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Fen-Hwa Wong

Publications and source records attributed to Fen-Hwa Wong.

13 recordsLinked to original sources
PubMed2006

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. In this study, we demonstrated that Borealin is a cell cycle-regulated gene and is upregulated at G2-M phases of the cell cycle. We showed that Borealin interacts with Survivin but not with Aurora B. The interaction domain of Survivin in Borealin was mapped to the N-terminal 92 amino-acid residues of Borealin. To examine the linkage between expression of Borealin and cancer, we performed immunohistochemistry analysis using anti-Borealin specific antibody on the paraffin-embedded gastric cancer tissues. Our results showed that Borealin expression is significantly correlated with Survivin (P = 0.003) and Ki67 (P = 0.007) in gastric cancer. Interestingly, an increased nuclear Borealin level reveals borderline association with a poor survival rate (P = 0.047). Taken together, our results demonstrated that Borealin is a cell cycle-regulated chromosomal passenger protein and its aberrant expression is linked to a poor prognosis for gastric cancer.

Cell Cycle Proteins↗
PubMed2006

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. The analysis demonstrated the selective upregulation of these Aurora members in various cancers. In general, Aurora-A exhibited the highest expression levels, with substantially decreased quantities of the Aurora-C transcript detected relative to Aurora-A and -B. Moreover, to characterize the roles of each Aurora member, which share many similarities, we investigated the expression profiles of the family in normal tissues and a panel of different phases of the HeLa cell cycle. Finally, both Aurora-A and -B were overexpressed in a majority of esophageal tumor tissues in comparison to the normal variants. Taken together, the results show that each Aurora member exhibits distinct expression patterns, implying that they are engaged in different biological processes to accomplish more elaborate cell physiological functions in higher organisms.

Aurora Kinase C↗
PubMed2004

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. A total of 14 patients from 1 month to 24 years of age were included. The skull images were rotated into standard orientation and reconfigured for evaluation of the cranium, endocranial base, and facial skeletal structures. The midlines of cranial base and facial bone, angle of midline deviation, width of each hemicranium and hemiface, and the orbital index were defined and measured. The results showed that the cranium and cranial base deformation took place as early as in infant stage, with the most prominent change occurring in the posterior cranial fossa. Facial bone asymmetry started to appear after 5 years of age, at which time the mandibular and occlusal abnormalities were observed. The deformity of the orbits and maxilla occurred at an older age, characterized by the deviation and decreased vertical height on the affected side. The severity of the observed deformities increased with age. The angle of midline deviation was 2.48 +/- 1.68 degrees in the cranial base and 3.26 +/- 3.28 degrees on the facial bone. Both of the midline deviations were significantly correlated with age. Compared with the contralateral side, the width of the ipsilateral posterior hemicranium was longer (54.36 +/- 6.72 mm versus 50.81 +/- 6.55 mm), and the width of the ipsilateral lower hemiface was shorter (35.30 +/- 7.27 mm versus 43.49 +/- 11.34 mm). Both differences were statistically significant. Measurement of the orbital index demonstrated a significantly flatter orbit on the ipsilateral side (89.48 +/- 0.11 versus 92.74 +/- 0.08). This study showed that the cranium and cranial base deformity occurred early in patients with uncorrected torticollis, while the facial bone deformity occurred in childhood stage. The cranial and facial deformity became more severe with age. Early release of the muscle restriction is advised to prevent craniofacial deformation.

Adolescent↗
PubMed2004

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. The purpose of this study was to use 3-dimensional computed tomographic data to evaluate the nerve in patients with prominent mandibular angles and to compare the nerve position with a normative group. A total of 28 female and 5 male adult patients who presented with a complaint of prominent angles or a "square-face" look, as well as 20 female and 22 male adult normal subjects were included, for a total of 150 hemimandibles for extraction of the inferior alveolar nerve. The nerve and the mandible were displayed. Point O was defined on the oblique line along the anterior cortex of ramus, where it intersected with a line extending from the alveolar arch. From the O point, linear distances were defined, including horizontal distances to the posterior cortex, oblique distances to the gonion, and the vertical distances to the inferior cortex. Mandibular width was defined as the distance between the 2 gonion points. Results demonstrated significant differences mainly in the oblique distances (ie, from the O point to the nerve [O1], from the nerve to the gonion [O2], and from the O point to the gonion [O1-O2]) in both female and male patients. The O2 distance was 23.69 mm versus 20.66 mm in women and 27.30 mm versus 23.28 mm in men (square face vs norm). The mandibular width was significantly larger in the male square-face patients, but the difference was not significant between the female groups. These results provide useful information for surgeons planning mandibular angle reduction. These findings suggest that the mandibular contouring procedure should be aimed at correcting regional osseous dysmorphology in the angle area and improving the relationship to the chin, rather than merely reducing the mandibular width.

Adult↗
PubMed2003

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. IL-6 stimulation induced a rapid phosphorylation of gp130 and STAT3, and a dominant-negative STAT3 completely abolished the antiapoptotic effect. IL-6 also activated ERK 1/2 in CE48T/VGH cells. Inhibition of the ERK activation by PD98059 and transfection of a dominant-negative ERK2 completely blocked the protection of IL-6 against apoptosis. Thus, both STAT and MAP kinase pathways are responsible for the IL-6-delivered survival signal in human esophageal carcinoma cells. In contrast, PI3-K inhibitors only partially attenuated the effect of IL-6, suggesting that PI3-K does not play a major role in the antiapoptotic signal of IL-6 in our system. To investigate whether IL-6 could induce the production of antiapoptotic molecules, proteins of the Bcl-2 family were measured. While Bcl-2, Bcl-x(L,), and Bax were not affected, Mcl-1 was induced by IL-6 in human esophageal carcinoma cells. Our results suggest that IL-6 may contribute to the progression of esophageal cancers in an autocrine or paracrine manner.

Apoptosis↗
PubMed2003

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). These patients were nonsyndromic, unoperated, and without other major deformities. The dental casts were scanned, and the computed tomography data were transferred to an imaging laboratory for processing and reconstruction of three-dimensional images. Surface area of the palate was delineated, which was defined as within the alveolar crest and the line connecting both tuberosities. In UCLP and BCLP, the edge of cleft formed the medial boundary of the area for each palatal shelf, and the palatal surface area was the combination of both palatal shelves and the premaxillary area in BCLP group. The surface area was measured. Repeated definition and measurement tasks were performed for calculation of errors. The imaging data management and measurement were performed using the Analyze program (Biomedical Imaging Resource, Mayo Foundation, MN). In addition, linear distances were measured between the canine points on the alveolar crest (line C) and the tuberosity points (line T). The measurements were compared among the different groups. Analysis of variance and multiple comparisons were used for statistical analyses. The results showed that the mean error between repeated area definitions and measurements in this study was 1.86%. The bilateral complete cleft lip and palate (BCLP) and unilateral complete cleft lip and palate (UCLP) groups had significantly smaller palatal surface area than the unilateral cleft lip without cleft palate (UCL) and isolated cleft palate of incomplete form (CP) groups. There was no significant difference between the BCLP and UCLP groups. Line C and line T distances were significantly longer in BCLP and UCLP groups than in UCL and CP groups. The findings suggest that compared with UCL and CP patients, there is an intrinsic tissue deficiency in the palate/maxilla of BCLP and UCLP patients.

Cleft Lip↗
PubMed2002

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. The patients' ages ranged from 5 to 30 years. All patients had undergone primary cleft lip repair and secondary nasal reconstruction, and had been followed for at least 6 months. One image for each patient, which included a digitized frontal, lateral, and worm's-eye view, was projected for evaluation by the raters. The raters included five cleft surgeons and five laypersons. A rating scheme was used in which a score of 3 was given for a good, close to normal nasal appearance, 2 for an average result that needed minor revision, and 1 for a poor result that needed major reconstruction. The scores were averaged for each patient in each group and for each group as a whole. The final outcome was judged as good, fair, or poor on the basis of the mean score for each patient. Statistical analysis was performed. The mean score for all patients was 2.08 as assessed by the laypersons and 2.18 as assessed by the cleft surgeon group. There was no statistically significant difference between the two groups. Comparisons on rating scores among different raters revealed a fair agreement on the ratings within each of the two groups. The results were found to be good in 29.7 percent, fair in 64.1 percent, and poor in 6.3 percent of patients when evaluated by the surgeons. When rated by the laypersons, the nasal appearance was found to be good in 26.6 percent, fair in 60.9 percent, and poor in 12.5 percent of patients. This difference in distribution between the two groups was not statistically significant. When comparing the results given by the two groups of assessors, there was agreement on the nasal appearance in 65.6 percent of patients, and a difference in grading in the rest. For the patients who received different grading, the surgeons rated them one grade higher in 63.6 percent and one grade lower in 36.4 percent. There was no difference in grading between any of the evaluators that reflected a two-grade discrepancy in evaluation of results. This study shows that the surgical outcome of bilateral cleft lip nose deformity repair, at the authors' institution, is less than optimal. When assessing bilateral cleft lip nose appearance, the judgment of results by cleft surgeons was similar to that of the laypersons. However, different rating of results existed within each of the two groups, supporting the importance of clearly assessing patient/parent expectations and defining realistic surgical goals.

Adolescent↗
PubMed2002

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. He had a family history of facial cleft and abdominal tumor. Lip repair was performed at 3 months of age. An abdominal mass was noticed at 12 months of age, which proved to be WT. Surgical excision of the tumor and chemotherapy were conducted. He subsequently underwent palate repair. His father had an unrepaired microform cleft lip. Three of his aunts were known to have similar problems: one had both facial cleft and WT, one had WT only, and the other had facial cleft only. One of his cousins also was affected with WT. CONCLUSIONS: This is a unique family affected with a rare association of CLP and WT. Pedigree study revealed an autosomal dominant hereditary pattern.

Adult↗
PubMed2002

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. METHODS: A total of 46 patients with complete medical records and CT images was included in this study. All of these patients were non-syndromic, had fibrous dysplasia involving only the craniofacial region, and had no skin pigmentation or other evidence of endocrine problems. Data analyses were performed on the clinical manifestations, time of onset, signs and symptoms, involvement of cranial and facial bones, and CT appearance of the tumors in this patient group. RESULTS: Painless swelling was the chief clinical problem in 78% of patients, followes by dental malocclusion in 22%. Onset of the disease was reported to have occurred before 6 years of age in 34%, between 6 and 10 years in 27%, and older than 10 years in 39% of patients. Extreme timings such as onset at infancy or older than 20 years of age were also noted. The average number of bones involved was 3.2 bones per patient. Involvement of more than one craniofacial bone occurred in 70% of patients. The maxilla, orbital, and frontal bones were most commonly involved. CT images appeared sclerotic or homogenous in 34%, mixed white and dark or heterogenous in 55%, and cystic in 11%. A correlation between the age of onset of the disease and the number of bones involved was not observed. CONCLUSIONS: Findings of this study demonstrate that craniofacial fibrous dysplasia displays a wide spectrum of clinical behaviors. CT imaging generally revealed extensive involvement of the tumor in the craniofacial region.

Adolescent↗
PubMed2002

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. The 3-dimensional images were rotated into a neutral position. Eight cephalometric landmarks were recorded: the pogonion (PG) and the infradentale (ID) from the frontal view; and the condylion (CO), the tip of coronoid process (CP), and the gonion (GO) from both sides of lateral views. The nasion was used as a reference point for the facial midline. Nine linear distances and four angular measurements were calculated from these landmarks. Each mandible was segmented into two hemi-mandibles for volume measurements. The image manipulation and measurements were performed using a personal computer running Analyze' program. Landmark deviation from the facial midline was computed, and comparisons were made between the cleft and non-cleft sides. RESULTS: The results showed that the precision and accuracy of landmark localization was high with an average error of 0.4%. Deviation from the midline of the ID and PG points, and spatial distances between bilateral CP, CO, and GO points varied without a specific pattern. The average differences were within 2 mm. The volume of the cleft side hemi-mandible was consistently larger than that of the non-cleft side (p < 0.0001). Among linear and angular measurements, CP-GO-PG, CO-ID, CP-ID, and CP-GO showed significant difference between the two sides. CONCLUSION: This study demonstrated that mandibular asymmetry and deformity existed and was measurable in patients with unilateral CLP. The influence of CLP to the mandibular development was expressed by the significant differences of hemi-mandible volume and some of the linear and angular measurements between the cleft and non-cleft sides.

Cleft Lip↗
PubMedDate not supplied

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. M13 phage peptide display showed that the reactive epitopes of mAbs 4-17 and 14-1 were amino acid residues 11-15 and 272-276 of human GNMT, respectively. The dissociation constants of the binding between GNMT and mAbs were 1.7 x 10(-8) M for mAb 4-17 and 1.8 x 10(-9) M for mAb 14-1. Both mAbs can identify GNMT present in normal human and mouse liver tissues using Western blotting (WB) and immunohistochemical staining assay (IHC). In addition, WB with both mAbs showed that none of 2 hepatoblastoma and 5 HCC cell lines expressed GNMT. IHC demonstrated that 50% (13/26) of nontumorous liver tissues and 96% (24/25) of HCC tissues did not express GNMT. Therefore, the expression of GNMT was downregulated in human HCC.

Animals↗
PubMedDate not supplied

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. Both the CE48T/VGH and CE81T/VGH cell lines showed proliferative responses to IGF-I stimulation. Autokinase activity of IGF-IR in these cells can be triggered by the exogenous addition of IGF-I. In addition, an IGF-I peptide antagonist, JB1, specifically inhibited ligand-induced receptor autophosphorylation in a dose-dependent manner. Under serum-free conditions, JB1 also reduced the degree of IGF-IR phosphorylation and cell numbers. Furthermore, the addition of JB1 decreased the number of CE81T/VGH colonies formed in methyl cellulose agar and the size and the incidence of tumors which grew in mice with severe combined immunodeficiency. These results imply that an IGF-I autocrine system in human esophageal carcinoma cells could stimulate tumor growth. Finally, we found that IGF-I prevented the apoptosis of CE81T/VGH cells induced by chemotherapeutic drugs, such as cisplatin, 5-fluorouracil and camptothecin. Thus, interruption of IGF-IR function may provide a way to retard tumor growth and increase the sensitivity of esophageal carcinoma to chemotherapy.

Animals↗