IRF6 and TAK1 coordinately promote the activation of HIPK2 to stimulate apoptosis during palate fusion.

Cleft palate is a common craniofacial defect caused by a failure in palate fusion. The palatal shelves migrate toward one another and meet at the embryonic midline, creating a seam. Transforming growth factor-β3 (TGF-β3)-induced apoptosis of the medial edge epithelium (MEE), the cells located along the seam, is required for completion of palate fusion.

The Effectiveness of an International Cleft Mission Model in Asia: An Update.

Background: Cleft lip/palate is a congenital craniofacial anomaly affecting patients physically and psychosocially and has contributed to the global burden of surgical disease, especially in underprivileged areas. For 20 years, Noordhoff Craniofacial Foundation (NCF) and the Chang Gung Craniofacial Center (CGCFC) have carried out missions to these areas. Rather than implementing short-term missions that lack proper follow-up care, the team has provided an effective, long-term, and multidisciplinary approach for the treatment of patients with cleft lip/palate.

IRF6 is the mediator of TGFβ3 during regulation of the epithelial mesenchymal transition and palatal fusion.

Mutation in interferon regulatory factor 6 (IRF6) is known to cause syndromic and non-syndromic cleft lip/palate in human. In this study, we investigated the molecular mechanisms related to IRF6 during palatal fusion using palatal shelves organ culture. The results showed that ablation of Irf6 resulted in a delay in TGFβ3-regulated palatal fusion.

Lower lip pits: van der woude or kabuki syndrome?

Kabuki syndrome (KS) is a multiple congenital anomaly/mental retardation syndrome with characteristic facial features. Despite more than 350 documented cases and recent correlation of MLL2 mutations as a genetic cause, its full clinical spectrum is still being defined. This report describes two patients who were initially diagnosed with Van der Woude syndrome (VWS) based on the presence of lower lip pits.

The suppression of thoc1 in cancer cell apoptosis mediated by activated macrophages is nitric oxide-dependent.

Activation of Toll-like receptor 4 (TLR4) triggers both innate and adaptive immunity. We previously identified a synthetic glycolipid, CCL-34, which can induce anticancer immunity in a TLR4-dependent manner. In the present study, we demonstrated the involvement of THO complex 1 (thoc1) in the CCL-34-induced anticancer mechanism.

In vitro and in vivo anticancer activity of a synthetic glycolipid as Toll-like receptor 4 (TLR4) activator.

Activation of Toll-like receptor 4 (TLR4) triggers the innate immune response and leads to the induction of adaptive immunity. TLR4 agonists are known to function as immunostimulants and exhibit promising therapeutic potential for cancer immunotherapy. We have previously developed a synthetic serine-based glycolipid (designated as CCL-34) that can activate TLR4-dependent signaling pathways.

Insulin-like growth factor 1 mediates 5-fluorouracil chemoresistance in esophageal carcinoma cells through increasing survivin stability.

Insulin-like growth factor 1 (IGF-1) inhibits 5-fluorouracil (5-Fu)-induced apoptosis in esophageal carcinoma cells; however, the mechanisms for IGF-1-induced 5-Fu chemoresistance remain unknown. In the human esophageal carcinoma cell line, CE48T/VGH, we show that IGF-1 up-regulated survivin expression at the post-transcriptional level and this up-regulation is mediated by both the PI3-K/Akt and casein kinase 2 signaling pathways. We then examine whether IGF-1-induced 5-Fu chemoresistance is mediated through up-regulation of survivin.

Combination of microarray profiling and protein-protein interaction databases delineates the minimal discriminators as a metastasis network for esophageal squamous cell carcinoma.

Microarray profiling of 15 adjacent normal/tumor-matched esophageal squamous cell carcinoma (ESCC) specimens identified 40 up-regulated and 95 down-regulated genes. Verification of the microarray measurement by quantitative real-time reverse transcription PCR in the same set of samples as well as an additional 15 normal/tumor-matched samples revealed >95% consistency. These signatures can also be used to classify a recently reported ESCC microarray dataset.

Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair.

The DNA damage response (DDR) has an essential function in maintaining genomic stability. Ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication forks, are two major DDRs processing structurally complicated DNA damage. In contrast, damage repaired by base excision repair (BER) is structurally simple, but whether, and how, the DDR is involved in repairing this damage is unclear.

Gene expression profiles of the aurora family kinases.

The evolutionarily conserved Aurora family kinases, a family of mitotic serine/threonine kinases, has three members in humans (Aurora-A, -B and -C). Overexpression of Aurora family members, particularly Aurora-A, has been reported in many human cancers and cell lines. In this study, we present evidence based on comparative gene expression analysis via quantitative RT-PCR to delineate the relative contributions of these kinases in 60 cell lines and statistical analysis in five different human cancer microarray datasets.

Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer.

Chromosomal passenger proteins including Aurora B, Survivin, and Borealin/Dasra B, also called CDCA8/FLJ10468, are known to play crucial roles during mitosis and cell division. Inappropriate chromosomal segregation and cell division may cause auneuploidy leading to cancer. However, it is still unclear how the expression of chromosomal passenger proteins may be linked to cancer.

The position of the inferior alveolar nerve at the mandibular angle:: an anatomic consideration for aesthetic mandibular angle reduction.

Mandibular angle reduction is a popular contouring surgery in Asia. Avoidance of injury to the inferior alveolar nerve is crucial during these procedures. Anatomic data regarding the position of the nerve in the mandibular angle area are sparse.

Craniofacial deformity in patients with uncorrected congenital muscular torticollis: an assessment from three-dimensional computed tomography imaging.

Congenital muscular torticollis is caused by idiopathic fibrosis of the sternocleidomastoid muscle that restricts movement and pulls the head toward the involved side. Deformation of the craniofacial skeleton will develop if the restriction is not released and result in aesthetic and functional problems. The purpose of this study was to use three-dimensional computed tomography imaging for qualitative and quantitative evaluation of the craniofacial deformity in a series of patients with uncorrected congenital muscular torticollis, and to assess age as a precipitating factor for severity of the deformity.

Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways.

The production of interleukin-6 (IL-6) has been discovered in a variety of human tumors. Here we report the expression of IL-6, IL-6 receptor alpha (IL-6Ralpha), and gp130 in human esophageal carcinoma tissues. We further demonstrate that IL-6 protects an esophageal carcinoma cell line CE48T/VGH from apoptosis induced by staurosporine.

Characterization of reduced expression of glycine N-methyltransferase in cancerous hepatic tissues using two newly developed monoclonal antibodies.

Glycine N-methyltransferase (GNMT) is a protein with multiple functions. Recently, two Italian siblings who had hepatomegaly and chronic elevation of serum transaminases were diagnosed to have GNMT deficiency caused by inherited compound heterozygosity of the GNMT gene with missence mutations. To evaluate the expression of GNMT in cell lines and tissues from hepatocellular carcinoma (HCC) patients, we produced two monoclonal antibodies (mAbs) 4-17 and 14-1 using two recombinant GNMT fusion proteins.

Palatal surface area measurement: comparisons among different cleft types.

The purpose of this study was to use three-dimensional imaging methods to measure the palatal surface of unrepaired cleft patients. The surface area of the palate was defined and measured on three-dimensional computed tomography images of dental plaster models in four different groups of cleft patients at 3 months of age. There were 30 unilateral complete cleft lips and palates (UCLP), 27 bilateral complete cleft lips and palates (BCLP), 23 isolated cleft palates of incomplete form (CP), and 19 unilateral cleft lips without cleft palates (UCL).

Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells.

Insulin-like growth factor I (IGF-I) receptor (IGF-IR)-mediated signals are known to be involved in cell growth and transformation and prevention of apoptosis. In this study, we demonstrated the coexpression of IGF-I and IGF-IR in human esophageal carcinoma tissues. We also demonstrated the IGF-I autocrine system in esophageal carcinoma cell lines.

Mandibular dysmorphology in patients with unilateral cleft lip and cleft palate.

Background: Conventional studies of the cleft lip/palate (CLP) dysmorphology have mainly focused on deformities of the lip, nose, and maxilla, while ignoring the mandible. Reasons for that were the lack of well-defined mandibular deformity and restriction from the research methodology.

Methods: This study used 3-dimensional computed tomography (CT) imaging data from 35 patients with unilateral CLP.

Assessment of bilateral cleft lip nose deformity: a comparison of results as judged by cleft surgeons and laypersons.

Reconstruction of bilateral cleft lip nose deformity is difficult and the outcome is inconsistent. This study was conducted to evaluate the gross outcome and the difference in the assessment of nasal appearance as judged by two groups of raters, cleft surgeons and laypersons. Sixty-four patients with bilateral cleft lip were selected for review.

Hereditary cleft lip/palate and Wilms tumor: a rare association.

Objective: The association of cleft lip/palate (CLP) with other anomalies is not uncommon, but its association with Wilms tumor (WT) is very rare, especially in a familial pattern. In this report, we present a family in which six members in two generations were affected with CLP, WT, or both.

Patients And Results: A male patient presented with right complete CLP.

Computed tomography characteristics of non-syndromic craniofacial fibrous dysplasia.

Background: Fibrous dysplasia is a benign fibro-osseous tumor of bones commonly involving the craniofacial region. Computed tomography (CT) imaging study of the disease is useful for evaluation and treatment planning. However, few studies have evaluated such large patient series.