scholarly journals Are the Somatic Mutation and Tissue Organization Field Theories of Carcinogenesis Incompatible?

2013 ◽  
Vol 12 ◽  
pp. CIN.S13013 ◽  
Author(s):  
Simon Rosenfeld

Two drastically different approaches to understanding the forces driving carcinogenesis have crystallized through years of research. These are the somatic mutation theory (SMT) and the tissue organization field theory (TOFT). The essence of SMT is that cancer is derived from a single somatic cell that has successively accumulated multiple DNA mutations, and that those mutations occur on genes which control cell proliferation and cell cycle. Thus, according to SMT, neoplastic lesions are the results of DNA-level events. Conversely, according to TOFT, carcinogenesis is primarily a problem of tissue organization: carcinogenic agents destroy the normal tissue architecture thus disrupting cell-to-cell signaling and compromising genomic integrity. Hence, in TOFT the DNA mutations are the effect, and not the cause, of the tissue-level events. Cardinal importance of successful resolution of the TOFT versus SMT controversy dwells in the fact that, according to SMT, cancer is a unidirectional and mostly irreversible disease; whereas, according to TOFT, it is curable and reversible. In this paper, our goal is to outline a plausible scenario in which TOFT and SMT can be reconciled using the framework and concepts of the self-organized criticality (SOC), the principle proven to be extremely fruitful in a wide range of disciplines pertaining to natural phenomena, to biological communities, to large-scale social developments, to technological networks, and to many other subjects of research.

2003 ◽  
Vol 31 (2) ◽  
pp. 444-446 ◽  
Author(s):  
B. Zhang ◽  
S. Ye ◽  
A.A. Sayer ◽  
S.R. Hammans ◽  
S. Adio ◽  
...  

Somatic mutation in the mitochondrial genome occurs much more rapidly than in the nuclear genome and is a feature, possibly contributory, of the aging of cells and tissues. Identifying mitochondrial sequence changes in blood DNA of elderly subjects may provide a maker for the epigenetic changes of mitochondrial DNA known to occur in tissues with lower cellular turnover, and would also have implications for immunosenescence. No large-scale epidemiological studies have been reported previously. In this study we have established long-PCR banks of the mitochondrial genome from peripheral lymphocytes for an elderly cohort of 716 individuals with a range of measured aging phenotypes, and we have established assays for three widely reported mutations: the 4977 bp and 8048 bp deletions and point mutation A3243G. No individuals were identified with detectable heteroplasmy for these changes. Implications for tissue and population prevalence are discussed. The mitochondrial long-PCR DNA banks established will be useful for a wide range of studies of somatic mutation and of germline haplotypes in relation to aging.


2016 ◽  
Vol 7 (4) ◽  
pp. 167-168
Author(s):  
Rahul Anand

ABSTRACT How to cite this article Sarode SC, Anand R, Sarode GS, Patil S. Somatic Mutation Theory/Tissue Organization Field Theory: Has the Premise been Wrong All along? World J Dent 2016;7(4):167-168.


Author(s):  
Christina Kiel ◽  
David Matallanas ◽  
Walter Kolch

RAS oncogenes are amongst the most commonly mutated proteins in human cancers. They regulate a wide range of effector pathways that control cell proliferation, survival, differentiation, migration and metabolic status. Including aberrations in these pathways, RAS dependent signaling is altered in more than half of human cancers. Targeting mutant RAS proteins and their downstream oncogenic signaling pathways has been elusive. However, recent results comprising detailed molecular studies, large scale omics studies and computational modeling have painted a new and more comprehensive portrait of RAS signaling that helps us to understand the intricacies of RAS, how its physiological and pathophysiological functions are regulated, and how we can target them. Here, we review these efforts particularly trying to relate the detailed mechanistic studies with global functional studies. We highlight the importance of computational modeling and data integration to derive an actionable understanding of RAS signaling that will allow us to design new mechanism based therapies for RAS mutated cancers.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 236
Author(s):  
Christina Kiel ◽  
David Matallanas ◽  
Walter Kolch

RAS oncogenes are among the most commonly mutated proteins in human cancers. They regulate a wide range of effector pathways that control cell proliferation, survival, differentiation, migration and metabolic status. Including aberrations in these pathways, RAS-dependent signaling is altered in more than half of human cancers. Targeting mutant RAS proteins and their downstream oncogenic signaling pathways has been elusive. However, recent results comprising detailed molecular studies, large scale omics studies and computational modeling have painted a new and more comprehensive portrait of RAS signaling that helps us to understand the intricacies of RAS, how its physiological and pathophysiological functions are regulated, and how we can target them. Here, we review these efforts particularly trying to relate the detailed mechanistic studies with global functional studies. We highlight the importance of computational modeling and data integration to derive an actionable understanding of RAS signaling that will allow us to design new mechanism-based therapies for RAS mutated cancers.


Author(s):  
V. C. Kannan ◽  
A. K. Singh ◽  
R. B. Irwin ◽  
S. Chittipeddi ◽  
F. D. Nkansah ◽  
...  

Titanium nitride (TiN) films have historically been used as diffusion barrier between silicon and aluminum, as an adhesion layer for tungsten deposition and as an interconnect material etc. Recently, the role of TiN films as contact barriers in very large scale silicon integrated circuits (VLSI) has been extensively studied. TiN films have resistivities on the order of 20μ Ω-cm which is much lower than that of titanium (nearly 66μ Ω-cm). Deposited TiN films show resistivities which vary from 20 to 100μ Ω-cm depending upon the type of deposition and process conditions. TiNx is known to have a NaCl type crystal structure for a wide range of compositions. Change in color from metallic luster to gold reflects the stabilization of the TiNx (FCC) phase over the close packed Ti(N) hexagonal phase. It was found that TiN (1:1) ideal composition with the FCC (NaCl-type) structure gives the best electrical property.


Author(s):  
О. Кravchuk ◽  
V. Symonenkov ◽  
I. Symonenkova ◽  
O. Hryhorev

Today, more than forty countries of the world are engaged in the development of military-purpose robots. A number of unique mobile robots with a wide range of capabilities are already being used by combat and intelligence units of the Armed forces of the developed world countries to conduct battlefield intelligence and support tactical groups. At present, the issue of using the latest information technology in the field of military robotics is thoroughly investigated, and the creation of highly effective information management systems in the land-mobile robotic complexes has acquired a new phase associated with the use of distributed information and sensory systems and consists in the transition from application of separate sensors and devices to the construction of modular information subsystems, which provide the availability of various data sources and complex methods of information processing. The purpose of the article is to investigate the ways to increase the autonomy of the land-mobile robotic complexes using in a non-deterministic conditions of modern combat. Relevance of researches is connected with the necessity of creation of highly effective information and control systems in the perspective robotic means for the needs of Land Forces of Ukraine. The development of the Armed Forces of Ukraine management system based on the criteria adopted by the EU and NATO member states is one of the main directions of increasing the effectiveness of the use of forces (forces), which involves achieving the principles and standards necessary for Ukraine to become a member of the EU and NATO. The inherent features of achieving these criteria will be the transition to a reduction of tasks of the combined-arms units and the large-scale use of high-precision weapons and land remote-controlled robotic devices. According to the views of the leading specialists in the field of robotics, the automation of information subsystems and components of the land-mobile robotic complexes can increase safety, reliability, error-tolerance and the effectiveness of the use of robotic means by standardizing the necessary actions with minimal human intervention, that is, a significant increase in the autonomy of the land-mobile robotic complexes for the needs of Land Forces of Ukraine.


1994 ◽  
Vol 29 (12) ◽  
pp. 149-156 ◽  
Author(s):  
Marcus Höfken ◽  
Katharina Zähringer ◽  
Franz Bischof

A novel agitating system has been developed which allows for individual or combined operation of stirring and aeration processes. Basic fluid mechanical considerations led to the innovative hyperboloid design of the stirrer body, which ensures high efficiencies in the stirring and the aeration mode, gentle circulation with low shear forces, excellent controllability, and a wide range of applications. This paper presents the basic considerations which led to the operating principle, the technical realization of the system and experimental results in a large-scale plant. The characteristics of the system and the differences to other stirring and aeration systems are illustrated. Details of the technical realization are shown, which conform to the specific demands of applications in the biological treatment of waste water. Special regard is given to applications in the upgrading of small compact waste water treatment plants.


2012 ◽  
Vol 9 (1) ◽  
pp. 175-180
Author(s):  
Yu.D. Chashechkin

According to the results of visualization of streams, the existence of structures in a wide range of scales is noted: from galactic to micron. The use of a fundamental system of equations is substantiated based on the results of comparing symmetries of various flow models with the usage of theoretical group methods. Complete solutions of the system are found by the methods of the singular perturbations theory with a condition of compatibility, which determines the characteristic equation. A comparison of complete solutions with experimental data shows that regular solutions characterize large-scale components of the flow, a rich family of singular solutions describes formation of the thin media structure. Examples of calculations and observations of stratified, rotating and multiphase media are given. The requirements for the technique of an adequate experiment are discussed.


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