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

Summary A protinin (Trasylol) is shown to enhance the response of spleen cells from normal and tumour bearing mice to PPD and tumour cells. This enhancement is greater in the tumour-bearing mice.Acknowledgments. We are grateful to Bayer (U.K.) Limited for generous supplies of aprotinin. The PPD was supplied by the Ministry of Agriculture. The work was supported by a grant from the North of England Cancer Research Campaign.     

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.

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.     

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).     

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.).     

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.

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.     

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.     

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.     

Spontaneous fusion between cancer cells and endothelial cells

Endothelial cells line the inside of blood and lymphatic vessels, and cancer cells must cross this barrier, first to gain access to the circulation, and, second, to exit and metastasize. How this occurs is incompletely understood. We now demonstrate that human cancer cells are able to fuse with endothelial cells to form hybrid cells displaying proteins and chromosomal markers characteristic of both parent cells. The hybrid cells are viable and capable of undergoing mitosis. Fusions between cancer cells and endothelial cells were shown to occur both in vitro, in co-cultures of human breast cancer cells and endothelial cells, and in vivo, following intravascular dissemination of human breast cancer cells in nude mice. These observations demonstrate a new type of cancer-endothelial cell interaction that may be of fundamental importance to the process of metastasis.Received 10 May 2004; received after revision 21 June 2004; accepted 2 July 2004     

Interaction of thymic cells and hemopoietic stem cells. Enhancing effect on irradiated thymus repopulation]

In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with the restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells.     

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.     

Lymph node metastases of EMT6 tumour in nude mice

Summary 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.We wish to thank Charles Gosse for breeding, maintenance and supply of the animals.     

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.     

Decrease of cholesterol and free fatty acids in cortisone-resistant lymphoid cells incubated with allogeneic tumor cells

Summary A marked decrease of cholesterol and free fatty acids was found in the cortisone-resistant lymphoid cells from thymus or spleen of mice immunized with Ehrlich carcinoma cells when incubated with the tumor cells.     

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.     

Increased release of tumour cells by collagenase at acid pH: A possible mechanism for metastasis

Summary The ability of collagenase to disaggregate a solid metastasizing lymphosarcoma has been shown to considerably increase with reducing environmental pH. It is suggested that this effect may be operating in vivo to release cells from a primary tumour.     

Monolayer cultures of normal adult rat adrenocortical cells: steroidogenic responses to nucleotides, bacterial toxins and antimicrotubular agents.

Monolayer cultures of normal rat adrenocortical cells were treated with agents which stimulate steroidogenesis by Y-1 adrenal tumour cells. Choleragen was active, whereas cyclic nucleotides other than cyclic AMP, bacterial endotoxins and antimicrotubular agents were inactive.     

Decrease of cholesterol and free fatty acids in cortisone-resistant lymphoid cells incubated with allogeneic tumor cells.

A marked decrease of cholesterol and free fatty acids was found in the cortisone-resistant lymphoid cells from thymus or spleen of mice immunized with Ehrlich carcinoma cells when incubated with the tumor cells.