Mitochondrial metabolism - neglected link of cancer transformation and treatment.

Physical processes in living cells were not taken into consideration among the essentials of biological activity, regardless of the fact that they establish a state far from thermodynamic equilibrium. In biological system chemical energy is transformed into the work of physical forces for various biological functions. The energy transformation pathway is very likely connected with generation of the endogenous electrodynamic field as suggested by experimentally proved electrodynamic activity of biological systems connected with mitochondrial and microtubule functions. Besides production of ATP and GTP (adenosine and guanosine triphosphate) mitochondria form a proton space charge layer, strong static electric field, and water ordering around them in cytosol - that are necessary conditions for generation of coherent electrodynamic field by microtubules. Electrodynamic forces are of a long-range nature in comparison with bond and cohesive forces. Mitochondrial dysfunction leads to disturbances of the electromagnetic field; its power and coherence may be diminished, and frequency spectrum altered. Consequently, defective electrodynamic interaction forces between cancer and healthy cells may result in local invasion of cancer cells. Further deformation of interaction forces connected with experimentally disclosed spatial disarrangement of the cytoskeleton and disordered electrodynamic field condition metastatic process. Cancer therapeutic strategy targeting mitochondria may restore normal physiological functions of mitochondria and open the apoptotic pathway. Apoptosis of too much damaged cancer cells was observed. Considerable experience with DCA (dichloroacetate) cancer treatment in humans was accumulated. Clinical trials should assess DCA therapeutic potential and collect data for development of novel more effective drugs for mitochondrial restoration of various cancers.

The comparison of methods for determination of humoral and cell-mediated immunity in patients with breast cancer.

We observed the immunological answer to antigens obtained from the human malignant breast tumor and from the blood of inbred mice strain C3H/H2K infected by LDH virus. We compared the modified ELISA method for humoral immunity with the leukocyte adherence inhibition (LAI) assay for cell-mediated immunity. The modified ELISA method is suitable for early diagnosing and monitoring antibodies in a malignant breast tumor simultaneously with senological examinations which include mammography and clinical examinations, because the antibodies are determined in a high number of samples by single application.

Cell-mediated immunity in cervical cancer evolution.

Cell-mediated immunity (CMI) response to different antigens was examined in healthy women, in patients with cervical precancerous lesions, and in patients with cervical cancer. Cervical lesions were diagnosed by cytological (PAP) smears, from examination by colposcopy, and from "punch" biopsy material by histology. CMI response is related to specific processes in healthy and cancer cells. CMI was investigated by leukocyte adherence inhibition (LAI) assay using specific antigen (prepared from cervical carcinoma tissue) and non specific antigen (prepared from blood of mice infected by LDH--lactate dehydrogenase--virus). The CMI responses of healthy women and cancer patients to the antigens used are different: the majority of T lymphocytes display adherence and non adherence, respectively (but the CMI responses elicited by the antigens are not equal and small quantitative differences are observed). Regardless of the CIN (cervical intraepithelial neoplasia) grades, CMI responses correspond either to healthy women or to cervical carcinoma patients (at about similar ratio of cases in all the CIN groups). Effect of non specific antigen suggests that cervical carcinoma transformation may be connected with reduction of mitochondrial activity similar to processes in LDH virus infection.

Changes of leukocyte adherence ability under the influence of magnetic field in the course of a treatment of patients with laryngeal and pharyngeal carcinoma.

The authors were monitoring adherence ability of T lymphocytes in vitro in patients with laryngeal and pharyngeal carcinoma at the presence of tumor-specific and viral LDH antigen. The results were assessed and expressed in percent of non adherent T lymphocytes (NAL). First, NAL in patients before initiating the treatment was compared with NAL control group (voluntary blood donors). The ability of the adherence in T lymphocytes in the control group is statistically significantly higher. Further on, NAL in the course of a successful oncological treatment was monitored at the interval of 6 months following the treatment, and further on at yearly intervals. NAL level drops statistically significantly within 6 months and then hold on at levels with no statistical difference unlike the control group, however, the ability of T lymphocyte in patients to adhere remains statistically significantly lower. Statistically significantly higher levels of NAL are at the presence of LDH viral antigen. Further on, the authors were following the influence of magnetic sinusoidal field of power frequency (50 Hz) of a low induction (0.5, 0.1, and 0.05 mT) on NAL. NAL values under the influence of an experimental magnetic field before initiating the treatment as well as in the course of a successful oncological treatment are statistically significantly lower. It means that magnetic filed increases the adherence ability of T lymphocytes in patients with laryngeal and pharyngeal cancer in vitro.

Effects of sinusoidal magnetic field on adherence inhibition of leucocytes: preliminary results.

The leucocyte surface properties manifest the cell-mediated immunity. The response of the cell-mediated immunity to external magnetic field was examined by observing leucocyte adherence to solid state surfaces. In the presence of antigen, leucocytes taken from cancer patients exhibit decreased adherence in contrast with adherence of leucocytes from healthy humans. After 1 h exposure to a sinusoidal magnetic field of 50 Hz and of 1 mT or 10 mT, adherence of leucocytes taken from cancer patients is strongly increased. The 1 mT magnetic field has stronger effect than the 10 mT field.

[The importance of hormone receptors in benign breast diseases]. / Význam hormonálních receptoru u benigních nemocí prsu.

Benign breast lesions are usually divided with regard to the proliferative activity into three categories. These lesions, depending on their histopathological characteristics and correlation with epidemiological studies differ as to the risk of breast cancer. 1. The concentration of hormonal receptors in the breast tissue in our group correlated with the proliferative activity of the lesion. 2. A major proliferative lesion and atypical hyperplasia of the ductal epithelium are a typical precancerous condition. 3. The hormonal receptor concentration defines, in addition to the histological classification, the biological activity more accurately. The prevalence of the oestrogen receptor or its trend to predominate over the progesterone receptor is a serious marker of imminent cancerogenesis. 4. Based on the prevalence of hormonal receptors it is possible to select suitable hormonal treatment to suppress the proliferative potential of the breast lesion. 5. A high level of the oestrogen receptor in non-malignant formations of the breast can be considered a manifestation of increased sensitivity of this target tissue to circulating oestrogens. It is a question whether it is the manifestation of mutation of the oestrogen receptor or the consequence of long-term exposure to uncovered levels of bioavailable oestrogens.

[Monitoring of malignant gynecologic tumors using the immune response to lactate dehydrogenase virus antigens]. / Monitorování gynekologických maligních nádoru imunitní odpovedí na LDH virový antigen.

The cell mediated immunity was examined by the leukocyte adherence inhibition (LAI) test in 21 patients with CIN III and 146 patients with invasive gynaecologic malignancies before treatment and at 3-month intervals. Our own LDV antigen and organ specific antigens were used. The test was highly specific (95.1%) in comparison with a control group of healthy blood donors. The sensitivity of the test was lower (64.7-86.8%). There was no correlation with the development of disease (remission or relapse). The test in a two-year investigation does not seem suitable for monitoring of disease. Depending the nature of LDV infection, only a longer investigation extending over more years would enable further conclusions.

[Leukocyte adherence in women with ovarian carcinoma]. / Adherence leukocytu u zen s karcinomem ovaria.

Dynamic follow-up of cell-mediated immunity in women with malignant neoplasms of the ovary provides more valuable information on the course of the disease than a single value. The properties of leukocytes in patients with malignant ovarian tumours must be followed up on a longitudinal basis, as a signal of an approaching relapse of the disease is apparent sooner than its clinical manifestations. It appears that changes of biophysical mechanisms participate not only in the course of malignant ovarian disease but perhaps also in its genesis.

[The LDH virus and changes in cellular immunity in schizophrenics and their relatives]. / LDH virus a zmeny celulární imunity u schizofreniku a jejich príbuzných.

In a long-term investigation the authors investigated in a group of schizophrenics and their grade 1 relatives the immunological response to schizophrenic cortex (from the frontal and temporal lobe) and to LDH viral antigen (lactate dehydrogenase virus). In the group of 261 subjects (84 patients, 60 parents, 37 siblings) a significant increase of a certain type of cytophil antibodies was detected, manifested by positive reactivity to gray matter of the schizophrenic and healthy brain, not only in patients but also in their parents and siblings who were healthy from the clinical and psychiatric aspect. At the same time a highly positive immune response to the LDH viral antigen was found not only in patients but also in their relatives. In some positive subjects, in particular as regards the viral antigen, the number of non-adhered cells in the LAI test (Leucocyte adherence inhibition) exceeded 100% which suggest leucocyte proliferation. Microscopic examination revealed repeatedly that during two-hour leucocyte incubation with antigen at 37 degrees C in these subjects enhanced mitotic leucocyte division occurs. This finding was recorded in 22% of all positive schizophrenics and in 13% of the parents; in healthy siblings (although they had a positive immune response to the viral antigen) direct cell division did no occur in any of the cases. Assessment of circulating immune complexes revealed positive values in a total of 93% of all investigated subjects. As compared with controls (80 mentally and physically healthy blood donors), the mean levels are more than double and the difference is highly significant (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of vaginal hormonal cytology and the leukocyte adherence inhibition test for the detection of malignancy.

Raised leukocyte adherence inhibition (LAI) test values were found for 25 women with endometrial carcinoma and 12 women with benign hyperplastic endometrium. Of 42 patients with oligomenorrheic and polymenorrheic disturbances of the menstrual cycle and whose hyperestrogenism was assessed by cytologic indices (i.e., eosinophilic and karyopyknotic indices), 38 exhibited positive or borderline LAI test values with either one or both of the antigens used. The LAI test was negative with both antigens in four women with hyperestrogenism associated with a 28-day menstrual cycle. The high correlation between hyperestrogenism and positive LAI test results as well as between the LAI test and the presence of tumors suggests that both hormonal cytology and the LAI test might be useful as screening methods for evaluating risk factors for the development of malignant tumors of the female reproductive tract. Both methods are fairly simple, reproducible and convenient for long-term follow-up.