tetracycline and Leukemia

Modelling human disease in the mouse has become an essential activity in biomedical research in order to unravel molecular mechanisms underlying pathological conditions as well as to determine in vivo the consequences of aberrant gene function. The mouse is by far the most accessible mammalian system physiologically similar to humans. Furthermore, the development of novel techniques for manipulating the murine genome, which allow the in vivo modification of virtually any genomic region in a time and/or tissue specific manner, renders the mouse an ideal model system to study human pathological conditions. Modelling human diseases in mice has reached an even greater relevance in the field of haematological malignancies, due to the already advanced characterization of the molecular basis of many haematological disorders. In this review, we describe the most important technological developments that made it possible to reproduce in the mouse the genetic lesions that characterize human haematological malignancies, thus often generating faithful mouse models of the human condition. We provide specific examples of the advantages and limitations of the various genetic approaches utilized to model leukaemia and lymphoma in the mouse. Finally, we discuss the power of mouse modelling in developing and testing novel therapeutic modalities in pre-clinical studies.

Topics: Animals; Disease Models, Animal; Fusion Proteins, bcr-abl; Hematologic Neoplasms; Humans; Leukemia; Leukemia, Promyelocytic, Acute; Lymphoma; Mice; Mice, Transgenic; Models, Biological; Tetracycline

Topics: Adolescent; Adult; Aged; Animals; Cat-Scratch Disease; Child; Child, Preschool; Disease Outbreaks; Female; Fever; Gastroenteritis; Humans; Indians, North American; Insect Vectors; Leukemia; Lymphogranuloma Venereum; Male; Middle Aged; New Mexico; Phagocytosis; Plague; Rodentia; Sciuridae; Siphonaptera; Streptomycin; Syphilis; Tetracycline; Tularemia; Yersinia pestis

To avoid destruction of the implanted biological material it may be separated from host immunological system by enclosure within a permiselective membrane. Two-directional diffusion through the membrane of nutrients, metabolic products, as well as bioactive products of encapsulated cells is required to ensure their survival and functional activities. The system of cells encapsulated within the membrane releasing the biologically active substance may be applied either locally to give an opportunity of therapeutic agent activity in the specified place and/or at some convenient site (tissue) for a prolonged period of time.The novel system of bacteria bio-encapsulation using modified membranes, and its assessment by flow cytometry is described and discussed. The encapsulated in membrane bacteria, functioning and releasing their products were evaluated in the systems in vitro and in vivo. The bacteria cells products impact on Eukariotic cells was evaluated. The cytometric evaluation demonstrates the membrane ability to avoid the release of bacteria enclosed within the membrane wall. In experiments with treatment of the bacteria with antibiotic to release products from damaged bacteria it was possible to distinguish stages of the applied antibiotic impact on encapsulated bacteria cells. In E. coli following stages were distinguished: induction of membrane permeability to PI, activation of proteases targeting GFP (protein) and subsequent nucleic acids degradation. In the another experiment the evidence was presented of the cytotoxic activity of live Bacillus subtilis encapsulated within the membrane system. The Bacilus products mediated by secreted listeriolysin O (LLO) on the chosen eukaryotic cells was evaluated. Similar systems releasing bacterial products locally and continuously may selectively affect different types of cells and may have possible application in the anticancer treatment at localized sites.

Topics: Animals; Anti-Bacterial Agents; Bacillus subtilis; Bacterial Toxins; Capsules; Cell Survival; Escherichia coli; Flow Cytometry; Green Fluorescent Proteins; Heat-Shock Proteins; Hemolysin Proteins; Humans; Jurkat Cells; Leukemia; Leukocytes, Mononuclear; Membranes, Artificial; Mice; Microbial Viability; Permeability; Polypropylenes; Recombinant Proteins; Tetracycline

To investigate effects of arsenic trioxide (As(2)O(3)) and alltrans retinoic acid (ATRA) on PLZF-RARalpha-positive cells.. PLZF-RARalpha-positive U937 cells (U937/PLZF) were used as an in vitro model. The change of cell morphology was observed by Wright-Giemsa staining. Cell growth and proliferation were detected by methyl thiazolyl tetrazolium(MTT) assay. Cell cycle distribution and expression of cell membrane surface differentiation-related antigens (such as CD11b, CD64 and CD14) were determined by flow cytometry assay. Expression of PLZF was analyzed by immunofluorescence. Functional differentiation was reflected by nitroblue tetrazolium(NBT) reduction ability and cytochemistry staining.. While U937/PLZF cells were incubated in tetracycline-withdrawn medium, the expression of PLZF-RARalpha; protein increased. After treated with As(2)O(3) (0.5 micromol/L) and ATRA (1 mumol/L), U937/PLZF cells presented some changes such as decreased nuclear/cytoplasm ratio, and partial disappearance of nucleoli, suggesting a certain degree of morphological differentiation. The cell growth and proliferation were inhibited in a dose- and time-dependent manner. The proportion of cells in S phage was decreased and CD11b level was increased. The expression of PLZF relocated in treated cells. However, no significant difference in NBT assay and cytochemistry staining was documented with the combination therapy.. The combination of As(2)O(3) with ATRA can cause a slight tendency to morphological differentiation but is insufficient to induce functional differentiation of PLZF-RARalpha positive U937 leukemia cells.

Topics: Antigens, CD; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Cell Cycle; Cell Proliferation; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Kruppel-Like Transcription Factors; Leukemia; Nitroblue Tetrazolium; Oxidation-Reduction; Oxides; Promyelocytic Leukemia Zinc Finger Protein; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Tetracycline; Tretinoin; U937 Cells

A variety of experimental evidence including findings in various mouse models indicates that the BCR-ABL oncogene is the cause of chronic myeloid leukemia (CML). Since normal hematopoietic cells in marrow and spleen are replaced with proliferating leukemic blasts, we determined whether this is an active process mediated by the leukemia cells. The lipocalin 24p3 was reported to be secreted by mouse hematopoietic cells deprived of IL-3, resulting in apoptosis induction in a variety of hematopoietic cells including bone marrow cells. Here, we show that BCR-ABL+ mouse hematopoietic cells induced persistent expression and secretion of 24p3. Importantly, BCR-ABL+ hematopoietic cells were resistant to the apoptotic effects of 24p3. The expression of the Bcr-Abl oncoprotein and its tyrosine kinase were required for induction of 24p3 expression. Co-culture studies showed that BCR-ABL+ cells induced apoptosis in BCR-ABL negative cells. Antisense 24p3/siRNA expression reduced the level of 24p3 protein in both BCR-ABL+ cells and in conditioned medium (CM) obtained from these cells. CM from BCR-ABL+ cells expressing antisense 24p3/siRNA had reduced apoptotic activity for target cells; 24p3 antibody also reduced the apoptotic activity of the CM. Leukemic mice induced by BCR-ABL+ cells expressing either antisense 24p3 or 24p3 siRNA had increased levels of normal hematopoiesis and reduced invasion of leukemia cells in marrow and spleen tissues. These findings indicate that suppression of normal hematopoiesis in BCR-ABL-induced leukemia is an active process involving secretion of the cell death-inducing factor 24p3 by mouse leukemia cells, raising the possibility that similar factors are involved in BCR-ABL+ CML.

Topics: Acute-Phase Proteins; Animals; Apoptosis; Blotting, Western; Bone Marrow Cells; Cell Death; Coculture Techniques; Dose-Response Relationship, Drug; Fusion Proteins, bcr-abl; Hematopoiesis; Hematopoietic Stem Cells; Humans; Interleukin-3; Lentivirus; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lipocalin-2; Lipocalins; Mice; Mice, Inbred C3H; Mice, Inbred NOD; Mice, SCID; Oligonucleotides, Antisense; Oncogene Proteins; Plasmids; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Spleen; Tetracycline; Time Factors

Tumor-seeking radiopharmaceuticals have been employed in the diagnosis of primary neoplasms, in the detection of distant disease, particularly in the localization of tumor foci to facilitate biopsies and the planning of radiation portals, and in assessing the response to tumor therapy. At the present, there is no ideal tumor-scanning agent. However, several approaches appear to be useful and offer promise for further study. The greatest experience has been with Gallium-67, which has major utility in the staging of Hodgkin's disease, in the diagnosis of bronchogenic carcinoma, in the detection of certain metastatic brain tumors, in the identification of recurrent disease, and in the noninvasive diagnosis of leukemic complications. A number of radiolabeled antibiotic and chemotherapeutic agents have shown promise, including tetracycline and bleomycin. A major drawback, however, of these agents which is shared with Gallium-67 is that they appear to be sequestered by inflammatory as well as neoplastic tissue. A most intriguing approach is the use of radiolabeled antibodies to tumor-associated antigens. Animal and clinical experiments have employed antifibrin, antifibrinogen, anticarcinoembryonic antigen, and antiferritin. Theoretically, agents such as these should allow for greater tumor specificity.

Topics: Antibodies, Neoplasm; Bleomycin; Brain Neoplasms; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Gallium Radioisotopes; Hodgkin Disease; Humans; Indium; Leukemia; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Radiography; Radioisotopes; Radionuclide Imaging; Technetium; Tetracycline

Topics: Adolescent; Aeromonas; Carbenicillin; Cephalothin; Chloramphenicol; Ecthyma; Enterobacteriaceae Infections; Erythromycin; Gentamicins; Humans; Kanamycin; Leg; Leukemia; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Polymyxins; Streptomycin; Sulfisoxazole; Tetracycline

Topics: Bacteria; Bacterial Infections; Doxycycline; Humans; Leukemia; Minocycline; Neoplasms; Tetracycline

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; Breast Neoplasms; Child; Colonic Neoplasms; Female; Genital Neoplasms, Female; Hospitals, Special; Humans; Leukemia; Lymphoma; Male; Middle Aged; Neoplasms; Pressure Ulcer; Sepsis; Surgical Wound Infection; Tetracycline; Time Factors

Topics: Animals; Bone Marrow; Dactinomycin; Disease Models, Animal; Humans; Hydrolases; Leukemia; Lincomycin; Mice; Mice, Inbred Strains; Mycoplasma; Mycoplasma Infections; Tetracycline

A Gram-negative bacillus isolated from the blood of a leukaemic patient with septicaemia was identified on the basis of common tests as Escherichia coli. However, the organism's antibiogram was atypical of E. coli and led to its re-examination and correct identification as Aeromonas hydrophila. A. hydrophila is sensitive to chloramphenicol and tetracycline, characteristics useful in differentiation from E. coli. A simple test differentiating this organism from the Enterobacteriaceae is the oxidase test. A. hydrophila is oxidase positive.

Topics: Adolescent; Aeromonas; Chloramphenicol; Enterobacteriaceae; Escherichia coli; Humans; Leukemia; Male; Microbial Sensitivity Tests; Oxidoreductases; Sepsis; Tetracycline

Topics: Adolescent; Adrenal Cortex Hormones; Aminopyrine; Blood; Blood Cell Count; Blood Transfusion; Capillaries; Child; Child, Preschool; Cyanosis; Dyspnea; Female; Humans; Lanatosides; Leukemia; Male; Methotrexate; Methylprednisolone; Nystatin; Penicillins; Plasma Cells; Prednisone; Pulmonary Circulation; Pulmonary Fibrosis; Purines; Tetracycline

Topics: Child, Preschool; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Leukemia; Listeriosis; Male; Methotrexate; Pregnancy; Pregnancy Complications, Infectious; Tetracycline

Topics: Bone Marrow; Child; Electrons; Kanamycin; Leukemia; Leukemia, Myeloid; Lupus Erythematosus, Systemic; Microscopy; Microscopy, Electron; Mycoplasma; Neoplasms; Neutralization Tests; Oncogenic Viruses; Sarcoma; Tetracycline; Tissue Culture Techniques; Virus Cultivation

Topics: Adenocarcinoma; Animals; Formaldehyde; Injections, Intraperitoneal; Leukemia; Leukemia, Experimental; Mice; Mustard Plant; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; Sarcoma 180; Tetracycline

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Bacterial Agents; Blood Protein Electrophoresis; Bone Marrow Examination; Drug Therapy; Humans; Leukemia; Prednisolone; Tetracycline

Topics: Child; Cytodiagnosis; Fluorescence; Humans; Infant; Leukemia; Tetracycline

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Bacteroides; Brucella; Chloramphenicol; Complement System Proteins; Endotoxins; Erythromycin; Hodgkin Disease; Humans; Leukemia; Leukopenia; Lymphadenitis; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Penicillins; Primary Myelofibrosis; Properdin; Research; Sarcoma; Streptomycin; Tetracycline

Topics: Adenoma; Aminosalicylic Acid; Aminosalicylic Acids; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Antitubercular Agents; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Chloramphenicol; Isonicotinic Acids; Leukemia; Leukemia, Experimental; Liver Neoplasms; Neoplasms; Neoplasms, Experimental; Oleandomycin; Pharmacology; Pyrazinamide; Research; Rolitetracycline; Sarcoma; Sarcoma, Experimental; Sarcoma, Yoshida; Streptomycin; Tetracycline

Topics: Adrenal Cortex Hormones; Blood Cell Count; Blood Transfusion; Bone Marrow Examination; Eosinophils; Hemostatics; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Pathology; Tetracycline; Thrombin; Vitamin B Complex

Topics: Adolescent; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Blood Transfusion; Bone Marrow Examination; Central Nervous System Diseases; Child; Dextrans; Hematoma; Hematoma, Subdural; Humans; Isoniazid; Leukemia; Leukemia, Lymphoid; Mercaptopurine; Norepinephrine; Oleandomycin; Paraplegia; Prednisone; Streptomycin; Tetracycline

Topics: Antineoplastic Agents; Blood Transfusion; Herpes Zoster; Herpesvirus 3, Human; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Methylprednisolone; Tetracycline; Toxicology

Topics: Abscess; Animals; Anti-Bacterial Agents; Bronchitis; Cross Infection; Diabetes Mellitus; Erythromycin; Furunculosis; Fusidic Acid; Gangrene; Humans; Leukemia; Lung Diseases; Penicillins; Pyelonephritis; Sepsis; Staphylococcal Infections; Streptomycin; Sulfonamides; Tetracycline

Topics: Abnormalities, Drug-Induced; Blood Transfusion; Dental Enamel; Female; Humans; Infant; Infant, Newborn; Leukemia; Leukemia, Myeloid; Mercaptopurine; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Tetracycline; Tooth Discoloration; Tooth, Deciduous; Toxicology

Topics: Anti-Bacterial Agents; Canada; Chloramphenicol; Cortisone; Erythromycin; Geriatrics; Humans; Leukemia; Leukemia, Lymphoid; Lung Diseases; Lung Diseases, Fungal; Mucormycosis; Pathology; Prednisone; Tetracycline; Zygomycosis

Topics: Adrenocorticotropic Hormone; Anemia; Anemia, Myelophthisic; Anti-Bacterial Agents; Ascorbic Acid; Benzene; Biopsy; Blood Transfusion; Cortisone; Female; Hematologic Diseases; Hematology; Leukemia; Liver Extracts; Mortality; Occupational Diseases; Pathology; Poisoning; Prednisolone; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Tetracycline; Toxicology; Vasopressins; Vitamin B 12

Topics: Anti-Bacterial Agents; Brain; Brain Diseases; Humans; Leukemia; Medical Records; Mycoses; Protein Synthesis Inhibitors; Tetracycline

Topics: Anti-Bacterial Agents; Humans; Leukemia; Leukemoid Reaction; Protein Synthesis Inhibitors; Tetracycline