ABSTRACT
Cell cycle deregulation is a common feature of human cancer. Tumor cells accumulate mutations that result in unscheduled proliferation, genomic instability and chromosomal instability. Several therapeutic strategies have been proposed for targeting the cell division cycle in cancer. Whereas inhibiting the initial phases of the cell cycle is likely to generate viable quiescent cells, targeting mitosis offers several possibilities for killing cancer cells. Microtubule poisons have proved efficacy in the clinic against a broad range of malignancies, and novel targeted strategies are now evaluating the inhibition of critical activities, such as cyclin-dependent kinase 1, Aurora or Polo kinases or spindle kinesins. Abrogation of the mitotic checkpoint or targeting the energetic or proteotoxic stress of aneuploid or chromosomally instable cells may also provide further benefits by inducing lethal levels of instability. Although cancer cells may display different responses to these treatments, recent data suggest that targeting mitotic exit by inhibiting the anaphase-promoting complex generates metaphase cells that invariably die in mitosis. As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic.
Subject(s)
CDC2 Protein Kinase/antagonists & inhibitors , Mitosis/drug effects , Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Protein Serine-Threonine Kinases/antagonists & inhibitors , Animals , Aurora Kinases , CDC2 Protein Kinase/genetics , CDC2 Protein Kinase/metabolism , Chromosomal Instability/drug effects , Chromosomal Instability/genetics , Humans , Mutation , Neoplasms/enzymology , Neoplasms/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Tubulin Modulators/therapeutic useABSTRACT
OBJECTIVE: To describe the use of filtration into the joints and soft tissue in the daily work of a Primary Care clinic. DESIGN: Observational and descriptive study. SETTING: Primary Care. PARTICIPANTS: Patients between 18 and 75, with pathologies that can be filtrated and who had not previously received treatment. MEASUREMENTS AND MAIN RESULTS: 148 filtrations were analysed, with pain and mobility before and after filtration being evaluated. 85.1% of the patients had intense or moderate pain before filtration, dropping to 5.4% a month afterwards (p < 0.05). 55.4% had limited mobility before filtration and 6.1% a month afterwards (p < 0.05). Complications from the technique were observed in 4 cases, but all were of a light character. CONCLUSIONS: The technique is effective and easy to apply in Primary Care, with scarce and light side-effects.
