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Biomedical subjects

R T Prehn

Publications and source records attributed to R T Prehn.

At least 19 recordsLinked to original sources

Cancers beget mutations versus mutations beget cancers.

Despite the plethora of "oncogenes" and "tumor suppressor genes," the hypothesis that cancer is usually the result of genomic mutations may be wrong. We should at least examine the alternative hypothesis, for which there is considerable evidence, that mutations do not commonly beget cancer, but rather that cancer phenotypes result from confused or aberrant patterns of normal-gene expression; the abnormal patterns are postulated to result from epigenetic mechanisms rather than from mutations. The epigenetic hypothesis that I am proposing suggests that cancers may exhibit mutations primarily because replicative errors at inactive sites in the cancer genome may be repaired slowly or not at all, but the mutations so produced, occurring at already inactivated sites in the genome, may have limited biological significance. Thus, it may be more correct to say that cancers beget mutations than it is to say that mutations beget cancers.

Animals

Many growth factors may not be growth factors.

Both organ growth and tumor growth are dependent upon a biased ratio of cell births to cell deaths; this ratio is independent of the frequency of mitosis. Thus, so-called growth factors that affect only the frequency of mitosis are not really growth factors. I shall advance two hypotheses: that the normal adult ratio of cell births to cell deaths is maintained by the activity of a factor or factors produced by the stem cells; and that the differentiating cells, as well as the stem cells, produce a different factor that limits the frequency of mitosis.

Animals

The inhibition of tumor growth by tumor mass.

Evidence suggests that a tumor behaves, in its pattern of growth, like an integrated organ rather than a collection of independently growing cells. Tumor growth tends to slow progressively as size increases and to undergo compensatory growth after partial resection. Consequently, therapies that reduce tumor mass may tend to accelerate the growth of the remaining tumor and tumor metastases. An approach to therapy based upon a simulated increase in tumor mass may be worthy of consideration.

Animals

Immunological tolerance to many self epitopes may be unnecessary.

The demonstration of the existence of antigenic mimicry suggests that immunological tolerance to self antigens may be an insufficient basis for distinguishing self from non-self. However, some data suggest that even in the absence of tolerance most self epitopes would not immunize the host and that tolerance to all self epitopes may, therefore, not be necessary for the prevention of autoimmune disease.

Animals

Tumor-specific antigens as altered growth factor receptors.

Most induced, as opposed to spontaneous, tumors possess tumor-specific transplantation antigens. Data suggest that the prevalence of these antigens, at least among tumors induced chemically in diffusion chambers, is dependent upon the density of the culture at the time of carcinogen application. Other data show that density inhibition of cell growth is mediated by the interaction of various "growth factors" with their respective cell surface receptors. The juxtaposition of these two observations leads me to hypothesize that the tumor-specific transplantation antigen is an altered growth factor receptor. Development of the hypothesis leads to rational explanations of some paradoxical features of tumor growth in nude mice, to a possible understanding of why spontaneous tumors are nonimmunogenic, and to an explanation of the phenomenon of facilitation of tumor growth by a weak immune reaction.

Animals

The flip side of tumor immunity.

A large amount of data suggest that tumors are, to some degree, dependent for their growth on a positive level of immune reaction, a level that is unique for each tumor. Each tumor gradually adjusts its immunogenicity to the level that will, in the immunologic context of its own particular host, maximize its growth. Thus, it follows that immunosuppression may be as likely as immunoaugmentation to have a therapeutic effect.

Animals

The autoimmune nature of cancer.

Four different kinds of data from the 3-methylcholanthrene-induced sarcoma system of the mouse show that the immune system stimulates oncogenesis; i.e., the presence of a tumor-specific immune reaction is a positive aid to tumor development. It seems proper, therefore, to consider cancer, at least in part, an autoimmune disease.

Animals

Surveillance, latency and the two levels of MCA-induced tumor immunogenicity.

Among 154 different, MCA-induced mouse sarcomas, the immunogenicities of those tumors that had had the shortest original latencies in their autochthonous hosts were of an intermediate level with relatively little scatter. This fact is not predicted by the theory of immunological surveillance, but does fit the predictions of the immunological facilitation theory of oncogenesis. The frequency distribution of the tumor immunogenicities showed 2 peaks; the cluster of higher immunogenicity had a shorter latency than did the cluster of lower immunogenicity. The data for tumors initiated within in vivo diffusion chambers also showed 2 immunogenicity clusters, suggesting that the discrete clusters were not caused by host immunity. However, immunity apparently reduced the mean latency of the more immunogenic cluster and/or lengthened the mean latency of the less immunogenic, a result also inconsistent with the theory of immunological surveillance.

Animals

Splenic variations affecting sarcomagenesis among mice of an inbred strain.

Among overtly identical mice of an inbred strain, some are relatively susceptible and some relatively resistant to sarcomagenesis by large concentrations of 3-methylcholanthrene (MCA) (Prehn, 1975 a). Spleen cells from mice, subsequently shown to be relatively susceptible, conveyed a relative resistance to oncogenesis when transferred to irradiated recipients; spleen cells from mice, subsequently shown to be relatively resistant, conveyed to secondary hosts a relative susceptibility.

Animals

Influence of immune status of host on immunogenicity of tumors induced with two doses of methylcholanthrene.

Previous studies by Prehn demonstrated a direct correlation between the dose of carcinogen used for tumor induction and the immunogenicity of the resulting tumors. The purpose of the present study was to determine the role of the host's immune response and the influence of the carcinogen on immune function in this relationship. For that reason, a comparison was made of the immunogenicities of tumors induced with two doses of carcinogen in immunologically normal mice and in mice immunodepressed by adult thymectomy and irradiation. If the direct relationship between dose and immunogenicity demonstrated in normal mice was due to the degree of immunosuppression produced by the carcinogen, this correlation should not be apparent in mice already immunosuppressed. Although there was some increase in the immunogenicity of tumors induced in the immunosuppressed mice, the same relationship between carcinogen dose and immunogenicity was observed in both groups of mice. These results indicate that the degree of immunogenicity of tumors induced with both high and low doses of carcinogen was influenced by immunoselection, but in addition another, non-immunologic factor was significant in the relationship between carcinogen dose and immunogenicity.

Animals

Genetic susceptibility to post-thymectomy autoimmune diseases in mice.

The strain distribution pattern of five different post-thymectomy autoimmune diseases was determined in 21 inbred and two congenic, resistant strains of mice. The results indicated that susceptibility genes outside the H-2 complex may be involved in the development of localized autoimmune diseases in neonatally thymectomized mice. Studies of recombinant inbred strains also showed that susceptibility to gastritis was not associated with the H-2 haplotype but appeared to be influenced by a minor histocompatibility locus. Possible linkage to the H-2 complex was suggested only in the development of coagulating gland adenitis. Although one experiment showed that susceptibility to orchitis and coagulating gland adenitis was inherited as a recessive trait, further studies are required to determine the exact mode of inheritance in each disease system.

Animals