Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia.

Monoclonal antibodies against GD(2) ganglioside, such as ch14.18, the human-mouse chimeric antibody, have been shown to be effective for the treatment of neuroblastoma. However, treatment is associated with generalized, relatively opiate-resistant pain.

11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

Objective: Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report.

Background: Despite the increasing cure rates for children with acute lymphoblastic leukemia (ALL), patients who relapse continue to have poor prognosis. The Children's Oncology Group (COG) conducted a limited institution Phase II trial of Campath-1H, a monoclonal antibody that targets CD52 on leukemic cells, in children with relapsed or refractory ALL.

Methods: From October 2005 to December 2006, 13 eligible patients were enrolled on the COG phase II study of Campath-1H (ADVL0222).

Inactivation of SHIP1 in T-cell acute lymphoblastic leukemia due to mutation and extensive alternative splicing.

To understand the mechanism behind aberrant Akt activation in T-ALL, PIK3CA, PTEN and SHIP1 expression and genotype were assessed. No cell lines or primary ALLs harbored PIK3CA mutations. PTEN was expressed in just one-third of the cell lines, but in two-thirds of the primary ALLs, though in the inactivated (phosphorylated) form.

Connective tissue growth factor induces extracellular matrix deposition in human trabecular meshwork cells.

The major structural change in the human trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG) is an increase in extracellular matrix (ECM) in the juxtacanalicular region of the TM. There is evidence that treatment with TGF-beta2 causes an induction of ECM deposition in cultured human TM cells and that TGF-beta2 is causatively involved in the JCT ECM increase in POAG. In the present study, we investigated the effects of connective tissue growth factor (CTGF) on the biology of cultured human TM cells.

A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells.

Although the human genome project has been completed for some time, the issue of the number of transcribed genes with identifiable biological functions remains unresolved. We used zebrafish as a model organism to study the functions of Ka/Ks-predicted novel human exons, which were identified from a comparative evolutionary genomics analysis.In this study, a novel gene, designated as puf-A, was cloned and functionally characterized, and its homologs in zebrafish, mouse, and human were identified as one of the three homolog clusters which were consisted of 14 related proteins with Puf repeats.

Subtoxic oxidative stress induces senescence in retinal pigment epithelial cells via TGF-beta release.

Purpose: The goal of the present study was to determine whether oxidative stress and transforming growth factor (TGF)-beta induce cellular senescence in human retinal pigment epithelial (RPE) cells.

Methods: Cultured human RPE cells were exposed to 50 to 150 microM hydrogen peroxide (H(2)O(2)) for 1 and 2 hours or treated with 1.0 ng/mL TGF-beta1 or -beta2 for 12, 24, and 48 hours.

Hypoxia/reoxygenation induces CTGF and PAI-1 in cultured human retinal pigment epithelium cells.

Early age-related macular degeneration (AMD) is characterized by thickening of Bruch's membrane due to the accumulation of extracellular matrix (ECM). This finding could be related to hypoxia of the retinal pigment epithelium (RPE). In the present study, we investigated the effects of hypoxia and reoxygenation on the expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), collagen type IV (Col IV) and fibronectin (Fn) in cultured human RPE cells.

BO-0742, a derivative of AHMA and N-mustard, has selective toxicity to drug sensitive and drug resistant leukemia cells and solid tumors.

This is a preclinical study of BO-0742, a derivative of 3-(9-acridinylamino)-5-hydroxymethyl-aniline (AHMA) and N-mustard, as an anti-cancer agent. MTS assays revealed a broad spectrum of anti-cancer activities in vitro, with the greatest cytotoxicity against leukemia and neuroblastoma including those with drug resistant characteristics, and a good therapeutic index with leukemia being 10-40 times more sensitive to BO-0742 than hematopoietic progenitors. Administration of BO-0742 at an optimal dose schedule based on its pharmacokinetics significantly suppressed the growth of xenografts of human breast and ovarian cancers in mice.

Biological effects of native and oxidized low-density lipoproteins in cultured human retinal pigment epithelial cells.

Age-related macular degeneration (AMD) and artherosclerosis share common characteristics in their pathogenesis. In this study, we investigated the effects of lipoproteins like native (n)-LDL, oxidized (ox)-LDL and high-density lipoprotein (HDL) on advanced senescence, extracellular matrix accumulation, cell loss, and transforming growth factor-beta2 (TGF-beta2) expression in cultured human retinal pigment epithelial (RPE) cells. Primary human RPE cells were incubated with 10-100 microg/ml n-LDL, ox-LDL, and HDL for 24h.

Phase I study of ch14.18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children's Oncology Group.

Purpose: Recurrence of high-risk neuroblastoma is common despite multimodality therapy. ch14.18, a chimeric human/murine anti-G(D2) antibody, lyses neuroblastoma cells.

Nonparametric estimation of LOH using Affymetrix SNP genotyping arrays for unpaired samples.

Studies of loss of heterozygosity (LOH) play an important role in cancer research. In this paper, we developed a two-step procedure to examine LOH by comparing unpaired tumour and normal samples. In the first step we determined which chromosomes significantly differ between the two sets of samples by using nonparametric procedures.

Effects of oxidative stress in trabecular meshwork cells are reduced by prostaglandin analogues.

Purpose: The trabecular meshwork (TM) of glaucomatous eyes is characterized by cell loss, increased accumulation of extracellular matrix (ECM), and cellular senescence. One factor increasingly discussed in the pathogenesis of primary open-angle glaucoma (POAG) is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these typical glaucomatous changes in vitro and whether these oxidative stress-induced TM changes can be reduced by the application of prostaglandin analogues.

Reactivation of optic nerve head astrocytes by TGF-beta2 and H2O2 is accompanied by increased Hsp32 and Hsp47 expression.

Purpose: Histologic studies have previously demonstrated increased expression of small heat shock proteins (Hsps) in reactive optic nerve head (ONH) astrocytes of patients with glaucoma. Transforming growth factor (TGF)-beta2 and hydrogen peroxide (H(2)O(2)) are known to induce ONH astrocyte reactivation. The goal of the present study was to determine whether new potentially involved Hsps, such as Hsp32, -47, -60, and -70, are expressed in the reactivation process of ONH astrocytes mediated by TGF-beta2 and H(2)O(2).

A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses.

H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these viruses to humans has been documented in over 380 cases, with a mortality rate of approximately 60%. There is great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat.

Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer.

Cancer-associated carbohydrate antigens are often found on the surface of cancer cells. Understanding their roles in cancer progression will lead to the development of new therapeutics and high-sensitivity diagnostics for cancers. Globo H is a member of this family, which is highly expressed on breast cancer cells.

Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis.

We examined the expression in breast cancer stem cells (BCSCs) of Globo H, a potential tumor-associated antigen for immunotherapy of epithelial cancers including breast cancer. Flow cytometry revealed Globo H expression in 25/41 breast cancer specimens (61.0%).

c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development.

Human c-Myb proto-oncogene is highly expressed in hematopoietic progenitors as well as leukemia and certain solid tumor. However, the regulatory mechanisms of its expression and biological functions remain largely unclear. Recently, c-Myb has been shown to be targeted by microRNA-150 (miR-150) which thereby controls B cell differentiation in mice.

Oxidative stress and TGF-beta2 increase heat shock protein 27 expression in human optic nerve head astrocytes.

Purpose: Reactive astrocytes of glaucomatous optic nerve heads (ONHs) are characterized by an increased expression of transforming growth factor (TGF)-beta2 and heat shock proteins (Hsps) such as Hsp27. The goal of the present study was to determine the effect of oxidative stress on TGF-beta2 and Hsp27 expression in human ONH astrocytes.

Methods: Cultured ONH astrocytes were exposed to 100, 200, and 400 muM hydrogen peroxide (H(2)O(2)) for 1 hour.

MPDA: microarray pooled DNA analyzer.

Background: Microarray-based pooled DNA experiments that combine the merits of DNA pooling and gene chip technology constitute a pivotal advance in biotechnology. This new technique uses pooled DNA, thereby reducing costs associated with the typing of DNA from numerous individuals. Moreover, use of an oligonucleotide gene chip reduces costs related to processing various DNA segments (e.

The protective effect of quercetin against oxidative stress in the human RPE in vitro.

Purpose: To investigate the possible protective effect of the dietary antioxidant quercetin on retinal pigment epithelial (RPE) cell dysfunction and cellular senescence occurring in age-related macular degeneration (AMD). The major flavonoid quercetin was studied on RPE cells in vitro.

Methods: Cultured human RPE cells were incubated with different concentrations of quercetin for 24 hours.

The effect of TGF-beta2 on elastin, type VI collagen, and components of the proteolytic degradation system in human optic nerve astrocytes.

Purpose: To investigate the effect of transforming growth factor (TGF)-beta2 on the expression of (1) elastin and type VI collagen (ColVI), (2) extracellular matrix (ECM)-degrading matrix-metalloproteinases (MMPs) and regulators of their activity/activation, and (3) the involvement of connective tissue growth factor (CTGF) in the TGF-beta2-mediated regulations in cultured human type-1A and -1B optic nerve astrocytes.

Methods: Astrocytes were isolated from the optic nerves of 11 donors aged 19 to 62 years without a history of eye disease from the prelaminar (type 1B, five explants) or postlaminar (type 1A, six explants) region. Cultures of passages 3 to 5 were treated with 1 ng/mL recombinant human TGF-beta2 for 72 hours, and regulatory effects on the expression of elastin and the ColVI chains alpha1, alpha2, and alpha3; MMP-1, -2, -3, -7, -9, -12, and -13; tissue inhibitors of MMPs (TIMPs) -1, -2, and -3; plasminogen activator inhibitor 1 (PAI-1); and urokinase and tissue plasminogen activators (uPA, tPA) were initially analyzed by RT-PCR and confirmed and quantified by real-time PCR (rtPCR).

Charge monitoring cell mass spectrometry.

An instrument to directly measure the charge carried by a cell or a microparticle as well as mass-to-charge ratio of the cell/microparticle was developed for rapid mass distribution measurement. A successful mass spectrum with a record high mass has been demonstrated. In this article, the details of the construction and operation of the charge monitoring cell mass spectrometer are reported.

Human TRIM71 and its nematode homologue are targets of let-7 microRNA and its zebrafish orthologue is essential for development.

Animal microRNAs (miRNAs) are short RNAs that function as posttranscriptional regulators of gene expression by binding to the target mRNAs. Noting that some miRNAs are highly conserved in evolution, we explored the possibility of evolutionary conservation of their targets. We identified human orthologues of experimentally verified let-7 miRNA target genes in Caenorhabditis elegans and used the luciferase reporter system to examine whether these human genes are still the targets of let-7 miRNA.