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C D Sherman

Publications and source records attributed to C D Sherman.

At least 19 recordsLinked to original sources
PubMed1997

The two-stage model of carcinogenesis: overcoming the nonidentifiability dilemma.

The two-stage mathematical model of carcinogenesis has been shown to be nonidentifiable whenever tumor incidence data alone is used to fit the model (Hanin and Yakovlev, 1996). This lack of identifiability implies that more than one parameter vector satisfies the optimization criteria for parameter estimation, e.g., maximum likelihood estimation. A question of greater concern to persons using the two-stage model of carcinogenesis is under what conditions can identifiable parameters be obtained from the observed experimental data. We outline how to obtain identifiable parameters for the two-stage model.

Animals↗
PubMed1996

Calculating tumor incidence rates in stochastic models of carcinogenesis.

Multistage models of carcinogenesis are increasingly used in the estimation of risks from exposure to environmental agents. The two-stage model of carcinogenesis is routinely used because it agrees with much of the existing tumor incidence data, parallels the biological two-stage model, and has much of its mathematical details derived. However, recent findings on the mechanisms of carcinogenesis has led researchers to believe that there are a greater number of stages and a more complex structure to these models than a single pathway. In this paper, a method for readily computing tumor incidence rates for arbitrarily complex multistage models is derived. The formulas for the two-stage model with time-varying rates are given explicitly. Simple rules for more complicated models are given, and computer code able to implement these formulas are provided.

Animals↗
PubMed1996

Modeling the number and size of hepatic focal lesions following exposure to 2,3,7,8-TCDD.

Data on the size and number of placental glutathione S-transferase-positive (PGST+) foci were collected from a two-stage hepatocarcinogenesis model in female Sprague-Dawley rats. the study consisted of multiple 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed dose groups including both diethylnitrosomine (DEN)-initiated and uninitiated animals. Groups were observed after 15 or 31 weeks of TCDD exposure. The parameters in the first half of a two-stage mathematical model of carcinogenesis were estimated from these data. If the model is valid, the results suggest that TCDD stimulates the production of PGST+ foci and promotes the growth of PGST+ foci. This finding suggests a complicated mechanism for TCDD-induced production of Hepatic foci that we refer to as activation, labeling TCDD as an activator. The analysis also indicates that there is an interaction between DEN and TCDD which results in dose-related formation of initiated cells throughout the study period. Best-fitting curves (using maximum likelihood methods) for TCDD-induced activation and promotion reached saturation levels at low doses of TCDD. In summary, the model fit the data well, but leads to an interpretation of the data which either questions the validity of the model or implies that our understanding of the effects of TCDD and DEN is incomplete.

Adenosine Triphosphate↗
PubMed1996

Stochastic simulation of a multistage model of carcinogenesis.

Stochastic mathematical models of carcinogenesis have been used to quantify cancer risks for about 40 years. As more detailed data of the cancer process are obtained, mathematical models try to incorporate this information and as a result become more complex and sometimes analytically and numerically intractable. Simulation studies have become an important tool for examining the operating characteristics of the models of interest. The many quantities one can examine using this tool include bias in parameter estimates, adequacy of approximation methods, and the appropriateness of large sample generalizations to small studies. This manuscript describes a general method of stochastic simulation that may be carried out for arbitrarily complicated stochastic models of carcinogenesis.

Cell Division↗
PubMed1995

Quantitative analysis of multiple phenotype enzyme-altered foci in rat hepatocarcinogenesis experiments: the multipath/multistage model.

The promotional effect of phenobarbital and 1-hydroxymethyl-pyren on enzyme altered lesions in the rat liver were quantified within the framework of two separate multipath/multistage models. The experiment analyzed followed an initiation-promotion protocol in which female Wistar rats were initiated with a single dose of diethylnitrosamine at 0.15 mumol/g body wt followed by a 3 week treatment-free period. A promotor, 1-hydroxymethyl-pyren or phenobarbital was then administered continuously in the diet for 120 days. All animals were sacrificed 3 weeks after treatment and their livers were examined for enzyme histological changes. Focal lesions were classified into three phenotype categories: adenosine triphosphatase altered (ATPase), sulfotransferase altered (ST) and jointly altered lesions (ATPase and ST). Quantitative methods were used to analyze the data, which consisted of the number and sizes of these enzyme-altered lesions. Both multipath/multistage models fitted to the data clearly demonstrate that phenobarbital promotion produced more observable and larger foci than promotion via 1-hydroxymethyl-pyren and that the growth kinetics of the jointly altered lesions were elevated relative to the lesions expressing a single marker. It was not possible with these data to determine if there was a predominant sequence in the formation of jointly altered lesions.

Adenosine Triphosphatases↗
PubMed1994

Multistage models of carcinogenesis: an approximation for the size and number distribution of late-stage clones.

Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two-stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth-death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth-death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic clones.

Animals↗
PubMed1993

Using cell replication data in mathematical modeling in carcinogenesis.

Risk estimation involves the application of quantitative models of dose versus response to carcinogenicity data. Recent advances in biology, computing, and mathematics have led to the application of mathematically complicated, mechanistically based models of carcinogenesis to the estimation of risks. This paper focuses on two aspects of this application, distinguishing between models using available data and the development of new models to keep pace with research developments.

Animals↗
PubMed1988

The development of "coordinating councils" for cancer education in Europe, Latin America, and the Asian-Pacific region.

This article described progressive interest in cancer education on three continents with an increasing number of national and multinational groups having a formalized role in cancer. A great deal of this activity has been stimulated by the International Union Against Cancer (UICC) through surveys, regional conferences, courses, etc. Further action at the continental, national, and local level will be strengthened considerably with the formation of new "coordinating councils" for cancer education in Europe, Latin America, and the Asian-Pacific region. These "coordinating councils" include representatives of most organizations with an interest in cancer education. A long list of projects for possible consideration by these councils is noted.

Asia↗
PubMed1986

The International Union Against Cancer (UICC) and its Professional Education Program.

The International Union Against Cancer (UICC) is a world federation composed of 242 member organizations. One of its functions is organizing a quadrennial international cancer congress. The next congress will be held in Budapest in August, 1986. Other UICC programs include a Detection and Diagnosis Program, a Tumor Biology Program, a Public Education Campaign, Fellowships and Awards Program, Epidemiology and Prevention Program, Smoking and Cancer Program, Treatment and Rehabilitation Program, and the Professional Education Program. The latter produces a UICC Manual of Clinical Oncology, sponsors regional education meetings, offers consultation visits on request, and offers courses and training programs. The American activities are coordinated by the USA National Committee on the UICC, comprised of representatives of the United States members of the UICC.

Congresses as Topic↗
PubMed1980

Assessment of jejunoileostomy for obesity--some observations since 1976.

In this review, which only partially covers the data available, it is pointed out that the evaluation of the results of jejunoileostomy may depend upon the criteria used by the observers, and disclosure of the true effects of the operation may depend upon the long-term follow-up of the patients. With increasing length of observation, it has become apparent that problems such as vitamin D deficiency, renal stone formation, continued steatorrhea, gallstones, zinc and copper deficiency, and even renal failure may be seen with disturbing frequency. Some of these may be preventable, others may be correctable and, indeed, the overall incidence of genuinely severe problems may, in the long run, be sufficiently low so as to make the benefits of jejunoileostomy outweigh the hazards. The rate of patient satisfaction is high, quality of life is generally improved and psychosocial and economic benefits of jejunoileostomy are apparent. The operation may also be a better alternative than the physical hazards of continuing obesity. Whether or not gastric bypass represents a true improvement over jejunoileostomy will depend upon the conclusions reached after applying to it the same searching scrutiny that is being used to examine the long-term results of jejunoileostomy.

Bile Acids and Salts↗