ABSTRACT
Background: The research of recent decades has demonstrated the participation of nitrogen monoxide in various metabolic and regulatory intracellular cascades. However, the majority of works in this field seeks to detect the functional activity of endogenous NO. In opposite, the biological effects of the exogenous nitrogen monoxide have been insufficiently looked into. That is why the aim of the present study was a comprehensive assessment of the effect of various NO-stimulation options on the state of human erythrocytes in vitro. Methods: This study used 15 healthy subjects’s (20-45 years old) blood samples divided into five portions. The first portion was allocated as the control; the second portion was treated with a flow from the Plazon apparatus (800 ppm NO); the third portion was processed in a stream tenfold diluted with air (80 ppm NO), fourth portion – with a gas mixture containing 75 ppm NO and fifth portion was introduced with a solution of dinitrosyl iron complexes (DNIC, 3 mM). In all blood samples we estimated the peroxide resistance of erythrocyte, levels of malonic dialdehyde and lactate, superoxide dismutase activity, activity of lactate dehydrogenase and aldehyde dehydrogenase. Results: We stated that blood processing with high NO dose (800 ppm) causes elevation of peroxide resistance of erythrocyte, levels of malonic dialdehyde and lactate with inhibition of activity of superoxide dismutase, lactate dehydrogenase (in forward reaction) and aldehyde dehydrogenase. In opposite, low NO dose (75 ppm) and DNIC induced the decreasing of peroxide resistance of erythrocyte and stimulation of enzymes catalytic activity. Conclusion: The study has revealed that low doses of gaseous NO and a solution of DNIC produce the most favorable effect on the oxidative and energy metabolism, as well as on the activity of aldehyde dehydrogenase of erythrocytes.
ABSTRACT
PURPOSE: Positive correlation between dosage of antineoplastic agents and tumor response is well demonstrated in advanced breast cancer. But severe bone marrow depression limit the clinical application of high dose chemotherapy. Autologous peripheral blood stem cell transplantation(PBSCT) after high dose chemotherapy(HDC) was introduced to promote rapid bone marrow recovery. This study was designed to establish the feasibility of combining high dose cyclophosphamide, thiotepa, and carboplatin chemotherapy followed by stem cell rescue in patients with responsive metastatic or high risk primary breast cancer. MATERIALS AND METHOD: Eligibility criteria included the presence of high risk primary breast cancer(10 or more involved axillary lymph node, n=4), recurrent disease after curative resection(n=6) or stage IV disease at the time of diagnosis(n=1). The responses of recurrent disease to initial chemotherapy were 4 complete responses and 1 partial responses. One recurrent case with solitary pulmonary metastasis underwent metastasectomy and got chemotherapy after operation. Colony stimulating factor was administered to mobilize stem cells from bone marrow to peripheral blood. The stem cell collection was performed 4~10 times(median 4) and the number of collected stem cell was 1.95~7.34x10(8)kg(median 4.87x10(8)/kg). High dose chemotherapy with CTCb (cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day, carboplatin 200 mg/m2/ day) was performed from day -7 to day -4 and peripheral stem cell infusion was performed on day 0 as planned. RESULT: Eleven patients were enrolled in this study. Their median age was 39 years old. The median time for bone marrow recovery was 11 days for neutrophil(>500/mm2) and 28 days for platelet(>50,000/mm2). Packed red blood cell and platelet transfusion were performed in 11 patients. The group whose infused mononuclear cell count was less than 4.0 x 10(8)/kg(n=9) needed longer time for bone marrow recovery than those(n=2) who had more than 4.0 x 10(8)/kg( 20 vs 13 day, p < 0.05 ). For non-hematologic toxicity, none have experienced toxicity more than grade III. There were 2 recurrences of 4 cases with high risk breast cancer at the 22 th, and 25 th month but they are still alive at the 28 th, and 29 th month each. The other 2 cases are alive without recurrences at the 18 th, and 20 th months each. In the recurrent disease group, one case who showed partial response to initial chemotherapy recurred at the 4 th month and died at the 13 th month after PBSCT. The other 5 cases are alive without recurrence at the 1st, 3 rd, 3 rd, 5 th, and 31 th month each. One case with stage IV disease(bone metastasis) is alive without evidence of progression at the 3 rd month. CONCLUSION: High dose chemotherapy with PBSCT can be performed safely. Long term survival of patients with advanced breast cancer would be possible by PBSCT after HDC. Further clinical trials based on larger patient population is required to evaluate clinical efficacy of PBSCT after HDC in high risk and recurrent breast cancer.