Tumor Incidence in a Chemical Carcinogenesis Study of Nonhuman Primates

Thorgeirsson, Unnur P.; Dalgard, Dan W.; Reeves, Jeanette; Adamson, Richard H.

doi:10.1006/rtph.1994.1013

Cited by 124 publications

(102 citation statements)

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“…Its phosphorylation was highly positive in immunohistochemical analysis of HCC biopsies [197] while increased STAT3 DNA binding activity was observed in chemically-induced HCC [198]. This is surprising, since rapid activation of the STAT3 transcriptional complex has been reported in the regenerating liver following partial hepatectomy [199]. Also, STAT3 antisense oligonucleotide has been reported to significantly reduce the amount of STAT3 protein and inhibit cell proliferation and tumorigenic growth of several human HCC cell lines transplanted into mice [195].…”

Section: Role Of Stat3 In Oncogenic Transformationmentioning

confidence: 99%

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Subramaniam

Shanmugam

Perumal

et al. 2013

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

203

229

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a b s t r a c t a r t i c l e i n f oHepatocellular carcinoma (HCC) is one of the most lethal malignancies, and is also the fourth most common cancer worldwide with around 700,000 new cases each year. Currently, first line chemotherapeutic drugs used for HCC include fluorouracil, cisplatin, doxorubicin, paclitaxel and mitomycin, but most of these are non-selective cytotoxic molecules with significant side effects. Sorafenib is the only approved targeted therapy by the U.S. Food and Drug Administration for HCC treatment, but patients suffer from various kinds of adverse effects, including hypertension. The signal-transducer-and-activator-of-transcription 3 (STAT3) protein, one of the members of STATs transcription factor family, has been implicated in signal transduction by different cytokines, growth factors and oncogenes. In normal cells, STAT3 activation is tightly controlled to prevent dysregulated gene transcription, whereas constitutively activated STAT3 plays an important role in tumorigenesis through the upregulation of genes involved in anti-apoptosis, proliferation and angiogenesis. Thus, pharmacologically safe and effective agents that can block STAT3 activation have the potential both for the prevention and treatment of HCC. In the present review, we discuss the possible role of STAT3 signaling cascade and its interacting partners in the initiation of HCC and also analyze the role of various STAT3 regulated genes in HCC progression, inflammation, survival, invasion and angiogenesis.

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Section: Role Of Stat3 In Oncogenic Transformationmentioning

confidence: 99%

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Subramaniam

Shanmugam

Perumal

et al. 2013

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

203

229

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“…Cancer (IARC) as human carcinogens (aflatoxin, arsenic, azathioprine, cyclophosphamide, melphalan) (17); of these, only aflatoxin and melphalan were evaluated as carcinogenic in these monkey studies. Table 2 indicates that only 1 1 of 25 chemicals were evaluated by NCI as monkey carcinogens under the conditions of these studies; 3 had equivocal results, and 11 were not carcinogenic (13,18). The NCI evaluations are based on malignant tumors only.…”

Section: Comparison Of Positivitymentioning

confidence: 99%

“…In contrast, all of the model carcinogens induce tumors in rodent experiments lasting less than 6 months, i.e., less than one-fourth the standard life span of 2 years (15,16). Under the conditions of the 5-year dosing protocol, the following model rodent carcinogens were not carcinogenic in monkeys: 2-acetylaminofluorene, 2,7-acetylaminofluorene, N,N-dimethyl-4-aminoazobenzene, 3'-methyl-4-dimethylaminoazobenzene, 3-methylcholanthrene (18). Urethane had the weakest evidence of carcinogenicity among the monkey carcinogens: the latency period was longer than those of other monkey carcinogens, and only one tumor of any type was induced, i.e., no site was a target site for more than one animal in a monkey experiment.…”

Section: Comparison Of Positivitymentioning

confidence: 99%

“…For the number of animals we took the total number of monkeys that started on test for both monkey species combined, as the NCI evaluation of carcinogenicity for a chemical did not distinguish between the two species (18). The median value of the number of monkeys on test for the 24 rodent carcinogens in Table 2 was 19.…”

Section: Comparison Of Positivitymentioning

confidence: 99%

“…The saccharin dose was equivalent to 5 cans of diet soda daily, and the cyclamate dose was equivalent to 30 cans daily (18). The average daily dose rate of sodium saccharin gave the lowest dose ratio of all chemicals (0.009) ( Table 2), and sodium cyclamate was also relatively low (0.3).…”

Section: Comparison Of Positivitymentioning

confidence: 99%

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Supplement to the Carcinogenic Potency Database (CPDB): results of animal bioassays published in the general literature in 1993 to 1994 and by the National Toxicology Program in 1995 to 1996.

Gold

Manley

Slone

et al. 1999

Environ Health Perspect

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The Carcinogenic Potency Database (CPDB) is a systematic and unifying analysis of results of chronic, long-term cancer tests. This paper presents a supplemental plot of the CPDB, including 513 experiments on 157 test compounds published in the general literature in 1993 and 1994 and in Technical Reports of the National Toxicology Program in 1995 and 1996. The plot standardizes the experimental results (whether positive or negative for carcinogenicity), including qualitative data on strain, sex, route of compound administration, target organ, histopathology, and author's opinion and reference to the published paper, as well as quantitative data on carcinogenic potency, statistical significance, tumor incidence, dose-response curve shape, length of experiment, duration of dosing, and dose rate. A numerical description of carcinogenic potency, the TD50, is estimated for each set of tumor incidence data reported. When added to the data published earlier, the CPDB now includes results of 5,620 experiments on 1,372 chemicals that have been reported in 1,250 published papers and 414 National Cancer Institute/National Toxicology Program Technical Reports. The plot presented here includes detailed analyses of 25 chemicals tested in monkeys for up to 32 years by the National Cancer Institute. Half the rodent carcinogens that were tested in monkeys were not carcinogenic, despite usually strong evidence of carcinogenicity in rodents and/or humans. Our analysis of possible explanatory factors indicates that this result is due in part to the fact that the monkey studies lacked power to detect an effect compared to standard rodent bioassays. Factors that contributed to the lack of power are the small number of animals on test; a stop-exposure protocol for model rodent carcinogens; in a few cases, toxic doses that resulted in stoppage of dosing or termination of the experiment; and in a few cases, low doses administered to monkeys or early termination of the experiment even though the doses were not toxic. Among chemicals carcinogenic in both monkeys and rodents, there is some support for target site concordance, but it is primarily restricted to liver tumors. Potency values are highly correlated between rodents and monkeys. The plot in this paper can be used in conjunction with the earlier results published in the CRC Handbook of Carcinogenic Potency and Genotoxicity Databases [Gold LS, Zeiger E, eds. Boca Raton FL:CRC Press, 19971 and with our web site (http.//potency.berkeley.edu), which includes a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency (TD50), and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Two summary tables permit easy access to the literature of animal cancer tests by target organ and by chemical. For readers using the CPDB extensively, a combined plot on diskette or other format is available from the first author. It i...

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Studies on the Proliferative Activity of Diethylnitrosamine-Induced Hepatocellular Carcinomas in Monkeys

et al. 1997

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Tumor Incidence in a Chemical Carcinogenesis Study of Nonhuman Primates

Cited by 124 publications

References 0 publications

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma

Supplement to the Carcinogenic Potency Database (CPDB): results of animal bioassays published in the general literature in 1993 to 1994 and by the National Toxicology Program in 1995 to 1996.

Studies on the Proliferative Activity of Diethylnitrosamine-Induced Hepatocellular Carcinomas in Monkeys

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