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Cancer-Associated Fibroblasts Induce a Collagen Cross-link Switch in Tumor Stroma
Pankova, Daniela,Chen, Yulong,Terajima, Masahiko,Schliekelman, Mark J.,Baird, Brandi N.,Fahrenholtz, Monica,Sun, Li,Gill, Bartley J.,Vadakkan, Tegy J.,Kim, Min P.,Ahn, Young-Ho,Roybal, Jonathon D.,Liu American Association for Cancer Research 2016 Molecular Cancer Research Vol.14 No.3
<P>Intratumoral collagen cross-links heighten stromal stiffness and stimulate tumor cell invasion, but it is unclear how collagen cross-linking is regulated in epithelial tumors. To address this question, we used Kras(LA1) mice, which develop lung adenocarcinomas from somatic activation of a Kras(G12D) allele. The lung tumors in KrasLA1 mice were highly fibrotic and contained cancer-associated fibroblasts (CAF) that produced collagen and generated stiffness in collagen gels. In xenograft tumors generated by injection of wild-type mice with lung adenocarcinoma cells alone or in combination with CAFs, the total concentration of collagen cross-links was the same in tumors generated with or without CAFs, but coinjected tumors had higher hydroxylysine aldehyde-derived collagen cross-links (HLCC) and lower lysine-aldehyde-derived collagen cross-links (LCCs). Therefore, we postulated that an LCC-to-HLCC switch induced by CAFs promotes the migratory and invasive properties of lung adenocarcinoma cells. To test this hypothesis, we created coculture models in which CAFs are positioned interstitially or peripherally in tumor cell aggregates, mimicking distinct spatial orientations of CAFs in human lung cancer. In both contexts, CAFs enhanced the invasive properties of tumor cells in three-dimensional (3D) collagen gels. Tumor cell aggregates that attached to CAF networks on a Matrigel surface dissociated and migrated on the networks. Lysyl hydroxylase 2 (PLOD2/LH2), which drives HLCC formation, was expressed in CAFs, and LH2 depletion abrogated the ability of CAFs to promote tumor cell invasion and migration.</P>
Features of the Discussion Method in the Training of Students in the Context of Distance Learning
Irina Gladilina,Svetlana Sergeeva,Lyudmila Pankova,Vladimir Kolesnik,Ekaterina Svishcheva International Journal of Computer ScienceNetwork S 2023 International journal of computer science and netw Vol.23 No.11
The article considers online discussion as an interactive learning method in the conditions of distance learning. The essence of discussion and the stages of its organization are described. The main objective of discussion in distance learning is defined as the stimulation of interest in learning and the involvement of various viewpoints in an active discussion of the stated problems. The key role in ensuring the efficiency of a discussion is identified. The article develops a model for organizing asynchronous online discussions on the Moodle platform, highlighting the sequence of stages and their content. An experimental study of the use of the discussion method in the training of students in distance learning conditions is carried out. Based on the results of the methodological experiment, conclusions are drawn about student interest in online discussions. The authors conclude that the interest of students of different specialties in asynchronous online discussions varies, and the greatest interest is demonstrated by linguistics students. Nevertheless, the differences in student interest in online discussions by groups (specialties) are more likely attributable to subjective factors, which do not affect the overall picture in a major way.
Tan, Xiaochao,Banerjee, Priyam,Guo, Hou-Fu,Ireland, Stephen,Pankova, Daniela,Ahn, Young-ho,Nikolaidis, Irodotos Michail,Liu, Xin,Zhao, Yanbin,Xue, Yongming American Society for Clinical Investigation 2017 The Journal of clinical investigation Vol.127 No.1
<P>Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the pro-metastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis.</P>
El-Rahman, Atef Abd El-Mohsen Abd,El-Shafei, Sally Mohamed Abd El-Aziz,Ivanova, Elena Vladimirovna,Fattakhova, Alfia Nurlimanovna,Pankova, Anna Victorovna,El-Shafei, Mohamed Abd El-Aziz,El-Morsi, El-M Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17
Trichoderma spp. are known as a rich source of secondary metabolites with biological activity belonging to a variety of classes of chemical compounds. These fungi also are well known for their ability to produce a wide range of antibiotic substances and to parasitize other fungi. In search for new substances, which might act as anticancer agents, the overall objective of this study was to investigate the cytotoxic effects of Trichoderma harzianum and Trichoderma asperellum cultural filtrates against human cervical and breast cancer cell lines (HeLa and MCF-7 cells respectively). To achieve this objective, cells were exposed to 20, 40, 60, 80 and 100 mg/ml of both T. harzianum cultural filtrate (ThCF) and T. asperellum cultural filtrate (TaCF) for 24h, then the cell viability and the cytotoxic responses were assessed by using trypan blue and 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assays. Morphological changes in cells were investigated by phase contrast inverted microscopy. The results showed that ThCF and TaCF significantly reduce the cell viability, have cytotoxic effects and alter the cellular morphology of HeLa and MCF-7 cells in a concentration dependent manner. A concentration of 80 and 100mg/ml of ThCF resulted in a sharp decline in the cell viability percent of HeLa and MCF-7 respectively (25.2%, 26.5%) which was recorded by trypan blue assay. The half-maximal inhibitory concentrations ($IC_{50}$) of ThCF and TaCF in HeLa and MCF-7 were recorded as 16.6, 12.0, 19.6 and 0.70mg/ml respectively by MTT assay. These results revealed that ThCF and TaCF have a substantial ability to reduce the viability and proliferation of human cervical and breast cancer cells.