Treatment Outcomes and Definition Inconsistencies in High-Risk Unilateral Retinoblastoma.

Purpose: To compare the clinical outcomes of children with unilateral retinoblastoma (Rb) and high-risk histopathology features (HRHF) following upfront enucleation with/without adjuvant chemotherapy, and investigate cases locally considered non-HRHF but converted to a standardized HRHF definition.

Design: Retrospective multinational clinical cohort study.

Methods: Children with Rb who presented to 21 centers from 12 countries between 2011-2020, and underwent primary enucleation were recruited.

Semiautomated MRI-Based Method for Orbital Volume and Contour Analysis.

Purpose: The architecture of the orbital cavity is intricate, and precise measurement of its growth is essential for managing ocular and orbital pathologies. Most methods for those measurements are by CT imaging, although MRI for soft tissue assessment is indicated in many cases, specifically pediatric patients. This study introduces a novel semiautomated MRI-based approach for depicting orbital shape and dimensions.

Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model.

Ocular melanoma research, the most common primary intraocular malignancy in adults, is hindered by limited models. In a series of experiments using melanoma cells injected intraocularly into mouse eyes, we developed a model for ocular melanoma. Inoculation of 5 × 10 B16F10 cells led to rapid tumor growth, extensive lung metastasis, and limited animal survival, while injection of 10 cells was sufficient for intraocular tumors to grow with extended survival.

Low thyroid hormone levels improve survival in murine model for ocular melanoma.

Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin.

Elutriated stem cells derived from the adult bone marrow differentiate into insulin-producing cells in vivo and reverse chemical diabetes.

An ongoing debate surrounds the existence of stem cells in the adult endowed with capacity to differentiate into multiple lineages. We examined the possibility that adult bone marrow cells participate in recovery from chemical diabetes through neogenesis of insulin-producing cells. Small-sized cells negative for lineage markers derived by counterflow centrifugal elutriation from the bone marrow were transplanted into mice made diabetic with streptozotocin and sublethal irradiation.

Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line.

Etoposide (VP-16) is a topoisomerase-II (topo II) inhibitor chemotherapeutic agent. Studies have shown that a combination of VP-16 with other drugs demonstrates better clinical responses. The aim of this study was to investigate the effects of moxifloxacin (MXF) and VP-16 on cellular topo II activity in drug-treated cells and evaluate the influence of MXF on the mode of action of VP-16, on proliferation and apoptosis of HT-29 cells.

Moxifloxacin increases anti-tumor and anti-angiogenic activity of irinotecan in human xenograft tumors.

Camptothecins (CPTs) are topoisomerase I inhibitors chemotherapeutic agents used in combination chemotherapy. We showed previously that combination of moxifloxacin (MXF) and CPT induced inhibitory effects on topoisomerase I activity, on proliferation of HT-29 cells in vitro and enhanced apoptosis, compared to CPT alone. Analysis of secretion of the pro-angiogenic factors IL-8 and VEGF showed significant reduction by MXF.

Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD.

Continuous efforts are dedicated to develop immunotherapeutic approaches to neuroblastoma (NB), a tumor that relapses at high rates following high-dose conventional cytotoxic therapy and autologous bone marrow cell (BMC) reconstitution. This study presents a series of transplant experiments aiming to evaluate the efficacy of allogeneic BMC transplantation. Neuro-2a cells were found to express low levels of class I major histocompatibility complex (MHC) antigens.

A method for isolating pluripotent/multipotent stem cells from blood by using the pluripotent and germ-line DAZL gene as a marker.

We have shown for the first time that pluripotent/multipotent stem cells can be isolated from blood in a relatively simple cell separation, which is fast and compatible with current standards. We used the germ line- and pluripotent-specific DAZL gene as a marker to demonstrate its use for identifying and isolating pluripotent/multipotent cells from blood. DAZL-expressing (DE) cells were identified in about 0.

Oxidative stress causes telomere damage in Fanconi anaemia cells - a possible predisposition for malignant transformation.

Fanconi anaemia (FA) is an autosomal recessive and X-linked disease characterized by severe genetic instability and increased incidence of cancer. One explanation for this instability may be the cellular hypersensitivity to oxidative stress leading to chromosomal breaks. This study explored the possible oxidative damage to telomeres of FA lymphocyte cell line, HSC536/N, and its possible effect on telomere function.

Quinolones as enhancers of camptothecin-induced cytotoxic and anti-topoisomerase I effects.

Camptothecins (CPTs) are topoisomerase I (topo I) inhibitor chemotherapeutic agents. Studies indicate that combination therapy is needed in most therapeutic protocols with camptothecins. Certain fluoroquionolones inhibit topoisomerase II activity in eukaryotic cells.

Interferon-gamma and bacterial lipopolysaccharide act synergistically on human neutrophils enhancing interleukin-8, interleukin-1beta, tumor necrosis factor-alpha, and interleukin-12 p70 secretion and phagocytosis via upregulation of toll-like receptor 4.

In human neutrophils, interferon (IFN)-gamma enhanced the expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Lipopolysaccharide alone did not affect TLR4 expression, but costimulation with IFN-gamma and LPS induced higher levels of TLR4 expression than stimulation with IFN-gamma alone. Using the protein synthesis inhibitor cycloheximide and measuring the expression of CD35 in neutrophils stimulated with IFN-gamma and LPS alone or in combination, we could demonstrate that IFN-gamma enhances TLR4 by de novo protein synthesis, whereas the addition of LPS acts synergistically by enhancing vesicular mobilization to the cell surface.

Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice.

Background: Crohn's exacerbation and pouchitis are commonly treated with ciprofloxacin and metronidazole. Few studies have shown an advantage of this regimen compared with other antibiotics. Most attributed the effect to its better antibacterial coverage.

Moxifloxacin but not ciprofloxacin or azithromycin selectively inhibits IL-8, IL-6, ERK1/2, JNK, and NF-kappaB activation in a cystic fibrosis epithelial cell line.

Cystic fibrosis (CF) is associated with severe neutrophilic airway inflammation. We showed that moxifloxacin (MXF) inhibits IL-8 and MAPK activation in monocytic and respiratory epithelial cells. Azithromycin (AZM) and ciprofloxacin (CIP) are used clinically in CF.

Anti-inflammatory effects of moxifloxacin on IL-8, IL-1beta and TNF-alpha secretion and NFkappaB and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus.

Objectives: We have previously shown that moxifloxacin conferred protective anti-inflammatory effects against Candida pneumonia in immunosuppressed mice. Further in vitro studies showed anti-inflammatory effects of moxifloxacin in LPS and cytokine-stimulated monocytic and epithelial cells. In the present study, concentrating on a more challenging pathogen of immunosuppressed hosts, we studied the effect of moxifloxacin on cytokine secretion and signal transduction mechanisms in monocytic cells stimulated with Aspergillus fumigatus.

Moxifloxacin inhibits cytokine-induced MAP kinase and NF-kappaB activation as well as nitric oxide synthesis in a human respiratory epithelial cell line.

Background: We previously demonstrated that the quinolone moxifloxacin prevents Candida albicans pneumonitis and epithelial nuclear factor kappaB (NF-kappaB) nuclear translocation in immunosuppressed mice.

Objectives: To explore the anti-inflammatory effects of moxifloxacin directly on a lung epithelial cell line.

Methods: We studied the effect of clinically relevant concentrations of moxifloxacin (2.

Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-kappaB and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines.

We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected with Candida albicans by inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-alpha) production in the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-kappaB translocation in lung epithelium and macrophages in MXF-treated mice. In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.

The p38 pathway partially mediates caspase-3 activation induced by reactive oxygen species in Fanconi anemia C cells.

Because Fanconi anemia (FA) cells display hypersensitivity to oxidative stress and reactive oxygen species (ROS) that act as second messengers in cellular signaling, we investigated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation in two FA-C lymphocyte cell lines (HSC536/N and PD149L) and one FA-A cell line (HSC99) exposed to interferon (IFN)-gamma or H2O2. IFN-gamma induced accumulation of ROS and activation of JNK and p38 in HSC536/N and PD149L but not in HSC99 cells. Higher concentrations of H2O2 were needed to induce moderate intracellular levels of ROS and phosphorylation of MAPKs in FA-A than in FA-C cells.

An oxidative mechanism of interferon induced priming of the Fas pathway in Fanconi anemia cells.

Hematopoietic progenitor cells from children with Fanconi anemia of the C complementation group (FA-C) are excessively apoptotic and hypersensitive to various extracellular cues including Fas-ligand, tumor necrosis factor-alpha and double-stranded RNA. Interferon (IFN)-gamma is known to augment apoptotic responses of these factors. The "priming" effect of IFN-gamma is not fully explained.

Immunomodulatory and protective effects of moxifloxacin against Candida albicans-induced bronchopneumonia in mice injected with cyclophosphamide.

In a previous study, moxifloxacin was shown to ameliorate immunosuppression and enhance cytokine production in several tissues, including the lungs of cyclophosphamide-injected mice. We examined here the effects of moxifloxacin on Candida albicans lung infection in cyclophosphamide-injected mice. Mice were injected on day 0 with 250 mg of cyclophosphamide/kg, and on days 1 to 4 they were given moxifloxacin at 22.

Protection by ascorbic acid from denaturation and release of cytochrome c, alteration of mitochondrial membrane potential and activation of multiple caspases induced by H(2)O(2), in human leukemia cells.

We investigated peroxide and superoxide accumulation, cytochrome c nature and release from mitochondria, as well as caspase activation during exposure of HL-60 cells to H(2)O(2) and the protective effect of ascorbic acid. Exposure of the cells to 100 microM H(2)O(2) resulted in intracellular accumulation of peroxides, denaturation of cytochrome c that was identified in the mitochondria and cytosol, release of native cytochrome c to the cytosol and fall in mitochondrial membrane potential (DeltaPsi(m)). Loading of cells with ascorbic acid before exposure to H(2)O(2) resulted in a dose-dependent protective effect against: intracellular accumulation of peroxides, DeltaPsi(m) alteration, cytochrome c denaturation and release.