Responses of Blood System to Doxorubicin/Docetaxel Chemotherapy in Patients with Breast Cancer.

We studied the effects of combined chemotherapy with doxorubicin/docetaxel on erythroid and granulocytic hematopoietic lineages with particular attention focused on their recovery in patients with stages III-IV breast cancer. Intensification of differentiation of erythroid and granulocytic CFU (even under conditions of their suppressed proliferation) provided the increase in the content of mature and morphologically differentiated elements in the bone marrow and peripheral blood. High proliferative activity of erythroid and granulomonocytic precursors resulted from enhanced production of hematopoiesis-stimulating activities by microenvironment elements.

Mechanisms of Granulocytopoiesis Recovery Stimulation with Filgrastim in Breast Cancer Patients Receiving Chemotherapy.

We studied myelotoxicity of modern schemes of chemotherapy for breast cancer (docetaxel/doxorubicin and cyclophosphamide/doxorubicin/5-fluorouracil) towards granulocytopoiesis, the mechanisms determining the differences of hematological effects of these schemes, and the efficiency of correction of the observed changes with granulocyte CSF (filgrastim). Granulocytopoiesis stimulation with filgrastim during the treatment with docetaxel/doxorubicin combination was more pronounced than during cyclophosphamide/doxorubicin/5-fluorouracil therapy. The observed differences were found at all levels of granulocyte lineage organization (central and peripheral), which is related to different effects of the cytostatic substances used in the proposed protocols on the structures controlling hemopoiesis.

[THE STATE OF HEPATIC AND SPLANCHNIC BLOOD FLOW IN VARIOUS TYPES OF COMPLICATED PANCREATIC PSEUDOCYSTS].

Investigations were conducted in 37 patients, suffering complicated pancreatic pseudocysts. In accordance to data of ultrasound Doppler flowmetry for the blood flow along portal vein, a. hepatis communis, a. mesenterica superior in complicated pancreatic pseudocysts compensatory--adaptive reactions on level of hepatic--spanchnic blood flow are directed towards restriction of the blood inflow through the portal vein system. This is accompanied by the common peripheral vascular resistence raising in basin of a. mesenterica superior, which have depended upon the patients' state severity, caused by reduction of the volume blood flow in a certan vascular collector. The oxygen debt of the liver in these patients is compensated by the volume blood flow enhancement along a. hepatis communis.

[DYNAMICS OF CHANGES OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINES, AS WELL AS SOME INDICES OF THE BLOOD PEROXIDATION SYSTEM, IN THE PATIENTS WITH VARIOUS PANCREATIC PSEUDOCYST TYPES].

The investigation was performed in 47 patients, operated on for pancreatic pseudocysts (PP). The PP type was established in accordance to A. D'Egidio, M. Schein (1991) classification. The blood plasma contents of proinflammatory and antiinflammatory cytokines, including interleukins (IL): IL-6, IL-8, IL-10, IL-18, as well as malonic dialdehyde and activity of glutationperoxidase, were determined for estimation of the immune state disorders. Mostly expressed changes in IL-8 content were registered in complicated PP in 72 h postoperatively, what was have characterized by more expressed raising of its level in systemic blood flow, than in a splanchnic one, in all types of PP and witnessed a hepatic capacity to guarantee a cytokine's clearance in all the patients. The contents of glutationperoxidase and IL-18 in the blood serum in various types of PP have correlated immediately with pancreatitis severity. Close correlative connection between these indices while unfavorable prognosis of postoperative period course was established.

[The role of matrix metalloproteinases and their inhibitors in pathogenesis of pancreatic pseudocysts].

The investigation was conducted in 47 patients, operated on for pancreatic pseudocysts (PP). Activity of matrix metalloproteinases (MMP-9) and content of their tissue inhibitor (TIMP-2) were determined in the blood serum for estimation of inflammatory factors, hypoxia severity and state of the pancreatic tissue reconstruction. High activity of MMP-9 and TIMP-2 in presence of PP types I and II was noted in patients, what, probably, is caused by compensation reaction, directed towards inhibition of the collagen system destruction (predominantly of collagen type IV) and prevention of further reconstruction of pancreatic connective tissue. While progressing of pancreatic fibrosis the MMP-9 activity and the TIMP-2 level have lowered in comparison with these indices while its absence. In PP type III the MMP-9 activity was by 83.6% higher, than in a control group, but, by 51.4 and 35.1% lower, than in PP types I and IV. In all the patients endothelial dysfunction with endothelial injury was observed, witnessed by significant rising of the VEGF content in the blood serum. It have created favorable conditions for pancreatic tissue remodeling while parenchymal defect have been constituted by tissue, owing lower level of organization, including a cicatricial one. In cases of cellular repeated affection more activation of pancreatic stellate cells and enhancement of production of extracellular matrix component were noted.