Inhibition of carcinogen-altered rat tracheal epithelial cell proliferation by normal epithelial cells <i>in vivo</i>

Terzaghi-Howe, M.

doi:10.1093/carcin/8.1.145

Cited by 48 publications

(24 citation statements)

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“…Reasoning from the cell culture model, the persistent bronchial hyperplasia might be expected to act as permissive microenvironment for progression to, and expression of, the neoplastic phenotype by the most transformable cells in the hyperplastic population. This view gains plausibility from experiments on the proliferation of neoplastic tracheal epithelial cells of rats in the presence of normal or preneoplastic tracheal epithelial cells (Terzaghi-Howe, 1987). The preneoplastic cells had been exposed to x-rays and, when cultured alone on denuded tracheal grafts, yielded a non-invasive, organized metaplastic or undifferentiated epithelium.…”

Section: Tumor Microenvironmentmentioning

confidence: 98%

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Rubin

2002

Oncogene

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Historically our knowledge about the direct carcinogenic activity of cigarette smoke and its constituents grew from painting experiments on the skin of mice to produce papillomas and carcinomas. The neutral fraction of cigarette smoke condensate had most of the carcinogenic activity in this test and was rich in carcinogenic polycyclic aromatic hydrocarbons (PAHs), the most abundant by far being BP. However, the concentration of BP in the condensate was only about 2% the amount of pure BP required to cause skin tumors. In other fractions there were non-carcinogenic constituents that promoted tumor formation when applied repeatedly to mouse skin that had been initiated by a single subcarcinogenic application of BP. There were also constituents of cigarette smoke that acted as cocarcinogens when applied simultaneously with repeated applications of BP. BP was effective as an initiator at lower concentrations than as a complete carcinogen, and some non-carcinogenic PAHs in the condensate were also active initiators. It was concluded from these studies that cigarette smoke condensate is primarily a tumorpromoting and co-carcinogenic agent with weak activity as a complete carcinogen. A major effect of promoters, and possibly of co-carcinogens, is a diffuse hyperplasia which includes selective expansion of clones carrying endogenous mutations and/or mutations induced by PAHs and other carcinogens such as NNK. The induced mutations as well as damaged cells would occur throughout the exposed region and, along with the hyperplasia, increase the permissiveness of the cellular microenvironment for neoplastic expression of any potential tumor cell in its midst. Since neither the promoters nor co-carcinogens in tobacco smoke are known to interact directly with DNA, their effects can be considered epigenetic processes that act upon genetically altered cells. Examples are cited from studies of experimental skin carcinogenesis, smoking-induced histopathological changes in human lung and spontaneous transformation in cell culture to illustrate the genetic and epigenetic interactions of neoplastic development in general and their significance for smoking-induced lung cancer in particular. Certain dietary modifications that appear to be effective in moderating the promotional phase of animal and human carcinogenesis are suggested for trial in managing lung cancer.

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Section: Tumor Microenvironmentmentioning

confidence: 98%

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Rubin

2002

Oncogene

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“…IC-12 rat tracheal carcinoma was derived from an F344 rat undifferentiated carcinoma induced in vivo in a trachea by exposure to DMBA (Terzaghi-Howe, 1987). It was cultured in B1 modified Ham's F12 medium and used at passage 33.…”

Section: Cells and Animalsmentioning

confidence: 99%

Radioimmunotherapy of micrometastases in lung with vascular targeted213Bi

et al. 1999

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Therapy of solid tumours using targeting agents such as tumour cell-directed monoclonal antibodies (mAbs) has proven to be difficult due to the relatively low fraction of the total dose delivered specifically to the tumour. It has been postulated for some time (Denekamp, 1984) that the tumour blood vessels are more accessible targets for directed therapy. Recent work has shown that agents which interfere with new blood vessel formation (angiogenesis) are capable of inhibiting tumour growth in experimental animals (Kim et al, 1993;O'Reilly et al, 1995O'Reilly et al, , 1997Borgström et al, 1996). The drawback of this approach is that once treatment is stopped, the tumours grow rapidly and eventually prove fatal. Another approach utilized immunotoxins specific for tumour blood vessels. In a model system, an immunotoxin, targeted to major histocompatability complex components induced in blood vessels through genetically altered tumour cells, proved to be therapeutic (Burrows and Thorpe, 1994) and infarction and cure of tumours was observed.For therapy of small metastases, it is desirable to destroy both the tumour blood vessels and the tumour cells. In this work, shortrange, high linear energy transfer (LET) radiation ( 213 Bi) was targeted to blood vessels feeding tumours in the lung. The mAb used, mAb 201B, binds to murine thrombomodulin (TM). TM is expressed selectively and in large amounts on the lumenal surfaces of capillaries and small blood vessels in the lung. mAb 201B injected intravenously (i.v.) localizes quickly and in high concentration in murine lung (Kennel et al, 1990). This system was used previously to target the β-particle emitter 131 I to lungs bearing tumours, resulting in a marginal therapeutic effect (Blumenthal et al, 1992). The localization characteristics of mAb 201B allow targeting of short half-lived isotopes such as the α-particle emitter 213 Bi (t 1 /2 = 45 min), with delivery of a large fraction of the absorbed dose to the lung as a target . The model of experimental lung tumour colonies has been used to test the efficiency of vascular-targeted 213 Bi for radioimmunotherapy. In this system, tumour cells injected i.v. lodge in the lung and form colonies. mAb 201B is then used to deliver 213 Bi to all the lung vessels, including those which feed the tumour colonies. The tissue range of the 213 Bi α-particle is 60-100 µ and thus should produce damage not only to lung vessels, but also to the tumour cells adjacent to the vessels. A preliminary paper has shown that high-dose therapy resulted in tumour cures, but that collateral lung damage occurred (Kennel and Mirzadeh, 1998). Dose-response experiments and radioimmunotherapy with different tumour types were necessary to assess the limits of effectiveness of this approach. We show herein that lung tumour colonies can be significantly reduced by this treatment in five different tumour types with relatively low doses of radioisotope and that tumours which are immunogenic in the host can be cured completely. Summary A model system has been used...

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“…and/or first subgrafts of epithelial cells and often epithelial cell cultures (8)(9)(10)(11)(12)(13).…”

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confidence: 99%

“…High frequencies of induced preneoplastic changes occurred in tracheal pouch grafts and in cultured tracheal epithelia (8)(9)(10)(11) as well as in a similar mouse mammary epithelial system (9,12). Cell number-dependent suppression of progression was seen in the tracheal system (8,11).…”

mentioning

confidence: 99%

Evidence that carcinogenesis involves an imbalance between epigenetic high-frequency initiation and suppression of promotion.

Kamiya¹,

Yasukawa-Barnes²,

Mitchen³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

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Evidence is presented in support of the hypothesis that cancer development depends on an imbalance between highly frequent epigenetic initiation and suppression of promotion ofthe initiated cells. When irradiated clonogenic mammary epithelial cells are transplanted and hormonally stimulated, they give rise to clonal glandular structures within which carcinomas may arise. In the current study, the cancer incidence in grafts of '13 7-Gy-irradiated clonogens per site indicated that at least 1 of -95 clonogens was radiogenically initiated. A similar initiation frequency had been seen in grafts of -5 methylnitrosourea (MNU)-treated clonogens. Such initiation is thus far more frequent than specific locus mutations. In sites grafted with larger cell inocula, cancer incidences per clonogen were suppressed inversely as the numbers of irradiated or MNU-treated clonogens per graft increased. Addition of unirradiated cells to small irradiated graft inocula also suppressed progression. Radiation and MNU thus produce quantitatively, and perhaps qualitatively, similar carcinogenesis-related sequelae in mammary clonogens.

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Inhibition of carcinogen-altered rat tracheal epithelial cell proliferation by normal epithelial cells in vivo

Cited by 48 publications

References 0 publications

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Radioimmunotherapy of micrometastases in lung with vascular targeted213Bi

Evidence that carcinogenesis involves an imbalance between epigenetic high-frequency initiation and suppression of promotion.

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