Biomedical subjects

Yann-Jang Chen

Publications and source records attributed to Yann-Jang Chen.

At least 19 recordsLinked to original sources

PubMed2006

Molecular cytogenetic analysis of de novo dup(5)(q35.2q35.3) and review of the literature of pure partial trisomy 5q.

An 11-year-old girl presented with the phenotype of microcephaly, moderate mental retardation, motor retardation, short stature, strabismus, brachydactyly, and facial dysmorphism. She had undergone surgery for inguinal hernias. Detailed examinations of the heart and other internal organs revealed normal findings. Her karyotype was 46,XX,dup(5)(q35.2q35.3) de novo. Molecular cytogenetic analysis showed a paternally derived 5q35.2 --> q35.3 direct duplication and led to a correlation between the particular genotype and phenotype. This is the first description of a direct duplication of 5q35.2 --> q35.3. Our case represents the smallest distal duplication of chromosome 5q that is not associated with congenital heart defects. Our case also represents the smallest distal duplication of chromosome 5q that is associated with short stature and microcephaly. Mutations or deletions of the NSD1 gene, mapped to 5q35.2 --> q35.3, has been known to cause Sotos syndrome with cerebral gigantism, macrocephaly, advanced bone age and overgrowth. Our case provides evidence that the gene dosage effect of the NSD1 gene causes a reversed phenotype of microcephaly and short stature.

Abnormalities, Multiple↗

PubMed2006

Array-comparative genomic hybridization to detect genomewide changes in microdissected primary and metastatic oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy. However, it is unclear what, if any, genomic alterations occur as the disease progresses to invasive and metastatic OSCC. This study used genomewide array-CGH in microdissected specimens to map genetic alterations found in primary OSCC and neck lymph node metastases. We used array-based comparative genomic hybridization (array-CGH) to screen genomewide alterations in eight pairs of microdissected tissue samples from primary and metastatic OSCC. In addition, 25 primary and metastatic OSCC tissue pairs were examined with immunohistochemistry for protein expression of the most frequently altered genes. The highest frequencies of gains were detected in LMYC, REL, TERC, PIK3CA, MYB, MDR1, HRAS, GARP, CCND2, FES, HER2, SIS, and SRY. The highest frequencies of losses were detected in p44S10, TIF1, LPL, MTAP, BMI1, EGR2, and MAP2K5. Genomic alterations in TGFbeta2, cellular retinoid-binding protein 1 gene (CRBP1), PIK3CA, HTR1B, HRAS, ERBB3, and STK6 differed significantly between primary OSCC and their metastatic counterparts. Genomic alterations in PRKCZ, ABL1, and FGF4 were significantly different in patients who died compared with those who survived. Immunohistochemistry confirmed high PIK3CA immunoreactivity in primary and metastatic OSCC. Higher FGF4 immunoreactivity in primary OSCC is associated with a worse prognosis. Loss of CRBP1 immunoreactivity is evident in primary and metastatic OSCC. Our study suggests that precise genomic profiling can be useful in determining gene number changes in OSCC. As our understanding of these changes grow, this profiling may become a practical tool for clinical evaluation.

Adult↗

PubMed2006

Perinatal findings and molecular cytogenetic analyses of de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome.

OBJECTIVES: To present the perinatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 9q (9q22.3-->q31.3) associated with Gorlin syndrome. METHODS: Amniocentesis was performed at 18 weeks' gestation on a 27-year-old woman at a community hospital because of a high Down syndrome risk of 1/178, a low maternal serum alpha-fetoprotein (MSAFP) level of 0.66 multiples of the median (MoM), and a high maternal serum human chorionic gonadotrophin (MShCG) level of 3.13 MoM. The karyotype was initially determined to be 46,XY. However, fetal macrocephaly and overgrowth were found at 30 weeks' gestation. Postnatally, the infant manifested characteristic features of Gorlin syndrome. High-resolution chromosomal bandings of the peripheral blood lymphocytes, polymorphic DNA marker analysis to determine the parental origin of the deletion, array comparative genomic hybridization (CGH) to determine the extent of the chromosomal deletion, and fluorescence in situ hybridization (FISH) to determine the deletion of the PTCH gene were performed. RESULTS: The 850-band level of resolution showed an interstitial deletion of 9q (9q22.3-->q31.3). The parental karyotypes were normal. The karyotype of the proband was 46,XY,del(9)(q22.3q31.3)de novo. Polymorphic DNA marker analysis revealed that the deletion was of paternal origin. Array CGH revealed that the deleted region was about 12 Mb, encompassing the segment from 9q22.32 to 9q31.3. FISH analysis using the BAC probe RP11-34D4 and the probe RP11-43505 indicated the deletion of the PTCH gene. CONCLUSIONS: Fetuses with an interstitial deletion of 9q (9q22.3-->q31.3) may be associated with a low level of MSAFP and a high level of MShCG in the second trimester, and sonographic findings of overgrowth and macrocephaly in the third trimester.

Adult↗

PubMed2006

Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome.

OBJECTIVES: We report two siblings, a boy and a girl, with Cornelia de Lange syndrome (CdLS), born to unaffected parents, and attempt to delineate the underlying molecular mechanism leading to familial recurrence. METHODS: Nipped-B-like (NIPBL) gene mutations were screened using in denaturing high-performance liquid chromatography and sequencing in peripheral blood samples, from one of the affected siblings and her parents, as well as from a sperm sample from the father. RESULTS: A heterozygous missense NIPBL mutation, D2433G, was identified in the peripheral blood sample of the affected girl, but not in the peripheral blood samples of her parents. The D2433G mutation was also found in the sperm sample of the father. CONCLUSION: Gonadal mosaicism represents an underappreciated feature of the inheritance pattern of CdLS. To our knowledge, the girl represents the first CdLS patient whose father was documented to have a population of mutant sperm. When a sperm analysis indicates the presence of a mutant allele, it may be reasonable to offer prenatal genetic testing to the family in subsequent pregnancies, given that the sensitivity of fetal ultrasonography is relatively low.

Cell Cycle Proteins↗

PubMed2006

Comparative genomic hybridization study of perivascular epithelioid cell tumor: molecular genetic evidence of perivascular epithelioid cell tumor as a distinctive neoplasm.

Perivascular epithelioid cell tumor (PEComa) is a neoplasm composed chiefly of HMB-45-positive epithelioid cells with clear to granular cytoplasm and a perivascular distribution. Such tumors have been reported in different organs under a variety of designations. The cytogenetic features of these neoplasms have not been well studied. We collected 9 tumors (5 of kidney, 1 of prostate, 1 of urinary bladder, 1 of the pelvic cavity soft tissue, and 1 of uterus) from 8 patients, including one patient with tuberous sclerosis complex. The paraffin blocks of tumor tissue were submitted for comparative genomic hybridization analyses. Gross chromosomal aberrances were observed in all cases. The frequent imbalances were losses on chromosome 19 (8 cases), 16p (6 cases), 17p (6 cases), 1p (5 cases), and 18p (4 cases) and gains on chromosome X (6 cases), 12q (6 cases), 3q (5 cases), 5 (4 cases), and 2q (4 cases). The frequent deletion of 16p in which TSC2 gene is located indicates the oncogenetic relationship of PEComas with angiomyolipoma as a TSC2-linked neoplasm. From a molecular genetic perspective, the recurrent chromosomal alterations in both renal and extrarenal tumors further support the concept of PEComa as a distinctive tumor entity regardless of anatomic location.

Adolescent↗

PubMed2006

Coexistence of peripheral primitive neuroectodermal tumor and tetralogy of Fallot.

We describe a little girl with tetralogy of Fallot (TOF) who was found to have a huge peripheral primitive neuroectodermal tumor (pPNET) when she developed progressive difficulty in standing and crawling at the age of 11 months. The tumor was located in the left paraspinal region (T4-T12), with intraspinal extension causing severe compression. Nine days after surgical decompression with laminectomy, chemotherapy was initiated with alternative courses of vincristine, doxorubicin, cyclophosphamide, etoposide, and ifosfamide every 3 weeks. The muscle power in her legs recovered substantially after 2 courses of chemotherapy. Although peripheral blood for cytogenetic study revealed no chromosome abnormality, recent cytogenetic analysis has revealed a high frequency of reciprocal translocation t(11;22)(q24;q12) detected in pPNET and a strong association between TOF and chromosome 22q11 microdeletion (del 22q11). Both genetic defects involve chromosome 22q in the close region. This case report illustrates the necessity of investigating for cytogenetic change in chromosome 22 and close follow-up due to the possibility of subsequent development of malignancies in patients with TOF.

Chromosome Aberrations↗

PubMed2005

Deglycosylation of Na+/K+-ATPase causes the basolateral protein to undergo apical targeting in polarized hepatic cells.

Polarized epithelia, such as hepatocytes, target their integral membrane proteins to specific apical or basolateral membrane domains during or after biogenesis. The roles played by protein glycosylation in this sorting process remain controversial. We report here that deglycosylation treatments in well-polarized hepatic cells by deglycosylation drugs, or by site-directed mutagenesis of the N-linked-glycosylation residues, all cause the Na+/K+-ATPase beta-subunit to traffic from the native basolateral to the apical/canalicular domain. Deglycosylated beta-subunits are still able to bind and therefore transport the catalytic alpha-subunits to the aberrant apical location. Such apical targeting is mediated via the indirect transcytosis pathway. Cells containing apical Na+/K+-ATPase appear to be defective in maintaining the ionic gradient across the plasma membrane and in executing hepatic activities that are dependent upon the ionic homeostasis such as canalicular excretion.

Anti-Bacterial Agents↗

PubMed2005

Copy number changes of target genes in chromosome 3q25.3-qter of esophageal squamous cell carcinoma: TP63 is amplified in early carcinogenesis but down-regulated as disease progressed.

AIM: By using comparative genomic hybridization, gain of 3q was found in 45-86% cases of esophageal squamous cell carcinoma (EC-SCC). Chromosome 3q25.3-qter is the minimal common region with several oncogenes found within this region. However, amplification patterns of these genes in EC-SCC have never been reported. The possible association of copy number changes of these genes with pathologic characteristics is still not clear. METHODS: Real-time quantitative PCR (Q-PCR) was performed to analyze the copy number changes of 13 candidate genes within this region in 60 primary tumors of EC-SCC, and possible association of copy number changes with pathologic characteristics was analyzed by statistics. Immunohistochemistry (IHC) study was also performed on another set of 111 primary tumors of EC-SCC to verify the association between TP63 expression change and lymph node metastasis status. RESULTS: The average copy numbers (+/-SE) per haploid genome of individual genes in 60 samples were (from centromere to telomere): SSR3: 4.19 (+/-0.69); CCNL1: 5.24 (+/-0.67); SMC4L1: 2.01 (+/-0.16); EVI1: 2.02 (+/-0.12); hTERC: 5.28 (+/-0.54); SKIL: 2.71 (+/-0.14); EIF5A2: 1.95 (+/-0.12); ECT2: 9.18 (+/-1.68); PIK3CA: 8.13 (+/-1.17); EIF4G1: 1.07 (+/-0.05); SST: 3.07 (+/-0.25); TP63: 2.51 (+/-0.22); TFRC: 2.42 (+/-0.19). Four clusters of amplification were found: SSR3 and CCLN1 at 3q25.31; hTERC and SKIL at 3q26.2; ECT2 and PIK3CA at 3q26.31-q26.32; and SST, TP63 and TFRC at 3q27.3-q29. Patients with lymph node metastasis had significantly lower copy number of TP63 in the primary tumor than those without lymph node metastasis. IHC study on tissue arrays also showed that patients with lymph node metastasis have significantly lower TP63 staining score in the primary tumor than those without lymph node metastasis. CONCLUSION: This study showed that different amplification patterns were seen among different genes within 3q25.3-qter in EC-SCC, and several novel candidate oncogenes (SSR3, SMC4L1, ECT2, and SST) were identified. TP63 is amplified in early stage of EC-SCC carcinogenesis but down-regulated in advanced stage of disease.

Carcinoma, Squamous Cell↗

PubMed2005

Is urorectal septum malformation sequence a variant of the vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects and radial dysplasia association? Report of a case and a review of the literature.

UNLABELLED: The urorectal septum malformation sequence (URSMS) consists of multiple systems anomalies including ambiguous genitalia, the absence of a perineal opening, an imperforate anus, and urogenital, colonic and lumbosacral anomalies. We describe a 3-day-old female infant with characteristic URSMS and review its clinical manifestations, outcomes and putative pathogenesis. We also compare its characteristics with those of the vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects and radial dysplasia (VATER) association. CONCLUSION: Although defects of the urorectal septum malformation sequence and the vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects and radial dysplasia association overlap, we believe that they are separate entities. Differentiating the urorectal septum malformation sequence from vertebral defects, anal atresia, tracheo-oesophageal fistula, renal defects and radial dysplasia association is helpful to develop appropriate clinical investigations and search for the aetiology and pathogenesis of these diseases.

Abnormalities, Multiple↗

PubMed2005

Genetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases--an analysis by comparative genomic hybridization.

About 10% of colorectal carcinoma patients develop pulmonary metastases during their lifetime. We address whether and how the chromosomal abnormalities differ between the primary cancers and their metastatic counterparts, what the clonality relationship (CR) is between them, and whether certain genomic aberrations contribute to this disease progression. Comparative genomic hybridization (CGH) experiments were performed on 18 paired samples of primary and pulmonary metastases obtained from patients who had undergone two consecutive surgeries and from whom clinical data had been collected. The CGH profiles also were used as indexes for determining the CR between the cancers. The overall CGH abnormality profiles were similar for the primary colorectal carcinomas and their pulmonary metastases. Frequent gains were found on chromosome arms 20q, 8q, 13q, and 7q, whereas common losses were found on 18q, 8p, and 18p. The pulmonary metastases, however, contained more CGH abnormalities than did the primary carcinomas (total aberration events per tumor: 12.6 +/- 5.0 vs. 8.3 +/- 5.7, respectively, P = 0.024; gains: 7.6 +/- 3.1 vs. 5.1 +/- 3.5, respectively, P = 0.036; losses: 5.0 +/- 2.8 vs. 3.3 +/- 2.9, respectively, P = 0.076). Comparing CGH profiles between individual primary and metastasis pairs, we found that 10 of the 18 (56%) paired samples examined exhibited a high degree of CR, indicating that they were likely to have originated from the same clone and/or that not many additional chromosomal changes had occurred in the metastases, except for 4q loss, whose incidence was much higher in the metastases than in the primaries (60% vs. 10%; P = 0.030). Also, the primary tumors of the high-CR group carried more genomic aberrations, especially 8p loss, than did the primary tumors in the low-CR group. We found more chromosomal changes associated with the pulmonary metastases of colorectal cancer compared with the corresponding primary tumors. We concluded that primary cancers containing more genomic lesions, especially 8p losses, are more likely to metastasize to the lungs. Loss of 4q is potentially a supplementary factor contributing to the dissemination of this disease.

Adult↗

PubMed2005

Comparative genomic hybridization analysis of thymic neuroendocrine tumors.

Thymic neuroendocrine (carcinoid) tumors are a rare neoplasm of the anterior mediastinum. The tumors frequently exhibit a wide spectrum of histology and appear to follow a more aggressive behavior than their nonthymic counterparts. Given the differing clinicopathologic manifestations, thymic neuroendocrine tumors may also possess different cytogenetic abnormalities from those that occur in foregut carcinoid tumors. In this study, we employed comparative genomic hybridization to detect genomic instability in 10 sporadic thymic neuroendocrine tumors and one multiple endocrine neoplasia type 1 (MEN1)-associated case. Gross chromosomal imbalances were found in nine cases, including gains of chromosomal material on regions X, 8, 18 and 20p and losses on 3, 6, 9q, 13q and 11q. We did not observe deletion at locus 11q13 where the MEN1 gene is located. These findings were essentially dissimilar to those reported in sporadic and MEN1-associated foregut carcinoid tumors. Consequently, we consider that a distinctive cytogenetic mechanism is at work in the development of thymic neuroendocrine tumors, which is different from that of foregut carcinoid tumors.

Adult↗

PubMed2005

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.

Cell Line↗

PubMed2005

Calpain inhibitor inhibits p35-p25-Cdk5 activation, decreases tau hyperphosphorylation, and improves neurological function after spinal cord hemisection in rats.

Aberrant calpain activation is a key mediator of neuron death. We examined the cell-permeable calpain inhibitor MDL28170 in the pathophysiological processes after spinal cord injury (SCI) including p35-p25- cyclin-dependent kinase-5 (Cdk5) activation, tau hyperphosphorylation, neuron cell death, calpain I activation, astrogliosis, and microglia activation. Our study showed that intrathecal administration of MDL28170 improved neurologic dysfunction, prevented neuron loss, decreased the number of apoptotic cells, and abated astrogliosis and microglia activation 7 days after spinal cord hemisection in rats. Reverse transcription polymerase chain reaction demonstrated calpain inhibition significantly attenuated the ratio of proapoptotic Bax/anti-apoptotic Bcl-2 mRNA in the lesion and penumbra after SCI. Calpain, the calcium-activated proteolytic enzyme, was found to digest p35 to its truncated product, p25. Moreover, abnormal Cdk5 activation by p25 and subsequent tau hyperphosphorylation triggers pathologic events leading to neurodegeneration and neurofibrillary tangles. We found p35-p25-Cdk5 activation and tau hyperphosphorylation in SCI, and then we showed that intrathecal MDL28170 treatment could diminish p35 truncation, and abrogate aberrant tau phosphorylation. Double labeling of calpain I and phosphorylated tau (AT8) in the same cells of spinal cord lesion further implicated pathogenesis of SCI. In conclusion, MDL28170 abated calpain I activation, inhibited apoptosis and neuron loss, quenched microglia and astrocyte activation, and significantly improved neurologic deficit one week after spinal cord hemisection. The neuroprotective mechanisms of calpain inhibitor in SCI could be attenuating upregulation of Bax/Bcl-2 ratio, preventing p35 truncation in the lesion and penumbra, and abrogating tau hyperphosphorylation.

Animals↗

PubMed2005

Elevation of plasma and cerebrospinal fluid osteopontin levels in patients with atypical teratoid/rhabdoid tumor.

Osteopontin, a cancer metastasis-associated gene, is specifically up-regulated in central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT), but its biological behavior in the progression of CNS AT/RT has never been studied. We obtained plasma, cerebrospinal fluid (CSF), and brain tissue specimens from lobectomy or hemispherectomy samples from 39 patients (medulloblastoma, 16; AT/RT, 8; epilepsy, 6; hydrocephalus, 9). By enzyme-linked immunosorbent assay, the median osteopontin levels in plasma and CSF in AT/RT (852.0 and 1,175.0 ng/mL, respectively) were significantly higher than in medulloblastoma (492.5 and 524.5 ng/mL, respectively) and hydrocephalus and epilepsy (208.0 and 168.0 ng/mL, respectively) (P < .05). The results of real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analysis demonstrated that osteopontin expression in AT/RT (n = 5) was significantly higher than in medulloblastoma (n = 8) samples. The differences in osteopontin expression in plasma, CSF, and tumor samples in AT/RT and medulloblastoma correlated with survival differences. In 5 patients with AT/RT, plasma osteopontin levels decreased after treatment but increased with relapse. Osteopontin might be a potential marker to aid in identifying AT/RT recurrence.

Adolescent↗

PubMed2004

Single injection of naked plasmid encoding alpha-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice.

Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with alpha-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the alpha-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IkappaBalpha, endogenous inhibitor of nuclear factor kappaB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-alpha mRNA levels were prevented in the alpha-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest alpha-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications.

Animals↗

PubMed2004

Chromosomal comparative genomic hybridization abnormalities in early- and late-onset human breast cancers: correlation with disease progression and TP53 mutations.

Nearly 30% of the breast cancer patients in the Taiwanese community have their diseases diagnosed before the age of 40. Their 5-year survival rate is poorer than that of their late-onset breast cancer counterparts. Genomic abnormalities between these two breast cancer age groups were compared using comparative genomic hybridization (CGH) analyses. The sample set was made up of 44 early-onset (<35 years old) and 54 late-onset cases (>63 years old). Frequent CGH changes were noted, such as gains on 8q, 1q, and 17q and losses on 16q, 17p, and 8p. These were very similar for the two age groups, as well as for Taiwanese women and other ethnic populations. In contrast, several less common lesions, such as gains on 16p and 8p and losses on 11q and 9p, were significantly different between the early- and late-onset breast tumors. In addition, more profound chromosomal changes were consistently associated with the more advanced-stage tumors, and less expression of the estrogen and the progesterone receptors, and of HER-2/neu. About 19% of the breast cancers examined carried a TP53 mutation in exons 4-9. Of these, 88% (15/17) were missense point mutations and these were distributed randomly along the tested gene fragments without apparent clustering, as has been shown in certain other ethnic or regional studies. On average, patients carrying these TP53 mutations had 9.5 CGH lesions per case, compared to only 2.8 changes in samples that had no TP53 mutation. Our results indicate that certain genomic lesions, especially 11q loss, may play a role in early-onset breast tumor formation, and that combined use of genomic patterns and molecular targets may provide a useful tool for diagnostic, therapeutic, and prognostic purposes.

Adult↗

PubMed2004

Genome-wide profiling of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignancy, the incidence of which is particularly high in some Asian countries due to the geographically linked areca quid (AQ) chewing habit. In this study, array-based comparative genomic hybridization was used to screen microdissected OSCCs for genome-wide alterations. The highest frequencies of gene gain were detected for TP63, Serpine1, FGF4/FGF3, c-Myc and DMD. The highest frequencies of deletion were detected for Caspase8 and MTAP. Gained genes, classified by hierarchical clustering, were mainly on 17q21-tel; 20q; 11q13; 3q27-29 and the X chromosome. Among these, gains of EGFR at 7p, FGF4/FGF3, CCND1 and EMS1 at 11q13, and AIB1 at 20q were significantly associated with lymph node metastasis. The genomic profiles of FHIT and EXT1 in AQ-associated and non-AQ-associated OSCCs exhibited the most prominent differences. RT-PCR confirmed the significant increase of TP63 and Serpine1 mRNA expression in OSCC relative to non-malignant matched tissue. A significant increase in Serpine1 immunoreactivity was observed from non-malignant matched tissue to OSCC. However, there was no correlation between the frequent genomic loss of Caspase 8 and a significant decrease in Caspase8 expression. These data demonstrate that genomic profiling can be useful in analysing pathogenetic events involved in the genesis or progression of OSCC.

Carcinoma, Squamous Cell↗

PubMed2004

Establishment of OC3 oral carcinoma cell line and identification of NF-kappa B activation responses to areca nut extract.

BACKGROUND: Cell lines derived from oral squamous cell carcinoma (OSCC) exposed to variable etiological factors can bestow advantages in understanding the molecular and cellular alterations pertaining to environmental impacts. Most OSCC cell lines have been established from smoker patients or areca chewing/smoker patients, carrying the genomic alterations in p53. METHODS: A new cell line, oral carcinoma 3 (OC3), was established from an OSCC in a long-term areca (betel) chewer who does not smoke. Cellular and molecular features of OC3 were determined by variable assays. RESULTS: The cultured monolayer cells were mainly polygonal and had the expression of cytokeratin 14. The chromosomal analysis using comparative genomic hybridization has revealed the gain in chromosomes 1q, 5q, and 8q, the loss in 4q, 6p, and 8p as well as the gain of entire chromosome 20. Loss of heterozygosity and instability in multiple microsatellite markers in chromosome 4q were also noted. OC3 cells bear wild-type p53 coding sequence and have a high level of p53 expression. Its p21 expression was similar to that in normal human oral keratinocyte (NHOK). Interestingly, activation of nuclear factor kappa B (NF-kappa B) in OC3 cells following the treatment of areca nut extract was observed. CONCLUSION: OC3 cell line could be valuable in understanding the genetic impairments and phenotypic changes associated with areca in oral keratinocyte.

Areca↗