Abstract PO-045: Targeting HNF1A-dependent cell proliferation and stemness in PDAC using BET inhibitors

Abstract Cell proliferation often experiences a density-dependent intrinsic proliferation rate (IPR) and negative feedback from growth-inhibiting molecules in culture media. The lack of flexible models with explanatory parameters fails to capture such a proliferation mechanism. We propose an extended logistic growth law with the density-dependent IPR and additional negative feedback. The extended parameters of the proposed model can be interpreted as density-dependent cell-cell cooperation and negative feedback on cell proliferation. Moreover, we incorporate further density regulation for flexibility in the model through environmental resistance on cells. The proposed growth law has similarities with the strong Allee model and harvesting phenomenon. We also develop the stochastic analog of the deterministic model by representing possible heterogeneity in growth-inhibiting molecules and environmental perturbation of the culture setup as correlated multiplicative and additive noises. The model provides a maximum sustainable stable cell density (MSSCD) and a new fitness measure for proliferative cells. The proposed model shows superiority to the logistic law after fitting to real cell culture datasets. We illustrate both MSSCD and the new cell fitness for a range of parameters. The cell density distributions reveal the chance of overproliferation, underproliferation, or decay for different parameter sets under the deterministic and stochastic setups.

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Identification of genes and genetic networks associated with BAG3‑dependent cell proliferation and cell survival in human cervical cancer HeLa cells

Molecular Medicine Reports ◽

10.3892/mmr.2018.9383 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yukihiro Furusawa ◽

Tatsuya Yunoki ◽

Tetsushi Hirano ◽

Satsuki Minagawa ◽

Hironori Izumi ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Cell Survival ◽

Hela Cells ◽

Genetic Networks ◽

Dependent Cell ◽

Human Cervical Cancer

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Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro

Frontiers in Immunology ◽

10.3389/fimmu.2020.592553 ◽

2020 ◽

Vol 11 ◽

Author(s):

Christian Binder ◽

Felix Sellberg ◽

Filip Cvetkovski ◽

Erik Berglund ◽

David Berglund

Keyword(s):

Cell Proliferation ◽

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Mixed Lymphocyte Reaction ◽

T Cell Proliferation ◽

Allogeneic Mixed Lymphocyte Reaction ◽

Dependent Cell

Antibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical application. The goal of this study was to contrast the mechanistic properties of siplizumab with Alemtuzumab and rabbit Anti-Thymocyte Globulin (rATG). Mechanistic assay systems investigating antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell phagocytosis and complement-dependent cytotoxicity were used to characterize siplizumab. Further, functional effects of siplizumab, Alemtuzumab, and rATG were investigated in allogeneic mixed lymphocyte reaction. Changes in T cell activation, T cell proliferation and frequency of naïve T cells, memory T cells and regulatory T cells induced by siplizumab, Alemtuzumab and rATG in allogeneic mixed lymphocyte reaction were assessed via flow cytometry. Siplizumab depleted T cells, decreased T cell activation, inhibited T cell proliferation and enriched naïve and bona fide regulatory T cells. Neither Alemtuzumab nor rATG induced the same combination of functional effects. The results presented in this study should be used for further in vitro and in vivo investigations that guide the clinical use of immune modulatory biologics.

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Corrigendum to “Sesamin suppresses NSCLC cell proliferation through cyclin D1 inhibition-dependent cell cycle arrest via Akt/p53 pathway” [Toxicology and applied pharmacology, 387 (2020) 114848]

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2020.115048 ◽

2020 ◽

Vol 400 ◽

pp. 115048

Author(s):

Yueming Chen ◽

Huachao Li ◽

Weinan Zhang ◽

Wanchen Qi ◽

Changpeng Lu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cyclin D1 ◽

Cell Cycle Arrest ◽

Nsclc Cell ◽

P53 Pathway ◽

Cycle Arrest ◽

Dependent Cell

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Aberrant Expression of Nucleostemin Activates p53 and Induces Cell Cycle Arrest via Inhibition of MDM2

Molecular and Cellular Biology ◽

10.1128/mcb.01662-07 ◽

2008 ◽

Vol 28 (13) ◽

pp. 4365-4376 ◽

Cited By ~ 123

Author(s):

Mu-Shui Dai ◽

Xiao-Xin Sun ◽

Hua Lu

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Ribosomal Proteins ◽

Cell Cycle Checkpoint ◽

Aberrant Expression ◽

Cycle Arrest ◽

Reduce Cell Proliferation ◽

Cycle Checkpoint ◽

Dependent Cell

ABSTRACT The nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis. Both depletion and overexpression of NS reduce cell proliferation. However, the mechanisms underlying this regulation are still unclear. Here, we show that NS regulates p53 activity through the inhibition of MDM2. NS binds to the central acidic domain of MDM2 and inhibits MDM2-mediated p53 ubiquitylation and degradation. Consequently, ectopic overexpression of NS activates p53, induces G1 cell cycle arrest, and inhibits cell proliferation. Interestingly, the knockdown of NS by small interfering RNA also activates p53 and induces G1 arrest. These effects require the ribosomal proteins L5 and L11, since the depletion of NS enhanced their interactions with MDM2 and the knockdown of L5 or L11 abrogated the NS depletion-induced p53 activation and cell cycle arrest. These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function.

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