scholarly journals Tumor and the Microenvironment: A Chance to Reframe the Paradigm of Carcinogenesis?

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mariano Bizzarri ◽  
Alessandra Cucina
Keyword(s):  
Experimental Data ◽  
Cancer Research ◽  
Tumor Microenvironment ◽  
Morphogenetic Field ◽  
Biological Organization ◽  
Somatic Mutation Theory ◽  
Theoretical Perspectives ◽  
Mutation Theory ◽  
Phenotype Transformation ◽  
New Framework

The somatic mutation theory of carcinogenesis has eventually accumulated an impressive body of shortfalls and paradoxes, as admittedly claimed by its own supporters given that the cell-based approach can hardly explain the emergence of tissue-based processes, like cancer. However, experimental data and alternatives theories developed during the last decades may actually provide a new framework on which cancer research should be reframed. Such issue may be fulfilled embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation and assuming radically different premises as well as new methodological frameworks. Within that perspective, the tumor microenvironment cannot be merely considered akin to new “factor” to be added to an already long list of “signaling factors”; microenvironment represents the physical-biochemical support of the morphogenetic field which drives epithelial cells towards differentiation and phenotype transformation, according to rules understandable only by means of a systems biology approach. That endeavour entails three fundamental aspects: general biological premises, the level of observation (i.e., the systems to which we are looking for), and the principles of biological organization that would help in integrating and understanding experimental data.

scholarly journals One hundred years of somatic mutation theory of carcinogenesis: Is it time to switch?

BioEssays ◽  
2013 ◽  
Vol 36 (1) ◽  
pp. 118-120 ◽  
Author(s):  
Ana M. Soto ◽  
Carlos Sonnenschein
Keyword(s):  
Somatic Mutation ◽  
Somatic Mutation Theory ◽  
Mutation Theory

scholarly journals Real world in cancer? Epistemology of the origin of cancer: new paradigm for the majority of cancers

2015 ◽  
Author(s):  
Björn LDM Brücher ◽  
Ijaz S Jamall
Keyword(s):  
Somatic Mutation ◽  
Cancer Biology ◽  
Preventive Measures ◽  
Chemical Stimulus ◽  
Cancer Model ◽  
New Paradigm ◽  
Somatic Mutation Theory ◽  
Mutation Theory ◽  
Passenger Mutations ◽  
Cancerous Cells

Background: The somatic mutation theory as the origin of cancer (carcinogenesis) was born some 100 years ago, when Theodor Boveri 1914 suggested that a combination of chromosomal defects may result in cancer. This was followed by Karl-Heinrich Bauer in 1928 suggesting that mutations could cause cancer. Subsequently, in 1953 Carl Nordling proposed that a number of mutated genes could cause cancer. Alfred Knudson in 1971 proposed that one hit (one mutation) would result in a clone of cancerous cells. This was modified to a 2-hit-theory later and it seems that cancer biology has continued to try to bolster the somatic mutation theory by recently suggesting that ‘driver’ and ‘passenger’ mutations were necessary and when this proved insufficient, others proposed the hyper-mutation theory in 2014. In the attempt to clothe the Emperor, it was forgotten that mutations found in advanced cancers are either late events or epiphenomena that occur after carcinogenesis (cancer development) and especially after the appearance of a pre-cancerous niche. Reality: Fewer than 10% of cancers are proven to be hereditary (i.e., causally related to germline mutations) and this ratio is even lower in cancers of the stomach (<1%), the colorectum (3-8%) and breast (8%). Infection-triggered cancers constitute some 15% of all cancers and the remaining about some 80% cancers are sporadic, meaning their cause is unknown. New cancer paradigm: Findings from the plant and animal kingdoms, molecular and clinical data over the last 250 years were critically reviewed and gave rise to a new cancer hypothesis containing a multi-step process of 6 sequences. These include, (1) a pathogenic biological or chemical stimulus is followed by (2) chronic inflammation, from which develops (3) fibrosis with associated changes in the cellular microenvironment. These remodeling changes result in a (4) pre-cancerous niche, which triggers the deployment of (5) a chronic stress escape strategy, and when this fails to resolve, (6) a transition of a normal cell to a cancer cell occurs. Consequences: This recently proposed cancer model explains the origins of the vast majority of cancers which are until now were referred to as ‘sporadic’ cancers. Furthermore, this theory points out the need to establish preventive measures long before a cancer becomes clinically apparent. The epistemology of the origin of cancer is reviewed and presented.

scholarly journals Organoid Models for Cancer Research

2019 ◽  
Vol 3 (1) ◽  
pp. 223-234 ◽  
Author(s):  
Hans Clevers ◽  
David A. Tuveson
Keyword(s):  
Cancer Research ◽  
Tumor Microenvironment ◽  
Personalized Medicine ◽  
High Throughput ◽  
Stromal Cells ◽  
Transcriptome Sequencing ◽  
Cancer Biology ◽  
Three Dimensional ◽  
Model Systems ◽  
Liver Cancers

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.

Historic Sites Archaeology on the Western American Frontier: Theoretical Perspectives and Research Problems

1981 ◽  
Vol 2 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Donald L. Hardesty
Keyword(s):  
Island Biogeography ◽  
Ad Hoc ◽  
Cultural Resource Management ◽  
Western United States ◽  
Historic Sites ◽  
American Frontier ◽  
Integrative Research ◽  
Theoretical Perspectives ◽  
Research Problems ◽  
New Framework

Historic sites archaeology in the western United States is booming but continues to be conducted ad hoc. The demands of assessing significance for cultural resource management purposes suggests that integrative research problems must be identified. One set of such problems emerge from the frontier concept. The use of synecological models from general ecology is proposed as a new framework within which to better understand frontier phenomena. As an illustration, one aspect of Frederick Jackson Turner's “frontier thesis” — the homogenization of frontier behavior — is examined in this light and related to historic sites research. In addition patterns of frontier colonization are studied with models of island biogeography developed by the late Robert MacArthur and E. O. Wilson.

The somatic mutation theory of cancer: growing problems with the paradigm?

BioEssays ◽  
2004 ◽  
Vol 26 (10) ◽  
pp. 1097-1107 ◽  
Author(s):  
Ana M. Soto ◽  
Carlos Sonnenschein
Keyword(s):  
Somatic Mutation ◽  
Somatic Mutation Theory ◽  
Mutation Theory

scholarly journals The mitochondrial basis of aging and related diseases

2021 ◽  
Vol 271 ◽  
pp. 03033
Author(s):  
Junxi Mou
Keyword(s):  
Biological Clock ◽  
Hair Color ◽  
Somatic Mutation Theory ◽  
Irreversible Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Cellular Energy ◽  
Mutation Theory ◽  
External Interventions ◽  
The Relationship

Aging is a programmed and spontaneous life course that organisms must undergo, and as an irreversible and relatively conservative process, several theories have tried to explain its causes. Among them, the somatic mutation theory, the free radical theory, the natural cross-linking of biomolecules, the immune theory, the telomere theory, the biological clock theory, and the toxic theory are among the most widely accepted hypotheses. However, no single doctrine can fully explain the aging process. Aging is mainly manifested in the structural and functional aging and decline of organisms, and as organisms continue to age, most organs will experience varying degrees of aging and irreversible damage, although it is directly related to many diseases, aging itself is generally not considered as a disease. Any organism ages slowly over time, with the most easily observable manifestations in external changes such as diminished hair color and sagging skin. Numerous studies have shown that mitochondria are instrumental in mitigating aging as the primary provider of cellular energy, providing energy for cell growth and development as well as being the center of cellular metabolism; therefore, once mitochondria become faulty, a large number of cells will lose function, age, and thus die. In this paper, we will discuss in detail the relationship between mitochondria and aging and how external interventions can promote the function of mitochondria in delaying aging.

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