The Sequential Analysis of Cancer Development

Farber, Emmanuel; Cameron, Ross

doi:10.1016/s0065-230x(08)60658-2

Cited by 538 publications

(190 citation statements)

References 226 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Preneoplastic enzyme-altered foci and nodules represent important steps in chemical hepatocarcinogenesis (Farber and Cameron, 1980;Satoh et al, 1989). Single cells and mini-foci positive for the placental form of glutathione S-transferase (GST-Pi) develop very early in hepatocarcinogen-treated rat livers prior to the formation of nodules.…”

Section: Inhibition Of Carcinogen Induced Enzyme-altered Focimentioning

confidence: 99%

K vitamins, PTP antagonism, and cell growth arrest

Carr

Wang

Kar

2002

Journal Cellular Physiology

View full text Add to dashboard Cite

The main function of K vitamins is to act as co-factors for g-glutamyl carboxylase. However, they have also recently been shown to inhibit cell growth. We have chemically synthesized a series of K vitamin analogs with various side chains at the 2 or 3 position of the core naphthoquinone structure. The analogs with short thio-ethanol side chains are found to be more potent growth inhibitors in vitro of various tumor cell lines. Cpd 5 or [2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone] is one of the most potent. The anti-proliferation activity of these compounds is antagonized by exogenous thiols but not by non-thiol antioxidants. This suggests that the growth inhibition is mediated by sulfhydryl arylation of cellular glutathione and cysteine-containing proteins and not by oxidative stress. The protein tyrosine phosphatases (PTP) are an important group of proteins that contain cysteine at their catalytic site. PTPs regulate mitogenic signal transduction and cell cycle progression. PTP inhibition by Cpd 5 results in prolonged tyrosine phosphorylation and activation of several kinases and transcription factors including EGFR, ERK1/2, and Elk1. Cpd 5 could activate ERK1/2 either by signaling from an activated EGFR, which is upstream in the signaling cascade, or by direct inhibition of ERK1/2 phosphatase(s). Prolonged ERK1/2 phosphorylation strongly correlates with Cpd 5-mediated growth inhibition. Cpd 5 can also bind to and inhibit the Cdc25 family of dual specific phosphatases. As a result, several Cdc25 substrates (Cdk1, Cdk2, Cdk4) involved in cell cycle progression are tyrosine phosphorylated and thereby inhibited by its action. Cpd 5 could also inhibit both normal liver regeneration and hepatoma growth in vivo. DNA synthesis during rat liver regeneration following partial hepatectomy, transplantable rat hepatoma cell growth, and glutathione-S-transferase-pi expressing hepatocytes after administration of the chemical carcinogen diethylnitrosamine, are all inhibited by Cpd 5 administration. The growth inhibitory effect during liver regeneration and transplantable tumor growth is also correlated with ERK1/2 phosphorylation induced by Cpd 5. Thus, Cpd 5-mediated inhibition of PTPs, such as Cdc25 leads to cell growth arrest due to altered activity of key cellular kinases involved in signal transduction and cell cycle progression. This prototype K vitamin analog represents a novel class of growth inhibitor based upon its action as a selective PTP antagonist. It is clearly associated with prolonged ERK1/2 phosphorylation, which is in contrast with the transient ERK1/2 phosphorylation induced by growth stimulatory mitogens.

show abstract

Section: Inhibition Of Carcinogen Induced Enzyme-altered Focimentioning

confidence: 99%

K vitamins, PTP antagonism, and cell growth arrest

Carr

Wang

Kar

2002

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…It is well established now that carcinogenesis is a multistep process (Bannasch et al, 1980;Farber & Cameron, 1980;Farber & Sarma, 1987). In rat hepatocarcinogenesis, many models are available which generate preneoplastic lesions as foci and nodules, which are believed to be preferential sites for ultimate cancer development (Farber & Cameron, 1980).…”

mentioning

confidence: 99%

“…In rat hepatocarcinogenesis, many models are available which generate preneoplastic lesions as foci and nodules, which are believed to be preferential sites for ultimate cancer development (Farber & Cameron, 1980). Some of these protocols allow a step-by-step analysis of these early preneoplastic foci and nodules, because of their synchroneous emergence (Farber et al, 1976;Lans et al, 1983).…”

mentioning

confidence: 99%

Cell population kinetics and ploidy rate of early focal lesions during hepatocarcinogenesis in the rat

Castelain

Deleener²,

Kirsch‐Volders³

et al. 1989

Br J Cancer

View full text Add to dashboard Cite

Summary We have studied the changes in cell population kinetics and DNA-content of cycling parenchymal cells during the very early steps of rat hepatocarcinogenesis in Faber's protocol. Adult rats were initiated by a single dose of diethylnitrosamine (DENA, 200 mg kg-1), followed 2 weeks later by a 2-week diet of 0.03% 2-acetylaminofluorene (2-AAF) as selection phase. In the middle of selection time, a single necrogenic dose of carbon tetrachloride (CCL4, 2 ml kg-) was administered by gavage. Twenty four hours thereafter, radiolabelled thymidine (3H-TdR, 1.5 ftCi g' ) was given by repeated injections during 24 h. An emergence of small, pyroninophilic ('tigroid') foci was observed at the second, fifth and eighth days after the proliferative stimulus. The focal putative precancerous cells presented a significant higher labelling index (LI) than the non-affected parenchymal cells for all exposure times. However, the labelling intensity decreased from the second to the eighth day after CC14, suggesting a dilution of the radiolabelled DNA by repeated divisions within the foci. The nuclei of the same foci were analysed for DNA-content by feulgen microdensitometry on neighbouring sections. A gradual reduction of nuclear DNA-content was observed in 66% of the foci at the fifth day and in 100% of foci at the eight day, as compared to surrounding tissue and untreated animals, where labelling and DNA-content remain in the same ratio.

show abstract

“…Much attention has been focused on the morphological, histological and biochemical properties of preneoplastic lesions such as enzyme-altered foci and hyperplastic nodules induced at the early stages of chemical hepatocarcinogenesis (Pitot et al, 1978;Farber and Cameron, 1980). One of the enzymes altered in early hepatocarcinogenesis is GST-P.…”

Section: Discussionmentioning

confidence: 99%

Potential effect of Nigella sativa against Diethylnitrosamine-induced hepatocarcinogenesis in rats

Ahmed

Brellou

Gameel

et al. 2017

J Hellenic Vet Med Soc

View full text Add to dashboard Cite

Objective of the investigation was the study of potential protective effects of the watery extract of Nigella sativa against diethylnitrosamine induced hepatocarcinogenesis in rats. N. sativa was administered to rats for protection against diethylnitrosamine-induced hepatocarcinogenesis. It was administered prior to, simultaneously with or after injection of diethylnitrosamine. Five groups of Wister rats were used. Group A was administered diethylnitrosamine and N. sativa simultaneously, group B was administered only diethylnitrosamine and group C received only N. sativa. These three groups were maintained for up to eight weeks. Group D received N. sativa six weeks after administration ofdiethylnitrosamine,while group E (“protective group”) received N. sativa on day 1 and diethylnitrosamine six weeks later. These two groups were maintained for up to 12 weeks. All rats were subjected to partial hepatectomy to enhance carcinogenesis. P-isoform of glutathione s transferase (GST-P) was detected in the cytoplasm and nuclei of hepatocytes. The number of GST-P positive foci was significantly smaller in test groups (A, D, E), particularly in groups A and E, when compared with to those in group B, indicating that N. sativa has protective effects against diethylnitrosamine induced liver cancer in rats, even in the very early stages of hepatocarcinogenesis.

show abstract

The Sequential Analysis of Cancer Development

Cited by 538 publications

References 226 publications

K vitamins, PTP antagonism, and cell growth arrest

K vitamins, PTP antagonism, and cell growth arrest

Cell population kinetics and ploidy rate of early focal lesions during hepatocarcinogenesis in the rat

Potential effect of Nigella sativa against Diethylnitrosamine-induced hepatocarcinogenesis in rats

Contact Info

Product

Resources

About