vitamin-k-semiquinone-radical and Kidney-Neoplasms

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.

Topics: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; cdc25 Phosphatases; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Enzyme Activation; Flow Cytometry; Humans; In Situ Nick-End Labeling; Kidney Neoplasms; Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Vitamin K

To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer.. Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups.. State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry.. 272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex.. Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis.. An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model.. This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.

Topics: Adolescent; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Female; Germany; Humans; Infant; Infant, Newborn; Injections, Intramuscular; Injections, Subcutaneous; Kidney Neoplasms; Leukemia; Male; Neoplasms; Neuroblastoma; Population Surveillance; Rhabdomyosarcoma; Risk Factors; Vitamin K; Vitamin K Deficiency; Wilms Tumor

We noted that patients treated with high-dose interleukin (IL)-2 (600,000 IU/kg every 8 h by intravenous bolus) at our institution frequently developed prolongation of their prothrombin time (PT). We therefore performed a prospective study of coagulation function during IL-2 treatment. Since IL-2 treated individuals are known to develop cholestatic liver dysfunction, we hypothesized that the hypoprothrombinemia was due to deficiency of liver-synthesized clotting factors and could be prevented by vitamin K replacement. Alternating patients served as controls or received prophylactic subcutaneous subcutaneous vitamin K. While the nine control patients did not exhibit a significant increase (mean +/- SD) in PT (13.6 +/- 0.6 s pretreatment, 15.0 +/- 2.2 on day 4, and 15.0 +/- 2.5 on day 7, p = 0.77 by repeated measures analysis), three patients developed marked increases in PT (greater than 18 s). Changes in partial thromboplastin time (PTT) over this interval were also not statistically significant. Factor VII levels decreased in all patients from 106 +/- 22 to 59 +/- 16 and 52 +/- 26% on days 4 and 7 (p = 0.0002). Factor VII levels in four patients dropped below the lower limit of normal. Prophylactic treatment of seven patients with vitamin K on days 1-8 of the IL-2 therapy protocol resulted in diminished changes in PT and factor VII compared to control patients (p = 0.02 and 0.003 respectively). No vitamin K-treated patient developed PT or Factor VII levels significantly outside the normal range. Prophylactic vitamin K can prevent hypoprothrombinemia in patients treated with IL-2. This may be of importance in patients with decreased hepatic vitamin K stores, who may be at risk for bleeding complications.

Topics: Blood Coagulation; Humans; Hypoprothrombinemias; Interleukin-2; Kidney Neoplasms; Liver; Melanoma; Neoplasm Metastasis; Parenteral Nutrition; Recombinant Proteins; Vitamin K

Previous studies have identified gamma-carboxyglutamic acid as a constituent of one or more protein(s) synthesized by rat and chicken kidney microsomes in vitro in a vitamin K-dependent post-translational reaction [1]. Incubation of microsomes from a mouse kidney cell line (RAG) with [14C]NaHCO3 results in formation of protein-bound [14C]gamma-carboxylglutamic acid. Incorporation is stimulated threefold by addition of the active vitamin K compound 2-methyl, 3-farnesyl, 1,4-naphthoquinone. At least 90% of incorporated, nondialyzable [14C] is situated in the gamma-carboxyl group of gamma-carboxyglutamic acid residues.

Topics: 1-Carboxyglutamic Acid; Adenocarcinoma; Animals; Calcium; Carbon-Carbon Ligases; Glutamates; Kidney; Kidney Neoplasms; Ligases; Mice; Neoplasms, Experimental; Protein Biosynthesis; Vitamin K

Topics: Adrenal Gland Diseases; Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Congenital Abnormalities; Diagnosis, Differential; Female; Hematoma; Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Kidney Neoplasms; Male; Pregnancy; Prognosis; Vitamin K

Topics: Adenocarcinoma; Adult; Aged; Animals; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Cystadenoma; Female; Humans; Iodine Radioisotopes; Kidney Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Peritoneal Neoplasms; Radiation-Sensitizing Agents; Radionuclide Imaging; Rats; Rectal Neoplasms; Sigmoid Neoplasms; Stomach Neoplasms; Vitamin K

Topics: Animals; Glycolysis; Humans; In Vitro Techniques; Kidney Neoplasms; Liver; Mitochondria; ortho-Aminobenzoates; Proteins; Rats; Urinary Bladder Neoplasms; Urine; Vitamin K