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The authors report a case of stomatitis, in a patient receiving antimitotic therapy, which was found to be due to an acute leukosis. They feel that patients on antimitotics who develop stomatitis should have a white cell count to exclude leukosis, which is not a very rare finding today.
A case of Wegener's granulomatosis is presented with control of lung lesions by corticosteriods and renal lesions by azathioprine. It supports previous experience of antimitotic therapy in this condition.
In order to sustain genomic stability by correct DNA replication and mitosis and thus avoid malignant transformation of cells, the cell cycle is a strictly regulated process. Aberrant cell cycle regulation and defects in mitosis in malignant cells are targets of various cancer therapies. Cancer cells may survive antimitotic treatment due to mitotic slippage with a residual activity of the ubiquitin ligase anaphase-promoting complex (APC/C) and a continuous slow ubiquitin-proteasome-dependent cyclin B-degradation leading to mitotic exit. The combination of antimitotic chemotherapeutics with proteasome inhibitors to block cyclin B-proteolysis or with targeted inhibitors of the APC/C and the antiapoptotic protein Mcl-1 seems a promising approach to improve treatment response in different malignancies by enhancing mitotic arrest and apoptosis.The influence of conventional spindle poisons and new targeted substances and of their combinations on mitosis and apoptosis has not yet been conclusively clarified. Most models have been verified on cell lines whose biology may differ from that of tumors growing in vivo. To study the impact of various antimitotic substances on cell proliferation, especially detect onset of apoptosis depending on different cell cycle phases and thus to identify a possibly entity-dependent mechanism of those agents and their combinations, a combined approach with live-cell imaging and soft-agar colony assays in cultured patient-derived xenografts (PDX) was established.
Post-operative infection is often due to a combination of several factors. A decrease in immune defence processes represents the first factor. This is seen in situations such as malnutrition (undernourishment or obesity), alcoholism, diabetes, neoplasms, infections and old age. It may also be induced by therapy such as immunodepressants, antimitotic chemotherapy, corticosteroids and radiotherapy. Finally, certain antibiotics have been accused of reducing immune defences. The second factor responsible for infection is bacterial flora. Errors such as broad spectrum antibiotic therapy prescribed in the presence of unexplored fever, or changed repeatedly, are responsible for imbalance in the bacterial flora and the acquisition of resistance to antibiotics. These errors firstly increased the prevalence of infections and, secondly their severity and the difficulty of their treatment. The last factor responsible for infection is rupture of the natural barriers formed by the skin and mucosae. This is related on the one hand to surgery itself and, secondly, to the intensive care techniques surrounding the surgical act: venous catheterization above all, but also bladder catheterization, tracheal intubation, etc.
Successful therapy of a genetic disorder, Ichthyosis Linearis Circumflexa, was achieved using a low dose systemic cyclophosphamide. Prior to such therapy, 80 to 90% of the body surface was affected; the use of antimitotic agents reduced the extent of the lesions to less than 15% of the body surface. As a result, the clinical status was changed from severely disabling to being compatible with a normal way of life. It is believed that this phenomenon is related to selective effects of cyclophosphamide, such as those on lymphocyte subpopulations. To our knowledge, successful chemotherapy for diseases of genetic or congenital origin has not been previously reported.
The results of non-randomized clinical trials in urological cancer are often contradictory because of the selection of patients which is usually biased. Such data cannot be used for planning a logical therapy for the future patients. In urological cancer, radomized controlled trials are few. Moreover, antimitotic chemotherapy has not been adequately tried.
Bacterial infections are the most common cause of death in patients with malignant blood diseases. After recalling the main bacteria responsible and the factors which predispose patients to infection, the authors consider various forms of treatment, including antibiotic therapy, transfusions of white blood cells, gammaglobulins, etc., and prophlyactic measures, such as antibiotics by mouth, isolation in a sterile ward, etc., which have been proposed for some years. During renal grafts, infective complications are also very frequenct. Their prevention is essential for on this, to a large extent, depends the success of the transplantation.
Following studies of problems regarding the phenomenon of synchronization and cell recruitment, the authors present the results obtained using antimitotic polychemotherapy (VCR, MTX, BLM, ADM or MTC) administered to 47 patients with squamous cell carcinoma of the oral cavity. This treatment resulted in a regression in 29/47 patients (61.7 %). All patients were subjected to X-ray therapy, while only a part of the responders were subjected to surgery. Survival after 18 months from the beginning of the treatment has been 24/47 patients (51.0%). Since the majority of patients were beyond the limits of surgery and/or radiotherapy, this can be considered as a positive result, even though the risk of death due to polychemotherapy has been rather high.
The simultaneous administration of colchicine (CC) with a T-independent antigen, e.g. 2,4,6-trinitrophenyl-keyhold limpet hemocyanin-Sepharose, to intact animals effectively enhanced their hapten-specific plaque-forming cell (PFC) response. However, in congenitally athymic nude mice in which T-cell regulation was absent, CC was ineffective in producing enhancement. These observations suggest that the target cell acted upon by CC is most likely thymus-derived. Furthermore, the injection of CC with the co-polymer of L-glutamic acid50-L-tyrosine50 (GT) abolished GT-specific suppression of the PFC response to GT-methylated bovine serum albumin. Spleen cells from CC-treated and GT-primed hosts could no longer transfer suppressive activity to normal recipients. These results provide evidence that CC is capable of inactivating or eliminating suppressor cells or their precursors. Thus, CC-induced enhancement of the antibody response may be explained, at least in part, by its antimitotic, and hence lethal effect on dividing suppressor T cells.
During acute lymphoblastic leukemia in children, bacterial infections occur during initial treatment, whereas virus infections are observed during remission. Mycoses and pneumocystis carinii infections are the commonest late complications. During agranulocytosis, any prolonged fever should be considered as due to infection and probably septicemia. The bacteria are usually of digestive origin. Antibiotic therapy is only very inconstantly efficacious, and the course follows closely the number of granular cells, thus justifying the use of white cell transfusions.
The present paper is the study of a micronodular encephalitis with inclusions occurring in a child suffering from acute leukemia treated with antimitotics and immunosuppressives. The role of the immunosuppressive treatment in the onset of the encephalitic syndrome is discussed.
Estracyt, a conjugate of an alkylating agent with an oestrogenic sterol, was given in a dose of 420 mg daily to a group of 44 postmenopausal patients with very advanced breast carcinoma. Thirty-eight of these were in relapse following chemotherapy and 32 had evidence of distant metastases. Seventeen patients had an objective response and marked or complete alleviation of symptoms, four others had a useful symptomatic response but no beneficial effect was observed in the remainder. Three who had shown no response to previous oestrogen therapy also failed to respond to Estracyt as did all nine patients with hepatic metastases. Oestrogen receptor status and age within the postmenopausal group seemed to have no bearing on the result. Side-effects were minimal with nausea in 18 patients but in only two did this necessitate withdrawal of the drug. Bone marrow depression did not occur. Changes in acute-phase reactant proteins suggested that part of the Estracyt was de-esterified in the liver liberating oestrone but the low incidence of vaginal haemorrhage and the recalcification of bony metastases suggested that on the whole Estracyt behaves as an anti-oestrogen as well as an antimitotic.
First, chemotherapy was used to reduce metastatic tumours. Then, instead of a limited number of antimitotic agents, it permited to increase both the number of complete remissions and the survival ratio, mostly in embryonal tumours and lymphomas. The essential purpose of chemotherapy is to kill occult metastases. Combination chemotherapy using many agents with differing modes of action took place of monochemotherapy. In sophisticated schedules, drugs are given intermittently, to synchronizing treatment with the tumour doubling time and the recovery of normal rapidly dividing tissues. Unhappily, its use remains empiric, according to uncertainty about tumoral cell kinetic and modes of drugs action. Immediate toxicity of aggressive schedules prescribe to realize them in specialized pediatric centres. At last, in the future, it will not be enough to cure infantile cancer, but to allow children to live with less sequelae than to day.