Results of combination therapy with amifostine, pentoxifylline, ciprofloxacin and dexamethasone in patients with myelodysplastic syndrome and acute myeloid leukemia.

Myelodysplastic syndrome (MDS) is a clonal disease of the bone marrow characterized by abnormal hematopoiesis and cytopenias. It has been shown that abnormal cytokine production together with apoptosis are major contributors to the cytopenias associated with the disorder. As the interaction of cytokines plays a role in the pathogenesis, suppression of the cytokine production by the administration of the combination of pentoxifylline, ciprofloxacin, and dexamethasone (PCD combination) has resulted in the correction of at least some aspects of the cytopenias in the majority of patients and in complete hematologic remission in a small percentage. The aminothiol prodrug amifostine, a compound to protect tissues from cytotoxic drugs and radiotherapy has been found to stimulate proliferation of normal hematopoiesis and suppress apoptosis in patients with MDS. In this study we report the results of combination therapy of amifostine and PCD in 12 patients with MDS and acute myeloid leukemia (AML). Amifostine was given in a dose of 200 mg/m(2), as an i.v. infusion administered in 10 min, three times a week; pentoxifylline 2400 mg/day, (3 x 800 mg) p.o.; ciprofloxacin, 1 g/day p.o.; dexamethasone 4.5 mg/day p.o. We achieved 66% response rate in our patients. In some cases responses were achieved in only thrombocytopenia or anemia whereas in others responses were achieved in multiple series. As a result it was found that amifostine + PCD combination may be beneficial in reversing cytopenias in the treatment of MDS and AML and is worth further study.

Peripheral blood gamma-delta T cells in advanced-stage cancer patients.

Gamma-delta T (gammadelta T) cells form a subgroup which has been reported to play a role in both natural and acquired immunity. Their levels have been found to increase in some tumour tissues. The aim of this study was to investigate the ratio of gammadelta T cells to all T cells in the peripheral blood of advanced-stage cancer patients; the level of gammadelta T cells expressing the Vdelta2-T-cell receptor (TCR) chain; NKG2D receptor expression; and apoptotic (Annexin-V) gammadelta T-cell levels. Twenty patients with advanced-stage cancer and 13 healthy controls were included. No statistical differences were found between control and patient groups in terms of the gammadelta T/total T-cell ratio (P=0.53), the Vgamma2-TCR expressing gammadelta T-cell ratio (P=0.19) or the Annexin-V ratio (P=0.48). However, NKG2D expression in gammadelta T cells was significantly different between the control and patient groups (P=0.014). In summary it was shown that the levels of NKG2D receptors, which are responsible for the cytolytic effect of gammadelta T cells, were lower in cancer patients than in healthy adults. However, no significant differences were observed in the other parameters studied between groups.

Hyperbaric oxygen therapy does not potentiate doxorubicin-induced cardiotoxicity in rats.

The current use of doxorubicin is regarded as an absolute contraindication for hyperbaric oxygen (HBO2) therapy because of the increased risk of cardiotoxicity. The aim of this study was to investigate whether additional exposure to HBO2 during the course of doxorubicin treatment would further increase the cardiotoxicity of doxorubicin in rats. Female Wistar rats were treated with either HBO2 (n = 10) or doxorubicin (n = 8) or a combination of both treatments (n = 10) for 4 consecutive weeks and followed up for an additional 4 weeks. Cardiomyopathy was evaluated using two-dimensional and M-mode echocardiography at baseline, at the fourth, sixth and eighth weeks, and by histopathological investigation of the rat hearts at the eighth week. Doxorubicin treatment significantly reduced ejection fraction and fractional shortening (P < 0.001) and caused severe histopathological injury (P < 0.05) indicating development of cardiotoxicity. Although the combination of doxorubicin and HBO(2) also markedly reduced ejection fraction and fractional shortening (P < 0.001), this reduction was significantly less than that of doxorubicin treatment (P < 0.05). HBO2 therapy also attenuated doxorubicin-induced histopathological changes in rat hearts (P < 0.05). HBO2 alone did not alter echocardiographic parameters or histopathological findings (P > 0.05). In conclusion, HBO2 therapy does not potentiate doxorubicin-induced cardiotoxicity in rats. Cardioprotection conferred by HBO2 against doxorubicin warrants further investigation.

Investigation of the role of hyperbaric oxygen therapy in cisplatin-induced nephrotoxicity in rats.

Cisplatin (CP) is an effective chemotherapeutic agent used in the treatment of a variety of solid tumours. The most frequently observed side-effect of the use of CP is nephrotoxicity. Recently, evidence has been demonstrated that reactive oxygen species forming in the tubular epithelium play an important role in CP-linked nephrotoxicity. The aim of the study was to observe the effect of hyperbaric oxygen (HBO) therapy on CP nephrotoxicity, a subject which has not been studied previously. Wistar rats were treated with CP (a single intraperitoneal (IP) dose of 0.6 mg/100 g) alone and in combination with HBO (60 min every day for seven days at 2.5 x atmospheric pressure). Effects of the treatment on renal function and histology were determined. In analyses at the end of the study it was observed that serum urea, creatinine, and daily urinary protein excretion levels of the CP group were higher than at the start of the study, and that the creatinine clearance level had fallen (P < 0.05). There was no significant difference between the CP+HBO group and HBO group serum urea, creatinine, creatinine clearance, and daily urinary protein excretion levels at the beginning and end of the study (P > 0.05). Histopathological examination showed that the necrosis score in the proximal tubule epithelial cells and average apoptitic cell numbers in the CP group were higher than those in the CP+HBO and HBO groups (P < 0.05). There was no statistical difference between the CP+HBO group and the HBO group in terms of necrosis score in the proximal tubule epithelial cells and the percentage of distal tubules containing hyaline casts in the lumen. In conclusion, in this study it was observed that in experimental study of CP nephrotoxicity the synchronous application of HBO therapy with CP prevents kidney damage.

Breast cancer in association with thyroid disorders.

BACKGROUND: The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease. METHODS: Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals. RESULTS: The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively). CONCLUSION: Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.