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The given data indicate the presence of a negative correlation between metabolic indices (a decrease of the tolerance to glucose, increase of the blood level of free fatty acids, insulin, cholesterol triglycerides, cortisol, stc) and the indices of cellular immunity, which is determined by the number of rosette-forming cells and blasttransformation reaction to PHA and skin tests. Accordingly, the administration of an antidiabetic drug-phenformin (phenetylbiguanide)--apart from the improvement of metabolic pattern, results in the restoration of the cell-mediated immunity indices. These findings provide a basis for stating the phenomenon of metabolic immunodepression. The metabolic immunodepression may be supposed to prevent immunological surveillance activation, which normally is realized through the signals, provided by cells subjected to somatic mutation. It is noteworthy that the given metabolic conditions (hypercholesterinemia, hyperinsulinemia, the enhanced utilization of free fatty acids) promote the division of somatic cells. Thus, the same metabolic shifts which increase the pull of proliferating cells and, accordingly, increase the possibility of mutation development, also cause the metabolic immunodepression at the same time. These opposite metabolic influences on somatic cells and T-dependent lymphocytes cause the development of the syndrome of cancrophilia. The syndrome of cancrophilia normally arises at pregnancy, in intensive growth of the organism in childhood, accelerated development, stress and during normal ageing. Many carcinogens cause the decrease of tolerance to glucose, the increase in blood-insulin level and elevation of the threshold of sensitivity of the hypothalamus to feedback suppression. This phenomenon is based on the decrease of catecholamine level in thehypothalamus in ageing, stress and the action of some carcinogens. Thus, the syndrome of cacrophilia provides the conditions for cancer development and tumor progression, besides, the tumor itself produces the metabolic shifts typical of cancrophilia. In the light of mutation-metabolic model of cancer development, it is possible to consider the fundamental factors which increase of hinder carcinogenesis.
Cells participating in an inflammatory response are derived from the bone marrow (i.e. granulocytes and monocytes) or lymphoid organes (i.e. T and B lymphocytes), or of mesenchymal origin (i.e. fibroblast, reticulum cells). The identification of these different kinds of cell in the inflammatory exudate is often difficult, because the morphological characteristics are not specific enough. For example, in the morphological description of pathological processes often terms such as round-cell infiltration and mononuclear cells are used, which is confusing. For the clear understanding of the course of an inflammatory reaction and the effect of anti-inflammatory drugs it is necessary, however, to define exactly the participating cells. Such an identification can be performed on the basis of morphological, cytochemical and immunological characteristics of the cells, together with their kinetic parameters. These characteristics have been established for murine mononuclear phagocytes. Recently these characteristics have also been studied in human promonocytes, monocytes and skin macrophages. The results show that human mononuclear phagocytes are in many respects similar to those of mice. On this basis an outline for the participation of mononuclear phagocytes in pathological processes (i.e. inflammatory processes, neoplastic processes, and storage disorders) has been made.
A critical review of the work done in this area indicates that, of the available enzyme systems now used in clinical diagnosis, the LDH system is the only one of significant value in the examination of pleural and peritoneal effusions. In terms of differential diagnosis, estimation of pleural or peritoneal fluid LDH levels will enable the examiner to distinguish between poorly cellular vs. abundantly cellular effusions. In the abundantly cellular effusions, estimation of levels of LDH do not distinguish with any degree of accuracy between those effusions due to inflammatory processes vs. neoplastic processes. Results of studies of LDH isoenzymes are at variance and require more study.
Criteria of the morphological diagnosis as well as the histogenesis of the lesions in Paget's disease are presented; the authors claim that the initial lesion occurs in the lactiferous ducts, the skin being secondarily involved. Likewise, the dyskeratotic lesions are considered as secondary to the neoplastic process, either by neoplastic induction or by mobilization and proliferation of cancerous cells from lactiferous ducts. The utility of biopsies in all cases of nipple eczema, and of the histologic investigation of the profound tissues is pointed out. In this way the canalicular starting point in the vicinity of the nipple can be noticed.
Numerical and structural chromosome aberrations are frequently found in neoplastic cells. As demonstrated by the new chromosome banding techniques these aberrations are not random, but tend to show a specific occurrence. A model example is the leukemias where many cytogenetical investigations have been done to date. In leukemia chromosome analysis serves the following purposes: to identify a neoplastic process, to confirm and strengthen the hematological diagnosis, for the early diagnosis of transformation from a chronic leukemia into its blastic phase and for following up the clonal evolution of a leukemic cell line. In the discussion of chromosomes and neoplasms it must be mentioned that individuals demonstrating chromosomal instability and some trisomic patients show a greater tendency toward the development of a malignancy. Malignancy is primarily a cellular phenomenon caused by a disturbance in cellular regulation, whose fine events are not known. Therefore the exact role of the chromosomes in neoplastic processes cannot be stated. From experimental investigations it appears that the affected chromosomes carry cell growth regulating factors and also that a specific aberration is the result of the action of a specific agent.
103 patients with neoplastic processes in the genitalia have been examined. Lymphography was performed in 73 patients, phlebography - in 52, a combined investigation (lympho- and phlebography) - in 22. Lymphography in malignant uterine and ovarian processes with the involvement of regional lymph nodes provides for direct and indirect signs of metastasization, that allows the stage to be determined with a greater precision and also the roentgenological control over the state of lymph nodes during the conservative therapy. Visceral phlebography gives a definite roentgenological characteristic depending on the site and character of a tumor. An associated use of lympho- and phlebography considerably enlarges the potentialities of these methods for determining the stage and character of tumors and seems to be a valuable adjunct for the differential diagnosis of neoplastic processes of the uterus and adnexa.
Interactions between epithelia and the extracellular matrix are important in the modulation of cellular growth, differentiation, and motility. To investigate the possible roles of these interactions in the neoplastic process, this study examines the expression of the integrin subunits a2, a6, beta 1, and beta 4 and the stromal protein tenascin in 53 breast carcinomas, non-involved breast tissue from 21 of these cases, and 32 normal/benign cases. Frozen tissue and an indirect immunoperoxidase technique were used throughout. Linear staining in relation to the basement membrane was seen for all integrins in the normal/benign cases. The carcinomas showed complete loss of reactivity in 65 per cent of cases for a2, 80 per cent for a6 and beta 4, and 90 per cent for beta 1. Those showing reactivity displayed a diffuse cytoplasmic type of staining. The non-involved breast tissue showed linear basement membrane type staining with a2 and beta 1, but for a6 and beta 4 66 per cent of cases displayed reactivity identical to that of the corresponding tumour. For tenascin, band-like staining around ducts was seen in normal/benign cases, with a diffuse coarse reactivity in all carcinomas. Most non-involved cases stained as for normal breast. The altered a6 beta 4 integrin staining in non-involved tissue in cancerous breast may be an early event in the neoplastic process, and as such, may be of use as a marker of pre-malignant change.
Zinc is essential for the growth of all species. Growth arrest results from its deficiency and presumably reflects important roles for this metal at critical points of metabolism. Studies of zinc metalloenzymes show that zinc serves as a coenzyme to more than 80 enzymes, among which are the reverse transcriptases which cause leukemia in many species. Its role in nucleic acid metabolism is emphasized.
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Experiments conducted on albino rats with a grafted tumour of transplantable alveolar mucinous carcinoma PC evidence that the cytostatic effect of thiophosphamide and sarcolysin equally grows in strenght with simultaneous introduction of thyroxin or insulin into the organism. In the same conditions the antineoplastic action of phthorafur is in a greater measure determined by the level of insulin and to a lesser degree by that of thyroxin. An analysis of the results subsequent to a biochemical examination (determination of the pyruvate, lactate, thiamine concentration in the blood and in the tumour, the rate of the 14C-glyxine incorporation in the protein of cancer cells) bears proof to the fact the neoplasm continues to definetly react in response to exogenously introduced hormones, this bringing changes into the kinetic and dynamic properties of the cytostatics.
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The analytical morphodynamic method, based on the study of the fate of the biogic units of an organ at the level of well or poorly developed lesions, has been applied to the analysis of chronic obliterating arteriopathies of the extremities, of benign tumors of the mammary parenchyma, and of malignant hepatomas. In morbid states as different as a reactive process and a benign or malignant neoplastic process, it allowed to reconstritute the histogenesis of complex tissue changes and led to interesting prospects, in the field of general biology and pathogenesis.
It has been shown experimentally that psychosocial processes influence the susceptibility to some infections, to some neoplastic processes, and to some aspects of humoral and cell-mediated immune responses. These psychosocial effects may be related to hypothalamic activity. Reviewing the mechanisms that may be involved in the role of the hypothalamus in immune responses indicates that there is no single mediating factor. Various processes may participate, including the autonomic nervous system and neuroendocrine activity. The research reviewed has been limited primarily to a consideration of the effect of hypothalamic lesions on humoral immune responses. There is some evidence (45, 80) indicating that hypothalamic lesions also modify cell-mediated immune responses. Further research is required to evaluate the effect of the hypothalamus on cell-mediated immunity.
Of 636 polyps removed during endoscopy between 1973 and 1975 at the University Hospital, Zurich, 36 (5.5%) were of the hyperplastic and 18 (2.8%) of the juvenile type. One polyp was seen in a female patient with Peutz-Jeghers syndrome. The vast majority of the polyps (581, 91.5%) were neoplastic in origin; 70% were tubular adenomas, 16% villous adenomas, and 14% intermediate forms or tubulo-villous adenomas. On the basis of a continuous spectrum in histologic structure and similar cellular dedifferentiation, these three types of adenoma may be viewed as different forms in the development of the same neoplastic process. Hyperplastic and hamartomatous polyps are innocuous, whereas the neoplastic forms may well turn aggressive. Malignant change was observed in 5.1% of our material, particularly in villous adenomas and in polyps exceeding 1 cm in diameter. The presence or absence of invasive growth through the muscularis mucosae is of prime importance for therapy. In accordance with WHO nomenclature, the term carcinoma is used only in the presence of such infiltration. If, in addition, the tumor tissue is not well differentiated, additional segmental resection may be required. The term "focal carcinoma" is no longer in use and has been replaced by "severe focal atypia". In these cases, primary polypectomy for diagnostic purposes is also the optimal therapy, and is as effective here as in cases of benign adenoma.
A case of chronic granulocytic leukemia was diagnosed in a ten year old miniature poodle and was observed for four and one half years. Methods of diagnosis and characteristic features are described. A persistent granulocytosis with a preponderance of mature forms and the absence of a detectable underlying pyogenic process were key diagnostic features which enabled distinction of this neoplastic process from acute granylocytic leukemia and a leukemoid reaction. Other features included dysplastic granulocytes in various developmental stages, marginal anemia and hyperplastic bone marrow (myeloid elements). No blast crisis occurred. This dog was euthanatized in August 1975.
To establish or exclude the diagnosis of bronchial carcinoma a series of 43 patients with peripheral pulmonary opacities was studied by lung scanning after intravenous injection of 75Se-sodium selenite. A diagnosis was ultimately obtained in all patients. The incidence of both false-positive and false-negative results was high. Selenite was taken up by a range of non-neoplastic processes including inflammatory lesions. The value of the procedure in distinguishing bronchial carcinoma from non-neoplastic conditions of the lung that radiographically mimic carcinoma was not confirmed.