scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Overall Survival ◽  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Carcinoma Cells ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

2020 ◽  
Author(s):  
Dorian Gottwald ◽  
Florian Putz ◽  
Nora Hohmann ◽  
Maike Büttner-Herold ◽  
Markus Hecht ◽  
...  
Keyword(s):  
Rectal Carcinoma ◽  
Cell Structure ◽  
Tumor Therapy ◽  
Carcinoma Cells ◽  
Pancreas Carcinoma ◽  
Poor Prognostic Factor ◽  
Long Time

Abstract Background: Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.Results: Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.Conclusion: Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

scholarly journals UPF1 Promotes Chemoresistance to Oxaliplatin Through Maintenance of Stemness by Increasing Phosphorylated TOP2A in Colorectal Cancer.

2020 ◽  
Author(s):  
Congcong Zhu ◽  
Long Zhang ◽  
Senlin Zhao ◽  
Weixing Dai ◽  
Yun Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cell Lines ◽  
Clinical Relevance ◽  
Poor Prognosis ◽  
Therapy Strategy ◽  
Underlying Mechanisms

Abstract Background: UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 on oxaliplatin resistance in colorectal cancer (CRC) remains unknown.Methods: Firstly, we investigated the clinical relevance of UPF1 in CRC patients. Then, we explored the influence of UPF1 on chemoresistance to oxaliplatin in vitro and in vivo. Finally, we disclosed the underlying mechanisms of oxaliplatin resistance induced by UPF1.Results: UPF1 is upregulated in CRC and overexpression of UPF1 more likely results in recurrence in CRC patients and predicts a poorer overall survival (OS). UPF1 maintains stemness in CRC cell lines and promotes chemoresistance to oxaliplatin in CRC. UPF1-induced oxaliplatin resistance can be associated with interaction with TOP2A and increasing phosphorylated TOP2A.Conclusions: UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced the stemness and chemoresistance to oxaliplatin by interaction with TOP2A and increase of phosphorylated TOP2A in CRC, which may provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

Ganoderma lucidum Polysaccharides: Immunomodulation and Potential Anti-Tumor Activities

2011 ◽  
Vol 39 (01) ◽  
pp. 15-27 ◽  
Author(s):  
Zengtao Xu ◽  
Xiuping Chen ◽  
Zhangfeng Zhong ◽  
Lidian Chen ◽  
Yitao Wang
Keyword(s):  
Ganoderma Lucidum ◽  
Tumor Therapy ◽  
White Rot ◽  
In Vivo Studies ◽  
White Rot Fungus ◽  
Bioactive Substances ◽  
Cytotoxic Effects

Ganoderma lucidum (G. lucidum), a basidiomycete white rot fungus, has long been prescribed to prevent and treat various human diseases, particularly in China, Japan, and Korea. Several classes of bioactive substances have been isolated and identified from G. lucidum, such as triterpenoids, polysaccharides, nucleosides, sterols, and alkaloids, among others. This paper examines the potential role of G. lucidum polysaccharide (GLPS) in tumor therapy and the possible mechanisms involved. Both in vitro and in vivo studies suggested that the anti-tumor activities of GLPS are mediated by its immunomodulatory, anti-angiogenic, and cytotoxic effects. GLPS affects immune cells and immune-related cells including B lymphocytes, T lymphocytes, dendritic cells, macrophages, and natural killer cells. In addition, recent data also suggest that GLPS suppresses tumorigenesis or inhibits tumor growth through direct cytotoxic effect and anti-angiogenic actions. However, many questions still need to be answered before both G. lucidum and GLPS can be widely accepted and used as anti-tumor agents.

scholarly journals Downstream Pathway of AML1-ETO Targeted ARHGEF12 Might be Targetable for Rock Inhibitor to Improve Therapy Outcome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3914-3914
Author(s):  
Yangyang Xie ◽  
Ruichi Wu ◽  
Xiaoxiao Chen ◽  
Xiao-Jian Sun ◽  
Shuhong Shen
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Fetal Liver ◽  
Conditional Knockout ◽  
Binding Motif ◽  
Rock Inhibitor ◽  
Poor Prognostic Factor

Abstract As a transcription factor AML1-ETO modulate gene expression of its targets. Scanning our ChIP-seq data we found AML1-ETO bind to an AML1 binding motif in the promotor region of ARHGEF12. Exploring acute myeloid leukemia (AML) microarray databases we confirmed that the expression of ARHGEF12 was up-regulated consistently in AML1-ETO-positive AML patient samples. To confirmed this finding, we quantitated expression of ARHGEF12 in pediatric AML samples from Shanghai children's medical center. Not out of expectation, all AML1-ETO-positive cases have higher ARHGEF12. Moreover, the ARHGEF12 expression was an independent poor prognostic factor for overall survival comparing between patients with higher and lower expressed ARHGEF12 (P=0.0258) (Figure A). To understand the role of ARHGEF12 in leukemogenic function of AML1-ETO fusion gene, we knocked down ARHGEF12 expression in kasumi-1 cells by shRNA. Growth of kasumi-1 cells in vitro was significantly inhibited with cell cycle exit and more apoptosis. Further, we transformed fetal liver cells of Arhgef12 conditional knockout mice to leukemia model by retrovirus conducted AML1-ETO9a(AE9a) expression. Induced Arhgef12 deletion delayed full blown of leukemia in vivo. The overall survival prolonged 15.5 days (median 83.5 vs. 68 days, P=0.0072). (Figure B) ARHGEF12 is a well-known guanine nucleotide exchange factor for RhoA GTPase. Arhgef12 deletion decreased activated GTP-RhoA and MYPT1 phosphorylation, which is one of ROCK kinase substrates. Spleen cells from leukemic mice were cultured in vitro, the ROCK inhibitor Y-27632 significantly decreased the cell proliferation, which mimic the tamoxifen-induced Arhgef12 knockout phenotype. Y-27632 combined with tamoxifen treated cells almost eradicate alive leukemia cells on the ninth day in vitro (Figure C) and delay leukemogenesis in vivo (Figure D). These findings suggest that ARHGEF12 as a transcriptional target of the AML1-ETO fusion protein and plays an essential role in leukemogenesis. The ARHGEF12-RHOA-ROCK pathway may serve as a new therapeutic target for AML1-ETO+ AML Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Microtubule-dependent subcellular organisation of pluripotent cells

Development ◽  
2021 ◽  
Vol 148 (20) ◽  
Author(s):  
Azelle Hawdon ◽  
Asma Aberkane ◽  
Jennifer Zenker
Keyword(s):  
Pluripotent Stem Cells ◽  
Cell Structure ◽  
Structure And Function ◽  
Pluripotent Cells ◽  
Differentiated Cells ◽  
Intracellular Movement ◽  
And Function

ABSTRACT With the advancement of cutting-edge live imaging technologies, microtubule remodelling has evolved as an integral regulator for the establishment of distinct differentiated cells. However, despite their fundamental role in cell structure and function, microtubules have received less attention when unravelling the regulatory circuitry of pluripotency. Here, we summarise the role of microtubule organisation and microtubule-dependent events required for the formation of pluripotent cells in vivo by deciphering the process of early embryogenesis: from fertilisation to blastocyst. Furthermore, we highlight current advances in elucidating the significance of specific microtubule arrays in in vitro culture systems of pluripotent stem cells and how the microtubule cytoskeleton serves as a highway for the precise intracellular movement of organelles. This Review provides an informed understanding of the intrinsic role of subcellular architecture of pluripotent cells and accentuates their regenerative potential in combination with innovative light-inducible microtubule techniques.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects
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