vitamin-k-semiquinone-radical and Lymphoma

This review summarizes the current knowledge of the epidemiology, prophylaxis, and treatment of venous thromboembolism (VTE) in patients with lymphoma, multiple myeloma or acute leukemia.. Hematologic malignancies are associated with a high risk of thrombotic complications. The incidence of these events is greatly variable and is influenced by many factors, including the type and the stage of disease, antitumor therapies, and the use of central venous device (CVD). Epidemiological data allow an estimate of the incidence of VTE in acute leukemia, lymphomas, and multiple myeloma. The effect of chemotherapy on the incidence of thrombosis is particularly evident in acute leukemia as it causes the exacerbation of the clotting/bleeding syndrome typical of this disease. The role of chemotherapy is also relevant in lymphoma, and in multiple myeloma, in which the use of immunomodulating agents, in combination with chemotherapy and steroids significantly increases the risk of VTE.. Thrombotic complications have a significant impact on morbidity and mortality of hematological cancer patients, therefore, in this setting, the issue of thromboprophylaxis to prevent VTE is important. However, no clear recommendation in these conditions is available, with the exception of multiple myeloma. Large prospective randomized clinical trials are needed to establish the best practice for prevention and treatment of VTE in these types of malignant diseases.

Topics: Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Incidence; Leukemia; Lymphoma; Multiple Myeloma; Platelet Transfusion; Venous Thromboembolism; Vitamin K

Topics: Agammaglobulinemia; Blood Protein Disorders; Bromides; Candidiasis, Cutaneous; Carcinoid Tumor; Dermatitis, Exfoliative; Drug Eruptions; Edema; Foot Dermatoses; Hand Dermatoses; Humans; Hypergammaglobulinemia; Keratosis; Leukemia; Lymphatic Diseases; Lymphoma; Penicillamine; Pruritus; Skin Diseases; Skin Manifestations; Vitamin K; Xanthomatosis

Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex-null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-). We show that Apex heterozygous mutant cells and animals are abnormally sensitive to increased oxidative stress. Additionally, such animals manifest elevated levels of oxidative stress markers in serum, and we show that dietary supplementation with antioxidants restores these to normal levels. Apex+/- embryos and pups manifest reduced survival that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells.

Topics: Adenocarcinoma, Papillary; Animals; Ascorbic Acid; Carbon-Oxygen Lyases; Cell Survival; Cells, Cultured; Dietary Supplements; Dinoprost; DNA-(Apurinic or Apyrimidinic Site) Lyase; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fibroblasts; Genotype; Heterozygote; Lipid Peroxides; Lung Neoplasms; Lymphoma; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Mutant Strains; Oxidative Stress; Paraquat; Phenotype; Vitamin E; Vitamin K

Suppression of the mitochondrial permeability transition pore (PTP) and induction of lymphoma P388 cell death were studied in the presence of cyclosporin A (CsA) and its derivatives. In experiments with permeabilized P388 cells, CsA and its nonimmunosuppressive derivative N-methyl-Val-4-CsA, but not cyclosporin H (CsH), enhanced Ca2+ accumulation in mitochondria and suppressed PTP opening. Moreover, CsA was able either itself to induce or to enhance a prooxidant-induced P388 programmed cell death. Blebbing and formation of apoptotic bodies were among the observed CsA effects. N-Methyl-Val-4-CsA showed similar effects, but CsH had no effect on P388 cell death. These results show that initial-stage P388 tumour cell death is not related to PTP opening but can be the result of PTP closing with a corresponding increase in the formation of reactive oxygen species.

Topics: Animals; Cell Cycle; Cell Death; Cell Membrane Structures; Cyclosporine; Immunosuppressive Agents; Intracellular Membranes; Lymphoma; Mice; Mitochondria; Permeability; Reactive Oxygen Species; Vitamin K

Experiments with cultured cells showed that most cellular stress resistance components are specialized for certain types of damage. For example, superoxide dismutase protects from oxidative damage; DNA repair enzymes guard against mutagens and other DNA-damaging agents. On the other hand, the major inducible heat shock protein Hsp72 protects cells from a large variety of stresses and thus represents a generalized repair/stress resistance component. Hsp72 not only refolds damaged proteins but also interferes with programmed cell death signaling pathways, thus providing cells with time to repair the damage, hence its universality as a stress protector. In the present study we demonstrate the occurrence in murine and human ascites fluids (AF) of a natural nontoxic extracellular factor (ascites Hsp72-inducing factor, AHIF) capable of activating Hsp72 expression in different types of cells via a pathway distinct from the heat shock response pathway. AHIF is unique in that it is the first physiological factor capable of inducing synthesis of Hsp72 not only in young cells but, remarkably, also in aged human cells that largely have lost the ability to express Hsp72 in response to stresses, a manifestation at the cellular level of a progressive impairment in the ability to adapt to environmental changes which characterizes aging. Pretreatment of aged human cells with AF triggers Hsp72 expression at levels seen in young stressed cells and protects cells from a variety of otherwise lethal stressful treatments such as heat shock, TNF, UV irradiation, etoposide, and menadione. Activation of Hsp72 expression is essential for antiapoptotic action of AHIF because specific inhibition of Hsp72 expression by antisense RNA abolishes the cytoprotective effect of AF. In view of an important link between stress resistance and longevity in different organisms, the abilities of AHIF make it a unique candidate for the role of a systemic regulator of the aging process. While a cell-autonomous stress response diminishes with aging, aged cells retain the ability to respond to an extracellular factor which induces the expression of Hsp72. This finding opens up exciting possibilities for using AF factor to restore stress resistance to old cells and organisms and the possibility of interfering with the aging process. The ability to induce stress resistance in young cells and to restore it in aged cells could serve as a basis for developing effective antiapoptotic therapies.

Topics: Adenoviridae; Animals; Antisense Elements (Genetics); Apoptosis; Ascites; Cellular Senescence; Fibroblasts; Genetic Vectors; Heat-Shock Proteins; Heat-Shock Response; Hot Temperature; HSP72 Heat-Shock Proteins; Humans; Hybridomas; JNK Mitogen-Activated Protein Kinases; Lymphoma; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases; Oxidative Stress; Tumor Cells, Cultured; Ultraviolet Rays; Vitamin K

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Denmark; Humans; Incidence; Infant; Infant, Newborn; Leukemia; Lymphoma; Neoplasms; Risk Factors; Vitamin K

The effect of menadiol (vitamin K3) on fresh specimens of human lymphatic neoplasms (HLN) was tested by means of the differential staining cytotoxicity assay. Menadiol was tested alone and in combination with standard antineoplastic agents. Drug effects were then compared with the effects of the same drugs in normal human lymphocytes and in fresh specimens of human non-small cell lung cancer. By itself, menadiol was moderately toxic to HLN, but not to normal lymphocytes or non-small cell lung cancer. Menadiol, menadione, and two structurally related congeners were equitoxic to HLN cells, but sodium metabisulfite (present in menadiol solutions as a preservative) was nontoxic. Menadiol increased the cytotoxic effects of a number of standard agents in HLN but not in normal lymphocytes. Cell survival times with mechlorethamine, vincristine, and dexamethasone were converted from a range characteristic of drug resistance (ie, range observed in relapsed patients) to a range characteristic of drug sensitivity (ie, range observed in untreated patients) in the presence of menadiol. These effects occurred at a concentration (2.0 micrograms/ml; 4.7 microM) of menadiol which is probably clinically achievable and which did not deplete intracellular glutathione. Menadiol should receive clinical testing as a chemosensitizing agent in HLN.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Colony-Forming Units Assay; Dexamethasone; Drug Evaluation, Preclinical; Glutathione; Humans; Leukemia; Lymphoma; Mechlorethamine; Tumor Stem Cell Assay; Vincristine; Vitamin K

Topics: 1-Carboxyglutamic Acid; Animals; Cell Line; Glutamates; Kinetics; Lymphoma; Mammary Neoplasms, Experimental; Mast-Cell Sarcoma; Melanoma; Mice; Mice, Inbred BALB C; Microsomes; Neoplasm Proteins; Neoplasms, Experimental; Vitamin K

Topics: Adenocarcinoma; Adult; Animals; Arsenicals; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Choriocarcinoma; DNA, Neoplasm; Female; Fluorides; Heparin; Humans; Lung Neoplasms; Lymphoma; Male; Malonates; Mandibular Neoplasms; Mice; Middle Aged; Neoplasms; Pregnancy; RNA, Neoplasm; Sarcoma; Testicular Neoplasms; Vitamin K

Topics: Animals; Ascites; Carbohydrate Metabolism; Cell Respiration; Glycolysis; Lymphoma; Metabolism; Mice; Naphthoquinones; Neoplasms, Experimental; Vitamin K

Topics: Animals; Antifibrinolytic Agents; Ascites; Carcinoma; Glycolysis; Lymphoma; Metabolism; Mice; Naphthoquinones; Neoplasms, Experimental; Vitamin K; Vitamin K 1; Vitamins