scholarly journals Gibbs Process Determines Survival and Reveals Contact-Inhibition Genes in Glioblastoma Multiforme

2019 ◽  
Author(s):  
Lavanya Kannan ◽  
Tarjani Agarwal ◽  
Matija Snuderl ◽  
David Zagzag ◽  
Erik Sulman ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Survival Time ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Hard Core ◽  
Contact Inhibition ◽  
Death Process ◽  
Integrated Analysis ◽  
Birth And Death Process ◽  
Gibbs Process

AbstractTumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor cells will result in Gibbs hard core process over long time scales. In order to verify if this is the case, we applied the Gibbs process to 411 TCGA Glioblastoma multiforme patient images. Our imaging dataset included all cases for which diagnostic slide images were available.The model revealed two clusters, one of which - the “Gibbs cluster,” showed the convergence of the Gibbs process with significant survival difference. Further smoothing the discretized (and noisy) inhibition metric, for both increasing and randomized survival time, we found a significant association of the patients in the Gibbs cluster with increasing survival time. The mean inhibition metric also revealed the point at which the homotypic CIL establishes in tumor cells. Besides, RNAseq analysis between patients with loss of heterotypic CIL and intact homotypic CIL in the Gibbs cluster unveiled cell movement gene signatures and differences in Actin cytoskeleton and RhoA signaling pathways as key molecular alterations. These genes and pathways have established roles in CIL. Taken together, our integrated analysis of patient images and RNAseq data provides for the first time a mathematical basis for CIL in tumors, explains survival as well as uncovers the underlying molecular landscape for this key tumor invasion and metastatic phenomenon.

The extinction time of a general birth and death process with catastrophes

1986 ◽  
Vol 23 (04) ◽  
pp. 851-858 ◽  
Author(s):  
P. J. Brockwell
Keyword(s):  
Laplace Transform ◽  
Size Distribution ◽  
Sufficient Conditions ◽  
Necessary And Sufficient Conditions ◽  
Death Process ◽  
Extinction Time ◽  
Birth And Death Process ◽  
Different Types ◽  
The Laplace Transform ◽  
Necessary And Sufficient

The Laplace transform of the extinction time is determined for a general birth and death process with arbitrary catastrophe rate and catastrophe size distribution. It is assumed only that the birth rates satisfyλ0= 0,λj> 0 for eachj> 0, and. Necessary and sufficient conditions for certain extinction of the population are derived. The results are applied to the linear birth and death process (λj=jλ, µj=jμ) with catastrophes of several different types.

Presence and significance of NK cells in glioblastomas

1989 ◽  
Vol 70 (5) ◽  
pp. 728-731 ◽  
Author(s):  
Jesús Vaquero ◽  
Santiago Coca ◽  
Santiago Oya ◽  
Roberto Martínez ◽  
Josefa Ramiro ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nk Cells ◽  
Survival Time ◽  
Tumor Cells ◽  
Lymphocytic Infiltration ◽  
Surface Marker ◽  
Content Type ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Fine Print

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

scholarly journals Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gautier Follain ◽  
Naël Osmani ◽  
Valentin Gensbittel ◽  
Nandini Asokan ◽  
Annabel Larnicol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Metastatic Progression ◽  
Metastatic Dissemination ◽  
Secondary Tumors ◽  
Flow Profiles ◽  
Endothelial Response ◽  
Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

scholarly journals Comprehensive Analysis of Transcriptome and Metabolome Reveals the Flavonoid Metabolic Pathway Is Associated with Fruit Peel Coloration of Melon

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2830
Author(s):  
Aiai Zhang ◽  
Jing Zheng ◽  
Xuemiao Chen ◽  
Xueyin Shi ◽  
Huaisong Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Fruit Peel ◽  
External Quality ◽  
Color Formation ◽  
Peel Color ◽  
Dark Green

The peel color is an important external quality of melon fruit. To explore the mechanisms of melon peel color formation, we performed an integrated analysis of transcriptome and metabolome with three different fruit peel samples (grey-green ‘W’, dark-green ‘B’, and yellow ‘H’). A total of 40 differentially expressed flavonoids were identified. Integrated transcriptomic and metabolomic analyses revealed that flavonoid biosynthesis was associated with the fruit peel coloration of melon. Twelve differentially expressed genes regulated flavonoids synthesis. Among them, nine (two 4CL, F3H, three F3′H, IFS, FNS, and FLS) up-regulated genes were involved in the accumulation of flavones, flavanones, flavonols, and isoflavones, and three (2 ANS and UFGT) down-regulated genes were involved in the accumulation of anthocyanins. This study laid a foundation to understand the molecular mechanisms of melon peel coloration by exploring valuable genes and metabolites.

scholarly journals Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1411
Author(s):  
Don Carlo Ramos Batara ◽  
Moon-Chang Choi ◽  
Hyeon-Uk Shin ◽  
Hyunggee Kim ◽  
Sung-Hak Kim
Keyword(s):  
Brain Tumor ◽  
Glioblastoma Multiforme ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Molecular Target ◽  
Therapeutic Strategies ◽  
Homeostatic Mechanism ◽  
Cellular Context ◽  
Cellular Components

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.

scholarly journals Early alterations of neurovascular unit in the retina in mouse models of tauopathy

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fan Xia ◽  
Yonju Ha ◽  
Shuizhen Shi ◽  
Yi Li ◽  
Shengguo Li ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Leukocyte Adhesion ◽  
Neurovascular Unit ◽  
Integrated Analysis ◽  
Therapeutic Effects ◽  
Retinal Ganglion ◽  
Potential Biomarker

AbstractThe retina, as the only visually accessible tissue in the central nervous system, has attracted significant attention for evaluating it as a biomarker for neurodegenerative diseases. Yet, most of studies focus on characterizing the loss of retinal ganglion cells (RGCs) and degeneration of their axons. There is no integrated analysis addressing temporal alterations of different retinal cells in the neurovascular unit (NVU) in particular retinal vessels. Here we assessed NVU changes in two mouse models of tauopathy, P301S and P301L transgenic mice overexpressing the human tau mutated gene, and evaluated the therapeutic effects of a tau oligomer monoclonal antibody (TOMA). We found that retinal edema and breakdown of blood–retina barrier were observed at the very early stage of tauopathy. Leukocyte adhesion/infiltration, and microglial recruitment/activation were constantly increased in the retinal ganglion cell layer of tau transgenic mice at different ages, while Müller cell gliosis was only detected in relatively older tau mice. Concomitantly, the number and function of RGCs progressively decreased during aging although they were not considerably altered in the very early stage of tauopathy. Moreover, intrinsically photosensitive RGCs appeared more sensitive to tauopathy. Remarkably, TOMA treatment in young tau transgenic mice significantly attenuated vascular leakage, inflammation and RGC loss. Our data provide compelling evidence that abnormal tau accumulation can lead to pathology in the retinal NVU, and vascular alterations occur more manifest and earlier than neurodegeneration in the retina. Oligomeric tau-targeted immunotherapy has the potential to treat tau-induced retinopathies. These data suggest that retinal NVU may serve as a potential biomarker for diagnosis and staging of tauopathy as well as a platform to study the molecular mechanisms of neurodegeneration.

scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

A stochastic process related to language change

1970 ◽  
Vol 7 (01) ◽  
pp. 69-78 ◽  
Author(s):  
Barron Brainerd
Keyword(s):  
Stochastic Process ◽  
Language Change ◽  
Death Process ◽  
Birth And Death Process ◽  
Standard Methods

The purpose of this note is two-fold. First, to introduce the mathematical reader to a group of problems in the study of language change which has received little attention from mathematicians and probabilists. Secondly, to introduce a birth and death process, arising naturally out of this group of problems, which has received little attention in the literature. This process can be solved using the standard methods and the solution is exhibited here.

Multi-Location Inventory Model Considering Bidirectional and Unidirectional Transshipments Simultaneously

2013 ◽  
Vol 694-697 ◽  
pp. 2742-2745
Author(s):  
Jin Hong Zhong ◽  
Yun Zhou
Keyword(s):  
Process Model ◽  
Approximate Calculation ◽  
Inventory Model ◽  
Inventory System ◽  
Death Process ◽  
Birth And Death Process ◽  
Inventory Models ◽  
Continuous Review ◽  
Poisson Demand ◽  
Queue Theory

Abstract. A cross-regional multi-site inventory system with independent Poisson demand and continuous review (S-1,S) policy, in which there is bidirectional transshipment between the locations at the same area, and unidirectional transshipment between the locations at the different area. According to the M/G/S/S queue theory, birth and death process model and approximate calculation policy, we established inventory models respectively for the loss sales case and backorder case, and designed corresponding procedures to solve them. Finally, we verify the effectiveness of proposed models and methods by means of a lot of contrast experiments.

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