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Biomedical subjects

C T Liew

Publications and source records attributed to C T Liew.

At least 19 recordsLinked to original sources
PubMed2004

In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes.

Acticoat is a polyethylene mesh coated with nanocrystalline silver. It has been used widely as a dressing for chronic wounds, acute partial-thickness burn wounds and donor sites. In this study, the in vitro cytotoxicity of Acticoat on cultured keratinocytes is tested. Human keratinocytes are cultivated on a pliable hyaluronate-derived membrane (Laserskin) using dermal fibroblasts as the feeder layer. When the cultured Laserskin (CLS) is subconfluent it is covered by Acticoat, which is exposed to water (Group 1), phosphate-buffered saline (Group 2) or culture medium (Group 3). The control group is not exposed to the Acticoat. After 30 minutes incubation at 37 degrees C, the inhibitory effect of the nanocrystalline silver on keratinocyte growth is measured by an MTT assay. Compared with the control, the relative viability of the CLS dropped to 0%, 0% and 9.3%, respectively. Thus, Acticoat is cytotoxic to cultured keratinocytes and should not be applied as a topical dressing on cultured skin grafts.

Bandages↗
PubMed2002

Expression of cyclooxygenase-2 in chronic hepatitis B and the effects of anti-viral therapy.

BACKGROUND: Cyclooxygenase-2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase-2 and chronic hepatitis B is unknown. AIM: To investigate the expression and cellular localization of cyclooxygenase-2 in chronic hepatitis B patients and the effects of anti-viral therapy. METHODS: Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase-2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non-viral-infected livers were used as controls. The cyclooxygenase-2 immunoreactivities of paired liver biopsies from 12 patients receiving anti-viral therapy were compared. RESULTS: Immunohistochemistry and in situ hybridization revealed that cyclooxygenase-2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase-2 expression compared with controls. The cyclooxygenase-2 expression of hepatitis B e antigen-positive and -negative chronic hepatitis B patients was not significantly different, although the necro-inflammatory activity of the latter group was significantly lower. Over-expression of cyclooxygenase-2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen-positive chronic hepatitis B patients received anti-viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro-inflammatory activity in all 12 patients, no significant change in cyclooxygenase-2 expression was found. CONCLUSIONS: Chronic hepatitis B is associated with elevated cyclooxygenase-2 levels in hepatocytes, and the over-expression of this enzyme does not reflect inflammatory activity. Up-regulation of cyclooxygenase-2 persists after successful anti-viral therapy.

Adolescent↗
PubMed2002

Cytomegalovirus infection of the nasopharynx.

This report describes a case of cytomegalovirus (CMV) infection of the nasopharynx. A 47 year old man presented with a nasopharyngeal mass of one month's duration. The patient had a history of pneumonia one month previously. Sinus computed tomography incidentally picked up a nasopharyngeal mass. The initial biopsy showed lymphoid hyperplasia. Repeated nasopharyngoscopy showed a prominent central nasopharyngeal mass without ulceration. Histology of the nasopharyngeal biopsy revealed several enlarged epithelial cells with characteristic CMV cytopathic changes. An immunohistochemical study, using a monoclonal IgG antibody against a CMV antigen, confirmed CMV infection. The patient's nasopharyngeal mass decreased in size gradually on follow up. To the best of our knowledge, this is the first reported case of CMV infection of the nasopharynx in the English literature. This disease entity should be considered in those patients presenting with nasopharyngeal mass, biopsy negative for malignancy, and no underlying immunosuppression or immunodeficiency.

Cytomegalovirus Infections↗
PubMed2001

Dermal fibroblasts do not enhance the graft take rate of autologous, cultured keratinocyte suspension on full-thickness wounds in rats.

Dermal fibroblasts are known to play an important role in wound healing. In this study, cultured autologous keratinocyte suspension was applied with fibrin glue to the full-thickness wounds in rats (N = 20). Histological analysis on day 14 showed regenerated epithelium in 10 wounds (50%). Keratinocytes were also premixed with allogeneic dermal fibroblasts in a ratio of 3:1 and 5:1 before application to other full-thickness wounds (N = 20) with fibrin glue. Regeneration of epithelium was observed in 10 (50%) and 9 (45%) wounds respectively. Acute inflammatory reaction and mild to moderate proliferation of fibroblasts in the subepithelial layer of the allogeneic fibroblasts were noted. The addition of dermal fibroblasts to keratinocytes/fibrin glue does not enhance the take rate of the cultured keratinocyte suspension.

Animals↗
PubMed2001

Preoperative systemic chemoimmunotherapy and sequential resection for unresectable hepatocellular carcinoma.

OBJECTIVE: To examine the surgical and pathologic findings of 15 patients who had initially unresectable hepatocellular carcinoma (HCC) and received preoperative systemic chemoimmunotherapy and sequential resection. SUMMARY BACKGROUND DATA: More than 80% of patients with HCC present for treatment at an unresectable stage. Conventional treatment has produced a low tumor response rate in this group of patients. Recently, new systemic chemoimmunotherapy has been found to be effective and able to make previously unresectable HCC resectable. Sequential resection after response to chemoimmunotherapy could therefore induce complete clinical remission. METHODS: From July 1996 to February 1999, 150 patients with unresectable HCC were treated with systemic chemoimmunotherapy consisting of cisplatin, alpha-interferon, doxorubicin, and 5-fluorouracil for a maximum of six cycles. The residual tumors were reassessed for resectability after treatment aiming at complete remission in the patients after combined modality treatment. Twenty-seven patients had a more than 50% regression in tumor size (2 complete remissions, 25 partial remissions). Fifteen patients had resectable disease after treatment, and all underwent sequential resection with curative intent. Treatment outcome and the surgical and pathologic features of these 15 patients were studied. RESULTS: Fifteen of 150 patients responded to chemoimmunotherapy and underwent sequential resection. They were considered to have unresectable disease as a result of extensive local disease (with and without major vascular involvement) in 10 patients and the presence of extrahepatic or metastatic disease in 5 patients. All patients except two were hepatitis B carriers. Surgical resection of the residual lesion after chemoimmunotherapy was successful for all patients. Eight of the patients had complete pathologic remission. The rest had minimal residual disease (<5%) only. All 15 patients entered complete clinical remission after surgery. Thirteen patients were still alive as of this writing and two had died of recurrent disease. The 1-, 2-, and 3-year survival rates were 100%, 100%, and 53%, respectively. The mean follow-up period was 27 months (range 15-37). Neither the median disease-free nor overall survival had been reached. Ten patients remained in complete remission as of this writing. CONCLUSION: Combined modalities with systemic chemoimmunotherapy and surgical resection can achieve complete clinical remission and long-term control of disease in patients with unresectable HCC.

Adolescent↗
PubMed2001

A new technique to resurface wounds with composite biocompatible epidermal graft and artificial skin.

BACKGROUND: The incorporation of cultured epidermal autograft on the neodermis of artificial skin (Integra, Integra LifeSciences, Plainsboro, NJ) has been met with some difficulties. A new engraftment technique to resurface the wounds with Integra and composite biocompatible epidermal graft (CBEG) has been successfully applied on three patients for elective reconstructive procedures. METHODS: A small skin biopsy was taken from the normal edge of the lesion for keratinocytes and dermal fibroblast cultures 2 weeks before surgery. When sufficient cells were grown, the patient was admitted for the excision of the lesions or scars. The wounds of the patients, ranging from 125 to 250 cm2, were covered with Integra. When the neodermis of the Integra was fully vascularized, the silicone membrane of the Integra was removed and replaced with the CBEG, which consisted of autologous keratinocytes cultivated on a hyaluronate-derived membrane (Laserskin; Fidia Advanced Biopolymers, Abano Terme, Italy)) using human dermal fibroblasts as a feeder layer. RESULTS: Clinically, there was good initial "take" of the CBEGs in these three patients, ranging from 50% to 100%. Biopsy specimens of the grafted wounds were taken 1 to 3 weeks after the application of the CBEGs. Epithelialization was noted in all patients. CONCLUSION: This engraftment technique has several advantages. The CBEG is much easier to handle than the conventional cultured epidermal autograft. It eliminates the invasive second procedure for skin harvesting, with resulting pain and scarring. The application of the CBEG can be easily performed at the bedside.

Adolescent↗
PubMed2001

US-guided percutaneous biopsy of small (< or = 1-cm) hepatic lesions.

PURPOSE: To determine the accuracy of ultrasonography (US)-guided percutaneous biopsy in diagnosing malignant neoplasms for hepatic lesions 1 cm or smaller. MATERIALS AND METHODS: In this prospective study, 64 consecutive patients with 74 discrete focal hepatic lesions depicted at US were referred for liver biopsy to confirm the exact nature of the lesions. Mean lesion size was 0.84 cm +/- 0.13 (range, 0.5-1.0 cm). Biopsy was performed with an 18-gauge automated biopsy gun in 46 lesions (once [n = 37], twice [n = 7], three times [n = 2]) or a 22-gauge needle in 28 lesions (once [n = 23], twice [n = 4], three times [n = 1]). Measures were taken to ensure accurate and effective lesion sampling. The histologic diagnosis of malignant tumor and findings on follow-up US images of "benign" nodules for 15-39 months were the criterion standard. RESULTS: No complications occurred. All specimens obtained were sufficient for diagnosis. Histologic examination revealed various types of primary and secondary malignant tumors (n = 44), hemangioma (n = 5), cirrhosis (n = 13), focal fatty change (n = 8), focal fatty sparing (n = 2), and abscess (n = 2). The diagnostic discrimination of US-guided biopsy in diagnosing malignant tumors in these small lesions was sensitivity, 98%; specificity, 100%; positive predictive value, 100%; negative predictive value, 97%; and accuracy, 99%. CONCLUSION: Percutaneous biopsy under US control is highly accurate in providing a definitive histologic diagnosis of malignant neoplasms for small hepatic lesions if measures for ensuring precise and effective lesion sampling are taken.

Adolescent↗
PubMed2001

In vitro inhibition of head and neck cancer-cell growth by human recombinant interferon-alpha and 13-cis retinoic acid.

Three nasopharyngeal carcinoma (NPC) cell lines (CNE-1, CNE-2 and NPC/HK-1), two squamous cell carcinoma (SCC) cell lines (T2/CUHK and PWH-S1) and six head and neck cancer specimens (NPC [n = 4], SCC tongue [n = 1] and a thyroid cancer [n = 1]) were incubated with interferon (IFN)-alpha (5 x 10(4) iu/mL) and/or 13-cis retinoic acid (13RA; 10(-5) mol/L) for two days at 37 degrees C. In vitro chemosensitivity was measured using MTT assay. Mild growth inhibition of the five cell lines by IFN-alpha ranged from 7.1% to 51.8% (mean: 18.5%), whereas with 13RA it was zero to 19.7% (mean: 7%). Greater inhibition (14.8-51.0%, mean: 31.8%) was achieved when the two drugs were used in combination. Growth inhibition of the six surgical specimens ranged from 6.9% to 21% (mean: 13.6%) with IFN-alpha; zero to 10.3% (mean: 6.0%) with 13RA; and 6.6-26.5% (mean: 17.7%) when the two agents were combined. Four of the 11 samples showed synergistic antitumour effect when IFN-alpha and 13RA were combined, and six showed subadditive effect. The results show that IFN-alpha and 13RA have a mild in vitro antitumour effect on head and neck cancer cells, and the drug synergistic effect demonstrated in this study suggests that the two agents should be used in combination in clinical application.

Antineoplastic Agents↗
PubMed2000

Differential gene expression of hepatocellular carcinoma using cDNA microarray analysis.

A cDNA microarray technique, which allows simultaneous analysis of differential expression of mRNA of over 4000 known human genes, was utilized to study the gene expression in 10 pairs of HCC and nontumorous tissues from ethnic Chinese patients in Hong Kong. A total of 211 genes were found to be highly expressed and 147 genes were downregulated in more than 1 out of 10 of the HCC pairs. The results were significant by two-tailed Wilcoxon test (P < or = 0.05 with 95% confidence) on the intensity of each DNA spot of the 10 HCC pairs. Six genes were highly expressed and 10 genes were downregulated in more than 30% of HCC pairs. Results are consistent with other published reports using traditional differential display, subtractive hybridization, or immunohistochemical staining methods. We also detected that beta-actin and glyceraldehyde 3-phosphate dehydrogenase (G3PDH), which have been commonly used as an internal standard control in mRNA expression studies, were highly expressed in HCC when compared with nontumorous tissue. It is concluded that cDNA microarray analysis is an effective method in the detection of differential gene expression in HCC.

Actins↗
PubMed1999

Frequent allelic loss on chromosome 9 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and highly associated with chronic virus-B or -C infection and cirrhosis. Molecular studies have shown high frequency of loss of heterozygosity (LOH) in some specific chromosome regions, but LOH on chromosome 9 in HCC has not been thoroughly investigated. In our investigation of chromosome 9 with 19 polymerase-chain-reaction (PCR)-based polymorphic microsatellite markers, 30 of 48 HCC tissue samples (63%) had LOH, and a distinct common deletion region and a region of loss were identified. The first region was located at the 9p21 region and the minimal deletion region was located between loci D9S1747 and D9S1748. This is a region of approximately 200 kb which includes the p16 tumor-suppressor gene. A region of loss was located on 9p13 to 9q33. The putative tumor-suppressor gene for nevoid-basal-cell-carcinoma syndrome (NBCCS) at 9q22.3 resides within this region. In addition to LOH, 4 HCC cases showed possible homozygous deletions at 9p21 with markers D9S1748, D9S1752 and D9S171 by multiplex PCR analysis. In 3 cases, the minimal region of possible homozygous deletion was approximately 300 kb and was defined between markers D9S1747 and D9S1752. Since this deletion region includes both the p15 and the p16 tumor-suppressor genes, these genes were possibly inactivated by homozygous deletion in HCC. In addition, a second region of possible homozygous deletion was present on the centromeric side of 9p21. However, these changes are not associated with age, gender, size or tumor-cell differentiation. Our data also suggest that inactivation of the p16 and the p15 genes and the possibility of other unknown tumor-suppressor genes located on these defined deleted regions of chromosome 9 may be involved in the pathogenesis of HCC.

Adolescent↗
PubMed1999

High frequency of p16INK4A gene alterations in hepatocellular carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR-SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

Carcinoma, Hepatocellular↗
PubMed1999

Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients.

We have studied the feasibility of detecting tumor-associated aberrant p16 methylation in the circulation of patients with hepatocellular carcinoma (HCC). We extracted DNA from the tumor tissues and peripheral blood plasma or serum of 22 HCC patients. p16 methylation was found in 73% (16 of 22) of HCC tissues using methylation-specific PCR. Among the 16 cases with aberrant methylation in the tumor tissues, similar changes were also detected in the plasma/serum samples of 81% (13 of 16) of the cases. No methylated p16 sequences were detected in the peripheral plasma/serum of the six HCC cases without these changes in the tumor, in 38 patients with chronic hepatitis/cirrhosis, or in 10 healthy control subjects. These results suggest that circulating liver tumor DNA may be detected using tumor-associated DNA methylation changes. Because methylation abnormalities have been found in many other genes and tumor types, this approach may have implications for the noninvasive detection of a wide variety of cancers.

Adult↗
PubMed1999

Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases, 48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3. No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3. A significant copy number loss of 4q11-q23 was, however, identified in those tumors larger than 3 cm in diameter. Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.

Adult↗
PubMed1999

Radiation hybrid mapping of human cytosolic malate dehydrogenase (hcMDH) to the short arm of chromosome 2.

Compartmentalization of human cytosolic malate dehydrogenase, hcMDH, together with its isozyme partner-mitochondrial form, hmMDH, plays an important role in the aerobic metabolism of the malate-aspartate shuttle and the citric acid cycle. However, they share few structural homology at the molecular level. The pseudogenes of mMDH has been reported in mice but hcMDH has no pseudogenes as shown by Southern blot analysis. A single band only was detected for the EcoRI digestion with 9.4 kb long of human genomic DNA and HindIII cutting with 2.8 kb long. hcMDH gene was mapped to chromosome 2 by somatic cell hybrid analysis and further localised to 268.72 cR from the top telomere of Chromosome 2 (near 2p15) by radiation hybrid mapping. The genes falling into this region may be related to dilated cardiomyopathy (DCM), several types of cancers and immunoregulation mechanism of cancers.

Chromosome Mapping↗