RESUMEN
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.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel/uso terapéutico , Doxorrubicina/uso terapéutico , Eritropoyesis/efectos de los fármacos , Leucopoyesis/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/metabolismo , Linaje de la Célula/efectos de los fármacos , Eritrocitos/citología , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Granulocitos/citología , HumanosRESUMEN
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.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Filgrastim/uso terapéutico , Granulocitos/citología , Granulocitos/efectos de los fármacos , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/metabolismo , HumanosRESUMEN
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.
Asunto(s)
Evolución Molecular , Transferencia de Gen Horizontal , Interacciones Huésped-Patógeno/genética , Microsporidios/genética , Proteínas de Transporte de Nucleótidos/genética , Animales , Línea Celular , Duplicación de Gen , Genoma Fúngico/genética , Redes y Vías Metabólicas/genética , Microsporidios/metabolismo , Proteínas de Transporte de Nucleótidos/metabolismo , Nucleótidos/metabolismo , Filogenia , ConejosRESUMEN
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.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Granulocitos/metabolismo , Neoplasias Pulmonares/metabolismo , Antraciclinas/farmacología , Antineoplásicos/farmacología , Diferenciación Celular/efectos de los fármacos , Cisplatino/farmacología , Disacáridos/farmacología , Docetaxel , Doxorrubicina/farmacología , Eritropoyesis/efectos de los fármacos , Granulocitos/citología , Granulocitos/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Humanos , Macrólidos/farmacología , Compuestos de Nitrosourea/farmacología , Compuestos Organoplatinos/farmacología , Taxoides/farmacologíaRESUMEN
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.