vitamin-k-semiquinone-radical and Skin-Neoplasms

Topics: Amino Acids; Animals; Ascorbic Acid; Cell Division; Cricetinae; Dietary Fats; Dietary Proteins; Humans; Melanoma; Mice; Nucleosides; Nutritional Physiological Phenomena; Pyridoxine; Skin Neoplasms; Trace Elements; Vitamin A; Vitamin D; Vitamin K

Topics: Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Carcinoma, Basal Cell; Facial Neoplasms; Female; Humans; Mohs Surgery; Postoperative Hemorrhage; Skin Neoplasms; Vitamin K; Warfarin

Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent protein (VKDP) with a high density of Gla residues and associated with ectopic calcifications in humans. Although VKDPs function has been related with γ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, the γ-carboxylation status, and its association with ectopic calcifications, in skin basal cell and breast carcinomas. GRP-F1 was identified as the predominant splice variant expressed in healthy and cancer tissues. Patterns of γ-carboxylated GRP (cGRP)/undercarboxylated GRP (ucGRP) accumulation in healthy and cancer tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both GRP protein forms were found colocalized in healthy tissues, while ucGRP was the predominant form associated with tumor cells. Both cGRP and ucGRP found at sites of microcalcifications were shown to have in vitro calcium mineral-binding capacity. The decreased levels of cGRP and predominance of ucGRP in tumor cells suggest that GRP may represent a new target for the anticancer potential of vitamin K. Also, the direct interaction of cGRP and ucGRP with BCP crystals provides a possible mechanism explaining GRP association with pathological mineralization.

Topics: alpha-Galactosidase; Breast Neoplasms; Calcinosis; Carcinoma, Basal Cell; Female; Humans; Naphthoquinones; Osteocalcin; Skin Neoplasms; Vitamin K

The intracellular molecular oxygen concentration in control and menadione-treated K562 (an erythroleukemic cell line that grows in suspension) and A431 (an epidermal carcinoma that grows in monolayer) cells was measured directly by using the new electron paramagnetic resonance (EPR) probe fusinite. Because the oxidizing agent menadione is known to damage mitochondria and the cytoplasmic membrane in other cell systems, before conducting measurements of oxygen concentration in K562 and A431 cells, it was necessary to establish injury in these systems as well. Consequently, morphological and flow cytometric analyses were conducted after menadione treatment. The data presented here show that the two cell lines are heavily damaged by menadione. Once this menadione-induced injury was demonstrated, measurements of oxygen concentration were carried out in both K562 and A431 cells. Treatment with this quinone induces a sharp increase in intracytoplasmic molecular oxygen in both cell lines (from about 1% to about 10 and 15% in K562 and A431 cells, respectively). In addition, to gain a more complete understanding of the effects of menadione on cells, the extracellular molecular oxygen concentration and the oxygen consumption rate were also measured in control and menadione-treated K562 cells. These measurements demonstrate that menadione treatment results in an increase in the extracellular oxygen concentration (from about 5% in controls to 15% in treated cells) as well as a decrease in the oxygen consumption rate (from about 10 ng O/min/10(6) cells in controls to 3 ng O/min/10(6) cells after menadione exposure). The importance of the new EPR probe fusinite in monitoring directly cellular functions in which oxygen is involved and the effects of menadione on cellular oxygen balance are discussed.

Topics: Calibration; Carbon; Electron Spin Resonance Spectroscopy; Flow Cytometry; Leukemia, Erythroblastic, Acute; Molecular Probes; Oxidants; Oxygen; Oxygen Consumption; Skin Neoplasms; Tumor Cells, Cultured; Vitamin K

Gammacarboxyglutamic acid (gla) is a non essential amino acid synthesized in presence of vitamin K, predominantly found in coagulation and bone proteins. In 14 cases of deep vein thrombosis and in 11 cases of disseminated intravascular coagulation, compared to 19 normal subjects and 9 patients hospitalized for leg pain, free plasma gla levels were found significantly elevated (respectively 372 +/- 244 and 559 +/- 361 versus 146 +/- 34 and 120 +/- 40 pmol/mL). In six paired plasma and serum, gla levels were similar. These results suggest an involvement of blood coagulation in gla generation with need of a catabolism of the activated factors. A significant decrease was noticed during vitamin K antagonist therapy and liver disease, both instances in which the synthesis of gla containing coagulation factors is affected. During hepatocellular carcinoma with elevated desgamma carboxyprothrombin, gla was found normal, denying an global impairement of the vitamin K metabolism.

Topics: 1-Carboxyglutamic Acid; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Hepatocellular; Chronic Disease; Disseminated Intravascular Coagulation; Female; Hemangioma; Humans; Leg; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Pain; Pulmonary Embolism; Skin Neoplasms; Thrombophlebitis; Vitamin K

Topics: Antineoplastic Agents; Colonic Neoplasms; Energy Transfer; Humans; Melanoma; Naphthols; Neoplasms; Pancreatic Neoplasms; Skin Neoplasms; Vitamin K

Topics: Carcinoma, Squamous Cell; Humans; Oxidoreductases; Skin Neoplasms; Succinate Dehydrogenase; Vitamin K

Topics: Adenocarcinoma; Autoradiography; Colonic Neoplasms; Dysgerminoma; Female; Gallbladder Neoplasms; Hodgkin Disease; Humans; Injections, Intra-Arterial; Injections, Intravenous; Melanoma; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms; Radiotherapy Dosage; Skin Neoplasms; Tritium; Vitamin K

Topics: Carcinoma, Basal Cell; Cheek; Facial Neoplasms; Geriatrics; Humans; Neoplasms; Pathology; Skin Neoplasms; Vitamin K

Topics: Animals; Brain; Histocytochemistry; Isocitrate Dehydrogenase; Kidney; L-Lactate Dehydrogenase; Liver; Lymph Nodes; Methylphenazonium Methosulfate; Mice; Myocardium; Oxidoreductases; Phenazines; Rats; Research; Salivary Glands; Skin; Skin Neoplasms; Succinate Dehydrogenase; Tetrazolium Salts; Vitamin K; Vitamin K 3

Topics: Antineoplastic Agents; Colchicine; Methotrexate; Podophyllum; Retinoids; Skin Neoplasms; Vitamin K

Topics: Angiokeratoma; Antifibrinolytic Agents; Fabry Disease; Heparin Antagonists; Humans; Naphthoquinones; Retinoids; Skin Neoplasms; Vitamin K; Vitamin K 3

Topics: Animals; Growth and Development; Mice; Neoplasms, Experimental; Skin Neoplasms; Vitamin K