Apoptotic Effects of a Thioether Analog of Vitamin K in a Human Leukemia Cell Line.

Research suggests that thioether analogs of vitamin K (VK) can act to preserve the phosphorylation of epidermal growth factor receptors by blocking enzymes (phosphatases) responsible for their dephosphorylation. Additionally, these derivatives can induce apoptosis via mitogen-activated protein kinase and caspase-3 activation, inducing reactive oxygen species (ROS) production, and apoptosis. However, vitamin K exhibits only weak inhibition of phosphatase activity, while the ability of VK to cause oxidative DNA damage has raised concerns about carcinogenicity.

Differences in apoptotic signaling and toxicity between dimethylmonothioarsinic acid (DMMTA) and its active metabolite, dimethylarsinous acid (DMA), in HepaRG cells: Possibility of apoptosis cascade based on diversity of active metabolites of DMMTA.

Dimethylmonothioarsinical acid (DMMTA), a metabolite of arsenosugars (AsSug) and arsenolipids (AsLP), which are major organoarsenicals contained in seafoods, has been a focus of our attention due to its toxicity. It has been reported that the toxicity of DMMTA differs according to the host cell type and that dimethylarsinous acid (DMA), which is a higher active metabolite of inorganic and organo arsenic compounds, may be the ultimate substance. To further elucidate the details of the mechanisms of DMMTA, we carried out toxicological characterization by comparing DMMTA and DMA using HepaRG cells, which are terminally differentiated hepatic cells derived from a human hepatic progenitor cell line that retains many characteristics, e.

Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.

Background: Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines.

Materials And Methods: We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines.

[Verification of Learning Effects by Team-based Learning].

 It has been recommended that active learning methods, such as team-based learning (TBL) and problem-based learning (PBL), be introduced into university classes by the Central Council for Education. As such, for the past 3 years, we have implemented TBL in a medical therapeutics course for 4-year students. Based upon our experience, TBL is characterized as follows: TBL needs fewer teachers than PBL to conduct a TBL module.

Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma.

Indirubin inhibits cyclin-dependent kinases by binding to their ATP-binding site, thereby exerting potent cytotoxicity on some tumor cells. We examined the anti-tumor effect of indirubin 3'-epoxide on human neuroblastoma cell lines (IMR-32, SK-N-SH, and NB-39). The results revealed potent cytotoxicity of indirubin 3'-epoxide against the IMR-32 (IC50: 0.

Effect of cell differentiation for neuroblastoma by vitamin k analogs.

Background: Lack of receptor tyrosine kinase (TrkA), a high-affinity nerve growth factor (NGF) receptor, is closely associated with the malignant progression of neuroblastoma (NB) and its prognosis. Vitamin K3 (VK3) analogs inhibit the activity of protein tyrosine phosphatases (PTPases), which causes hydrolysis of the phosphate groups bound to the tyrosine residues on tyrosine kinase, resulting in sustained tyrosine phosphorylation.

Methods: In order to reverse this abnormal NGF/TrkA signal transduction in NB cells, we synthesized new VK3 analogs and examined their activity against NB cells.

Useful markers for detecting minimal residual disease in cases of neuroblastoma.

Neuroblastoma (NB), which is a malignant tumor of young children derived from neural crest cells that occurs in children, exhibits a wide range of clinical behaviors, from spontaneous regression to rapid progression. Advanced NB patients have a poor prognosis, and recently, autologous bone marrow transplantation (BMT) and autologous peripheral blood stem cell transplantation (PBSCT) have been attempted to improve the prognosis of these patients. In this study, we attempted to detect the expression of tyrosine hydroxylase (TH), neuroendocrine protein gene product (PGP) 9.

Treatment of Ewing's sarcoma using an antisense oligodeoxynucleotide to regulate the cell cycle.

Ewing's sarcoma (ES) is one of the most malignant tumors of bone and soft tissue in children and young adults. ES belongs to a group of small round cell tumors (SRCTs) that also includes neuroblastoma, rhabdomyosarcoma, and malignant lymphoma. However, ES exhibits several specific chimeric genes (EWS-FLI1, EWS-ERG, EWS-ETV1, EWS-E1AF, and EWS-FEV) caused by chromosomal translocations that are not shared by other SRCTs.

Analyses of novel prognostic factors in neuroblastoma patients.

Neuroblastoma (NB) is the most common malignant solid tumor in childhood. There are well-recognized prognostic factors in NB such as age at diagnosis, organ of origin, stages, MYCN gene amplification, and expression of H-ras, trkA and survivin. Moreover, we investigated the expression of vascular endothelial growth factor (VEGF), tyrosine hydroxylase (TH), p53, stem cell factor (SCF) and c-kit of its receptor with quantitative real-time polymerase chain reaction (PCR) in 22 NBs and 4 other tumors (one malignant lymphoma, one malignant teratoma, and 2 rhabdomyosarcomas) samples.

Different patterns in the induction of metallothionein mRNA synthesis among isoforms after acute ethanol administration.

The induction of metallothionein (MT) isoform synthesis was investigated in mouse cerebral cortex 18 h after oral ethanol administration. The expression of MT-I isoform mRNA increased in a dose-dependent manner after ethanol loading at doses between 2 g/kg (ethanol/body weight) and 8 g/kg. Lipid peroxide formation, measured as the amount of malondialdehyde- reactive substances, remained at the control level after all of the administered ethanol doses.

A novel cyclophane compound, CPPy, facilitates NGF-induced TrkA signal transduction and induces cell differentiation in neuroblastoma.

Neuroblastoma (NB) often causes spontaneously regression, and can mature to ganglioneuroma. The form with the most favorable prognosis expresses high levels of TrkA, a high-affinity receptor for nerve growth factor (NGF), whereas advanced NB and associated cell lines have abnormalities in the NGF/TrkA signaling pathway. A novel cyclophane, cyclophane pyridine (CPPy), was designed to conserve the tyrosine phosphorylation of TrkA, thereby enhancing NGF/TrkA signal transduction.

Survivin as a prognostic factor for osteosarcoma patients.

Purpose: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult -tissues. However, survivin expression has been detected in various human cancers and -correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expression in osteosarcoma tissues and clinicopathological parameters.

Upregulation of metallothionein-I mRNA expression in a rodent model for amyotrophic lateral sclerosis.

Metallothionein (MT) mRNA expression was investigated in a rodent model (G93A SOD1 transgenic mouse) for a lethal motor neuron disease, amyotrophic lateral sclerosis (ALS). In 8-wk-old mice that did not yet exhibit motor paralysis, MT-I mRNA expression was already significantly upregulated in the region of the spinal cord responsible for motor paralysis. The expression of another isoform, MT-III, was not changed.

Survivin expression levels as independent predictors of survival for osteosarcoma patients.

Survivin expression has been detected in various cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. However, the aforementioned authors did not evaluate correlations between prognosis and survivin expression levels using surgically resected samples. In this study, we retrospectively investigated outcomes by examining the correlations between expression of this gene and clinicopathological parameters.

Xanthoangelol, a major chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma and leukemia cells.

Xanthoangelol, a major chalcone constituent of the stem exudates of Angelica keiskei, was evaluated for cell toxicity and apoptosis-inducing activity in human neuroblastoma (IMR-32) and leukemia (Jurkat) cells. Xanthoangelol concentration-dependently reduced the survival rates of both cell lines as revealed by the trypan blue exclusion test. Early apoptosis induced by 4 h incubation with xanthoangelol was detected using flow cytometry after double-staining with annexin V and propidium iodide (PI).

Significance of survivin mRNA expression in prognosis of neuroblastoma.

Neuroblastoma (NB) is the most common malignant solid tumor in childhood, and among all childhood malignancies is second in prevalence only to leukemia. In NB we need to both make an accurate diagnosis and rapidly analyze the expression of genetic prognostic factors such as MYCN, H-ras, and trkA. Moreover, it has recently become important to analyze the expression of survivin mRNA, a member of the inhibitor of apoptosis protein family.

Usefulness of tyrosine hydroxylase mRNA for diagnosis and detection of minimal residual disease in neuroblastoma.

Neuroblastoma (NB) is the most common malignant solid tumor in childhood and, among all childhood malignancies, is second only to leukemia. NB originates before birth in the neural crest, which develops into the adrenal medullae and sympathetic ganglia. In the adrenal medulla, tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis.

Diagnostic significance and clinical applications of chimeric genes in Ewing's sarcoma.

Ewing's sarcoma (ES) is one of the most malignant bone and soft tissue tumors in childhood. Morphologically, ES belongs to the small round cell tumors (SRCT). ES, peripheral primitive neuroectodermal tumor (PNET), and Askin's tumor are classified as ES family tumors (ESFT) because they share a common chromosomal translocation.

Detection of chimeric genes in Ewing's sarcoma and its clinical applications.

Ewing's sarcoma (ES), most commonly an undifferentiated tumor of bone, belongs to the enigmatic diagnostic category of small round cell tumors (SRCT) of childhood. The consistent presence of the translocation t (11; 22) in the vast majority of tumors provides evidence for a common histogenesis in ES and its family of tumors (ESFT), and also provides a unique diagnostic characteristic to discriminate this tumor family from SRCT. Molecular analysis of this translocation has revealed that it forms a chimeric gene between EWS on chromosome 22 and FLI-1 on chromosome 11.