Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

718 records · Page 40Linked to original sources

PubMedDate not supplied

Autoimmune disease and allergy are controlled by vitamin C treatment.

The present study was started to investigate the problem of whether or not vitamin C administration may help control autoimmune disease and allergy by stimulating the glucocorticoid mechanism of a patient with an immune disorder. Our study was expected to give an answer to the long-lasting enigma of endocrinology--why is the adrenal cortex so rich in the vitamin C content? Our investigation represents the complex of experimental and clinical study. A healthy male volunteer served as the test subject in the experimental study, and we investigated the effect of vitamin C injection or infusion treatments on the eosinophil count and 5 plasma steroids in plasma on the one hand, and also tested the effect of vitamin C treatments on diuresis and 17-hydroxycorticoids (17-OHCS) excretion on the other hand. In the clinical study, the effect of the vitamin C infusion treatment on immune disorders was assessed in 4 patients with autoimmune disease. Results obtained are as follows: 1) the vitamin C injection or infusion treatments induced an increase of plasma glucocorticoid activity with a delay of about 2 hours, as assessed in terms of the eosinophil count and plasma cortisol concentration. 2) Within 2 hours after vitamin C challenge, however, a remarkable decline of plasma cortisol was found to proceed without any corresponding change of the eosinophil count, a finding to suggest the presence of some cortisol absorber, of which the function was triggered by vitamin C. 3) The same vitamin C treatments also accelerated diuresis and 17-OHCS excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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Hormonal implication of diet and reproductive activity in the genesis of cervical cancer.

The incidence of cervical cancer is known to decrease with the Westernization of life style. The purpose of this study was to see whether or not the practice of pseudopregnancy conditioning (psp-c) and/or non-Western (rice-rich or rice-and salt-rich) diet conditioning (dt-c) in female mice can reproduce a specific steroidal disorder that is associated with cervical cancer--general depression of androgen and partial depression of corticoid in urine. The effects of psp-c and dt-c were assessed by estimating various steroids in urine and plasma of mice, as collected at the terminal stage of the experiment. Macroscopic and microscopic changes of genital organs were also investigated by dissection. Results obtained are as follows: 1) the practice of psp-c and/or dt-c induced a total of 13 deciduomas in the vagina, the cervix and the corpus of experimental mice. No deciduoma was found in virgin mice fed a standard (Western-style) diet. 2) The combination of 2 reproductive markers (psp-c and non-psp-c) and 3 dietary markers (standard diet, rice-rich diet and rice- and salt-rich diet) produced a variety of changes in the excretions of all androgens, progestins and corticoids in the urine of mice for each of 5 experimental groups. A common steroidal trait was extracted from the urinary steroid data of 5 experimental groups--general depression of androgens, progestins and majority corticoids relative to tetrahydrocortisol. By the collation test, the combination of psp-c and rice- and salt-rich diet conditioning was found to be the best choice for reproducing the urinary steroid changes specific for cervical cancer. 3) The results of plasma steroid analysis, though not incompatible with the urinary steroid data, were fragmentary and not very informative in this study. The observed resistance of mice to carcinogenic insults together with the possible role of deciduoma in cervical carcinogenesis is discussed in the light of relevant information including the anti-carcinogenic action of vitamin C.

Animals↗

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Interrelation between Western type cancers and non-Western type cancers as regards their risk variations in time and space. VI. Chronological transition of various cancer risks of the world from 1975 to 1985.

We comparatively investigated the age-adjusted incidence rates (AAIRs) of overall cancers of the world between 1975 and 1985 to see whether or not any consistent change is in progress in the risk for cancer in general on a world scale. Results obtained are summarized as follows: 1) the total male population of the world, but not the total female population, experienced a significant rise in AAIR for cancers of all sites during the above 10 years. 2) In the comparison study of geographical subgroups, the above integral cancer risk significantly increased with time in the male population of Canada, USA-White, USA-Black, European continent (EC)-West, EC-others and Great Britain, and also in the female populations of both USA-Black and Great Britain. In other geographical subgroups the cancer risks for 1985 were also higher than those for 1975, but the differences were not statistically significant. 3) The above increase of cancer risk in general was accounted for by a surplus in weight of the increasing contribution of Western-type cancers over the decreasing contribution of non-Western type cancers to the integral cancer risk of a population. 4) Japan was found to be an exceptional case in that the risk for liver cancer (a non-Western type cancer) increased 3 to 8 fold from 1975 to 1985 in both male and female populations of Japan. Evidence was presented to suggest that the above increase of liver cancer incidence could be related to the persistence of social tension following the first oil crisis in 1973. In summary, the chronological transition patterns of cancer risk in Japan as well as in other parts of the world support our interpretation that social tension linked to the economic recession plays a crucial role in the production of recent changes of cancer risk in the world.

Age Factors↗

PubMedDate not supplied

Diabetes mellitus is controlled by vitamin C treatment.

The present study was started to investigate the question of whether or not vitamin C administration may help control diabetes mellitus (DM) by stimulating the insulin mechanism of a DM patient. We were motivated to take up the above thesis by the anticipation that vitamin C, being detectable in abundance in endocrine cells, may play a cardinal role in the production of hormones. In the preliminary experiment, we investigated the relation between glucose, insulin and vitamin C in the plasma of a non-diabetic male volunteer in whom vitamin C was introduced intravenously either by injection or by infusion, and with or without concomitant administration of glucose. In the follow-up study of 3 DM patients, the effect of the vitamin C infusion therapy on DM was assessed by summing up multiple clinical information. Results obtained are as follows: 1) the drip infusion system was superior to the ordinary injection system for maintaining plasma concentration of vitamin C at a high level and for a long period. 2) The plasma concentration of insulin, when tested in the vitamin C infusion system, followed a bimodal curve--a finding to suggest that vitamin C may stimulate the insulin mechanism in 2 distinct ways. The early mode was glucose-dependent at its height, but the late mode was independent of glucose charge. 3) The praxis of vitamin C infusion produced clinical improvements in 3 DM patients. The therapeutic efficacy of the treatment varied from patient to patient. In all cases, control of DM was started by combined use of the vitamin C infusion treatment and the insulin injection treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

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Interrelation between Western type cancers and non-Western type cancers as regards their risk variations in time and space. V. Mathematical analysis of the environment-sensing signal transmission system in carcinogenesis.

The purpose of this study was to elucidate the nature of the control mechanism of human carcinogenesis by applying regression analysis technique to the world statistics of various human neoplasias. The information used in the present study covers 19 cancers in the tumor spectrum, 47 cancer registration areas in space, and the years 1978 to 1982 in time. The risk for each cancer was expressed in terms of the annual age-adjusted incidence rate (AAIR). Results obtained are as follows: 1) The regression analysis of the world statistics demonstrated the existence of 3 subfamilies of cancer: a) Western type subfamily including 13 cancers; b) non-Western type subfamily including 4 cancers; c) independent type subfamily including 2 cancers. 2) Further regression analysis of the world statistics data revealed the presence of a mathematical regularity that characterized the relationship between various cancers and their risk changes in 47 areas of the world. The mathematical regularity of the above intercancer linkage closely resembled that of intersteroidal linkage of urine that was derived from the law of mass action. On the basis of the calculation results with the intercancer linkage, the international risk differences of various cancers are explained by use of the equilibrium model that resembles that of the chemical equilibrium model. Evidence is also presented to suggest that the intercancer equilibrium is maintained through the interaction between a proto-oncogen and a tumor suppressor gene in carcinogenesis. The significance of the environment-dependent control mechanism of human carcinogenesis is discussed in the light of population ecology.

Female↗

PubMedDate not supplied

The interference of geographical changes of cancer risk in tumor etiology in Japan.

An attempt was made to elucidate the relation between various human neoplasias in their geneses by comparatively investigating the geographical changes of cancer risk either between 2 sexes with one neoplasia or between two neoplasias for each sex with the data of multiple local populations of Japan as well as of the world. Specific cancer death rates for 11 sites in 46 prefectures of Japan, 1969-1971, were used in the domestic study, and age-adjusted cancer incidence rates for the corresponding 11 sites in 40 selected cancer registration areas of the world were used in the international study. The relation between 2 cancer risks was analyzed by calculating a 1st order regression equation using log-transformed data sets. Results obtained are as follows: 1) both the domestic and international data sets confirmed positive correlations of a high degree between the male and the female cancer risks in 6 out of 7 cancer sites tested (esophagus, stomach, colon, rectum, liver and bladder). A positive intersex correlation was also observed in lung cancer with the international data, but not with the domestic one. It was indicated that the male and female populations of Japan as well as of the world were under the influence of a common risk modifier in the course of geographical changes of cancer risk for each of 6 neoplasias except lung cancer. 2) Intercancer correlation was lacking in 11 out of 23 cancer pairs in the domestic study, whereas all 22 intercancer correlations but one in the international study were found to be statistically significant. Further insight into the correlation data of the international study led to the conclusion that the observed combination of positive and negative correlation in the 22 cancer pairs were explainable in terms of the differential cancer risk changes of Western type and Non-Western type cancers due to the transition of life style between the Western extreme and the Non-Western extreme in the world. In contrast, a high proportion of non-correlations (11 out of 23 cancer pairs) and emergence of opposite or new correlations (3 out of 23 pairs) were observed in the domestic study, a finding which indicates that the domestic cancer risk modifier, as evidenced in the intersex correlation test, is site-specific, and is to be differentiated from the Westernization-sensitive cancer risk modifiers of the international study.(ABSTRACT TRUNCATED AT 400 WORDS)

Climate↗

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Formation of free radicals and active oxygen species from diethylstilbestrol and its derivatives.

Diethylstilbestrol (DES), an estrogen analogue, was converted into a free radical in alkaline dimethyl sulfoxide as well as in an H2O2/peroxidase system. The presence of the hydroxyl group of the DES molecule was essential to free radical formation. Indenestrol A (IA), a microsomal metabolite of DES, showed a paramagnetic property without enzymatic activation. The electron spin resonance spectrum of IA seemingly corresponded to that of the enzymatically formed DES radical. In an NADH/peroxidase system, DES induced concomitant production of active oxygen species, which were also produced by IA. Related compounds of IA were also examined to compare with DES and IA. The significance of the free radical is discussed in relation to the process of carcinogenesis by DES.

Dienestrol↗

PubMedDate not supplied

Vitamin C and the genesis of autoimmune disease and allergy (review).

The purpose of this review paper is to present relevant information for assessing the validity of our clinical investigation on the clinical usefulness of vitamin C infusion treatment tested in the control of autoimmune disease and allergy. Firstly, we describe the historical background of this study and then present the results of both experimental and clinical investigations as regards the therapeutic effect of vitamin C infusion treatment for the control of immune disorders including diabetes mellitus. Secondly, we discuss the interdisciplinary nature of our studies in the light of recent progress in clinical vitaminology, endocrinology and immunology. Thirdly, we suggest the possibility that the use of our vitamin C infusion treatment may be beneficial in the clinical management of AIDS, of which the immunological background data are in favor of the participation of an autoimmune mechanism in the genesis of this disease. Finally, we stress the importance of paradigm change in the achievement of a breakthrough in natural science.

Ascorbic Acid↗

PubMedDate not supplied

Intraperitoneal administration of ascorbic acid delays the turnover of 3H-labelled cortisol in the plasma of an ODS rat, but not in the Wistar rat. Evidence in support of the cardinal role of vitamin C in the progression of glucocorticoid synthesis.

The purpose of this investigation was to reproduce in rats the enhancing effect of vitamin C on adrenal glucocorticoid production, a phenomenon that has been repeatedly observed in our human experiments. Here, we tried to assess the impact of vitamin C pretreatment on the turnover of exogenous 3H-labelled cortisol tracer in rats. 500 mg ascobic acid in 15 ml isotonic liquid per rat was administered intraperitoneally into rats of the experimental group, and 15 ml physiological saline per rat was similarly introduced into rats of the control group. At various times after the loading of either vitamin C or saline, 3H-labelled cortisol, 20 muc/0.5 ml saline/rat, was injected subcutaneously into rats of both the experimental and control groups. Thirty minutes later, all rats were sacrificed by exsanguination, and the radioactivity content was measured in the lipophilic fractions as well as in the purified corticosteroid compounds of blood, adrenal, testis and liver samples. To test the specificity of vitamin C action, experimental results from scurvy-prone ODS rats were compared with those of scurvy-resistant Wistar rats. Results obtained are as follows: a) the practice of vitamin C loading markedly delayed the turnover of 3H-cortisol in both the plasma lipophilic fraction and the plasma cortisol fraction, a finding which indicates that the above vitamin C pretreatment enhanced the release of endogenous glucocorticoid in such as to delay the turnover of the tracer cortisol in plasma. b) The above "dilution" effect of endogenous glucocorticoid surge was very distinct in both the lipophilic fraction and the cortisol fraction of ODS rats, and was less distinct (lipophilic fraction) or insignificant (cortisol fraction) in Wistar rats, a finding to indicate that the observed effect of vitamin C was of physiological significance. c) The responses of the adrenal glands, testes and liver to vitamin C pretreatment were generally more distinct in ODS rats than in Wistar rats, but varied from one organ to another. The significance of the functional linkage between vitamin C and adrenal glucocorticoid, which has been confirmed both in both the humans and rats in our laboratory, was discussed in the light of the historical development of vitamino-endocrinology.

Adrenal Glands↗

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The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient.

A series of publications from our laboratory have indicated that the practice of megadose vitamin C drip infusion treatment enhanced the activity of endogenous glucocorticoids in such a way as to improve the clinical course of allergy and autoimmune disease-a disease entity that is known to respond to the therapeutic effect of glucocorticoids. The present paper represents an extention of our vitamin C studies, and intends to investigate the problem whether or not chronic fatigue syndrome (CFS), an acquired immunodeficiency disease, can also be counted as one of the candidate diseases for the vitamin C infusion treatment. We prepared two kinds of vitamin C infusion sets for the clinical use: the dehydroepiandrosterone-annexed vitamin C infusion set (the new set) and the annex-free vitamin C infusion set (the old set). The new set was expected to enhance the endogenous activities of both glucocorticoids and gonadal steroids. We followed the clinical course of a male CFS patient using the old and new vitamin C infusion sets, and with and without the oral intake of erythromycin and chloramphenico. Results obtained are as follows: a) the observation period of a study subject covered a period of August 1995 to May 1996. Combination of pneumonia signs and dermatomyositis signs marked the onset of his CFS. b) Old infusion treatment together with the short term antibiotics treatment was found effective for the control of pneumonia in the first stage of the disease (from August to October, 1995). c) Signs of pneumonia recurrence gradually became eminent in the second stage of disease (from November, 1995, to January, 1996) in spite of the moderate frequency of the old treatment together with stepwise prolongation of the antibiotics treatment. d) The alternate practice of the old and new infusion treatments together with the long-term antibiotics treatment, as conducted in the 3rd stage of disease (from February to May, 1996) led to substantial extinction of pneumonia signs (leucocytosis, tachycardia etc). e) The practice of the new infusion treatment markedly increased the excretion of both 17-ketosteroids and 17-hydroxycorticosteroids in the urine. Evidence was also available to indicate that the dehydroepiandrosterone annex was converted to testosterone, which in turn made a contribution to the control of CFS. f) The immunological survey of lymphocyte subsets including NK cell percent failed to find a coherent change in a study subject with CFS. In conclusion, the above results could be taken as evidence to indicate that the new vitamin C infusion treatment effectuates the clinical control of CFS by fortifying the endogenous activities of both cortisol and testosterone. The significance of parallelism between pulmonary infection and CFS, as observed in the clinical course of the test subject, was discussed in the light of the focal infection theory of nephritis.

17-Hydroxycorticosteroids↗

PubMedDate not supplied

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons: i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS. We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows: a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes. b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies. c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS. d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment. e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS. f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS. g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

Ambulatory Care Facilities↗

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Free radical chemistry of cigarette smoke and its implication in human cancer.

Multiple components in cigarette smoke were analyzed for their ability to form active oxygen species using a spin trapping agent, 5, 5-dimethyl-1-pyrroline-N-oxide. The main source of O2 and H2O2 was ascribed to polyphenols in a particulate phase, whereas a synergistic effect was also observed between these polyphenols and nicotine. The vapor phase contained a factor which produced OH from H2O2 which was identified as carbonyl sulfide. Nitric oxide in the vapor phase did not show such reactivity. The formation of an active oxygen species in cigarette smoke could provide an important clue to elucidate the mechanism of tobacco carcinogenesis, since they show genotoxic effects to induce DNA strand breaks as well as epigenetic effects to act as cell proliferation signals.

Humans↗

PubMedDate not supplied

Formation of free radicals from steroid hormones: possible significance in environmental carcinogenesis.

In order to clarify the mechanism of environmental carcinogenesis, steroid hormones were checked for formation of free radicals and active oxygen species. In alkaline DMSO in vitro, glucocorticoids, progestines, androgens and estrogens exhibited distinct ESR signals with characteristic hyperfine structures. Accumulated data on a great number of steroid derivatives suggest that an unpaired electron is localized at position 20 in the case of glucocorticoids, whereas it is at position 3 in other steroid hormones. Since experimental conditions include oxygenation reactions and more or less reflect enzymatic reactivity, the results obtained suggest further study on the physiological formation of free radicals from steroid hormone is warranted. Although detection of the free radicals of steroid hormones in several enzyme systems was limited to estrogens, evidence suggests that glucocorticoids as well as androgens may also share the physiological formation of free radicals. The production of active oxygen species was confirmed in certain cases.

Animals↗

PubMedDate not supplied

Differential implications of the oncogene-tumor suppressor gene complex in the geneses of 19 human neoplasias. Evidence in support of the steroid carcinogenesis hypothesis.

The cancer risk changes of 19 human neoplasias over time and space, as expressed in terms of the logarithm of age-adjusted incidence rate (log AAIR), were found to hold a linear correlation with each other--a finding suggesting that the distribution pattern of log AAIR data sets of 2 cancers, when plotted on a two dimension diagram, may show a good fitness to the chemical equilibrium model a product of the law of mass action. On the basis of the statistical analysis of the data, we reached the conclusion that the risk changes of a given neoplasia in space represents the function of the centripetal force of an activated oncogene and the centrifugal force of an inactivated tumor suppressor gene, both of which should cooperate with each other to create a thermodynamic equilibrium under the law of mass action. The purpose of this study was to test the contribution of the oncogene-tumor suppressor gene complex to the sex discrimination of cancer risk in 19 human neoplasias. The results obtained are as follows: a) the correlation coefficient r seq of the sequential regression analysis, as applied to 47 log AAIR data sets of one tumor pair, served as a criterion in testing the balance of power between oncogene activation and tumor suppressor gene inactivation. Sole activation of the oncogene should give an r seq value of -1.0, whereas sole inactivation of the tumor suppressor gene should give an r seq value of +1.0. b) Esophageal cancer and laryngeal cancer, two sex-discriminating tumors with distinct male predominance were each associated with differential implications of the oncogene-tumor suppressor gene complex between the male and female populations: in both tumors, the male populations were associated with a complex of activated oncogene and inactivated tumor suppressor gene, whereas the female population was associated with another complex of weakly activated (esophageal cancer) or non-activated (laryngeal cancer) oncogene and inactivated tumor suppressor gene, as assessed by the r seq criteria. c) The intersex correlation of cancer risk in both esophageal cancer and laryngeal cancer for 47 populations throughout the world, was rather weak, when compared with other members of human neoplasias. The intersex difference of r seq as expressed in terms of t value of Student's t test for each of 19 human neoplasias, was negatively correlated with the correlation coefficient r of the intersex regression analysis with the same 47 populations. It was indicated that a change in the intersex linkage of cancer risk may be related to the differential implication of the oncogene-tumor suppressor gene complex in carcinogenesis. In summary, we conclude that the hormonal milieu of the host plays a cardinal role as the modifier of the oncogene-tumor suppressor gene impact.

Esophageal Neoplasms↗

PubMedDate not supplied

Topological evidence of differential oncogene activation-tumor suppressor gene inactivation features in 10 human neoplasias, as revealed by sequential regression analysis of world cancer incidence data.

Recent progress in the molecular biology of cancer research indicates that oncogene activation and tumor suppressor gene inactivation are the two key events in the carcinogenesis of humans as well as of animals. The purpose of this investigation was to assess separately the impact of oncogene activation and tumor suppressor gene inactivation on the genesis of a given neoplasia using the log-transformed age-adjusted incidence rates (log AAIRs) data from 47 cancer registration areas world wide. In practice, the sequential regression analysis test was applied to each of 15 (male) or 16 (female) tumor pairs, in which the neoplasia in question (marker tumor) was designated as the common x partner in the calculation of the 1st order regression equation. The correlation coefficient of the sequential regression analysis, r seq, served as an index of fitness to the equilibrium models of both oncogene activation and tumor suppressor gene inactivation, in which the expected values of r seq for sole oncogene activation and sole tumor suppressor gene inactivation were each -1.00 and +1.00. The calculation results with the sequential regression analysis were given as the profile of 15 (male) or 16 (female) r seq data for each marker tumor. The r seq profile of a given neoplasia was also prepared using each the original coordinates (the "Org" coordinates) and 2 variant coordinates (the "Rect" coordinates and the "Para" coordinates). The "Rect" and the "Para" coordinates were so designed as to allow their x-axes to run at a right angle and parallel to the regression line of the tumor pair data block. Results obtained are as follows: a) The "Org" coordinates gave an oncogene activation- type r seq profile for each of all marker tumors tested; b) The "Rect" coordinates gave a tumor suppressor inactivation-type r seq profile for each of all marker tumors tested; c) The r seq profile of the "Para" coordinates was classified as of the intermediate type as regards the direction (+ or -) as well as the amplitude of r seq values; d) Remarkable amplification of oncogene activation was noted in the r seq profile of the dominant gender as compared with the recessive gender in 3 cancers with sex-discriminant cancer risks (cancers of the esophagus, liver and breast). In summary, the use of the "Org"- and the "Rect"-coordinates in the sequential regression analysis was found to be useful for assessing separately the impact of oncogene activation and tumor suppressor gene inactivation on the genesis of a tumor. Amplification of oncogene activation was very often responsible for the emergence of sex difference in cancer risk. The association of the 2 coordinates with the 2 contrasting r seq profiles was explained by the topology of the tumor pair data distribution in the 2 dimensional diagram. Finally, the findings with sex-differential tumors are discussed in the light of the steroid carcinogenesis hypothesis.

Female↗

PubMedDate not supplied

Relationship between the oncogene activation profiles and the tumor suppressor gene inactivation profiles in 19 human neoplasias - a regression analysis study of the intercancer linkage with the world cancer incidence data.

This study represents an extension of our statistical studies of age-adjusted incidence rates (AAIRs) of 19 neoplasias from 47 population units of the world. We have invented 2 data manipulation methods (topological data conversion and sequential regression analysis method) to estimate separately the intensities of each oncogene activation and tumor suppressor gene inactivation of a given tumor (marker tumor) relative to a counterpart tumor (reference tumor) in terms of r seq value. This study prepared the r seq table of all permutations of tumor pairs for each of the 2 cancer genes and for each sex first, and then investigated the relation between the r seq profile of oncogene activation and that of tumor suppressor gene inactivation for each tumor. A profile containing 16 (male) or 17 (female) r seq data was prepared for each tumor pair, for each cancer gene, and for each sex. The extent of similarity between 2 r seq profiles was assessed by the 1st order regression analysis in terms of the correlation coefficient r value. Results obtained are given as follows: a) The proportions of both the tumor pairs with r seq values of less than -0.90 in the oncogene activation tables of two sexes and those with r seq values of more than +0.90 in the tumor suppressor gene inactivation tables of the two sexes were all more than 50%. A small number of tumor pairs in both the oncogene activation tables and the tumor suppressor gene inactivation tables have invaded deep into each the plus- and the minus-areas to constitute the very end of long tails of the r seq profiles. b) In spite of the above symmetry of data distribution between the 2 cancer-gene tables, individual cancer pairs very rarely gave 2 cancer-gene profiles that fit the definition of symmetry. Taken together, our data manipulation was a success in presenting an oncogene activation profile and a tumor suppressor gene inactivation profile separately. c) The similarity test was conducted with all combinations of tumor pair profiles for each cancer gene and for each sex. The frequency distributions of r values in the oncogene activation tables of both sexes looked normal with long tails to both the plus- and the minus-areas. In contrast, the corresponding frequency distributions of r in the tumor suppressor gene inactivation tables of both sexes were skewed towards the direction of +1.0. It was indicated that the morphological specificity of the oncogene activation profiles was much higher than that of the tumor suppressor gene inactivation profiles. d) Male versus female comparison in 2 neoplasias with sex discrimination of cancer risk revealed that the combination of the general depression of r seq values in the oncogene profile of dominant gender and the general elevation of r seq values in the oncogene profile of recessive gender was the common trait of female-dominant breast cancer and male-dominant laryngeal cancer. It is suggested that the predominance of oncogene activation impact over the tumor suppressor gene inactivation impact was implicated in the creation of sex discrimination of cancer risk. e) Application of a new test method (reciprocal regression analysis) to the r seq table data led to the conclusion that the 2 cancer genes are interfering with each other, and that the balance of power between the 2 cancer genes varies from one marker tumor to the other. f) The results obtained in this study together with the consistency of data interpretation is discussed in light of thermodynamics.

Female↗