'A major concern in cancer therapy is resistance of tumors such as glioblastoma to current treatment protocols. Here, we report that transfer of the gene encoding second mitochondria-derived activator of caspase (Smac) or Smac peptides sensitized various tumor cells in vitro and malignant glioma cells in vivo for apoptosis induced ... More
Simulated microgravity culture system for a 3-D carcinoma tissue model.
AuthorsNakamura K, Kuga H, Morisaki T, Baba E, Sato N, Mizumoto K, Sueishi K, Tanaka M, Katano M,
JournalBiotechniques
PubMed ID12449385
'An in vitro organotypic culture model is needed to understand the complexities of carcinoma tissue consisting of carcinoma cells, stromal cells, and extracellular matrices. We developed a new in vitro model of carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCS-4D) that provides a simulated microgravity ... More
The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation.
Authors Yang Jiang-Yan; Widmann Christian;
JournalJ Biol Chem
PubMed ID11847220
'RasGAP, a regulator of Ras GTPase family members, is cleaved at low levels of caspase activity into an N-terminal fragment (fragment N) that generates potent anti-apoptotic signals. At higher levels of caspase activity, fragment N is further cleaved into two fragments that strongly potentiate apoptosis. RasGAP could thus function as ... More
The p53-activated gene, PAG608, requires a zinc finger domain for nuclear localization and oxidative stress-induced apoptosis.
'The p53-activated gene PAG608, which encodes a nuclear zinc finger protein, is a p53-inducible gene that contributes to p53-mediated apoptosis. However, the mechanisms by which PAG608 is involved in the apoptosis of neuronal cells are still obscure. In this study, we demonstrated that expression of p53 was induced by 100 ... More
Size, concentration and incubation time dependence of gold nanoparticle uptake into pancreas cancer cells and its future application to X-Ray Drug Delivery System.
AuthorsTrono JD, Mizuno K, Yusa N, Matsukawa T, Yokoyama K, Uesaka M
JournalJ Radiat Res
PubMed ID21187668
'One of the restrictions in the potential use of gold markers for medical imaging/tracking of harder tumors is its size. We propose to use gold nanoparticles which, due to its small size, can be administered conveniently via intravenous injection. One of the factors that determine the clinical utility of nanoparticles ... More
Delay between fusion pore opening and peptide release from large dense-core vesicles in neuroendocrine cells.
Peptidergic neurotransmission is slow compared to that mediated by classical neurotransmitters. We have studied exocytotic membrane fusion and cargo release by simultaneous capacitance measurements and confocal imaging of single secretory vesicles in neuroendocrine cells. Depletion of the readily releasable pool (RRP) correlated with exocytosis of 10%-20% of the docked vesicles. ... More
Apoptosis induces efflux of the mitochondrial matrix enzyme deoxyguanosine kinase.
AuthorsJüllig M, Eriksson S,
JournalJ Biol Chem
PubMed ID11294860
Deoxyguanosine kinase (dGK) initiates the salvage of purine deoxynucleosides in mitochondria and is a key enzyme in mitochondrial DNA precursor synthesis. The active form of the enzyme is a 60-kDa protein normally located in the mitochondrial matrix. Here we describe the subcellular distribution of dGK during apoptosis in human epithelial ... More
Functional analysis of cathepsin B-like cysteine proteases from Leishmania donovani complex. Evidence for the activation of latent transforming growth factor beta.
Cathepsin B-like genes from Leishmania donovani and Leishmania chagasi have been isolated and characterized. It is a single gene, which is constitutively expressed in all the life cycle stages of the parasite. Studies using cathepsin B-specific inhibitor treatment suggested that cathepsin B does not seem to play a role in ... More
Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1-phosphate hydrolysis on mesangial cells cultured at low cell density.
The lipid mediator sphingosine 1-phosphate (S1P) may alter the proliferation of mesangial cells during pathophysiological processes. Here, S1P stimulated proliferation of rat mesangial cells and phosphorylation of MAPKs at subconfluent cell density. Both effects were inhibited by pertussis toxin treatment. Mesangial cells expressed several S1P receptors of the endothelial differentiation ... More
Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device.
Authors Yang Mengsu; Li Cheuk-Wing; Yang Jun;
JournalAnal Chem
PubMed ID12199565
We have developed a microfluidic device for on-chip monitoring of cellular reactions. The device consists of two primary analytical functions: control of cell transport and immobilization, and dilution of an analyte solution to generate a concentration gradient. In this device, a dam structure in parallel to the fluid flow was ... More
Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.
Authors Deng Hong Bing; Parekh Hemant K; Chow K-C; Simpkins Henry;
JournalJ Biol Chem
PubMed ID11842089
We employed cDNA microarrays to identify the differentially expressed genes in a cisplatin-sensitive parental (2008) human ovarian carcinoma cell line and its cisplatin-resistant variant (2008/C13*). Differential expression of five genes was found in the 2008/C13* cells, a result confirmed by semi-quantitative reverse transcription-PCR. The five genes were identified as fibroblast ... More
Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia.
Authors Lee Hyangkyu; Park David S; Razani Babak; Russell Robert G; Pestell Richard G; Lisanti Michael P;
JournalAm J Pathol
PubMed ID12368209
Caveolin-1 (Cav-1) is the principal structural protein of caveolae membranes that are found in most cells types, including mammary epithelial cells. Recently, we mapped the human CAV1 gene to a suspected tumor suppressor locus (7q31.1/D7S522) that is deleted in a variety of human cancers, as well as mammary tumors. In ... More
EMR4, a Novel Epidermal Growth Factor (EGF)-TM7 Molecule Up-regulated in Activated Mouse Macrophages, Binds to a Putative Cellular Ligand on B Lymphoma Cell Line A20.
Authors Stacey Martin; Chang Gin-Wen; Sanos Stephanie L; Chittenden Laura R; Stubbs Lisa; Gordon Siamon; Lin Hsi-Hsien;
JournalJ Biol Chem
PubMed ID12023293
A novel member of the EGF-TM7 family, mEMR4, was identified and characterized. The full-length mouse EMR4 cDNA encodes a predicted 689-amino acid protein containing two epidermal growth factor (EGF)-like modules, a mucin-like spacer domain, and a seven-transmembrane domain with a cytoplasmic tail. Genetic mapping established that mEMR4 is localized in ... More
Malignant effusions and immunogenic tumour-derived exosomes.
BACKGROUND: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with ... More
Dipterinyl calcium pentahydrate inhibits intracellular mycobacterial growth in human monocytes via the C-C chemokine MIP-1ß and nitric oxide.
Tuberculosis remains one of the top three leading causes of morbidity and mortality worldwide, complicated by the emergence of drug-resistant Mycobacterium tuberculosis strains and high rates of HIV coinfection. It is important to develop new antimycobacterial drugs and immunomodulatory therapeutics and compounds that enhance antituberculous immunity. Dipterinyl calcium pentahydrate (DCP), ... More
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
Authors Black Gillian F; Weir Rosemary E; Floyd Sian; Bliss Lyn; Warndorff David K; Crampin Amelia C; Ngwira Bagrey; Sichali Lifted; Nazareth Bernadette; Blackwell Jenefer M; Branson Keith; Chaguluka Steven D; Donovan Linda; Jarman Elizabeth; King Elizabeth; Fine Paul E M; Dockrell Hazel M;
JournalLancet
PubMed ID11978337
BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents ... More