The combination of venetoclax and quercetin exerts a cytotoxic effect on acute myeloid leukemia.

Venetoclax is a BH3 mimetic that was recently approved for the treatment of acute myeloid leukemia (AML) treatment. However, the effect of venetoclax on AML remains limited, and a novel strategy is required. Here, we demonstrate for the first time that the cytotoxic effect of venetoclax drastically increased when by combined with the naturally occurring flavonoid quercetin.

Venetoclax efficacy on acute myeloid leukemia is enhanced by the combination with butyrate.

Venetoclax has been approved recently for treatment of Acute myeloid leukemia (AML). Venetoclax is a BH3-mimetic and induces apoptosis via Bcl-2 inhibition. However, venetoclax's effect is still restrictive and a novel strategy is needed.

Caspase inhibition improves viability and efficiency of liposomal transfection.

High transfection efficiency is the most important point for experiments of DNA and RNA introduction into cells. Decrease of cell viability during the transfection procedure is a crucial issue, resulting in transfection failure. However, the mechanism underlying cell growth inhibition has not been fully elucidated.

, a novel RUNX1 target gene, is down-regulated by RUNX1-ETO.

The fusion protein RUNX1-ETO is an oncogenic transcription factor generated by t(8;21) chromosome translocation, which is found in FAB-M2-type acute myeloid leukemia (AML). RUNX1-ETO is known to dysregulate the normal RUNX1 transcriptional network, which should involve essential factors for the onset of AML with t(8;21). In this study, we screened for possible transcriptional targets of RUNX1 by reanalysis of public data , and identified as a novel RUNX1 target gene because its expression was down-regulated in the presence of RUNX1-ETO.

Tumor necrosis factor‑related apoptosis‑inducing ligand is a novel transcriptional target of runt‑related transcription factor 1.

Runt‑related transcription factor 1 (RUNX1), which is also known as acute myeloid leukemia 1 (AML1), has been frequently found with genomic aberrations in human leukemia. RUNX1 encodes a transcription factor that can regulate the expression of hematopoietic genes. In addition, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) performs an important function for malignant tumors in immune surveillance.

Cytopathological Features of a Severe Type of Corneal Intraepithelial Neoplasia.

Purpose: To report the cytopathological features of corneal intraepithelial neoplasia (CIN) through the investigation of cytokeratin expression pattern, keratinization, cell proliferation, apoptosis, and epithelial mesenchymal transition.

Patient And Methods: Corneal tissue excised from a CIN patient was examined in this study. Cryosections of the excised CIN epithelial tissue were examined by immunostaining analysis using antibodies against cytokeratins, keratinization-related proteins, Ki-67, human telomerase reverse transcriptase (hTERT), and epithelial mesenchymal transition (EMT)-related proteins.

Establishment of a human corneal epithelial cell line lacking the functional TACSTD2 gene as an in vitro model for gelatinous drop-like dystrophy.

Purpose: Gelatinous drop-like corneal dystrophy (GDLD) is characterized by subepithelial amyloid deposition that engenders severe vision loss. The exact mechanism of this disease has yet to be elucidated. No fundamental treatment exists.

A novel mutation (p.Glu1389AspfsX16) of the phosphoinositide kinase, FYVE finger containing gene found in a Japanese patient with fleck corneal dystrophy.

Purpose: The phosphoinositide kinase, FYVE finger containing (PIKFYVE) gene has been identified as a gene responsible for fleck corneal dystrophy (FCD). The purpose of this study is to report a novel mutation of the PIKFYVE gene in a Japanese patient with fleck corneal dystrophy.

Methods: Slit-lamp microscopy, corneal topography, and optical coherence tomography were performed for the clinical examination of the patient's eye.

Clinical outcomes of phototherapeutic keratectomy in eyes with Thiel-Behnke corneal dystrophy.

Purpose: To investigate the functional and morphologic midterm outcome of phototherapeutic keratectomy (PTK) for Thiel-Behnke corneal dystrophy diagnosed by gene-mutation analysis.

Design: Retrospective, single-center clinical study.

Methods: Between July 2001 and May 2010, 10 consecutive PTKs were performed in 10 eyes of 5 patients (2 male, 3 female; mean age: 55 ± 13 years) with superficially accentuated opacities caused by Thiel-Behnke corneal dystrophy and were followed up for at least 12 months (range: 12-108 months).

Two novel mutations of TACSTD2 found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization.

Purpose: To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD).

Methods: Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis.

Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: implications in the pathogenesis of gelatinous drop-like corneal dystrophy.

Gelatinous drop-like dystrophy (GDLD) is a rare autosomal recessive form of corneal dystrophy characterized by subepithelial amyloid depositions on the cornea. Previous clinical and laboratory observations have strongly suggested that epithelial barrier function is significantly decreased in GDLD. Despite the decade-old identification of the tumor-associated calcium signal transducer 2 (TACSTD2) gene as a causative gene for GDLD, the mechanism by which the loss of function of this causative gene leads to the pathological consequence of this disease remains unknown.

Lattice corneal dystrophy type IV (p.Leu527Arg) is caused by a founder mutation of the TGFBI gene in a single Japanese ancestor.

Purpose: Lattice corneal dystrophy (LCD) type IV (LCD4) is a late-onset corneal dystrophy with amyloid deposition at the deep stromal layer of cornea. As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, beta-induced (TGFBI) gene.

Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency.

Purpose: To determine the feasibility of cultivated conjunctiva as a viable epithelial sheet for transplantation and corneal resurfacing in eyes with limbal stem cell deficiency (LSCD).

Methods: Human corneal epithelial (HCE) and human conjunctival epithelial (HCjE) cells were cultivated on human amniotic membrane (AM) to confluence and then air lifted to allow further stratification and differentiation. Denuded AM and cultivated HCE and cultivated HCjE cells were then transplanted into 18 eyes of rabbits with induced LSCD.

Genomic aberrations and cellular heterogeneity in SV40-immortalized human corneal epithelial cells.

Purpose: Simian virus (SV)40-immortalized human corneal epithelial (HCE-T) cells have been widely used as an in vitro model of human corneal epithelial cells. The nature of this cell line was assessed for genomic aberrations and cellular heterogeneity.

Methods: For the quantitative measurement of genomic aberrations, array-based comparative genomic hybridization (CGH) analysis was performed.

Cytomegalovirus as an etiologic factor in corneal endotheliitis.

Purpose: To investigate clinical manifestations and response to antiviral therapy of 8 patients with cytomegalovirus (CMV)-induced corneal endotheliitis who were diagnosed and treated at 2 university hospitals in Japan.

Design: Retrospective, consecutive, multicenter case series.

Participants: Eight eyes of 8 patients diagnosed with active CMV corneal endotheliitis at Kyoto Prefectural University of Medicine and Ehime University School of Medicine.

Controlled-release of epidermal growth factor from cationized gelatin hydrogel enhances corneal epithelial wound healing.

We designed a new ophthalmic drug-delivery system for epidermal growth factor (EGF) from the biodegradable hydrogel of cationized gelatin. We placed a cationized gelatin hydrogel (CGH) with incorporated (125)I-labelled EGF in the conjunctival sac of mice and measured the residual radioactivity at different times to evaluate the in vivo profile of EGF release. Approximately 60-67% and 10-12% of EGF applied initially remained 1 and 7 days after application, respectively; whereas EGF delivered in topically applied solution or via EGF impregnation of soft contact lenses disappeared within the first day.

Establishment of a cultivated human conjunctival epithelium as an alternative tissue source for autologous corneal epithelial transplantation.

Purpose: The corneal epithelium is essential for maintaining corneal transparency, and efforts have been made to develop improved techniques for corneal epithelial transplantation in patients with total limbal failure. We evaluated the suitability of transplanted cultivated human conjunctival epithelium (HCjE) as a corneal epithelium replacement in rabbits with total corneal and limbal deficiency.

Methods: HCjE cells, cultivated on human amniotic membrane (AM) to confluence and exposed to an air-liquid interface (air-lifted), were transplanted onto denuded rabbit corneas and monitored for 2 weeks.

Clusters of corneal epithelial cells reside ectopically in human conjunctival epithelium.

Purpose: The ocular surface is covered by two biologically distinct epithelia: corneal and conjunctival. The expression of keratin12 (K12) is currently considered a hallmark of cornea-type differentiation. In the current study, the biological features of K12-positive cells in human bulbar conjunctival epithelium were examined.

Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis.

Purpose: To report cytomegalovirus (CMV) DNA in aqueous humor from a patient with unilateral corneal endotheliitis.

Design: Case report.

Methods: A 51-year-old man presented with unilateral corneal endotheliitis with linear keratic precipitates and coin-shaped lesions.

Gene expression and immunolocalisation of a calcium-activated chloride channel during the stratification of cultivated and developing corneal epithelium.

The spatial and temporal localisation of a calcium-activated chloride channel (CLCA) and its mRNA was investigated, during the in vivo and in vitro development of stratified epithelia, by fluorescence immunohistochemistry and quantitative polymerase chain reaction in embryonic chicken corneas and the expansion of excised human corneal stem cells on amniotic membrane. Single-layered human epithelial cultures on amniotic membrane and early day embryonic chicken corneas expressed relatively little human CLCA2 or its chicken homologue. However, as the epithelium in both models matured and the number of cell-layers increased, the gene expression level and protein staining intensity increased, primarily within the basal cells of both the cultured and embryonic tissues.

Pathological keratinisation in the conjunctival epithelium of Sjögren's syndrome.

Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated.

Expression and tissue distribution of p63 isoforms in human ocular surface epithelia.

The functional significance of p63 in regulating cell proliferation in various stratified epithelial cells has previously been proposed. More than six isoforms have been reported for this protein; however, it is not yet clearly understood how functionally different these isoforms are. To investigate how these isoforms are used in ocular surface epithelia, we studied the spatial distribution of p63 isoforms within human ocular surface epithelia.

The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia.

Human calcium-activated chloride channel 2 (hCLCA2) belongs to a family of multifunctional proteins and is localised mainly in basal cells of squamous epithelia. However, its function is still not fully understood. Relative amounts of hCLCA2 were analysed using real-time PCR in several human epithelial tissues and tissues expressing high amounts were identified.