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Biomedical subjects

W T Chen

Publications and source records attributed to W T Chen.

At least 55 records · Page 3Linked to original sources
PubMed2004

Selection and validation of differentially expressed genes in head and neck cancer.

We applied a robust combinatorial (multi-test) approach to microarray data to identify genes consistently up- or down-regulated in head and neck squamous cell carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two differentially expressed probe sets (representing 38 genes and one expressed sequence tag) satisfied all statistical tests of significance and were selected for further validation. Selected probe sets were validated by hierarchical clustering, multiple probe set concordance, and target-subunit agreement. In addition, real-time PCR analysis of 8 representative (randomly selected from 38) genes performed on both microarray-tested and independently obtained samples correlated well with the microarray data. The genes identified and validated by this method were in comparatively good agreement with other rigorous HNSCC microarray studies. From this study, we conclude that combinatorial analysis of microarray data is a promising technique for identifying differentially expressed genes with few false positives.

Algorithms↗
PubMed2002

The biological behaviour of human adenoid cystic carcinoma cells transduced with interleukin-2-gene.

Adenoid cystic carcinoma (ACC) of the salivary glands is a highly infiltrative malignant tumour with a tendency for lung metastasis. Gene therapy could be a potentially effective therapy for ACC and its metastasis. The aims of the study were: To transduce interleukin-2 (IL-2) gene into an ACC cell line with predisposition for lung metastasis (ACC-M); to compare the bioactivity of the gene-transduced cells and the parent cell line in vitro and in vivo. The IL-2 gene was transduced via a bicistronic retroviral vector into the ACC-M cells. The growth rate and DNA cell cycles of the parent ACC-M, the control viral vector AmGCEN, and the gene transduced AmIL-2 cell cultures were compared quantitatively and by flow cytometry, respectively. The tumourigenic ability of the three cell lines was verified by inoculation in athymic nude mice. The tumours developed were extracted and compared quantitatively and histologically. There was no difference in the growth rate and the DNA count between the ACC-M, AmGCEN, and AmIL-2 cell cultures. In the animal experiment, both the ACC-M and AmGCEN cells stimulated lung metastasis in all the mice, whereas there was no tumour found in the 1 x 10(6) AmIL-2 cells inoculation. On 3 x 10(6) AmIL-2 cells stimulation, three out of six mice developed tumours but the mass and volume of the tumours were smaller than the other two groups. Under light microscopy, the ACC-M tumours were mainly poorly differentiated with minimal cellular matrix, whereas the AmIL-2 tumours were well differentiated with ample matrix. The transduction of IL-2 gene can reduce the tumourigenicity of ACC-M cells and induces tumour cell differentiation in mice. The IL-2 gene can be a potential effective gene for the treatment of adenoid cystic carcinoma of salivary glands and its lung metastasis.

Animals↗
PubMed2001

Chronic daily headache in Taipei, Taiwan: prevalence, follow-up and outcome predictors.

We conducted a two-stage population-based headache survey among subjects aged > or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past year were identified, interviewed and followed-up. CDH was defined as a headache frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants, 108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2-year follow-up, 35% of the CDH subjects still had CDH. The significant predictors for persistent CDH at follow-up included: older age ( > or = 40 years) (RR = 2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR = 2.0), medication overuse (RR = 1.8), and "daily" headache (RR = 2.1). We found that CDH is not uncommon in the community and its prevalence is similar among different populations. Older subjects and those with medication overuse may have a more protracted course of illness.

Adolescent↗
PubMed2001

Persistent migrainous visual phenomena might be responsive to lamotrigine.

Two patients with migraine reported having experienced persistent auralike visual phenomena for months to years. All laboratory investigations were normal except for occipital hypoperfusion on the brain single photon emission computed tomography. After lamotrigine treatment for 2 weeks, they both had a resolution of the visual symptoms. Persistent migrainous visual phenomena are potentially benign and probably a status of spontaneous aura.

Adult↗
PubMed2001

Vertebral bone marrow perfusion evaluated with dynamic contrast-enhanced MR imaging: significance of aging and sex.

PURPOSE: To investigate blood perfusion of nonfractured, normal-appearing vertebral bodies with regard to age and sex. MATERIALS AND METHODS: Dynamic magnetic resonance imaging (160 images obtained in 80 seconds) was performed from T10 to L5 in 66 patients. Patients were assigned to three groups: group 1, those 50 years or younger without compression fracture; group 2, those older than 50 years without compression fracture; or group 3, those older than 50 years with compression fracture. Peak enhancement percentage and enhancement slope were determined from the time-intensity curve of normal (nonfractured) vertebral body. Comparisons were made between groups, and the effect of age and sex interaction was analyzed. RESULTS: Higher peak enhancement percentage was demonstrated for group 1 compared with group 2 (58.21 +/- 44.65 [SD] vs 21.88 +/- 14.77, P <.005). Group 1 women revealed a higher enhancement percentage compared with group 1 men (87.17 +/- 54.13 vs 38.16 +/- 21.69, P <.05), which significantly decreased in those older than 50 years (from 87.17 +/- 54.13 to 17.98 +/- 13.80, P <.005). For men, this decrease in those older than 50 years was not as pronounced (from 38.16 +/- 21.69 to 25.38 +/- 15.43, P >.05). Presence of compression fracture at other levels of the spine (group 3) was not associated with a different enhancement percentage for normal vertebrae. CONCLUSION: Rate of vertebral bone marrow perfusion revealed a significant decrease in subjects older than 50 years. Women demonstrated a higher marrow perfusion rate than men younger than 50 years and a more marked decrease than men older than 50 years.

Adult↗
PubMed2001

Paget's disease of the bone: a case report.

Paget's disease of bone is rare in Asia. We report a case of Paget's disease in a 58-year-old Taiwanese man who was admitted with a 3-month history of bilateral numbness in the buttock region. Laboratory data disclosed an elevated serum alkaline phosphatase level (510 U/L). Plain radiographs of the lumbar spine showed generalized increased density at the third lumbar vertebra, associated with cortical thickening, loss of cortico-cancellous definition, and increased anteroposterior diameter. The T1-weighted magnetic resonance image of the lumbar spine showed diffuse, heterogeneous low signal intensity at the third lumbar vertebral body, pedicle, laminae, and spinal process; these areas showed mixed high and low signal intensity on the T2-weighted image. Technetium-99m bone scan revealed abnormal uptake in the involved vertebra. Histologic examination of the third lumbar spinal process confirmed the diagnosis of Paget's disease of bone. The patient remained well during a follow-up period of 6 months.

Humans↗
PubMed2001

Valproate-induced encephalopathy.

A 50-year-old woman taking carbamazepine (CBZ) 1200 mg daily for her partial epilepsy developed acute confusion after valproate (VPA) add-on treatment for 10 days. The administration of VPA started from 1000 mg daily and, 3 days later, increased to 1500 mg daily. Beside a mildly elevated serum ammonia level (81 microg/dL), her electroencephalogram showed diffuse background slowing intermixed with 2-2.5 Hz of high-amplitude slow waves, which indicated a diffuse encephalopathy. The serum levels of VPA and CBZ were 49.1 mg/L and 8.6 mg/L, both being non-toxic. The liver functions appeared normal. She recovered rapidly after discontinuation of VPA. In this patient, a safe previous administration of VPA did not preclude the occurrence of encephalopathy. A relatively large initial VPA dosage could possibly be the culprit.

Ammonia↗
PubMed2001

[Comparison of anti-proliferation effects of two IFNs on Tca8113, ACC-M in vitro].

OBJECTIVE: Comparison of anti-proliferation and anti tumor specificity of two IFNs on Tca8113, ACC-M in Vitro. METHODS: MTT assay and HTCA were performed to determine direct anti-proliferation effects of two IFNs on Tca8113, ACC-M and L929 cells, respectively. RESULTS: When Tca8113 cells were treated with 1000U/ml alpha-IFN, gamma-IFN, respectively, cell proliferation inhabition rate was (45.4+/-4.1)% by gamma-IFN, (45.9+/-5.4)% by gamma-IFN; inhibition rate of colony formation was (52.0+/-2.9)% by alpha-IFN, (54.6+/-4.1)% by gamma-IFN; and ACC-M cell proliferation inhibition rate was (23.1+/-2.1)% by alpha-IFN,(26.5+/-1.3)% by gamma-IFN; inhibition rate of colony formation was (23.1+/-2.1)% by alpha-IFN, (26.5+/-1.3)% by gamma-IFN; inhibition rate of colony formation was (26.2+/-2.0)% by alpha-IFN, (27.3+/-1.8)% by gamma-IFN. There was no significant difference between two IFNs (P>0.05). When L929 cells were treated with 1000U/ml alpha-IFN, gamma-IFN,respectively, cell proliferation inhibition rate was (3.9+/-1.1)% by alpha IFN, (4.1+/-0.7)% by gamma-IFN; There was significant difference in antiproliferation on Tca8113 cells and L929 cells (P<0.01). CONCLUSION: Both alpha-IFN and gamma-IFN have better direct anti-cancer effect on tongue squamous cell cancer and anti-tumor specificity. But anti-proliferation effect of two IFNs on ACC-M cells was not obvious.

English Abstract↗
PubMed2001

[Experimental study of the effect of TNP-470 on human salivary adenoid cystic carcinoma cell in vitro].

OBJECTIVE: To investigate the effects of TNP-470 on human salivary adenoid cystic carcinoma cell line ACC M in vitro. METHODS: Cell proliferation was assessed by MTT assays and dye exclusion counting. Morphological changes of apoptosis were observed with fluorescent microscope. DNA ladder, apoptosis rate and cell cycle were examined by DNA agarose gel electronphores and fluorescence flow cytometry (FCM), respectively. RESULTS: The 50% inhibitory concentrations (IC50) of TNP-470 on ACC-M cells proliferation by MTT assays and dye exclusion counting were 40.68microg/ml and 46.38microg/ml. Apoptosis were observed by fluorescent microscope. DNA electrophoresis for the cells treated with TNP-470 showed brighter DNA ladder; Sub-G1 peak and G2/M arrest were also determined by FCM (P<0.01). CONCLUSION: TNP-470 has the effect of inducing apoptosis in ACC-M cells in vitro, which may be one of its antitumor mechanisms.

English Abstract↗
PubMed2001

[Establishment and biological characteristics of cisplatin resistant cell line from human tongue squamous cell carcinoma Tca8113].

OBJECTIVE: To establish a CDDP-resistant cell line from human tongue squamous cell carcinoma cell line Tca8113 and to study the characteristics of this cell line. METHODS: The concentration of CDDP added to Tca8113 cells was increased gradually and the chemotherapeutic drug was added continually, which was to induce the CDDP resistance in Tca8113 cells. The doubling time of Tca8113/CDDP cell line and the oncogenicity of this cell line in nude mice indicated its change on CDDP resistance. The sensibility to drugs of the cell line was assayed by MTT method. DNA fragmentation was detected by electrophoresis. Immunocytochemistry was utilized to examine the expression of P-gp and GST-pi. RESULTS: Tca8113 /CDDP was established and the cells grew steadily in 10 micromol/L CDDP medium. The Tca8113/CDDP cells were also resistant to Vm-26, BLM, VDS, E-ADM, Taxol and other drugs in different degrees. The doubling time of the cells was 29.9 hours and after a month it changed to 16.7 hours. When inoculated in nude mice, the cells showed the typical features of squamous cell carcinoma ultra-structurally and pathologically. Agarose gel electrophoresis of DNA from Tca8113 cells treated with CDDP revealed "ladder"pattern, which was the symbol of apoptosis, but there was no "ladder" in Tca8113/CDDP. The expression of P-gp and GST-pi in Tca8113/CDDP was much higher than that in Tca8113, which was the proof of the up-regulating translation of MDR-1 mRNA. CONCLUSION: CDDP induced Tca8113 cells resistance, and resistant cell line Tca8113/CDDP was established. The multi-drug resistance of Tca8113/CDDP cells were related to the GSH/GST system.

English Abstract↗
PubMed2001

[Ultramicrostructural observation on epithelial cell disdifferentiation in rat tongue carcinogenesis induced by 4NQO].

OBJECTIVE: To clarify epithelial cell ultramicrostructure changes in oral carcinogenesis. METHODS: The epithelial cell ultramicrostructures in tongue carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO) were observed by transmission electron microscope. RESULTS: With the progress of oral carcinogenesis, regular changes of epithelial cell were showed: decrease in tonofibril, keratohyaline granules, desmosome; and increase in mitochondria. The basement membrane was broken in some severe dysplasia (sDP) and was broken through by parts of cell processes in in situ carcinoma (ISC). CONCLUSION: Oral carcinogenesis is a multistep process. Epithelial cell aberrant differentiation is showed by a decrease in the synthetic products of epithelium cell.

English Abstract↗
PubMed2000

Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment.

Experimental studies performed prior to 1990 led to the widely held belief that matrix metalloproteinases (MMPs) produced by cancer cells are of critical importance in tumor invasion and metastasis. Based on this evidence, the pharmaceutical industry produced several well tolerated, orally active MMP inhibitors (MMPIs) which demonstrated efficacy in mouse cancer models. Phase III clinical trials initiated in 1997-98 using marimastat, prinomastat (AG3340), and BAY 12-9566 alone or in combination with standard chemotherapy in patients with advanced cancers (lung, prostate, pancreas, brain, GI tract) have recently been reported; no clinical efficacy was demonstrated. Bayer and Agouron have discontinued their ongoing Phase III drug trials of MMPIs in advanced cancer. In retrospect, the failure of MMPIs to alter disease progression in metastatic cancer might have been anticipated since MMPs appear to be important in early aspects of cancer progression (local invasion and micrometastasis) and may no longer be required once metastases have been established. Our understanding of MMP pathophysiology in cancer has expanded considerably in the past 10 years. Current views indicate that: (1) most MMPs in tumors are made by stromal cells, not carcinoma cells; (2) cancer cells induce stromal cells to synthesize MMPs using extracellular matrix metalloproteinase inducer (EMMPRIN) and cytokine stimulatory mechanisms; and (3) MMPs promote cell migration and the release of growth factors sequestered in the extracellular matrix. MMPs have a dual function in tumor angiogenesis: MMP-2 and MT1-MMP are required in breaking down basement membrane barriers in the early stage of angiogenesis, while other MMPs are involved in the generation of an angiogenic inhibitor, angiostatin. In spite of considerable recent progress in identifying multiple roles of MMPs in disease, our understanding of MMP function in cancer is far from complete (see Table 1). Based on accumulated data, it is recommended that future MMPI trials focus on: (1) patients with early stage cancer; (2) the use of MMPIs along with chemotherapy; (3) the measurement of MMPs in tumor tissue and blood as a means of identifying patients who are more likely to respond to MMPI therapy; and (4) identification of biomarkers that reflect activation or inhibition of MMPs in vivo.

Animals↗
PubMed2000

Identification of an alternatively spliced seprase mRNA that encodes a novel intracellular isoform.

Seprase is a homodimeric 170-kDa integral membrane gelatinase that is related to the ectoenzyme dipeptidyl peptidase IV. We have identified an alternatively spliced seprase messenger from the human melanoma cell line LOX that encodes a novel truncated isoform, seprase-s. The splice variant mRNA is generated by an out-of-frame deletion of a 1223-base pair exonic region that encodes part of the cytoplasmic tail, transmembrane, and the membrane proximal-central regions of the extracellular domain (Val(5) through Ser(412)) of the seprase 97-kDa subunit (seprase-l). The seprase-s mRNA has an elongated 5' leader (548 nucleotides) that harbors at least two upstream open reading frames that inhibit seprase-s expression from a downstream major open reading frame. Deletion mutagenesis of the wild type splice variant cDNA confirms that initiation of the seprase-s coding sequence begins with an ATG codon that corresponds to Met(522) of seprase-l. The seprase-s open reading frame encodes a 239-amino acid polypeptide with an M(r) approximately 27,000 that precisely overlaps the carboxyl-terminal catalytic region of seprase-l.

Alternative Splicing↗
PubMed2000

Human papillomavirus infection and p53 alteration in oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to examine human papillomavirus 16/18 infection incidence and p53 alteration in oral squamous cell carcinoma and to determine whether a correlation existed between HPV infection incidence and p53 alteration in this disease. METHODS: A series of 60 oral tissues (40 oral squamous cell carcinomas, 20 normal oral mucosas) was studied by polymerase chain reaction (PCR) to detect HPV 16 and 18 infection, and was studied by single strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively. RESULTS: HPV sequences were detected in 29 of 40 (72.5%) tumor specimens. A higher incidence (P = 0.037) of HPV 16/18 infection was observed in oral squamous cell carcinomas than in normal oral mucosas. Altered p53, either in genetic sequence or protein overexpression, was observed in 18 of 40 (45%) oral squamous cell carcinomas. Eleven of the 29 HPV-positive tumors contained observed alterations in either p53 protein expression or DNA sequence. No significant correlation (P = 0.145) was observed between HPV infection and p53 alteration. CONCLUSIONS: These data suggest that HPV16/18 infection and/or p53 alterations are associated with oral squamous cell carcinoma. No inverse correlation exists between oncogenic HPV infection and p53 alteration.

Adult↗
PubMed2000

[Detection of high risk human papillomavirus DNA in oral squamous cell carcinoma].

OBJECTIVE: To ascertain the prevalence of human papillomavirus(HPV) DNA in oral squamous cell carcinomas(OSCCs) and normal oral mucosa and to correlate the virologic data with other factors obtained from patients' records. METHODS: 113 paraffin embedded tissue blocks including 73 OSCCs and 40 normal oral mucosa were studied by polymerase chain reaction (PCR) for HPV type 16 and 18 DNA. Medical records of patients were reviewed to obtained the following factors: age, sex, tobacco and alcohol usage, site of tumor, histologic grade and clinical stage. RESULTS: 74%(54/73) of OSCCs and 55%(22/40) of normal oral mucosa were HPV 16/18 DNA positive. The presence of HPV DNA showed significant difference between OSCCs and normal oral mucosa (P=0.040). Statistical analysis indicated that age (60</=years) and sex (male) were associated with the presence of HPV16/18 DNA in the tumor. There were no significant association between HPV presence and other factors, include tobacco and alcohol usage, site of tumor, histologic grade and clinical stage. CONCLUSION: High risk HPV genotypes have a significant association with oral squamous cell carcinoma. It is a co-factor in oral carcinogenesis, particularly in male patients and patients under the sixth decade. HPV infection in the oral mucosa is common. HPV is not the single etiological factor responsible for human oral neoplasia.

English Abstract↗