± 12.34% (5 µg/ml) and 151.73 ± 12.28% (6.25 µg/ml) promoting effects on IEC-6 proliferation, respectively, and both peptides showed greater promoting effects than the positive control (proglumide) at the same concentration under LPS stimulation culture conditions. This study indicated that oyster peptides could serve as a potential source of a functional food constituent for intestinal epithelium protection. [ABSTRACT FROM AUTHOR]
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- 2019
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23. Fabp3 Inhibits Proliferation and Promotes Apoptosis of Embryonic Myocardial Cells
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Yao-Qiu Liu, Kejiang Cao, Jinsong Zhang, Chun Zhu, Q Zhang, De-Liang Hu, Xiangqing Kong, Lingmei Qian, and F. K. Chen
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Cellular differentiation ,LYRM1 ,Biophysics ,Apoptosis ,Embryoid body ,Biology ,Fatty Acid-Binding Proteins ,Transfection ,Biochemistry ,Heart development ,Mice ,Cell Line, Tumor ,Animals ,Myocyte ,Myocytes, Cardiac ,RNA, Messenger ,Embryoid Bodies ,Cell Proliferation ,Original Paper ,Cell growth ,Cell Differentiation ,General Medicine ,Cell Biology ,Molecular biology ,P19 cells ,CHD ,P19 cell ,Cell culture ,Fatty Acid Binding Protein 3 - Abstract
Fatty acid binding protein 3 (FABP3) is a member of a family of binding proteins. The protein is mainly expressed in cardiac and skeletal muscle cells, and it has been linked to fatty acid metabolism, trafficking, and signaling. Using suppression subtractive hybridization, we previously found that FABP3 is highly regulated in ventricular septal defect (VSD) patients and may play a significant role in the development of human VSD. We therefore aimed to identify the biological characteristics of the FABP3 gene in embryonic myocardial cells. On the basis of RT-PCR and western blotting analyses, we demonstrated that the expression levels of FABP3 mRNA and protein were up-regulated initially and then gradually decreased with P19 cell differentiation. MTT assays and cell cycle analysis showed that FABP3 inhibits P19 cell proliferation, and data from annexin V-FITC assays revealed that FABP3 can promote apoptosis of P19 cells. Further data from quantitative real-time RT-PCR revealed lower expression levels of cardiac muscle-specific molecular markers (cTnT, alpha-MHC, GATA4, and MEF2c) in FABP3-overexpressing cell lines than in the control cells during differentiation. Our results demonstrate that FABP3 may be involved in the differentiation of cardiac myocytes.
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24. Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis
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Mizuho A. Kido, Toshihiro Seike, Haruo Iguchi, Mami Noda, Soichi Takiguchi, Kyota Fujita, Yukiko Yamakawa, and Norihiro Teramoto
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Male ,Pathology ,medicine.medical_specialty ,Cancer Research ,Lung Neoplasms ,Biology ,Plasminogen activator inhibitor-1 ,Metastasis ,Mice ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Lung cancer ,Cell Proliferation ,Macrophage migration inhibitory factor ,Inflammation ,Mice, Knockout ,Mice, Inbred BALB C ,Tumor microenvironment ,Glial fibrillary acidic protein ,Interleukin-6 ,Brain Neoplasms ,Interleukin-8 ,General Medicine ,Human brain ,respiratory system ,medicine.disease ,Interleukin-1β ,Tumor necrosis factor-α ,medicine.anatomical_structure ,Oncology ,Astrocytes ,biology.protein ,Cytokines ,Tumor necrosis factor alpha ,Research Paper ,Brain metastasis - Abstract
The incidence of brain metastasis is increasing, however, little is known about molecular mechanism responsible for lung cancer-derived brain metastasis and their development in the brain. In the present study, brain pathology was examined in an experimental model system of brain metastasis as well as in human brain with lung cancer metastasis. In an experimental model, after 3–6 weeks of intracardiac inoculation of human lung cancer-derived (HARA-B) cells in nude mice, wide range of brain metastases were observed. The brain sections showed significant increase in glial fibrillary acidic protein (GFAP)-positive astrocytes around metastatic lesions. To elucidate the role of astrocytes in lung cancer proliferation, the interaction between primary cultured mouse astrocytes and HARA-B cells was analyzed in vitro. Co-cultures and insert-cultures demonstrated that astrocytes were activated by tumor cell-oriented factors; macrophage migration inhibitory factor (MIF), interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). Activated astrocytes produced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), which in turn promoted tumor cell proliferation. Semi-quantitative immunocytochemistry showed that increased expression of receptors for IL-6 and its subunits gp130 on HARA-B cells. Receptors for TNF-α and IL-1β were also detected on HARA-B cells but down-regulated after co-culture with astrocytes. Insert-culture with astrocytes also stimulated the proliferation of other lung cancer-derived cell lines (PC-9, QG56, and EBC-1). These results suggest that tumor cells and astrocytes stimulate each other and these mutual relationships may be important to understand how lung cancer cells metastasize and develop in the brain. Electronic supplementary material The online version of this article (doi:10.1007/s10585-010-9354-8) contains supplementary material, which is available to authorized users.
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25. Inhibition of caspase mediated apoptosis restores muscle function after crush injury in rat skeletal muscle
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Thomas Mittlmeier, Philipp Herlyn, Robert Rotter, Zhengdong Li, Brigitte Vollmar, and Ioannis Stratos
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Male ,Crush injury ,Muscle tissue ,medicine.medical_specialty ,Cancer Research ,Clinical Biochemistry ,Pharmaceutical Science ,Apoptosis ,Caspase 3 ,Cysteine Proteinase Inhibitors ,Biology ,Amino Acid Chloromethyl Ketones ,Muscle regeneration ,Internal medicine ,medicine ,Animals ,Myocyte ,Muscle Strength ,Rats, Wistar ,Muscle, Skeletal ,Cell Proliferation ,Pharmacology ,Biochemistry, medical ,Original Paper ,Cell growth ,Biochemistry (medical) ,Skeletal muscle ,Anatomy ,Cell Biology ,medicine.disease ,Caspase Inhibitors ,Rats ,z-VAD.fmk ,medicine.anatomical_structure ,Endocrinology ,Caspases ,Wounds and Injuries ,Tetanic contraction ,medicine.symptom - Abstract
Although muscle regeneration after injury is accompanied by apoptotic cell death, prolonged apoptosis inhibits muscle restoration. The goal of our study was to provide evidence that inhibition of apoptosis improves muscle function following blunt skeletal muscle injury. Therefore, 24 rats were used for induction of injury to the left soleus muscle using an instrumented clamp. All animals received either 3.3 mg/kg i.p. of the pan-caspase inhibitor Z-valinyl-alanyl-DL: -aspartyl-fluoromethylketone (z-VAD.fmk) (n = 12 animals) or equivalent volumes of the vehicle solution DMSO (n = 12 animals) at 0 and 48 h after trauma. After assessment of the fast twitch and tetanic contraction capacity of the muscle at days 4 and 14 post injury, sampling of muscle tissue served for analysis of cell apoptosis (cleaved caspase 3 immunohistochemistry), cell proliferation (BrdU immunohistochemistry) as well as of muscle tissue area and myofiber diameter (HE planimetric analysis). Muscle strength analysis after 14 days in the z-VAD.fmk treated group revealed a significant increase in relative muscle strength when compared to the DMSO treated group. In contrast to the DMSO treated injured muscle, showing a transient switch towards a fast-twitching muscle phenotype (significant increase of the twitch-to-tetanic force ratio), z-VAD.fmk treated animals showed an enhanced healing process with a faster restoration of the twitch-to-tetanic force ratio towards the physiological slow-twitching muscle phenotype. This enhancement of muscle function was accompanied by a significant decrease of cell apoptosis and cell proliferation at day 4 as well as by a significant increase of muscle tissue area at day 4. At day 14 after injury z-VAD.fmk treated animals presented with a significant increase of myofiber diameter compared to the DMSO treated animals. Thus, z-VAD.fmk could provide a promising option in the anti-apoptotic therapy of muscle injury.
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26. Dynamic analysis of lung metastasis by mouse osteosarcoma LM8: VEGF is a candidate for anti-metastasis therapy
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Takaaki Tanaka, Norifumi Naka, Kiyoko Yoshioka, Hideki Yoshikawa, Toru Wakamatsu, Yoshihiro Yui, Nobuhito Araki, and Kazuyuki Itoh
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Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Cancer Research ,Indazoles ,Lung Neoplasms ,medicine.drug_class ,Blotting, Western ,Angiogenesis Inhibitors ,Apoptosis ,Bone Neoplasms ,Biology ,Real-Time Polymerase Chain Reaction ,Tyrosine-kinase inhibitor ,Metastasis ,Pazopanib ,Immunoenzyme Techniques ,chemistry.chemical_compound ,Mice ,Circulating tumor cell ,Cell Movement ,medicine ,Tumor Cells, Cultured ,Animals ,RNA, Messenger ,Transendothelial migration ,Cell Proliferation ,Mice, Inbred C3H ,Osteosarcoma ,Sulfonamides ,Reverse Transcriptase Polymerase Chain Reaction ,Circulating tumor cells ,General Medicine ,medicine.disease ,Extravasation ,Coculture Techniques ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Pyrimidines ,chemistry ,Oncology ,medicine.drug ,Research Paper - Abstract
Osteosarcoma (OS) is the most common malignant bone tumor and the prognosis depends on pulmonary metastases, which arise from multi-step progression of malignant tumors. We herein aimed to clarify the critical step of pulmonary metastasis using the syngeneic mouse spontaneous highly metastatic OS LM8 and parental Dunn cell lines, to identify new candidate molecules to suppress pulmonary metastasis. We first investigated the chronological detection of circulating tumor cells (CTCs) from mice with either cell line. LM8 CTCs appeared faster, at a higher rate and with a greater number compared to Dunn CTCs. Cultured cells from CTCs of LM8 showed higher proliferative ability than cells from the primary site in suspension culture, which mimicked the environment of the bloodstream for CTCs. The proliferative ability of LM8 cells was also higher than that of Dunn cells in 3D collagen culture with low stiffness (−150 Pa; close to conditions in the lung). We next focused on the extravasation step. LM8 showed higher migration ability compared to Dunn with transendothelial migration assay. We also found a disruption in endothelial barrier function throughout co-culture with LM8 using time-lapse imaging. In addition, LM8 secreted high levels of vascular endothelial growth factor (VEGF), while VEGF signal inhibition with a small molecule tyrosine kinase inhibitor (pazopanib) decreased disruption of the vascular barrier and transendothelial migration of LM8. Finally, daily oral administration of pazopanib reduced the rate and size of pulmonary metastasis in vivo. Collectively, these results show anti-VEGF therapy as a candidate for pulmonary metastasis of OS. Electronic supplementary material The online version of this article (doi:10.1007/s10585-012-9543-8) contains supplementary material, which is available to authorized users.
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27. Polyclonal rabbit anti-murine plasmacytoma cell globulins induce myeloma cells apoptosis and inhibit tumour growth in mice
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Zhi-hui Cheng, Yuqin Yao, Zhi-yong Li, Huashan Shi, Yan Zhou, Feng-Yu Cui, Fei Leng, Jinliang Yang, Lantu Gou, Yuquan Wei, Bo Mu, Yuan Wen, and Tian-Tai Ma
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Cancer Research ,medicine.drug_class ,Clinical Biochemistry ,Immunoglobulins ,Pharmaceutical Science ,Apoptosis ,Biology ,Monoclonal antibody ,Flow cytometry ,Cell Line ,Mice ,Multiple myeloma ,immune system diseases ,medicine ,In Situ Nick-End Labeling ,Animals ,Polyclonal antibodies ,Viability assay ,Cell Proliferation ,Pharmacology ,Biochemistry, medical ,Original Paper ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Cell growth ,Biochemistry (medical) ,DNA ladder ,Cell Biology ,medicine.disease ,Molecular biology ,Disease Models, Animal ,biology.protein ,DNA fragmentation ,Plasmacytoma ,Immunotherapy ,Rabbits ,Protein Binding - Abstract
Multiple myelomas (MMs) are etiologically heterogeneous and there are limited treatment options; indeed, current monoclonal antibody therapies have had limited success, so more effective antibodies are urgently needed. Polyclonal antibodies are a possible alternative because they target multiple antigens simultaneously. In this study, we produced polyclonal rabbit anti-murine plasmacytoma cell immunoglobulin (PAb) by immunizing rabbits with the murine plasmacytoma cell line MPC-11. The isolated PAb bound to plasma surface antigens in several MM cell lines, inhibited their proliferation as revealed by MTT assay, and induce apoptosis as indicated by flow cytometry, microscopic observation of apoptotic changes in morphology, and DNA fragmentation on agarose gels. The cytotoxicity of PAb on MPC-11 cell lines was both dose-dependent and time-dependent; PAb exerted a 50% inhibitory effect on MPC-11 cell viability at a concentration of 200 µg/ml in 48 h. Flow cytometry demonstrated that PAb treatment significantly increased the number of apoptotic cells (48.1%) compared with control IgG (8.3%). Apoptosis triggered by PAb was confirmed by activation of caspase-3, -8, and -9. Serial intravenous or intraperitoneal injections of PAb inhibited tumour growth and prolonged survival in mice bearing murine plasmacytoma, while TUNEL assay demonstrated that PAb induced statistically significant apoptosis (P < 0.05) compared to control treatments. We conclude that PAb is an effective agent for in vitro and in vivo induction of apoptosis in multiple myeloma and that exploratory clinical trials may be warranted.
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28. Expression and function of NET-1 in human skin squamous cell carcinoma
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Guilan Wang, Li Chen, Jie Zhang, Yu-Yin Xu, Jing Qin, Xingyu Li, and Jianli Wang
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Adult ,Male ,RNA interference (RNAi) ,Skin Neoplasms ,Transplantation, Heterologous ,Down-Regulation ,Mice, Nude ,Dermatology ,Biology ,Flow cytometry ,Small hairpin RNA ,Mice ,Western blot ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,NET-1 (TSPAN1, TSPAN1/C4–8) ,Skin squamous cell carcinoma (SSCC) ,RNA, Small Interfering ,Aged ,Cell Proliferation ,Skin ,Aged, 80 and over ,Oncogene Proteins ,Mice, Inbred BALB C ,Original Paper ,medicine.diagnostic_test ,Cell growth ,General Medicine ,Transfection ,Middle Aged ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Ki-67 Antigen ,Cell culture ,Carcinoma, Squamous Cell ,Female ,RNA Interference ,A431 cells ,Immunostaining ,Neoplasm Transplantation - Abstract
To evaluate the clinicopathological significance of NET-1 in human skin squamous cell carcinoma (SSCC). The expression of NET-1 and Ki67 protein was detected using immunostaining from 60 SSCC cases, 50 SIN samples and ten normal skin tissues. The vectors expressing NET-1, siRNA NET-1 and shRNA NET-1 were constructed, as well as negative controls (target-off). In transfected A431 cells, the expression of NET-1 was detected by qRT-PCR, Western blot and immunofluorescence staining; the proliferation and migration of cells was evaluated by MTT, flow cytometry, wound healing and transwell chamber assays. The stable cell lines transfected with shRNANET-1 was inoculated in nude mice for in vivo study. (1) The levels of NET-1 were significantly higher in SSCC (96.67 %) and SIN III (93.75 %) than that in SIN I and II (41.18 %), (P
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29. Expression of TweakR in breast cancer and preclinical activity of enavatuzumab, a humanized anti-TweakR mAb
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Mel Fox, Gary C. Starling, Mian Su, Sonia Tanlimco, Debra Chao, Shiming Ye, Donghee Choi, Johnny Yin, Lisa Durkin, Patricia Culp, Yongke Zhang, Eric D. Hsi, Mien Sho, and Han Kim
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medicine.medical_specialty ,Cancer Research ,Receptor, ErbB-2 ,medicine.drug_class ,Cell ,Drug Evaluation, Preclinical ,Gene Expression ,Antineoplastic Agents ,Biology ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,Receptors, Tumor Necrosis Factor ,Mice ,Breast cancer ,Cell Movement ,Trastuzumab ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Receptor ,skin and connective tissue diseases ,Antibody ,Cytokine TWEAK ,Cell Proliferation ,Original Paper ,Hematology ,Cell growth ,TweakR ,Carcinoma, Ductal, Breast ,Fn14 ,Drug Synergism ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,medicine.anatomical_structure ,Oncology ,TWEAK Receptor ,Immunology ,Cancer research ,Female ,medicine.drug - Abstract
Background The receptor for the cytokine TWEAK (TweakR) is a cell surface member of the tumor necrosis factor receptor superfamily with diverse biological roles. TNFRSF family members are appealing therapeutic targets in oncology due to their aberrant expression and function in tumor cells. The goal of the current study was to examine the potential of TweakR as a therapeutic target in breast cancer. Methods Expression of TweakR in primary breast cancer tissues and metastases was characterized using immunohistochemistry. To determine the functional relevance of TweakR, breast cancer cell lines were treated in vitro and in vivo with enavatuzumab, a humanized mAb against TweakR. Results Overexpression of TweakR was observed in infiltrating tumors compared to normal adjacent breast tissues, and strong staining of TweakR was observed in all subtypes of invasive ductal breast cancer. In addition, a positive correlation of TweakR and HER2 expression and co-localization were observed, irrespective of ER status. TweakR expression was also observed in bone metastasis samples from primary breast cancer but rarely in benign tumors. Enavatuzumab inhibited the in vitro growth of TweakR-expressing breast cancer cell lines, and this activity was augmented by cross-linking the mAb. In addition, enavatuzumab significantly inhibited the in vivo growth of multiple breast cancer xenograft models including a model of metastasis. Conclusions TweakR is highly expressed in all subtypes of invasive ductal breast cancer, and enavatuzumab administration exhibited a dose-dependent inhibition of primary tumor growth and lung metastasis and enhanced the antitumor activity of several chemotherapy agents currently used to treat breast cancer. These data provide the rationale to evaluate enavatuzumab as a potential therapy for the treatment of breast cancer. Electronic supplementary material The online version of this article (doi:10.1007/s00432-012-1332-x) contains supplementary material, which is available to authorized users.
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30. The Effects of Wubeizi Ointment on the Proliferation of Keloid-Derived Fibroblasts
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Xiang-hui Chen, Zhi-ming Tang, Jing-guo Li, Cui-xia Zhang, Ji-Cun Ding, and Xiao-xiang Zhai
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medicine.medical_specialty ,Dependent manner ,Rhus ,Pharmacology toxicology ,Biophysics ,Biochemistry ,Andrology ,Ointments ,Keloid ,medicine ,Humans ,Primary cell culture ,Fibroblast ,skin and connective tissue diseases ,Cell proliferation ,Original Paper ,business.industry ,Cell growth ,Cell Cycle ,General Medicine ,Cell Biology ,Cell cycle ,Fibroblasts ,medicine.disease ,Dermatology ,eye diseases ,medicine.anatomical_structure ,Cell culture ,Wubeizi ointment ,business ,Drugs, Chinese Herbal - Abstract
To evaluate the effectiveness of the Wubeizi (WBZ) ointment on keloid-derived fibroblasts. The primary cells of the keloid-derived fibroblasts were cultured and the effectiveness of the WBZ ointment at different concentrations was examined by MTT colorimetric methods on keloid-derived fibroblasts. The WBZ ointment showed inhibitory effects on proliferating the keloid-derived fibroblasts (P P2 + M stage cells was significantly lower than that of control group, which was statistically significant (P 2 + M stage increased with higher drug concentrations (P
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31. The General Growth Logistics of Cell Populations
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Dieter Kaufmann, D. Bartkowiak, H. G. Kilian, and Ralf Kemkemer
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Cell type ,Relaxation ,Cell ,Biophysics ,CHO Cells ,Saccharomyces cerevisiae ,Biology ,Models, Biological ,Biochemistry ,Quantitative Biology::Cell Behavior ,Colonies ,Mice ,Cricetulus ,Cell Line, Tumor ,Cricetinae ,medicine ,Escherichia coli ,Animals ,Humans ,Structure and dynamics ,Cell Proliferation ,Genetics ,Growth logistics ,Original Paper ,Cell growth ,Large cell ,Cell Cycle ,Populations ,General Medicine ,Cell Biology ,Cell cycle ,Culture Media ,medicine.anatomical_structure ,Distribution (mathematics) ,Transmission (telecommunications) ,Melanocytes ,Cell multiplication ,Relaxation (approximation) ,Biological system - Abstract
An increment model based on thermodynamics lays bare that the cell size distributions of archaea, prokaryotes and eukaryotes are optimized and belong to the same universal class. Yet, when a cell absorbs mass or signals are processed, these conditions are disturbed. Relaxation re-installs ideal growth conditions via an exponential process with a rate that slows down with the cell size. In a growing ensemble, a distribution of relaxation modes comes in existence, exactly defined by the universal cell size distribution. The discovery of nano-mechanic acoustic activities in cells led us to assume that in a growing ensemble acoustic signals may contribute significantly to the transmission of essential information about growth-induced disturbances to all cells, initiating that way coordinated relaxation. The frequency increases with the cell number shortening the period between successive signals. The completion of rearrangements occurring at a constant rate is thus progressively impaired, until cellular growth stops, totally. Due to this phenomenon, the so-called "relaxation-frequency-dispersion" cell colonies should exhibit a maximum cell number. In populations with large cell numbers, subsystems, behaving similar-like colonies, should form network-like patterns. Based on these ideas, we formulate equations that describe the growth curves of all cell types, verifying that way the general nature of the growth logistics.
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32. Androgen receptor footprint on the way to prostate cancer progression
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Wayne Bowden, Irina U. Agoulnik, and Myles C. Hodgson
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Male ,medicine.medical_specialty ,Urology ,Apoptosis ,Castration resistance ,Androgen suppression ,Metastasis ,Mice ,Prostate cancer ,Internal medicine ,Androgen Receptor Antagonists ,medicine ,Animals ,Humans ,Cell Proliferation ,business.industry ,Prostatic Neoplasms ,Cancer ,Topic Paper ,medicine.disease ,Androgen receptor ,Disease Models, Animal ,Endocrinology ,Cistrome ,Receptors, Androgen ,Tumor progression ,Disease Progression ,Cancer research ,business ,Signal Transduction - Abstract
The prostate gland is exquisitely sensitive to androgen receptor (AR) signaling. AR signaling is obligatory for prostate development and changes in AR levels, its ligands or shifts in AR mode of action are reflected in the physiology of the prostate. The AR is intimately linked to prostate cancer biology through the regulation of epithelial proliferation, suppression of apoptosis and the development of castration-resistant disease. Thus, AR is the primary therapeutic target in various prostate diseases such as BPH and cancer. Although some tumors lose AR expression, most retain the AR and have elevated levels and/or shifts in activity that are required for tumor progression and metastasis. New AR inhibitors currently in clinical trials with higher receptor affinity and specificity may improve prostate cancer patient outcome. Several events play an important role in initiation, primary tumor development and metastatic spread. Androgen receptor activity and promoter specificity change due to altered coregulator expression. Changes in epigenetic surveillance alter the AR cistrome. Both systemic and local inflammation increases with PCa progression affecting AR levels, activity, and requirement for ligand. Our current understanding of AR biology suggest that global androgen suppression may drive the development of castration-resistant disease and therefore the question remains: Does effective inhibition of AR activity mark the end of the road for PCa or only a sharp turn toward a different type of malignancy?
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33. Lidocaine inhibits staphylococcal enterotoxin-stimulated activation of peripheral blood mononuclear cells from patients with atopic dermatitis
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Jianying Liang, Weiqin Yang, Hui Zhang, Yin Zhuang, Honglin Wang, Ming Li, Xia Yu, Qingqing Jiao, Xilan Chen, Ruhong Cheng, Zhirong Yao, Zhenglin Hu, and Yifeng Guo
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Keratinocytes ,Male ,Staphylococcus aureus ,Lidocaine ,medicine.medical_treatment ,T cell ,Activation ,Down-Regulation ,Enterotoxin ,Dermatology ,Filaggrin Proteins ,Lymphocyte Activation ,Peripheral blood mononuclear cell ,Cell Line ,Dermatitis, Atopic ,Enterotoxins ,Th2 Cells ,Intermediate Filament Proteins ,Humans ,Medicine ,Atopic dermatitis ,Cell Proliferation ,Original Paper ,business.industry ,hemic and immune systems ,General Medicine ,Th1 Cells ,medicine.disease ,Coculture Techniques ,Staphylococcal enterotoxin B ,Staphylococcal enterotoxin A ,HaCaT ,Cytokine ,medicine.anatomical_structure ,Peripheral blood mononuclear cells ,Immunology ,Cytokines ,Female ,business ,medicine.drug ,Filaggrin - Abstract
Atopic dermatitis (AD) is an inflammatory, chronically relapsing, pruritic skin disease and lesions associated with AD are frequently colonized with Staphylococcus aureus (S. aureus). Activation of T cells by staphylococcal enterotoxins (SE) plays a crucial role in the pathogenesis of AD. Previous studies have demonstrated that lidocaine could attenuate allergen-induced T cell proliferation and cytokine production in peripheral blood mononuclear cells (PBMCs) from asthma patients. The purpose of this study was to investigate the effects of lidocaine on SE-stimulated activation of PBMCs from AD patients. PBMCs were isolated from ten AD patients and stimulated by staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB) in the presence or absence of lidocaine in various concentrations. Cellular proliferation and the release of representative TH1- and TH2-type cytokines were measured. The effect of lidocaine on filaggrin (FLG) expression in HaCaT cells co-cultured with SE-activated PBMCs was also examined. Our results demonstrated that lidocaine dose-dependently inhibited the proliferative response and the release of IL-4, IL-5, IL-13, TNF-α, and IFN-γ from SEA- and SEB-stimulated PBMCs and also blocked the down-regulation of FLG expression in HaCaT cells co-cultured with SEA- and SEB-activated PBMCs. These results indicate that lidocaine inhibited SEA- and SEB-stimulated activation of PBMCs from patients with AD. Our findings encourage the use of lidocaine in the treatment of AD.
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34. Mechanisms Behind the Inhibition of Lung Adenocarcinoma Cell by Shikonin
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Weiqing Gu, Heyong Wang, Shengbang Wan, Wen-jing Lan, and Songwen Zhou
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Cell cycle checkpoint ,Lung Neoplasms ,Biophysics ,Adenocarcinoma of Lung ,Antineoplastic Agents ,Apoptosis ,Biology ,Cell cycle ,Adenocarcinoma ,Resting Phase, Cell Cycle ,Biochemistry ,Cyclin D1 ,Cell Line, Tumor ,medicine ,Humans ,Shikonin ,Cell proliferation ,A549 cell ,Lung adenocarcinoma cell ,Original Paper ,Cell growth ,General Medicine ,Cell Biology ,medicine.disease ,G1 Phase Cell Cycle Checkpoints ,Cell biology ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,Cell culture ,Caspases ,Cancer research ,Cell apoptosis ,Naphthoquinones - Abstract
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, can exert inhibitory effect on tumor cell growth. However, little has been known concerning the effect of shikonin on lung adenocarcinoma cell and underlying mechanisms. In the present study, we investigated the effect of shikonin on the proliferation, cell cycle arrest, and apoptosis in human lung adenocarcinoma cells. We found that shikonin significantly suppressed the proliferation of lung adenocarcinoma cells compared with control in dose- and time-dependent manner (P < 0.05). In the meantime, our results showed that shikonin markedly increased the proportion of A549 cells at stage G1 as well as induced apoptosis in A549 cells. Furthermore, suppressed CCND1 and elevated caspase3 and caspase7 expression levels at mRNA were found in this study, indicating that shikonin may inhibit the growth of lung adenocarcinoma cell by changing cell cycle and promoting cell apoptosis through the regulation of CCND1, caspase3, and caspase7. Although more studies are needed, this study suggests that shikonin has the potential to be used as an anti-cancer agent in the treatment of lung adenocarcinoma.
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35. Kynurenic Acid Induces Impairment of Oligodendrocyte Viability: On the Role of Glutamatergic Mechanisms
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Waldemar A. Turski, Ewa Langner, Wojciech Rzeski, Marta Kinga Lemieszek, Grażyna Rajtar, and Jacek M. Kwiecien
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0301 basic medicine ,Cell viability ,Cell Survival ,Central nervous system ,Biology ,Kynurenic Acid ,Biochemistry ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Glutamatergic ,Myelin ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Kynurenic acid ,Glutamates ,Excitatory Amino Acid Agonists ,medicine ,Animals ,Viability assay ,Cell Proliferation ,Original Paper ,Oligodendrocytes ,OLN-93 ,Glutamate receptor ,Glutamate receptors ,Kynurenic acid (KYNA) ,General Medicine ,Oligodendrocyte ,Rats ,Cell biology ,Oligodendroglia ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cell culture ,Excitatory Amino Acid Antagonists ,030217 neurology & neurosurgery - Abstract
Kynurenic acid (KYNA) is an end stage product of tryptophan metabolism with a variety of functions in the human body, both in the central nervous system (CNS) and in other organs. Although its activity in the human brain has been widely studied and effects on neural cells were emphasized, the effect of KYNA on oligodendroglial cells remains unknown. Present study aims at describing the activity of high concentration of KYNA in OLN-93 cells. The inhibition of OLN-93 oligodendrocytes viability by KYNA in a medium with reduced serum concentration has been demonstrated. Although decreased metabolic activity of KYNA treated OLN-93 cells was shown, the cells proliferation was not altered. KYNA treatment did not alter morphology as well as expression level of cell cycle and proliferation regulating proteins. Furthermore, glutamate receptor antagonists and agonists did not alter the inhibitory effect of KYNA on viability of OLN-93 oligodendrocytes. This study contributes to the elucidation of effects of KYNA on oligodendrocytes in vitro, yet further analyses are necessary to explain the mechanisms behind the damage and loss of myelin sheaths.
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36. Cryopreserved CD90+ cells obtained from mobilized peripheral blood in sheep: a new source of mesenchymal stem cells for preclinical applications
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Carlos Landa-Solís, Ricardo Gómez García, Clemente Ibarra, Cecilia Hernández-Flores, Carlos Pineda, Carmina Ortega-Sánchez, Brenda Olivos-Díaz, Julio Granados-Montiel, Maria Cristina Velasquillo-Martínez, María Eugenia Chang-González, Monica Cruz-Lemini, and Anell Olivos-Meza
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0301 basic medicine ,Male ,Cellular differentiation ,Population ,Biomedical Engineering ,Fluorescent Antibody Technique ,Cell Separation ,Biology ,Immunophenotyping ,Biomaterials ,03 medical and health sciences ,Cryopreserved CD90+ cells ,Tissue engineering ,Mobilized peripheral blood ,medicine ,Animals ,CD90 ,education ,Cell Shape ,Stem cell transplantation for articular cartilage repair ,Cell Proliferation ,Cryopreservation ,education.field_of_study ,Original Paper ,Transplantation ,Sheep ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Flow Cytometry ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Peripheral Blood Stem Cells ,Thy-1 Antigens ,Bone marrow ,Stem cell - Abstract
Mobilized peripheral blood (MPB) bone marrow cells possess the potential to differentiate into a variety of mesenchymal tissue types and offer a source of easy access for obtaining stem cells for the development of experimental models with applications in tissue engineering. In the present work, we aimed to isolate by magnetic activated cell sorting CD90+ cells from MPB by means of the administration of Granulocyte-Colony Stimulating Factor and to evaluate cell proliferation capacity, after thawing of the in vitro culture of this population of mesenchymal stem cells (MSCs) in sheep. We obtained a median of 8.2 ± 0.6 million of CD90+ cells from the 20-mL MPB sample. After thawing, at day 15 under in vitro culture, the mean CD90+ cells determined by flow cytometry was 92.92 ± 1.29 % and cell duplication time determined by crystal violet staining was 47.59 h. This study describes for the first time the isolation, characterization, and post-in vitro culture thawing of CD90+ MSCs from mobilized peripheral blood in sheep. This population can be considered as a source of MSCs for experimental models in tissue engineering research.
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37. High Therapeutic Efficiency of Magnetic Hyperthermia in Xenograft Models Achieved with Moderate Temperature Dosages in the Tumor Area
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Gorka Salas, Vijay R. Patel, Gabriella Rimkus, Volker Ettelt, Ingrid Hilger, Susanne Kossatz, Heidi Dähring, Francisco J. Teran, Robert Ludwig, Marzia Marciello, Ministerio de Economía y Competitividad (España), and European Commission
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Hyperthermia ,Pathology ,medicine.medical_specialty ,CEM43T90 ,Pharmaceutical Science ,Apoptosis ,02 engineering and technology ,Ferric Compounds ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Iron oxide nanoparticles ,Electromagnetic Fields ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Magnetic hyperthermia ,Pharmacology (medical) ,Cell Proliferation ,Pharmacology ,Therapeutic effect ,Organic Chemistry ,Temperature ,Hyperthermia, Induced ,Neoplasms, Experimental ,021001 nanoscience & nanotechnology ,medicine.disease ,Xenograft Model Antitumor Assays ,3. Good health ,in vivo ,Ki-67 Antigen ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Temperature dose ,Nanoparticles ,Magnetic nanoparticles ,Molecular Medicine ,0210 nano-technology ,Research Paper ,Biotechnology - Abstract
[Purpose] Tumor cells can be effectively inactivated by heating mediated by magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress inside the tumor remain to be identified. The present study investigates the therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC-3) xenografts in mice in vivo., [Methods] Superparamagnetic iron oxide nanoparticles, synthesized either via an aqueous (MF66; average core size 12 nm) or an organic route (OD15; average core size 15 nm) are analyzed in terms of their specific absorption rate (SAR), cell uptake and their effectivity in in vivo hyperthermia treatment., [Results] Exceptionally high SAR values ranging from 658 ± 53 W*gFe −1 for OD15 up to 900 ± 22 W*gFe −1 for MF66 were determined in an alternating magnetic field (AMF, H = 15.4 kA*m−1 (19 mT), f = 435 kHz). Conversion of SAR values into system-independent intrinsic loss power (ILP, 6.4 ± 0.5 nH*m2*kg−1 (OD15) and 8.7 ± 0.2 nH*m2*kg−1 (MF66)) confirmed the markedly high heating potential compared to recently published data. Magnetic hyperthermia after intratumoral nanoparticle injection results in dramatically reduced tumor volume in both cancer models, although the applied temperature dosages measured as CEM43T90 (cumulative equivalent minutes at 43°C) are only between 1 and 24 min. Histological analysis of magnetic hyperthermia treated tumor tissue exhibit alterations in cell viability (apoptosis and necrosis) and show a decreased cell proliferation., The described work was carried out within the project “Multifunctional Nanoparticles for the Selective Detection and Treatment of Cancer” (Multifun), which is funded by the European Seventh Framework Program (FP7/2007–2013) under grant agreement no. 262943. F.J.T acknowledges financial support from Ramon y Cajal subprogram (RYC-2011-09617).
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38. Localization of decorin gene expression in normal human breast tissue and in benign and malignant tumors of the human breast
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Annele Sainio, Mikko Savontaus, Hannu Järveläinen, Tanja Kakko, Mirva Söderström, and Pia Boström
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Adult ,Pathology ,medicine.medical_specialty ,Stromal cell ,Histology ,Decorin ,Apoptosis ,Breast Neoplasms ,In situ hybridization ,Transfection ,Breast cancer ,Stroma ,Transduction, Genetic ,Cell Adhesion ,medicine ,Humans ,RNA, Messenger ,skin and connective tissue diseases ,Molecular Biology ,Aged ,Cell Proliferation ,Aged, 80 and over ,Original Paper ,biology ,Gene Expression Profiling ,Carcinoma ,Extracellular matrix ,Cell Biology ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,carbohydrates (lipids) ,Medical Laboratory Technology ,Proteoglycan ,Cell behavior ,Cancer cell ,MCF-7 Cells ,biology.protein ,Cancer research ,Female ,Stromal Cells - Abstract
The small extracellular matrix proteoglycan decorin which possesses a potent antitumor activity has been shown to be present in various amounts in the stroma of several tumors including those of the breast. Regarding decorin in breast malignancies the published data are conflicting, i.e., whether breast cancer cells express it or not. Here, we first compared decorin gene expression levels between healthy human breast tissue and selected types of human breast cancer using GeneSapiens databank. Next, we localized decorin mRNA in tissue specimen of normal human breast, intraductal breast papillomas and various histologic types of human breast cancer using in situ hybridization (ISH) with digoxigenin-labeled RNA probes for decorin. We also examined the effect of decorin transduction on the behavior of cultured human breast cancer MCF7 cells. Analysis of GeneSapiens databank revealed that in various human breast cancers decorin expression is significant. However, ISH results clearly demonstrated that human breast cancer cells independently of the type of the cancer do not express decorin mRNA. This was also true for papilloma-forming cells of the human breast. Indeed, decorin gene expression in healthy human breast tissue as well as in benign and malignant tumors of human breast was shown to take place solely in cells of the original stroma. Decorin transduction using decorin adenoviral vector in decorin-negative MCF7 cells resulted in a significant decrease in the proliferation of these cells and changed cell cohesion. Decorin-transduced MCF7 cells also exhibited increased apoptosis. In conclusion, our study shows that in human breast tissue only cells of the original stroma are capable of decorin gene expression. Our study also shows that transduction of decorin in decorin-negative human breast cancer cells markedly modulates the growth pattern of these cells.
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39. The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis
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Berit Berne, A. Bergström, G. Ghiasifarahani, and Hans Törmä
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Adult ,Keratinocytes ,Transcriptional Activation ,medicine.medical_specialty ,Cellular differentiation ,Primary Cell Culture ,Retinoic acid ,Chromosome Disorders ,Genes, Recessive ,Tretinoin ,Dermatology ,Biology ,Transcriptome ,chemistry.chemical_compound ,3,4-didehydroretinoic acid ,Internal medicine ,Retinoic acid receptors ,Congenital ichthyosis ,Keratin ,medicine ,Humans ,Dermatologi och venereologi ,RNA, Messenger ,Cells, Cultured ,Cell Proliferation ,chemistry.chemical_classification ,Original Paper ,Epidermis (botany) ,Microarray analysis techniques ,All-trans retinoic acid ,Cell Differentiation ,MicroRNA ,General Medicine ,Ichthyosiform Erythroderma, Congenital ,Microarray Analysis ,Dermatology and Venereal Diseases ,Endocrinology ,chemistry ,4-didehydroretinoic acid ,Cancer research ,Female ,medicine.drug - Abstract
Retinoids (natural forms and synthetic derivatives of vitamin A) are used as therapeutic agents for numerous skin diseases such as keratinization disorders (e.g. ichthyoses) and psoriasis. Two endogenous ligands for retinoic acid receptors exist, retinoic acid (atRA) and 3,4-didehydroretinoic acid (ddRA). In primary human epidermal keratinocytes many transcriptional targets for atRA are known, whereas the targets for ddRA are unknown. In an attempt to determine the targets, we compared the effect of atRA and ddRA on transcriptional profiles in undifferentiated and differentiating human primary keratinocytes. First, as expected, many genes were induced or suppressed in response to keratinocyte differentiation. Furthermore, the two retinoids affected substantially more genes in differentiated keratinocytes (>350) than in proliferating keratinocytes (≈20). In differentiating keratinocytes markers of cornification were suppressed suggesting a de-differentiating effect by the two retinoids. When comparing the expression profile of atRA to that of ddRA, no differently regulated genes were found. The array analysis also found that a minor number of miRNAs and a large number of non-coding transcripts were changed during differentiation and in response to the two retinoids. Furthermore, the expression of all, except one, genes known to cause autosomal recessive congenital ichthyosis (ARCI) were found to be induced by differentiation. These results comprehensively document that atRA and ddRA exert similar transcriptional changes in keratinocytes and also add new insights into the molecular mechanism influenced by retinoids in the epidermis. Furthermore, it suggests which ARCI patients could benefit from therapy with retinoids. Electronic supplementary material The online version of this article (doi:10.1007/s00403-014-1476-4) contains supplementary material, which is available to authorized users.
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40. Subtypes of oligodendroglioma defined by 1p,19q deletions, differ in the proportion of apoptotic cells but not in replication-licensed non-proliferating cells
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Stephen B. Wharton, D. Crimmins, Gordon H. Williams, S. Hibberd, Kai Stoeber, D A Jellinek, E. Maltby, D. Levy, and N. Atkey
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Adult ,DNA Replication ,Male ,Cell Survival ,Oligodendroglioma ,Clinical Neurology ,Replication ,Apoptosis ,Biology ,Pathology and Forensic Medicine ,Tumor grade ,Cytogenetics ,Cellular and Molecular Neuroscience ,medicine ,Humans ,Proliferation Marker ,Cytogenetic ,In Situ Hybridization, Fluorescence ,Cell Proliferation ,Retrospective Studies ,Original Paper ,DNA replication licensing ,DNA replication ,Cancer ,Geminin ,Middle Aged ,medicine.disease ,Molecular biology ,Ki-67 Antigen ,Chromosomes, Human, Pair 1 ,In situ hybridisation ,biology.protein ,Female ,Neurology (clinical) ,Chromosome Deletion - Abstract
Oligodendrogliomas may be divided into those with deletion of chromosomes 1p and 19q (Del+), and those without (Del−). Del+ tumours show better survival and chemoresponsiveness but the reason for this difference is unknown. We have investigated whether these subgroups differ in (a) apoptotic index, (b) the proportion of cells licensed for DNA replication but not in-cycle, and (c) the relative length of G1-phase. Fluorescence in situ hybridisation with probes to 1p and 19q was used to determine the deletion status of 54 oligodendrogliomas, including WHO grades II and III. The apoptotic index was determined using counts of apoptotic bodies. Replication-licensed non-proliferating cells were determined from the Mcm2 minus Ki67 labelling index, whilst the geminin to Ki67 ratio was used as a measure of the relative length of G1. Del+ oligodendrogliomas showed a higher apoptotic index than Del− tumours (P = 0.037); this was not accounted for by differences in tumour grade or in proliferation. There were no differences in the Mcm2 − Ki67 index or in the geminin/Ki67 ratio between the subgroups, but grade III tumours showed a higher proportion of licensed non-proliferating cells than grade II tumours (P = 0.001). An increased susceptibility to apoptosis in oligodendrogliomas with 1p ± 19q deletion may be important in their improved clinical outcome compared to Del− tumours.
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41. Different physiology of interferon-α/-γ in models of liver regeneration in the rat
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Danko Batusic, Sabine Blaschke, Jozsef Dudas, Alexander von Bargen, and Giuliano Ramadori
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Male ,Partial hepatectomy ,medicine.medical_treatment ,Physiology ,NK cells ,Monocytes ,0302 clinical medicine ,Interferon gamma ,Acute phase ,Cells, Cultured ,Liver injury ,Interferons ,Oval cells ,Mononuclear phagocytes ,0303 health sciences ,Stem Cells ,2-Acetylaminofluorene ,Liver regeneration ,3. Good health ,Killer Cells, Natural ,STAT Transcription Factors ,Medical Laboratory Technology ,Cytokine ,030211 gastroenterology & hepatology ,Stem cell ,medicine.drug ,Histology ,Biology ,Interferon-gamma ,03 medical and health sciences ,medicine ,Animals ,Hepatectomy ,RNA, Messenger ,Rats, Wistar ,Progenitor cell ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,Original Paper ,Cell growth ,Interferon-alpha ,Medicine & Public Health ,Anatomy ,Medicine/Public Health, general ,Janus Kinase 1 ,Cell Biology ,medicine.disease ,Liver Regeneration ,Rats ,Hepatocytes - Abstract
Liver regeneration may take place after liver injury through replication of hepatocytes or hepatic progenitor cells called oval cells. Interferons (IFN) are natural cytokines with pleiotrophic effects including antiviral and antiproliferative actions. No data are yet available on the physiology and cellular source of natural IFNs during liver regeneration. To address this issue, we have analyzed the levels and biologic activities of IFN-α/IFN-γ in two models of partial hepatectomy. After 2/3rd partial hepatectomy (PH), hepatic levels of IFN-α and IFN-γ declined transiently in contrast to a transient increase of the IFN-γ serum level. After administration of 2-acetylaminofluorene and partial hepatectomy (AAF/PH model), however, both IFN-α and IFN-γ expression were up-regulated in regenerating livers. Again, the IFN-γ serum level was transiently increased. Whereas hepatic IFN-γ was up-regulated early (day 1–5), but not significantly, in the AAF/PH model, IFN-α was significantly up-regulated at later time points in parallel to the peak of oval cell proliferation (days 7–9). Biological activity of IFN-α was shown by activation of IFN-α-specific signal transduction and induction of IFN-α specific-gene expression. We found a significant infiltration of the liver with inflammatory monocyte-like mononuclear phagocytes (MNP) concomitant to the frequency of oval cells. We localized IFN-α production only in MNPs, but not in oval cells. These events were not observed in normal liver regeneration after standard PH. We conclude that IFN-γ functions as an acute-phase cytokine in both models of liver regeneration and may constitute a systemic component of liver regeneration. IFN-α was increased only in the AAF/PH model, and was associated with proliferation of oval cells. However, oval cells seem not to be the source of IFN-α. Instead, inflammatory MNP infiltrating AAF/PH-treated livers produce IFN-α. These inflammatory MNPs may be involved in the regulation of the oval cell compartment through local expression of cytokines, including IFN-α. peerReviewed
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42. MicroRNA-138-5p regulates pancreatic cancer cell growth through targeting FOXC1
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Min Wang, Zhipeng Li, Chengyi Sun, Jie Xiao, Jianxin Jiang, Deng Yazhu, Chao Yu, Xingjun Guo, and Feng Peng
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Adult ,Male ,Cancer Research ,miR-138-5p ,Blotting, Western ,Mice, Nude ,Biology ,Real-Time Polymerase Chain Reaction ,Transfection ,Mice ,Pancreatic cancer ,microRNA ,medicine ,Carcinoma ,Animals ,Humans ,Aged ,Cell Proliferation ,Regulation of gene expression ,Cisplatin ,Medicine(all) ,Original Paper ,Cell growth ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,Forkhead Transcription Factors ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,MicroRNAs ,Real-time polymerase chain reaction ,Oncology ,Immunology ,Cancer research ,Molecular Medicine ,Heterografts ,Female ,FOXC1 ,medicine.drug ,Carcinoma, Pancreatic Ductal - Abstract
Purpose The prognosis of pancreatic cancer ranks among the worst of all cancer types, which is primarily due to the fact that during the past decades little progress has been made in its diagnosis and treatment. Here, we set out to investigate the role of microRNA 138 (miR-138-5p) in the regulation of pancreatic cancer cell growth and to assess its role as putative therapeutic target. Methods qRT-PCR was used to examine the expression of miR-138-5p in 8 pancreatic cancer cell lines and 18 primary human pancreatic cancer samples. A lentivirual vector containing miR-138-5p mimics (lv-miR-138-5p) was used to exogenously over-express miR-138-5p in the pancreatic cancer cells lines Capan-2 and PANC-1. The effect of this over-expression on cell proliferation was examined using an in vitro propidium iodide fluorescence assay. Capan-2 cells exogenously over-expressing miR-138-5p were transplanted into nude mice to examine its in vivo effect on tumor growth. A predicted target of miR-138-5p (FOXC1) was first validated using a luciferase assay and, subsequently, down-regulated by siRNA to assess its effect on pancreatic cancer cell growth. Results We found that miR-138-5p was markedly down-regulated in both pancreatic cancer cell lines and primary human pancreatic cancer samples, compared to a human pancreas ductal epithelial (HPDE) cell line and normal pancreatic tissues, respectively (P
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43. Thalidomide influences atherogenesis in aortas of ApoE−/−/LDLR−/− double knockout mice: a nano-CT study
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Alexander C. Langheinrich, Anne Brinkmann, Erik L. Ritman, Gabriele A. Krombach, Marian Kampschulte, Irina Gunkel, Daniel Sedding, and Philipp Stieger
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Apolipoprotein E ,Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Vasa vasorum ,Angiogenesis ,Aortic Diseases ,Angiogenesis Inhibitors ,Aortography ,Neovascularization ,Mice ,Apolipoproteins E ,Cell Movement ,medicine.artery ,medicine ,Animals ,Humans ,Nanotechnology ,Radiology, Nuclear Medicine and imaging ,Aorta ,Cells, Cultured ,Nano-CT ,Cell Proliferation ,Mice, Knockout ,Original Paper ,Neovascularization, Pathologic ,business.industry ,Endothelial Cells ,Histology ,Atherosclerosis ,Plaque, Atherosclerotic ,Thalidomide ,Disease Models, Animal ,medicine.anatomical_structure ,Receptors, LDL ,Radiology Nuclear Medicine and imaging ,Disease Progression ,medicine.symptom ,business ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,Artery ,medicine.drug - Abstract
Plaque progression in atherosclerosis is closely connected to angiogenesis due to vasa vasorum (VV) growth. Objective of this study was to determine the unknown long-term effect of thalidomide on adventitial VV neovascularization and plaque progression using nano-focussed computed tomography (nano-CT). Proliferation and migration assays in human coronary artery endothelial cells (HCAEC) measured number of viable cells after incubation with thalidomide. Male ApoE(-/-)/LDLR(-/-) (AL) mice (n = 5) received a thalidomide containing western diet (WD) over 29 weeks. Another five male AL mice (WD without thalidomide) served as control group. Descending aortas were scanned with nano-CT at (1.5 μm)(3) isotropic voxel size. Number and area of adventitial VV as well as plaque cross sectional area were measured. Results were complemented by histology. Thalidomide inhibited proliferation and migration of HCAEC dose-dependently. VV neovascularization decreased in number per cross section (7.66 ± 0.301 vs. 8.62 ± 0.164, p 0.001) and in cross sectional area (0.0183 ± 0.0011 vs. 0.0238 ± 0.0008 mm(2), p 0.001). Cross sectional area of plaque decreased significantly when treated with thalidomide (0.57 ± 0.0187 vs. 0.803 ± 0.0148 mm(2), p 0.001). Nano-CT imaging revealed a reduced plaque growth and VV neovascularization after long-term application of thalidomide. Therefore, nano-CT can be considered as a new method to detect therapeutic effects in experimental models of atherosclerosis.
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44. The functional role of Notch signaling in HPV-mediated transformation is dose-dependent and linked to AP-1 alterations
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Peter J.F. Snijders, Frank Rösl, Renske D.M. Steenbergen, Chris J.L.M. Meijer, Johanna De-Castro Arce, Florianne E. Henken, Leontien Bosch, Pathology, and CCA - Oncogenesis
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Keratinocytes ,Cancer Research ,HPV ,Notch ,Transcription, Genetic ,Cell Survival ,Notch signaling pathway ,Uterine Cervical Neoplasms ,Gene dosage ,c-Fos ,Cell Line, Tumor ,Fra1 ,Cell Adhesion ,Gene silencing ,Humans ,Gene Silencing ,RNA, Messenger ,Cell adhesion ,Cell Proliferation ,Medicine(all) ,Original Paper ,Human papillomavirus 16 ,biology ,Receptors, Notch ,Cell growth ,General Medicine ,AP-1 ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Transcription Factor AP-1 ,Cell Transformation, Neoplastic ,Oncology ,Hes3 signaling axis ,Cancer research ,biology.protein ,Cervical cancer ,Molecular Medicine ,Female ,Signal transduction ,Proto-Oncogene Proteins c-fos ,Signal Transduction - Abstract
Background The role of Notch signaling in HPV-mediated transformation has been a long standing debate, as both tumor suppressive and oncogenic properties have been described. We examined whether the dual findings in literature may be explained by gene dosage effects and determined the relation with AP-1, a downstream target of Notch. Methods SiHa cervical cancer cells were transfected with two doses of intracellular active Notch. Non-tumorigenic HPV16-immortalized keratinocytes (FK16A) were transfected with Fra1 specific siRNAs and non-targeting controls. Transfectants were analysed for Notch, Hes, cJun, cFos and Fra1 mRNA expression, Notch pathway activation using luciferase assays, cell viability using MTT assays, anchorage independent growth, AP-1 activity and/or AP-1 complex composition using EMSA. Results In SiHa cells two activation states of Notch signaling pathway were obtained. Moderate Notch activation contributed to increased viability and anchorage independent growth, whereas high level Notch activation decreased anchorage independent growth. The shift in phenotypical outcome was correlated to altered AP-1 activity and complex composition. Moderate Notch expression led to an increased AP-1 transcriptional activity and DNA binding activity, but did not affect complex composition. High levels of Notch additionally led to a change in AP-1 complex composition, from cJun/cFos to cJun/Fra1 dimers, which is exemplary for non-tumorigenic HPV-immortalized cell lines. Conversely, silencing of Fra1 in non-tumorigenic HPV16-immortalized keratinocytes, leading to an enrichment of cJun/cFos dimers, was accompanied with increased colony formation. Conclusion The functional role of Notch in HPV-mediated transformation is dosage dependent and correlated to a change in AP-1.
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45. Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile
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Marco Jenzsch, Stefan Gnoth, Andreas Lübbert, Rimvydas Simutis, and Martin Kleinschmidt
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Quality Control ,Computer science ,Cell Culture Techniques ,Biomass ,Bioengineering ,Models, Biological ,Feedback ,Bioreactors ,Escherichia coli ,Bioreactor ,Process control ,Production (economics) ,Computer Simulation ,Therapeutic Hormone ,Cell Proliferation ,Recombinant proteins ,Original Paper ,Reproducibility ,E. coli fed batch ,business.industry ,Reproducibility of Results ,Equipment Design ,General Medicine ,Biotechnology ,Equipment Failure Analysis ,Scientific method ,Biochemical engineering ,Industrial and production engineering ,business ,PAT - Abstract
In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also.
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46. Author Correction: CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation.
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Ayaz, Gamze, Razizadeh, Negin, Yaşar, Pelin, Kars, Gizem, Kahraman, Deniz Cansen, Saatci, Özge, Şahin, Özgür, Çetin-Atalay, Rengül, and Muyan, Mesut
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DINUCLEOTIDES ,CELL proliferation - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2020
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47. High-quality human preimplantation embryos actively influence endometrial stromal cell migration.
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Berkhout, R. P., Lambalk, C. B., Huirne, J., Mijatovic, V., Repping, S., Hamer, G., and Mastenbroek, S.
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EMBRYO transfer ,ENDOMETRIAL diseases ,ENDOMETRIUM ,CELL proliferation ,HUMAN embryonic stem cells ,BLASTOMERES ,THERAPEUTICS - Abstract
Purpose: The purpose of this paper is to study whether human preimplantation embryos regulate endometrial stromal cell (hESC) migration.Methods: Primary hESCs were isolated from fertile patients undergoing hysterectomy for benign conditions (uterine scar niche
n = 3, dysmenorrhean = 2; no hormonal treatment). Migration and proliferation assays were performed by culturing decidualized or non-decidualized hESCs in the presence of embryo conditioned medium (ECM) from high-quality embryos (fragmentation ≤ 20%) or from low-quality embryos (fragmentation > 20%) or in non-conditioned medium from the same dishes (control). ECM samples from 425 individually cultured human embryos were used in this study.Results: ECM from high-quality embryos, i.e., with a low percentage of fragmentation, actively stimulated decidualized hESC migration (p < 0.001). This effect was consistent throughout embryonic development from cleavage stage embryos with 2-7 cells (high quality vs. control;p = 0.036), 8-18 cells (high quality vs. control;p < 0.001) to morulae (high quality vs. control;p = 0.003). Additionally, linear regression analysis showed that hESC migration was influenced by embryo quality (fragmentation, β − 0.299;p = 0.025) and not developmental stage (cell number, β 0.177;p = 0.176) or maternal age (β − 0.036;p = 0.78). Opposite to decidualized hESCs, the migration response of non-decidualized hESCs was inhibited by ECM from high-quality embryos (p = 0.019). ECM from low-quality embryos, i.e., with a high percentage of fragmentation, did not cause an altered migration response in decidualized hESCs (p = 0.860) or non-decidualized hESCs (p = 0.986). Furthermore, ECM of both high- and low-quality human embryos did not influence the number of proliferating cells (p = 0.375) and the cell cycle time (p = 0.297) of non-decidualized or decidualized hESCs.Conclusion: This study reveals a mechanism by which high-quality human preimplantation embryos actively interact with the endometrium to increase their chances of successful implantation. [ABSTRACT FROM AUTHOR]- Published
- 2018
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48. Feasibility study of a biocompatible pneumatic dispensing system using mouse 3T3-J2 fibroblasts.
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Lee, Sangmin, Kim, Hojin, and Kim, Joonwon
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FEASIBILITY studies ,FIBROBLASTS ,BIOMATERIALS ,CELL proliferation ,LABORATORY mice - Abstract
This paper presents results for dispensing living cells using a pneumatic dispensing system to verify the feasibility of using this system to fabricate biomaterials. Living cells (i.e., mouse 3T3-J2 fibroblast) were dispensed with different dispensing pressures in order to evaluate the effect of dispensing process on cell viability and proliferation. Based on the results of a live-dead assay, more than 80% of cell viability has been confirmed which was reasonably similar to that in the control group. Furthermore, measurement of cell metabolic activity after dispensing confirmed that the dispensed cell proliferated at a rate comparable to that of the control group. These results demonstrate that the pneumatic dispensing system is a promising tool for fabrication of biomaterials. [ABSTRACT FROM AUTHOR]
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- 2017
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49. Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators.
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Li, Zhelin, Xu, Shuxing, Xu, Zijie, Shu, Sheng, Liu, Guanlin, Zhou, Jianda, Lin, Ding, and Tang, Wei
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NANOGENERATORS ,ELECTRONIC equipment ,CELL cycle ,ELECTRIC stimulation ,CELL proliferation ,SKIN permeability ,SKIN regeneration - Abstract
Triboelectric nanogenerators (TENGs) have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices. Despite their potential benefits, the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy. Therefore, further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications. In this study, we present a flexible silk fibroin-based triboelectric nanogenerator (SFB-TENG) that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability. The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926, NIH-3T3 and RSC96 cells. However, apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz. In addition, the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells. This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design, as well as its safe operating conditions for use in biomedical applications. These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Conserved regulatory switches for the transition from natal down to juvenile feather in birds.
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Chen, Chih-Kuan, Chang, Yao-Ming, Jiang, Ting-Xin, Yue, ZhiCao, Liu, Tzu-Yu, Lu, Jiayi, Yu, Zhou, Lin, Jinn-Jy, Vu, Trieu-Duc, Huang, Tao-Yu, Harn, Hans I-Chen, Ng, Chen Siang, Wu, Ping, Chuong, Cheng-Ming, and Li, Wen‐Hsiung
- Subjects
ELECTRICAL conductivity transitions ,FEATHERS ,ZEBRA finch ,WNT signal transduction ,CELL proliferation ,DINOSAURS - Abstract
The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs. Natal downs adapted for heat conservation transition to juvenile feathers that support simple flight during bird development. Here the authors characterize gene expression networks and epigenetic changes and use functional perturbations to characterize evolutionarily conserved regulatory switches that control this transition in birds. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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