Reentry of nondividing leukemic cells into a proliferative phase in acute childhood leukemia.

Reentry of small leukemic blast cells into a proliferative phase was demonstrated in a 3 yr old girl with untreated acute lymphoblastic leukemia. Since the proliferating leukemic cell compartment in this disease is not self-maintaining, continual entry of cells into this compartment is necessary to prevent depletion of proliferating cells. In order to identify the source of replacement cells, the rate of change of tritiated thymidine-labeled cells in the proliferating compartment was observed by means of serial bone marrow samples under two conditions. In the first study period only 10% of small leukemic blast cells were labeled, and in the second study period 72% of this population had become lebeled. During the first period the proliferating blast cells were rapidly replaced by unlabeled cells, while during the second period the replacement cells were coming largely from a labeled cell source. The only identifiable source of cells for maintenance of the proliferating population which was virtually unlabeled during the first period and largely labeled during the second period was the population of small leukemic blast cells. The finding that the small blast cells are only temporarily nonproliferative could account for effectiveness of therapy directed primarily against a dividing cell population. Persistence of some cells with longer resting times into remission could provide a focus for subsequent relapse.

Cancer metastasis: experimental approaches, theoretical concepts, and impacts for treatment strategies.

It has been the purpose of this article to describe recent advances in cancer metastasis research. Clinical realities and experimental approaches to the study of underlying basic mechanisms of metastasis formation were discussed. Wherever possible, results were reported which led to the development of theoretical concepts. Such results and concepts were finally evaluated in light of their possible impact for the design of new treatment strategies. Experimental findings from many diverse research fields were summarized with the help of tables, figures, and references. It was concluded that the process of metastasis is a dynamic event that can be described as a sequence of interrelated steps. Experimental results indicated that malignant cells that migrate and disseminate from the primary organ to distant sites and there eventually develop into metastases have to survive a series of potentially lethal interactions. Intimate tumor-host interactions were reported to take place all along the metastatic process. They were elucidated at the steps of angiogenesis, invasion, organ interaction, dormancy, tumor rejection, and tumor immune escape. The outcome of such tumor-host interactions seemed to depend on intrinsic properties of the tumor cells themselves as well as on the responsiveness of the host. Metastasis does not appear as a merely random process. Both clinical and experimental studies revealed that the whole process can be described more appropriately in terms of stochastic, sequential, and selective events, each of which is controlled and influenced by a number of mechanisms. With regard to therapeutic intervention, a selective event offers more possibilities than a random one because it is governed by rules that can be exploited experimentally. Various impacts from experimental studies for the design of antimetastatic cancer treatment strategies were discussed. Sequential steps of the metastatic cascade could become new therapy targets. Conventional empirically derived treatment modalities should become flanked by methods aimed more specifically at critical steps of cancer spread in order to prevent progression of the disease. This is where basic research on mechanisms could make significant contributions to therapy planning in the future. Furthermore, possible negative effects of surgery, radiotherapy, and adjuvant chemotherapy or immunotherapy that could result in enhancement of metastatic progression need to be critically evaluated to limit them as much as possible.(ABSTRACT TRUNCATED AT 400 WORDS)

[Chemotaxis and collagen]. / Chimiotactisme et collagène.

The authors evaluate the chemotactic properties of collagen and collagen derived fragments, according to literature datas. In experimental conditions, collagen can be chemotactic for human blood monocytes, fibroblasts and various malignant cells but not polymorphonuclear. The meaning of these facts and their possible role in the genesis of osteo-articular diseases are also discussed.

Clinical aspects of metastases.

In the short term the major hope for reducing cancer mortality is to effect a reduction in the number of patients who develop malignant disease and in the proportion of cancer patients who present with metastases. Hitherto the major emphasis of clinical research on metastases has been directed at detection and elimination rather than prevention or early diagnosis. Extensive data relating histological class and tumour stage to risk of metastasis and metastatic pattern have been compiled from studies of relapse and from invasive and non-invasive staging procedures. However, the biological events involved in the metastatic process and the factors which influence it in relation to the natural history of primary human tumours are poorly understood. Information describing metastatic heterogeneity in individual patients, in terms of therapeutic response or intrinsic sensitivity to cytotoxic agents, is scanty. Similarly, the characteristics of human metastases in relation to the clonal heterogeneity of primary tumours are poorly defined. The clinical application of molecular biological techniques, which has led to the association of gene amplification with tumour behaviour in a range of sites, offers the prospects of improved tumour localization and therapy and, in the longer term, of tumour control by interventions based on a knowledge of the mechanisms that regulate cell growth and differentiation.