Autonomy and dependence of preneoplastic mammary nodules in mice.

HYPERPLASTIC alveolar nodules have been shown to represent the preneo-plastic state in mouse mammary tumour development (Bern and Nandi, 1961). With little or no mammary gland substrate (due to the inherited hormonal pattern), neither nodules nor tumours arise unless an appropriate level of activity is artificially induced in the tissue. LAF1 mice (generally considered to be free of the mammary tumour agent), had previously been shown to be refractory to methylcholanthrene mammary carcinogenesis (Haran-Ghera, 1961). This failure could, however, be overcome by stimulating the mammary glands with increased prolactin secretion which in-duced hyperplastic nodules in this tissue. Simultaneous action of the carcinogen and mammary gland stimulation were foumd to induce preneoplastic lesions that eventually developed in intact LAF1 mice into autonomous mammary tumours (Haran-Ghera, 1963). The present experiments were set up on the basis of these findings, in order to determine the hormonal requirements for further neoplastic transformatio

The mechanism of radiation action in leukaemogenesis. The role of radiation in leukaemia development.

RADIATION-INDUCED tumours in low leukaemic strains are actually produce

The mechanism of radiation action in leukaemogenesis. Isolation of a leukaemogenic filtrable agent from tissues of irradiated and normal C57BL mice.

IRRADIATION of C57B1 mice induced a high incidence of lymphatic leukaemia, while being refractory to the spontaneous development of the disease. Several investigators have isolated a leukaemogenic agent from these radiation-induced tumours, which produces lymphoid leukaemia when injected into isologous newborn or young adult non-irradiated mice (Lieberman and Kaplan, 1959; Latarjet and Duplan, 1962; Laznicka and Smetanova, 1963; Ilbery and Winn, 1964). It has been assumed that the leukaemogenic agent is present during post-natal life in non-irradiated C57B1 mice, and that ionizing irradiation causes the release of a leukaemogenic agent, in addition to thymus and bone marrow injury, which are essential factors in radiation leukaemogenesis (Kaplan, 1964). Experimental support for this hypothesis was provided by demonstrating the presence of a leukaemogenic agent, for a limited period after completion of the irradiation treatment, in centrifugates prepared from pooled, irradiated, non-]eukaemic thymus and bone marrow (Haran-Ghera, 1966). The aim of the present studies was to isolate a leukaemogenic filtrate fro

Immune Recovery after Cyclophosphamide Treatment in Multiple Myeloma: Implication for Maintenance Immunotherapy

Multiple myeloma (MM) is a progressive B-lineage neoplasia characterized by clonal proliferation of malignant plasma cells. Increased numbers of regulatory T cells (Tregs) were determined in mouse models and in patients with MM, which correlated with disease burden. Thus, it became rational to target Tregs for treating MM. The effects of common chemotherapeutic drugs on Tregs are reviewed with a focus on cyclophosphamide (CYC). Studies indicated that selective depletion of Tregs may be accomplished following the administration of a low-dose CYC. We report that continuous nonfrequent administrations of CYC at low doses block the renewal of Tregs in MM-affected mice and enable the restoration of an efficient immune response against the tumor cells, thereby leading to prolonged survival and prevention of disease recurrence. Hence, distinctive time-schedule injections of low-dose CYC are beneficial for breaking immune tolerance against MM tumor cells

Endocrine Disorders as a Contributory Factor to Neoplasia in SJL/J Mice

We studied the endocrine status of SJL/J mice. Light and electron microscopy revealed that the adenohypophyses of both sexes became progressively infiltrated with an abnormal number of gonadotropinproducing cells that probably secreted large amounts of luteotropic hormone. The ovaries had numerous large corpora lutea even in animals over 1 year of age with reticulum cell neoplasms. The adrenal cortexes of female mice showed no regression of the reticular zone. In accordance with the anomalous condition of the adenohypophysis and ovary, females had abnormal estrous cycles, with prolonged diestrus and consequent reduction in fertility. These data were discussed in the context of hormone environment versus onset of systemic neoplastic disease and the relationship between hormone dependence and leukemic virus expressio