The in vitro effect of aprotinin upon spleen cells from normal and tumour-bearing mice exposed to PPD and tumour cells

Aprotinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD nd tumour cells. This enhancement is greater in the tumour-bearing mice.     

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice.

The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.     

Immunity and cancer: suppressor effect on the cytotoxic activity of lymphoid cells from animals carrying syngeneic tumors]

When it is tested in vitro, the cytotoxic action of lymphocytes from mice bearing a syngeneic tumour (T2) vary with the age of the graft. At a time when it is very low, the lymphoid cells are cultivated for 3 days and then can be fractionated in two subpopulations on a glass bead column: a cytotoxic "non adherent" group of cells and an "adherent" group that inhibits the activity of the first group when it is added to it.     

Effect of synthetic polynucleotides on the growth of transplantable tumours in BALB/c mice

Summary The effect of BALB/c mice pretreatment with tumour cells (a mammary adenocarcinoma, ADK-1t and an IgA secreting plasmocytoma, MOPC-315) adsorbed with poly I:C, poly I and poly C is examined. Only mice pretreated with cells of both tumours adsorbed with poly I:C and poly C proved to be extensively protected against challenge by homologous untreated tumour cells, whereas this was not so in the case of poly I. A possible explanation of this phenomenon is discussed.This work was supported by a research contract with the Italian National Research Council (C.N.R.).     

Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

The mammary gland undergoes major developmental changes during puberty and pregnancy. It is thought that stem cells drive mammary gland development during puberty and are responsible for tissue maintenance as well as the major growth and remodelling that occurs with every pregnancy. The use of sophisticated cell separation procedures has facilitated the prospective isolation of mammary epithelial stem and differentiated cell subpopulations from the mouse mammary gland, while studies of primary human breast cancers have described sub-populations of tumourigenic cells capable of initiating tumour growth in immuno-compromised mice. These potential tumour 'stem cells' constitute an important therapeutic target population with respect to cancer therapy, as these are likely to be the cells which maintain tumour growth. Understanding the origin of these cells, their relationship to breast cancer subtypes, and how and why they differ from normal breast stem cells will lead to a revolution in tumour understanding, treatment and prevention. (Part of a Multi-author Review).     

Activation of cytotoxic T cells by solid tumours?

Tumour-specific cytotoxic T cells (CTLs) are among the best-defined biological anticancer weapons. Nevertheless, they often fail to control tumour growth in vivo. Many reasons for this have been evoked tumours may actively inhibit CTLs, or may protect them selves from CTL recognition by various means. However, one does not necessarily need to postulate such active immune evasion mechanisms specifically acquired by tumour cells. In this review we argue that the failure of immune protection is due to the intrinsic inability of tumours to activate an effective immune response, and that many tumours are similar to normal issues in this respect. It is striking to see that the majority of the so-called immune escape mechanisms are not specifically acquired by selected tumour cells, but are common mechanisms shared between solid tumours and normal, healthy tissues. Immune responses are poor because tumour antigens do not efficiently localize to lymph follicles in lymphoid tissues, and are not efficiently presented to CTLs in an immunogenic context. The fact that tumours do not induce CTLs but are often susceptible to lymphocyte-mediated cytotoxicity indicates that more intensified immunization protocols should result in improved clinical outcome.     

Lymphatic metastasis of tumour; persistent transport of cells

Summary A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumou cells was continuou over periods up to 90 min and ranged from 10²–10⁵ cells/min.Acknowledgment. This work was supported by a grant from the National Cancer Institute of Canada to C.R.F. and I.C. We are grateful to Mrs W. Kao and Mr I. Etches for meticulous technical help and to the Photographic Section, Department of Pathology for illustrations. Dr V.S. Gupta of Veterinary Physiology, University of Saskatchewan supplied the tumour for transplantation.     

Adenosine-5'-triphosphate levels in experimental CaNT and Fib/t tumours of varying volume and degree of hypoxia

The variation of adenosine-5'-triphosphate (ATP) content per unit mass of tumour, versus tumour volume was measured in vivo under normoxic conditions, using CaNT and Fib/t murine tumours grown in CBA and WHT mice respectively. A monotonically decreasing relation was found. Artificially induced tumour hypoxia resulting from 15 min of clamping was accompanied by reduced ATP levels.     

Mast cells in the skin of normal,hairless and athymic mice

Summary The skin of congenitally athymicnu/nu mice is rich in mast cells which stain metachromatically, contain histamine and 5-hydroxytryptamine, and participate in the PCA reaction. Mast cells of athymic mice have thus the attributes of normal mast cells.This work was supported by grants from the Swiss National Science Foundation (No. 3.516.71 and 3.234.74) and the Fritz Hoffmann-La-Roche-Stiftung.The skilful technical assistance of MissR. Keist is gratefully acknowledged.     

A highly active glutathione peroxidase in red blood cells of normal and acatalasemic mice

The activities of catalase (E.C.1.11.1.6) and glutathione peroxidase (E.C.1.11.1.9) were compared in red blood cells from humans, ducks and normal and acatalasemic mice. In the cells from both strains of mice, an equally high activity of GSH-Px was found which could be inhibited completely by iodoacetate but was not sensitive to N-ethylmaleimide.     

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ^?/? mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.     

Detection of human antigens on the surface of mouse cells transformed by chromosome transfer]

Mouse embryo cells, transformed in vitro by the transfer of chromosomes from HeLa human tumour cells, express a surface antigen (s) also found on HeLa cells. This antigen(s), which has been detected both by indirect immunofluoresence and by a 125I-protein A binding assay, is not an antigen(s) shared by both Human and Mouse cells.     

A highly active glutathione peroxidase in red blood cells of normal and acatalasemic mice

Summary The activities of catalase (E.C.1.11.1.6) and glutathione peroxidase (E.C.1.11.1.9) were compared in red blood cells from humans, ducks and normal and acatalasemic mice. In the cells from both strains of mice, an equally high activity of GSH-Px was found which could be inhibited completely by iodoacetate but was not sensitive to N-ethylmaleimide.Acknowledgment. This work was supported by a postdoctoral fellowship from the Gesellschaft für Strahlen- und Umwelt-forschung, München, Federal Republic of Germany, and was performed under contract with the U. S. Energy Research and Development Administration at the University of Rochester Biomedical and Environmental Research Project and has been assigned Report. No. UR-3490-1138.     

Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells,granulocyte, macrophage and erythroid progenitor cells,and hemopoietic stromal cells

Summary Glucan, a beta-1, 3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistantly exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.     

Different biological behavior of AKR lymphoma cells from primary and metastatic tumors

AKR lymphoma cells derived from primary s.c. tumors (PT) and cells from their metastases (MT) were inoculated into recipient mice in order to compare their malignant behavior. A higher malignant potential of MT compared to PT cells was found. The results support the hypothesis that metastasis is a process of selection of cells possessing a potential to metastasize, which preexist in the primary tumor. In the model used, both the selection of 'variants' of malignancy and the assay of malignancy were as close as possible to natural tumor progression.     

Suppression of PHA-induced lymphocyte blastogenesis by concomitant presence of PPD in the culture

Summary PHA-induced lymphocyte blastogenic response was remarkably suppressed by the simultaneous presence of PPD in cultures of lymphocytes derived from individuals sensitized to PPD, but not affected by the presence of PPD when the cultures contained lymphocytes from an individual not sensitized to the protein. This double stimulation blastogenesis study with PHA and a specific antigen is feasible as a simple and rapid test to measure cell-mediated immunity to the antigen.Supported by United States grant USPHS Grant AM 27384.     

Freeze-induced shrinkage of individual cells and cell-to-cell propagation of intracellular ice in cell chains from salivary glands

The formation of intracellular ice (IIF), usually a lethal event to be avoided when cryopreserving cells, should, however, be enforced during the cryosurgical destruction of tumour cells. IIF has been investigated so far only in single cells in suspension. Because cells in tissues cannot be successfully cryopreserved, in contrast to single cells in suspension, the mechanism of IIF in tissues may depend on factors that facilitate IIF. We studied IIF in cell strands from salivary glands, which represent a simple form of a tissue. Their cells are connected by channels responsible for intercellular communication. A substantial fraction of cell dehydration during freezing occurs before cells are encapsulated by ice, and the degree of this pre-ice-front shrinkage appears to influence IIF. In strands with coupled cells IIF spread from one cell to adjacent cells in a sequential manner with short delays (200–300 ms), suggesting cell-to-cell propagation via intercellular channels. In strands pretreated with decoupling agents (dinitrophenol, heptanol), sequential IIF was absent. Instead, formation of ice was random, with longer and variable delays between consecutive darkenings indicating IIF. Results suggest that the mechanism of IIF spread, and consequently the degree of cryodamage in tissue, can be influenced by the presence of intercellular channels (gap junctions).     

Lymph node metastases of EMT6 tumour in nude mice

Metastatic axillary lymph nodes following the injection of EMT6 tumour cells were observed in athymic nude mice, more often in female animals, and had a rapid growth rate. These metastases did not develop in syngeneic hosts. The latency of their appearance was inversely related to the number of injected cells.