Cancer and normal ageing

Ebbesen, Peter

doi:10.1016/0047-6374(84)90001-0

Cited by 31 publications

(7 citation statements)

References 90 publications

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“…The incidence of invasive cancers rises exponentially with advanced age in humans (1) and other mammals (2). This dramatic increase in cancer risk during the final period of life is largely based on an increase in epithelial carcinomas, including lung carcinomas (3).…”

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confidence: 99%

Age‐associated changes of extracellular matrix collagen impair lung cancer cell migration

et al. 2008

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Although advanced age is linked with an increased incidence of lung carcinomas, elderly patients develop fewer metastatic tumors than their younger counterparts. Since extracellular matrix controls carcinogenesis, we studied the effect of aged fibrillar collagen (rat tail) on the invasiveness of lung carcinoma cells (H322, H358). Two- and three-dimensional invasion assays revealed a reduced migration of lung cancer cells through a matrix of collagen from old (24 mo) compared with young (2 mo) or adult (12 mo) rats. This was most strongly observed for H322 cells, which had a better migration behavior than H358 cells. Since old collagen was increasingly modified by advanced glycation end products (AGEs; fluorescing AGEs, nonfluorescing carboxymethyllysine), we generated different AGE-collagens by treating collagen with ribose or alpha-dicarbonyls. Similarly to old collagen, AGE-collagen reduced the invasive migration of H322 cells. Subsequent analyses demonstrated that old and AGE-collagens impair distinct mechanisms contributing to cell migration, i.e., efficient cell adhesion and proteolytic degradation of collagen by membrane-type matrix metalloproteinase (MT-MMP; MT-MMP3 in H322 cells). Our data indicate that age-related alterations of the extracellular matrix contribute to a less invasive behavior of lung carcinoma cells, in which AGE modifications of aged collagen seem to play an important role.

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confidence: 99%

Age‐associated changes of extracellular matrix collagen impair lung cancer cell migration

et al. 2008

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“…have led to the concept that aging is accompanied by a decline in the functional integrity of genetic material (1-3). There is a decrease in replicative capacity (4) and cellular viability (5), and an increased tendency toward cellular transformation and oncogenesis with age (6). Chromosomal alterations occur more frequently;…”

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confidence: 99%

Comparative analysis of DNA mutations in lacI transgenic mice with age

Lee¹,

DeSimone²,

Cerami³

et al. 1994

FASEB j.

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Transgenic mice have been developed recently that contain copies of the well-defined mutagenesis reporter gene, lacI, in an integrated bacteriophage-based shuttle vector. The lacI gene, which is present in all cells of the mouse, can be excised specifically from isolated genomic DNA and efficiently packaged into bacteriophage particles after the addition of packaging extracts. Mutations of the lacI gene are easily detected by the derepression of beta-galactosidase resulting in blue plaques in the presence of X-gal. Originally developed as a short-term in vivo mutagenesis assay to screen genotoxic agents, we have used this system to measure naturally occurring DNA mutations as a function of chronological age. There was a linear increase in the presence of phenotypic lacI mutants from birth to 24 months (r = 0.731, P < 0.001), such that 24-month-old mice have accumulated approximately fourfold more mutants than newborn pups. Molecular analysis of these spontaneously arising DNA mutations showed them to result predominantly from base substitutions (80.6-98.5%) that were equally distributed between transitions and transversions. However, lacI mutations in animals > 3 months of age demonstrated a higher percentage of mutations (12-19.4% vs. 1.2%) resulting from discriminable size changes (> 20 bp) than was observed for mice 1-2 months old. Sequence analysis of mutations resulting from a > 20 bp size change revealed them to be due to a duplication of adjacent lacI sequence. These results indicate that there is a gradual accumulation of DNA mutations with age and that the types of mutations also are influenced by the age of the animal.

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“…DeVita [ 37 ] contains some 33 papers discussing issues that impinge on the age-related incidence of various types of cancer. Ebbesen [ 38 ] discusses the probable mechanisms of cancer development and "those aspects of 'normal' aging that he believes to be most relevant to the etiologic and pathogenetic bonds between the two biological processes." These mechanisms are explored in Macieria-Coelho & Azzarone [ 39 ].…”

Section: The Aging-cancer Questionmentioning

confidence: 99%

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

Feizabadi

Witten

2010

Theor Biol Med Model

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BackgroundIn this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts) is considered as logistic only.ResultsWe demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can lead to different evolutionary patterns for normal and tumor cells during a course of therapy.ConclusionsThese results have significance for understanding appropriate pharmacotherapy for elderly patients who are also undergoing chemotherapy.

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Cancer and normal ageing

Cited by 31 publications

References 90 publications

Age‐associated changes of extracellular matrix collagen impair lung cancer cell migration

Age‐associated changes of extracellular matrix collagen impair lung cancer cell migration

Comparative analysis of DNA mutations in lacI transgenic mice with age

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

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