Enhancement of thermal response of normal and malignant tissues by Corynebacterium parvum

Further studies were carried out on the combined effects of Corynebacterium parvum and hyperthermia on animal tissues and cultured Chinese hamster ovary cells. Experimental animals were C3Hf/Sed mice derived from our defined flora mouse colony. Tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma, FSa-II. Hyperthermia was given by immersing the mouse foot or culture flasks in the constant temperature water bath. Present experiments include thermal enhancement of C. parvum at different temperatures, effect of the agent on the kinetics of thermal resistance, and the mechanism of the thermal enhancement. The thermal enhancement by C. parvum was independent of temperature in a range between 42.5 and 46.5 degrees, and it increased with decreasing temperature. The analysis of the Arrhenius plot suggested a comparable activation energy for combined treatments and for heat alone between 42.5 and 46.5 degrees. The thermal resistance developed very rapidly in both normal and tumor tissues. Systemic administration of C. parvum failed to modify the kinetics of thermal resistance. Several experiments were attempted in order to disclose the mechanism. A single injection of C. parvum-induced macrophages failed to enhance thermal response of the mouse foot, while 3 daily injections of the macrophages enhanced the response, indicating that the enhancement by C. parvum is at least partly attributed to the C. parvum-induced macrophages. Whole-body irradiation of 6 Gy and/or administration of anti-mouse T-cell serum and histamine failed to inhibit the C. parvum enhancement of thermal response. No thermal enhancement was observed for Chinese hamster ovary cells treated at 43.0 degrees in vitro with C. parvum or thiomersalate , a preservative supplemented in C. parvum, although cytotoxic effect was shown at a high concentration of thiomersalate .     

The oxygen dependence of protection by aminothiols: implications for normal tissues and solid tumors

This paper reviews the role of oxygen in the protection of both normal tissues and tumors in vivo by WR-2721. Although the presence of hypoxic cells in tumors is well accepted, data are presented that suggest there is a range of oxygen concentrations and thus OERs in normal tissues in vivo, too, and that some may, in fact, be radiobiologically hypoxic. Thus, the range of protection factors in normal tissues (which appears unrelated to tissue drug levels), as well as tumors can perhaps be explained by the range of OERs in these same tissues. The question of whether protection decreases with radiation dose per fraction is related to the distribution of oxygen in both normal tissues and tumors, i.e., whether oxygen is homogeneously or heterogeneously distributed among the cells. It is hypothesized that sulphydryl compounds may equalize the OER differential between tumors and normal tissues and thus remove the natural advantage (radioresistance) of the tumor when treated with radiation. Thus, no loss of therapeutic benefit would occur when sulphydryl compounds were given with radiation if the normal tissue were better oxygenated than the tumor.     

Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues

The specific tissue distribution of melanoma-associated ganglioside II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) was studied on 175 cryopreserved, unfixed human tissue sections with R-24 mouse monoclonal antibody by indirect immunoperoxidase staining. A striking specificity of monoclonal antibody R-24 for malignant melanoma tissues was established. Ganglioside GD3 was detected in all 21 tissue sections of 21 patients with primary melanoma and in all 37 probes of 24 patients with metastatic malignant melanoma. The majority of tumor cells in the samples of primary malignant melanoma expressed GD3; however, GD3 expression was more heterogeneous in samples of metastatic lesions even in different metastases of the same patient. Of 11 nevi, 9 reacted with monoclonal antibody R-24, while melanocytes in the basal layer of normal skin stained only weakly and irregularly. None of the 32 normal and 12 fetal human tissue types were R-24 positive, but a strong cytoplasmic staining was observed with single cells in the dermis and in the interstitial tissue of the gastrointestinal tract, in the interlobular septa of the thymus, and in other distinct locations. Only two malignant carcinoid tumors of 38 nonmelanomatous tumors tested reacted with monoclonal antibody R-24.     

Prognosis in malignant tumors of soft tissues]

The author reports the data on 348 patients with malignant tumors of soft tissues, operated upon within the period of 1946--70 inclusively, children being excluded from this number. Various factors were studied from the prognostic viewpoint. The data obtained enabled estimating the morphological tumor structures, other conditions being equal, as a factor of great importance. None of the factors should be regarded separately. The accumulation of observations and systematization of prognostic criteria seems to be absolutely essential. Prognostication in malignant tumors of soft tissues may aid in selecting an adequate extent of surgical intervention, in avoiding too traumatic procedures, thus contributing to patients' rehabilitation.     

Investigations of tissue folates in normal and malignant tissues

The folates present in liver, gut and tumour tissue were examined before and after autolysis. Before autolysis 10-formylfolate tetraglutamate (10-CHOFA(glu)4), 5-methyltetrahydrofolate triglutamate (5-CH3THF(glu)3) and possibly tetrahydrofolate polyglutamate(s) (THF(glu)n) were detected. Liver contained all 3 species whereas no 5-CH3THF(glu)3 was present in the tumours; gut showed an intermediate situation. After autolysis the predominant monoglutamates formed were 5-CH3THF in the liver, 10-formylfolates in the gut and possibly tetrahydrofolate (THF) in the tumour extracts. These differences illustrate changes in tissue folates with the proliferation rate of the tissue and suggest an explanation for the methionine auxotrophy of Walker 256 carcinosarcoma cells.     

Discrimination between normal and malignant human gastric tissues by Fourier transform infrared spectroscopy

The aim of this study was to determine whether malignant and normal human gastric tissues can be distinguished by Fourier transform infrared (FTIR) spectroscopy. Compared with normal tissue, malignant tissues showed significant increases in infrared (IR) absorption in 10 bands lying in a region of 925-1660 cm(-1). Using the 10 IR absorption bands as markers, discriminant analysis was carried out for tissue discrimination. As a result, 22 out of the 23 gastric cancer samples and 9 out of the 12 gastric normal samples were correctly segregated, yielding 88.6% accuracy. The present results suggest that FTIR spectroscopy is a useful tool for screening gastric cancer.     

The role of miR-26 in tumors and normal tissues (Review)

miR-26, a functional miRNA, has received much attention from researchers in recent years. miRNAs may play crucial roles in numerous biological processes such as cell proliferation, apoptosis, tumorigenesis at different stages of non-tumor diseases, growth and development of normal tissues, and other biological processes. The expression of miR-26 has been found to be specific to different biological processes. Furthermore, its expression is frequently abnormal in tumors, indicating that miR-26 may play significant roles in tumor formation. Various reports exist regarding miR-26 involvement in non-tumor diseases, as well as the process of growth and development of normal tissues. In this review, we report findings of recent studies on the expression of miR-26 in different types of diseases and the process of growth and development and its predicted target genes in different tissue types. In conclusion, it is useful for researchers to understand the role of miR-26 in different biological processes.     

O(2) extraction is a key parameter determining the oxygenation status of malignant tumors and normal tissues

The aim of this study was to assess pivotal factors determining the oxygenation status of malignant tumors, and, for comparison, of normal tissues. For this purpose, microvascular patterns, blood flow data, O2 consumption rates and O2 extractions were correlated to the median pO2 values of isografted rodent and xenografted human tumors, and of various normal tissues. No correlations were found between median pO2 values and vascular patterns, O2 consumption rate or blood flow rate. When O2 extraction, however, was considered (a comprehensive parameter which encompasses all of the above factors), a strong inverse correlation was found between this parameter and the median pO2 values, both for malignant tumors (r2=0.917) and normal tissues (r2=0.959). At similar O2 extraction values, the median pO2 values in the solid tumors were substantially lower than those in normal tissues, a finding which most probably reflects the chaotic microcirculation found in tumors, the loss of flow regulation which in normal tissues meets the metabolic demands of the cells, and in some cases, tumor-associated anemia.     

The distribution of the c-myc oncogene product in malignant lymphomas and various normal tissues as demonstrated by immunocytochemistry

The expression of c-myc was studied in 51 malignant lymphomas and in a variety of normal tissues by immunocytochemistry using monoclonal antibodies raised to different synthetic peptides and reacting monospecifically with the c-myc product (p62c-myc). The c-myc product was detected in only a minority of malignant lymphomas principally those containing cells with immunoblastic characteristics, and was predominantly localised to the cytoplasm. In normal lymphoid tissues only plasma cells and histiocytes were found to have immunoreactivity. In non-lymphoid normal tissues, however, the c-myc product was distributed widely. Marked differences in its intracellular distribution were apparent in different tissues. These findings suggest that the relationship of p62c-myc expression to cell division may be more complex than previously suggested by in vitro studies, and raise the possibility that it may have other functions within the cell.