[Cloning--ethical aspects]. / Klonování--etické aspekty.

Ethical problems related to cloning are discussed on three model situations: cloning of human beings (for example by utilizing the techniques of embryo splitting or nuclear transfer), use of embryonic cells in cloning techniques and cloning of nonembryonic cells. The first situation is strictly condemned, the second has been examined up present (it should be condemned as well) and the third is--under certain conditions--fully acceptable. The issue is discussed from the point of view of relevant Council of Europe documents as well.

[Ethical aspects of treatment in patients with advanced oncologic diseases]. / Etické aspekty lécby pokrocilých stavu u onkologických nemocných.

Ethical aspects of treatment are discussed from the aspect of medical objectives and the doctor-patient relationship. The authors draws attention to various dangers of incorrect approaches which may ensue for the patient: unnecessary and excessively burdening antitumourous treatment, inadequate treatment--in particular of pain, queer views on palliative treatment, a paternalistic approach of the physician with insufficient respect for the patient's wishes, inadequate information provided to the patient, "abuse" of patients for different experimental treatments etc. The author discusses in detail the double effect principle and draws attention to classification of means into ordinary and extraordinary with regard to the patient's own evaluation.

Genetic susceptibility to malignant diseases--ethical issues. Minireview.

Ethical problems connected with genetic testing with the intention of the measurement of the susceptibility or predisposition to malignant tumors are presented (respect for autonomy, beneficence, nonmaleficence, confidentiality, privacy, veracity and truth-telling, informed consent, right to know, right not to know, informational self-determination, etc.). Various aspects dealing with ethics of screening and research projects involving human subjects are discussed as well.

[Psychology and ethics of care of oncology patients]. / Psychologie a etika péce o onkologické nemocné.

The author discusses the necessity of perception of the uniqueness of oncological patients and the necessity to treat all their dimensions (physical, social, mental and spiritual). She analyzes the concept of total pain according to Cecilia Saunders who discusses the mentioned dimensions of man. Total pain is made up of mutually linked components which are difficult to separate: physical pain, social pain, emotional pain, and spiritual pain. Contemporary alarming statistics provide evidence that in many patients suffering is not alleviated correctly. One of the important reasons of failure is also failure of health workers as regards knowledge of the complexity of suffering.

[The attitude of students regarding human dignity]. / K postojum studentu k otázce lidské dustojnosti.

Contemporary secular thinking concerning human dignity is discussed. The opinions of a great majority of 523 students (Medical Faculty, Masaryk University, Brno) do not agree with the suggestion that suffering and terminal illness can rob the patient of his dignity (as, e.g. Motion of European Parliament for a resolution on care of the terminally ill in 1991 suggested). On the contrary the students claim that it is necessary to fight against such possible feeling of patients and that this feeling might be brought about by disrespectful behaviour of medical staff. The question "Which ethics for bioethics" is discussed as well. Because of the existing pluralism in the actual moral and philosophical situation the values and principles which are proposed in bioethics are extremely diversified. The necessity of a philosophical point of view that justifies respect for human life and its dignity in all its aspects is pointed out.

Fusion-induced malignancy? A preliminary study. (a challenge to today's common wisdom).

Five fusions between mouse embryonic cells and syngeneic adult peritoneal macrophages were performed. The resulting hybrids as well as both parental cells (6 cultures of embryonal cells and 6 cultures of adult macrophages) were grown in vitro under the same culture conditions. All populations of explanted macrophages died during the second month in primary culture and five populations of cultured embryonic cells were lost within six months under in vitro conditions as well. One embryonic cell line survived and acquired transformed and/or malignant phenotype: When inoculated into either newborn or adult syngeneic mice, progressive growth of tumors with 100% take (6/6), histologically classified as poorly differentiated fibrosarcoma with areas of metaplastic bone and osteoid, was observed. Two out of five wild hybrid strains died within six months of cell culture. The resulting three hybrid cultures adapted themselves to in vitro conditions and finally permanent lines were established with all features of transformed phenotype in vitro and with the capacity to grow as undifferentiated fibrosarcomas with 100% take (6/6) when inoculated into syngeneic mice either s.c. or i.p. Cytogenetic studies were performed and phenotypic characteristics of these lines were explored as well. Biological assays performed for the presence of oncogenic viruses were negative and none of the malignant cell lines showed positive staining with the monoclonal antibody specific for large T-antigen. It is suggested that cell fusion of two normal partners may switch on the cascade of abnormal processes which may culminate in neoplastic conversion. Cell fusion might play also a significant role in the so called "spontaneous" transformation.

Transformation of blood monocytes to multinucleated giant cells in vitro: are there any differences between malignant and nonmalignant states?

Blood monocytes (BMs) from 139 subjects (70 malignant melanoma patients, 31 breast cancer patients, 38 healthy controls) were cultured for at least 7 days. The formation of multinucleated giant cells (MGCs), which was checked during the whole time of culture, was observed in all cases. By the seventh day MGCs represented 25-50% and during the second and third month more than 90% of all cells. Lymphokines and/or concanavalin A stimulation (16-34 cases respectively) of BMs was performed as well. This stimulation greatly accelerated MGC formation. There were no differences either in spontaneous or in stimulated fusion between the different groups compared.

Do some malignant melanoma cells share antigens with the myeloid monocyte lineage?

Melanoma cells freshly isolated from 63 advanced primary lesions and 103 metastases were analyzed by staining with monoclonal antibodies MEM 28 directed against a 200 kDa antigen present on all leukocytes and tissue macrophages (CD 45), MEM 18 directed against a monocyte antigen of 53 kDa, anti CD 14--Immunotech, Marseille and 3.9 directed against a 150 kDa antigen expressed on monocytes and to even greater degree on most tissue macrophages (CD 11 c). All antibodies showed variable reactivity with melanoma cells, percentage of positive tumor cells ranged from 0 to 70.

Multinucleated tumor cells and malignant melanoma.

Multinucleated cells (MC) were counted in cell preparations obtained by dissociation of representative part of tumor lesions immediately after excision. MC were present in almost all specimens examined (39 advanced primary lesions, 90 lymph node metastases and 33 dermal plus subcutaneous metastases); in one third of the samples they were very rare (less than 1% of all cells). There were no significant differences in quantity of MC between primary tumors, node metastases and dermal plus subcutaneous metastases, between node metastases seen early in the course of the disease and those seen later, and between regional node metastases taken from Stage II patients with rapidly progressing disease and regional node metastases taken from patients of the same stage whose disease-free intervals were longer. No unique pattern of similarities or differences in quantity of MC was found when comparing autologous tumor samples excised simultaneously and/or successively during the course of the disease.

Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition.

To study mutagen-induced chromosome instability in cancer disposition, late S and G2 lymphocytes of 15 patients with common variable immunodeficiency and 14 healthy controls were exposed to bleomycin in vitro. The groups did not differ in the frequency of spontaneous chromosome aberrations. In bleomycin-treated samples we found higher numbers of break events per cell and increased frequency of cells with aberrations compared to the control group. A slightly reduced breakage of chromosome group D was noted in patients. These results support the hypothesis that a higher incidence of cancer in patients with genetically determined immunodeficiencies may be explained by an increased mutagen-induced chromosome instability in at least some of them.

HLA-DR antigen expression on melanoma metastases and the course of the disease.

Melanoma cells freshly isolated from regional lymph node metastases of 59 stage II malignant melanoma patients were analyzed by indirect immunofluorescence staining with monoclonal antibody TAL 1B5, detecting the HLA-DR alpha chain. The expression of HLA-A,B,C antigens, using antibody W6/32, was also investigated in 45 of these cases. There were no substantial differences in the course of the disease with respect to the percentage of positive cells. In 13 malignant melanoma patients two to four simultaneous and/or successive metastases (both locoregional and distant-subcutaneous) were analysed for HLA-DR. With simultaneous metastases (7 cases) the percentage of HLA-DR-positive cells was mostly very similar, and in no case was there more than 25% variation. As to successive metastases (9 cases) the percentage of HLA-DR-positive cells remained practically unchanged or decreased during the course of the disease.

Skin tests with autologous cholesteryl hemisuccinate-treated tumor cells, DNCB and PPD and their relationship to prognosis in malignant melanoma patients.

Skin tests with autologous cholesteryl hemisuccinate-treated tumor cells were performed in Stage II malignant melanoma patients. In the majority of cases an evident reaction having features of delayed type hypersensitivity was noted. No significant correlation between this reactivity and subsequent course of the disease was found. The same was true for the results of DNCB and PPD skin testing. An analysis of the results of all three tests in the same patient revealed no prognostic significance of this score either.

Is cancer a macrophage-mediated autoaggressive disease?

As part of their physiological functions macrophages secrete various products that influence tissue environment. They can also secrete tumour growth promoting substances and it is highly probable that they help to establish tumour supporting fibrovascular stroma. Macrophages may fuse with other cells (including neoplastic cells) and many malignant properties of these hybrids or of their progeny may be maintained by the macrophage genome. In addition processes that occur after fusion might be important in inducing malignant transformation, especially when fusion has occurred with initiated cells. Superficial spreading melanoma is an example that is in keeping with the hypothesis of cell fusion.

Expression of HLA-DR antigens on tumour cells does not contribute to skin reactivity to autologous cholesteryl hemisuccinate (CHS)-treated tumour cells in patients with metastatic melanoma.

Skin tests with autologous cholesteryl hemisuccinate (CHS)-treated and untreated cells were performed in ten metastatic melanoma patients. In the majority of cases evident reaction was noted with CHS-treated cells (9/10) while the reaction with untreated cells was mostly negative (7/10). Tumour cell suspensions used for skin tests were characterized for reactivity with monoclonal antibody TAL 1B5 detecting the HLA-DR alpha chain. There were no differences between CHS-treated and untreated cells with respect to HLA-DR expression and no correlation was found between grade of skin reaction to CHS-treated cells and the proportion of HLA-DR positive cells in the injected cell sample.