ABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Docetaxel/therapeutic use , Doxorubicin/therapeutic use , Erythropoiesis/drug effects , Leukopoiesis/drug effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/metabolism , Cell Lineage/drug effects , Erythrocytes/cytology , Female , Granulocyte Colony-Stimulating Factor/metabolism , Granulocytes/cytology , HumansABSTRACT
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.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Filgrastim/therapeutic use , Granulocytes/cytology , Granulocytes/drug effects , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , Fluorouracil/therapeutic use , Granulocyte Colony-Stimulating Factor/metabolism , HumansABSTRACT
The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD+, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.
Subject(s)
Evolution, Molecular , Gene Transfer, Horizontal , Host-Pathogen Interactions/genetics , Microsporidia/genetics , Nucleotide Transport Proteins/genetics , Animals , Cell Line , Gene Duplication , Genome, Fungal/genetics , Metabolic Networks and Pathways/genetics , Microsporidia/metabolism , Nucleotide Transport Proteins/metabolism , Nucleotides/metabolism , Phylogeny , RabbitsABSTRACT
The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Granulocytes/metabolism , Lung Neoplasms/metabolism , Anthracyclines/pharmacology , Antineoplastic Agents/pharmacology , Cell Differentiation/drug effects , Cisplatin/pharmacology , Disaccharides/pharmacology , Docetaxel , Doxorubicin/pharmacology , Erythropoiesis/drug effects , Granulocytes/cytology , Granulocytes/drug effects , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/metabolism , Humans , Macrolides/pharmacology , Nitrosourea Compounds/pharmacology , Organoplatinum Compounds/pharmacology , Taxoids/pharmacologyABSTRACT
A granulovirus (GV) isolated from Epinotia aporema (Lepidoptera: Tortricidae)-a major soybean pest-was studied in terms of its main morphological, biochemical, and biological properties. The ovoidal occlusion bodies were 466 by 296 nm in size, and their most prominent protein had an apparent molecular mass of 29 kDa. Its amino-terminal sequence was remarkably homologous to that of the granulins of other GVs. The DNA genome size was estimated to be 120 kbp. The high specificity and pathogenicity of this newly described granulovirus (EpapGV) indicate that it is indeed a good candidate for the biological control of this pest.
