scholarly journals PCa dynamics with neuroendocrine differentiation and distributed delay

2021 ◽  
Vol 18 (6) ◽  
pp. 8577-8602
Author(s):  
Leo Turner ◽  
◽  
Andrew Burbanks ◽  
Marianna Cerasuolo
Keyword(s):  
Prostate Cancer ◽  
Mathematical Models ◽  
Sufficient Conditions ◽  
Distributed Delay ◽  
Neuroendocrine Differentiation ◽  
Delay Distribution ◽  
Delay Dynamical System ◽  
Neuroendocrine Transdifferentiation ◽  
The Stability

<abstract><p>Prostate cancer is the fifth most common cause of death from cancer, and the second most common diagnosed cancer in men. In the last few years many mathematical models have been proposed to describe the dynamics of prostate cancer under treatment. So far one of the major challenges has been the development of mathematical models that would represent <italic>in vivo</italic> conditions and therefore be suitable for clinical applications, while being mathematically treatable. In this paper, we take a step in this direction, by proposing a nonlinear distributed-delay dynamical system that explores neuroendocrine transdifferentiation in human prostate cancer <italic>in vivo</italic>. Sufficient conditions for the existence and the stability of a tumour-present equilibrium are given, and the occurrence of a Hopf bifurcation is proven for a uniform delay distribution. Numerical simulations are provided to explore differences in behaviour for uniform and exponential delay distributions. The results suggest that the choice of the delay distribution is key in defining the dynamics of the system and in determining the conditions for the onset of oscillations following a switch in the stability of the tumour-present equilibrium.</p></abstract>

scholarly journals MicroRNA-1205 Regulation of FRYL in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Michelle Naidoo ◽  
Fayola Levine ◽  
Tamara Gillot ◽  
Akintunde T. Orunmuyi ◽  
E. Oluwabunmi Olapade-Olaopa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Differentiation ◽  
Castration Resistant Prostate Cancer ◽  
Chromosomal Locus ◽  
Protein Coding ◽  
Castration Resistant ◽  
Dendritic Branching ◽  
Very High

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors in vivo. To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced in vitro and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.

scholarly journals Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells

2007 ◽  
Vol 14 (3) ◽  
pp. 531-547 ◽  
Author(s):  
Ta-Chun Yuan ◽  
Suresh Veeramani ◽  
Ming-Fong Lin
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanism ◽  
Biochemical Properties ◽  
Normal Prostate ◽  
Independent State ◽  
Epithelial Compartment ◽  
Neuroendocrine Transdifferentiation ◽  
A Minor

Neuroendocrine (NE) cells represent a minor cell population in the epithelial compartment of normal prostate glands and may play a role in regulating the growth and differentiation of normal prostate epithelia. In prostate tumor lesions, the population of NE-like cells, i.e., cells exhibiting NE phenotypes and expressing NE markers, is increased that correlates with tumor progression, poor prognosis, and the androgen-independent state. However, the origin of those NE-like cells in prostate cancer (PCa) lesions and the underlying molecular mechanism of enrichment remain an enigma. In this review, we focus on discussing the distinction between NE-like PCa and normal NE cells, the potential origin of NE-like PCa cells, and in vitro and in vivo studies related to the molecular mechanism of NE transdifferentiation of PCa cells. The data together suggest that PCa cells undergo a transdifferentiation process to become NE-like cells, which acquire the NE phenotype and express NE markers. Thus, we propose that those NE-like cells in PCa lesions were originated from cancerous epithelial cells, but not from normal NE cells, and should be defined as ‘NE-like PCa cells’. We further describe the biochemical properties of newly established, stable NE-like lymph node carcinoma of the prostate (LNCaP) cell lines, transdifferentiated from androgen-sensitive LNCaP cells under androgen-deprived conditions. Knowledge of understanding NE-like PCa cells will help us to explore new therapeutic strategies for treating PCa.

scholarly journals TRIM59 is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Neuroendocrine Differentiation in Prostate Cancer

2021 ◽  
Author(s):  
Liancheng Fan ◽  
Yiming Gong ◽  
Yuman He ◽  
Wei-Qiang Gao ◽  
Baijun Dong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Neuroendocrine Differentiation ◽  
Tumor Model ◽  
Strongly Correlated ◽  
Neuroendocrine Prostate Cancer ◽  
In Vitro Effects

Abstract Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.

ON THE STABILITY OF A POPULATION DYNAMICS MODEL WITH DELAY

2018 ◽  
pp. 456-465
Author(s):  
Vera Vladimirovna Malygina
Keyword(s):  
Differential Equation ◽  
Sufficient Conditions ◽  
Distributed Delay ◽  
Isolated Population ◽  
Dynamics Model ◽  
Population Dynamics Model ◽  
Three Stages ◽  
Pass Through ◽  
The Stability ◽  
Concentrated And Distributed Delay

We consider a model of the dynamics of an isolated population whose individuals pass through the three stages of evolution. We use a nonlinear autonomous differential equation with concentrated and distributed delay for description of the model. Effective sufficient conditions for the asymptotic stability of the nontrivial equilibrium point are obtained.

scholarly journals LncRNA AC245100.4 binds HSP90 to promote the proliferation of prostate cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1257-1271
Author(s):  
Rongjun Cui ◽  
Chi Liu ◽  
Ping Lin ◽  
Hui Xie ◽  
Wei Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Counting ◽  
Chaperone Function ◽  
In Vivo Assays ◽  
Iκb Kinase ◽  
Rna Immunoprecipitation ◽  
The Stability

Aim: To investigate the role and mechanisms of AC245100.4 in prostate cancer. Materials & methods: The expression and location of AC245100.4 were examined using real-time PCR and  in situ hybridization. Cell Counting Kit-8, clone formation, flow cytometry and in vivo assays were conducted to determine the role of AC245100.4. RNA antisense purification with mass spectrometry and RNA immunoprecipitation were performed to identify proteins that bind to AC245100.4. Western blotting was performed to quantify the expression of protein. Results: AC245100.4 expression was upregulated in prostate cancer and mainly located in the cytoplasm. Knockdown of AC245100.4 inhibited proliferation of prostate cancer. Mechanistically, AC245100.4 bound to HSP90 and altered its chaperone function, increased the stability of IκB kinase and activated the NFκB signaling pathway. Conclusion: AC245100.4 promotes the proliferation of prostate cancer via binding of HSP90.

scholarly journals Does Valproic Acid Induce Neuroendocrine Differentiation in Prostate Cancer?

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Abhinav Sidana ◽  
Muwen Wang ◽  
Wasim H. Chowdhury ◽  
Antoun Toubaji ◽  
Shabana Shabbeer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Neuroendocrine Differentiation ◽  
Immunohistochemical Analysis ◽  
Dependent Manner

Valproic Acid (VPA) is a histone deacetylase inhibitor that holds promise for cancer therapy. Here, we investigate whether VPA treatment induces neuroendocrine differentiation of Prostate Cancer (PCa). A tissue microarray of VPA-treated and untreated tumor xenografts and cell lines of human PCa (LNCaP, C4-2, DU145, and PC-3) were generated and were analyzed by immunohistochemical analysis (IHC) for NE markers chromogranin A (CgA), synaptophysin, and NCAM (neural cell adhesion molecule). Western blot analysis for CgA was performed to confirm the results of the TMA. IHC analysis did not reveal any induction of CgA, synaptophysin, or NCAM in any xenograft after VPA treatmentin vivo.In vitro, VPA treatment induced little synaptophysin expression in C4-2 and PC-3 cells and NCAM expression in LNCaP and PC-3 cells. In the case of CgA, VPA treatment decreased its expressionin vitroin a dose-dependent manner, as determined by western blot analysis. Thus our data demonstrates that VPA does not induce NE differentiation of PCa cells in the physiologically relevantin vivosetting.

scholarly journals Dynamical Analysis of SIR Epidemic Models with Distributed Delay

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Wencai Zhao ◽  
Tongqian Zhang ◽  
Zhengbo Chang ◽  
Xinzhu Meng ◽  
Yulin Liu
Keyword(s):  
Equilibrium Points ◽  
Sufficient Conditions ◽  
Distributed Delay ◽  
Epidemic Models ◽  
Dynamical Analysis ◽  
Sir Epidemic ◽  
Dynamical Behaviors ◽  
The Stability ◽  
Sir Epidemic Models

SIR epidemic models with distributed delay are proposed. Firstly, the dynamical behaviors of the model without vaccination are studied. Using the Jacobian matrix, the stability of the equilibrium points of the system without vaccination is analyzed. The basic reproduction numberRis got. In order to study the important role of vaccination to prevent diseases, the model with distributed delay under impulsive vaccination is formulated. And the sufficient conditions of globally asymptotic stability of “infection-free” periodic solution and the permanence of the model are obtained by using Floquet’s theorem, small-amplitude perturbation skills, and comparison theorem. Lastly, numerical simulation is presented to illustrate our main conclusions that vaccination has significant effects on the dynamical behaviors of the model. The results can provide effective tactic basis for the practical infectious disease prevention.

375 RADIATION INDUCES NEUROENDOCRINE DIFFERENTIATION OF PROSTATE CANCER CELL LINES IN VITRO AND IN VIVO

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Chang-Deng Hu ◽  
Bennett Elzey ◽  
Jean Poulson ◽  
Wallace Morrison ◽  
Xuehong Deng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Neuroendocrine Differentiation ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines

scholarly journals Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shubham Dwivedi ◽  
Maricris Bautista ◽  
Sanskriti Shrestha ◽  
Hussain Elhasasna ◽  
Tanaya Chaphekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuroendocrine Differentiation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Intervention Point ◽  
High Concentrations ◽  
Potential Therapeutic Intervention

AbstractThe progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.

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