Biomedical subjects

Jin-Ching Lin

Publications and source records attributed to Jin-Ching Lin.

At least 19 recordsLinked to original sources

PubMed2007

Impact of recurrence interval on survival of oral cavity squamous cell carcinoma patients after local relapse.

OBJECTIVE: The aim of this study was to investigate whether the recurrence interval influenced the survival of oral cavity squamous cell carcinoma patients after relapse. STUDY DESIGN AND SETTING: Retrospective charts were reviewed at a medical center. METHODS: We retrospectively reviewed 1687 chart records of oral cancer patients. Statistical methods included descriptive statistics, bivariate analyses, Kaplan-Meier survival analyses, and Cox proportional hazard models for investigating the relationship between the recurrence interval and survival of oral cancer patients after relapse. RESULTS: Local recurrence rate was 31.3 percent. Kaplan-Meier survival analyses showed the 5-year overall survival after recurrence was 31.56 percent. Cox proportional hazard model revealed that those with recurrence interval less than 18 months tended to have a higher probability of death than those with recurrence interval greater than or equal to 18 months (relative risk, 1.743; 95% confidence interval, 1.298-2.358). CONCLUSION: The interval from initial treatment to recurrence is an independent prognostic factor for oral squamous cell carcinoma patients. Those with a shorter disease-free interval tend to have a less favorable outcome.

Adult↗

PubMed2006

Experience in fractionated stereotactic body radiation therapy boost for newly diagnosed nasopharyngeal carcinoma.

PURPOSE: Radiotherapy is the most effective treatment for nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the efficacy and toxicity of fractionated stereotactic body radiation therapy (SBRT) boost for NPC. METHODS AND MATERIALS: Sixty-four patients with newly diagnosed, nonmetastatic NPC were treated with conventional radiotherapy 64.8-68.4 Gy followed by fractionated SBRT boost 12-15 Gy between January 2002 and July 2004. Most patients (72%) presented with Stage III-IV disease. Fifty-two patients also received cisplatin-based concurrent (38) or neoadjuvant (14) chemotherapy. The major endpoints were local control, overall survival, and complications. RESULTS: All patients finished the planned dose of radiotherapy. After a median follow-up of 31 months (range, 22-54), 15 patients developed tumor recurrences--3 in the nasopharynx, 4 in the neck, 5 in distant sites, 1 in both nasopharynx and neck, 2 in the neck and a distant site. The 3-year actuarial rate of local control was 93.1%, regional control 91.4%, freedom from distant metastasis 90.3%, and overall survival 84.9%, respectively. There were no Grade 4 acute or chronic radiation-related complications. CONCLUSIONS: Fractionated SBRT boost for NPC is technically feasible and provides good local control without any severe complications.

Adult↗

PubMed2006

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. METHODS AND MATERIALS: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. RESULTS: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p = 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. CONCLUSION: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

Adult↗

PubMed2006

Socio-demographic factors in the prognosis of oral cancer patients.

The aim of this study was to determine the survival rate of oral cancer patients treated in a medical center in central Taiwan and to investigate whether socio-demographic factors influence their survival. We retrospectively reviewed 1010 chart records of oral cancer patients. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model was used for investigating the relationship between socio-demographic factors and survival. The overall 5-year survival rate was 63.24%. Multivariate analysis revealed that those without religious belief tended to have higher probability of death than those who had religious belief (relative risk (RR): 2.057, p<0.001). In addition, those who were single, widow/widower or divorced/separated had a poorer prognosis than those who were married (RR: 1.528, p=0.008). Apart from clinical features, socio-demographic factors also significantly influenced the survival of oral cancer patients. Therefore, care providers should take socio-demographic issues into consideration aside from ordinary clinical health care.

Adult↗

PubMed2006

Nutritional factors and survival of patients with oral cancer.

BACKGROUND: Our objective was to determine the survival rate of patients with oral cancer who were treated at a medical center in central Taiwan. Furthermore, we attempted to investigate whether nutritional factors influence the survival. METHODS: We carried out a retrospective review of 1010 chart records of patients with oral cancer. We used the Kaplan-Meier method for survival analysis and the Cox proportional hazard models to investigate the prognosticators. RESULTS: Kaplan-Meier survival analysis showed an overall 5-year survival rate of 63.24%. The Cox proportional hazard model revealed that those with a preoperative body mass index (BMI) of <22.8 kg/m(2) tended to have a higher probability of death (relative risk [RR] = 1.292, p = .022). In addition, those with a preoperative serum albumin level of <4.15 g/dL were generally associated with a poorer prognosis (RR = 1.313, p = .016). CONCLUSIONS: Apart from clinical features, nutritional factors also had a significant influence on the survival of patients with oral cancer. Therefore, good nutritional status is crucial for patients with oral cancer in improving their survival.

Adult↗

PubMed2006

Association of p53 codon 72 polymorphism with risk of hypopharyngeal squamous cell carcinoma in Taiwan.

BACKGROUND: p53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit. METHODS: Genomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Patients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04). CONCLUSION: This study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer.

Adult↗

PubMed2005

ERK activation in arsenite-treated G1-enriched CL3 cells contributes to survival, DNA repair inhibition, and micronucleus formation.

Arsenite is known to induce chromosomal damage and extracellular signal-regulated kinases 1/2 (ERK) signaling transduction pathway. Arsenite also perturbs mitotic spindle and induces G2/M prolongation, leading to genomic instability. However, little is known concerning whether G1 phase is susceptible to arsenite in causing genomic instability and ERK activation. In this study, we investigate the roles of ERK activation in survival, micronucleus formation, and nucleotide excision repair (NER) synthesis in arsenite-treated G1-enriched CL3 human non-small-cell lung carcinoma cells. We found that G1 was the most insensitive phase to arsenite cytotoxicity, yet it was highly susceptible to arsenite in micronucleus induction. After arsenite exposure, the G1 cells exhibited a marked retard in the formation of binucleated cells when they were cultured in cytochalasin B, an inhibitor of cytokinesis, suggesting that arsenite delays the cell cycle progression. Arsenite activated sustained-ERK signal in G1 cells whose suppression further decreased cell proliferation and survival and could lower the micronucleus induction. The NER synthesis activity of G1 cells was inhibited by arsenite as a function of the extent of ERK activation. Intriguingly, blockage of ERK activation recovered NER synthesis activity in the arsenite-treated G1 cells. Together, these results suggest that ERK activation in arsenite-treated G1 cells counteracts cytotoxicity and contributes to genomic instability via NER synthesis inhibition and micronucleus induction.

Arsenites↗

PubMed2005

Mitochondrial genome instability and mtDNA depletion in human cancers.

An increase in the rate of glycolysis is one of the metabolic alterations in most cancer cells. However, the role of alterations in mitochondrial function and mitochondrial DNA (mtDNA) in carcinogenesis still remains unclear. In this study, we analyzed the nucleotide sequence of the D-loop and the copy number of mtDNA in 54 hepatocellular carcinomas (HCCs), 31 gastric, 31 lung, and 25 colorectal cancers as well as their corresponding non-tumorous tissues. The results revealed that 42.6% (23/54) of the HCCs, 51.6% (16/31) of the gastric cancers, 22.6% (7/31) of the lung cancers, and 40.0% (10/25) of the colorectal cancers harbored mutation(s) in the D-loop of mtDNA. The mtDNA mutations in 43.5% (10/23) of the HCCs, 62.5% (10/16) of the gastric cancers, 57.1% (4/7) of the lung cancers, and 90.0% (9/10) of the colorectal cancers were changes in the mononucleotide or dinucleotide repeats, deletions, or multiple insertions. Moreover, we found that there is a significant decrease in mtDNA copy number in 57.4% (31/54) of the HCCs, 54.8% (17/31) of the gastric cancers, 22.6% (7/31) of the lung cancers, and 28.0% (7/25) of the colorectal cancers compared with the corresponding non-tumorous tissues. It is noteworthy that the incidence of somatic mutations in the D-loop of mtDNA in the cancers of later stages was higher than that of the early-stage cancers. Taken together, our findings suggest that instability in the D-loop region of mtDNA, together with the decrease in mtDNA copy number, is involved in the carcinogenesis of human cancers.

DNA, Mitochondrial↗

PubMed2004

Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate?

PURPOSE: To evaluate a simple risk grouping system and determine whether concurrent chemoradiotherapy (CCRT) is adequate for patients with advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 284 patients with 1992 American Joint Committee on Cancer (AJCC) Stage III to IV (M0) NPC were analyzed retrospectively. They were treated by either radiotherapy (RT) alone or CCRT. We divided patients into high-risk and low-risk subgroups according to our experience. High-risk patients met at least one of the following criteria: (1) nodal size >6 cm, (2) supraclavicular node metastases, (3) 1992 AJCC stage T4N2, (4) multiple neck node metastases with 1 node >4 cm. The disease extent of each patient was stratified by our risk grouping system, AJCC 1992 and 1997 staging systems. Survival analyses-including nasopharynx disease free (TS), neck disease free (NS), distant metastasis disease free (MS), overall survival (OS), and progression-free (PFS) survival curves-were compared between these three different classifications. RESULTS: According to the 1992 AJCC staging system, 80.3% (228/284) of NPC patients are Stage IV, whereas only 19.7% are Stage III. Most patients are downstaged by the 1997 AJCC staging system with 28.5% (81/284) Stage IV and 71.5% (203/284) Stage III/II. Our risk criteria stratify more even patient distribution, because 119 patients (41.9%) are assigned to the high-risk group and 165 patients (58.1%) to the low-risk group. Log-rank test of Kaplan-Meier survival curves, multivariate comparison of the Cox proportional hazards model, and 3 goodness-of-fit indices validated that our risk grouping system seemed to be at least as efficacious as, or slightly superior to, the 1992 and 1997 AJCC systems. The 5-year TS (95.1% vs. 76.8%, p = 0.0012), NS (100% vs. 95.7%, p = 0.0974), MS (90.5% vs. 78.1%, p = 0.0282), OS (83.2% vs. 59.7%, p = 0.0041), and PFS (87.3% vs. 61.5%, p = 0.0003) were significantly better in patients receiving CCRT than RT alone for the low-risk group. However, the corresponding survival rates between CCRT and RT for high-risk patients were 74.9% vs. 67.6% (p = 0.2545) for TS, 92.1% vs. 86.8% (p = 0.4744) for NS, 59.7% vs. 60.0% (p = 0.5537) for MS, 55.8% vs. 46.3% (p = 0.1761) for OS, and 44.5% vs. 43.1% (p = 0.3911) for PFS, respectively. CONCLUSIONS: Concurrent chemoradiotherapy is superior to RT alone for low-risk patients but inadequate for high-risk patients. Adding neoadjuvant and/or adjuvant chemotherapy would be a reasonable approach for high-risk patients. Our risk grouping criteria are a simple and useful guide that will have important implications in the design of future therapeutic trials.

Adolescent↗

PubMed2004

Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma.

BACKGROUND: We investigated the clinical significance of plasma concentrations of Epstein-Barr virus (EBV) DNA in patients with advanced nasopharyngeal carcinoma. METHODS: Ninety-nine patients with biopsy-proven stage III or IV nasopharyngeal carcinoma and no evidence of metastasis (M0) received 10 weekly chemotherapy treatments followed by radiotherapy. Plasma samples from the patients were subjected to a real-time quantitative polymerase-chain-reaction assay. EBV genotypes of paired samples from plasma and primary tumor were compared. RESULTS: Plasma EBV DNA was detectable before treatment in 94 of the 99 patients, but not in 40 healthy controls or 20 cured patients. The median concentrations of plasma EBV DNA were 681 copies per milliliter among 25 patients with stage III disease, 1703 copies per milliliter among 74 patients with stage IV disease, and 291,940 copies per milliliter among 19 control patients with distant metastasis (P<0.001). Patients with relapse had a significantly higher plasma EBV DNA concentration before treatment than those who did not have a relapse (median, 3035 vs. 1202 copies per milliliter; P=0.02). The consistent genotyping of EBV DNA between paired samples of plasma and primary tumor suggested that the circulating cell-free EBV DNA may originate from the primary tumor. Unlike the rebound of plasma EBV DNA concentrations in the patients who had a relapse, the plasma EBV DNA concentration was persistently low or undetectable in patients with a complete clinical remission. Overall survival (P<0.001) and relapse-free survival (P=0.02) were significantly lower among patients with pretreatment plasma EBV DNA concentrations of at least 1500 copies per milliliter than among those with concentrations of less than 1500 copies per milliliter. Patients with persistently detectable plasma EBV DNA had significantly worse overall survival (P<0.001) and relapse-free survival (P<0.001) than patients with undetectable EBV DNA one week after the completion of radiotherapy. CONCLUSIONS: Quantification of plasma EBV DNA is useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment.

Adult↗

PubMed2004

Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma.

Somatic mutations in mitochondrial DNA (mtDNA) have been detected in many human cancers, including hepatocellular carcinoma (HCC). The D-loop region was found to be a "hot spot" for mutation in mtDNA of the tumors. However, effects of the D-loop mutations on the copy number of mtDNA in tumor tissues are poorly understood. Using direct sequencing, we examined mutations in the D-loop region of mtDNA in 61 HCCs and the corresponding non-tumor liver tissues. The results revealed that 39.3% of the HCCs carried somatic mutation(s) in the D-loop of mtDNA, and most of these mutations were homoplasmic. Moreover, 37.0% (10/27) of these mutations were T-to-C and G-to-A transitions and 40.7% (11/27) of them were located in the polycytidine stretch between nucleotide position (np) 303 and 309 of mtDNA. In addition, we found that mtDNA copy number of HCC was significantly decreased in 60.5% of the patients with hepatoma, especially in those with somatic mutation(s) in the D-loop of mtDNA (17/24). This decrease in mtDNA copy number was highly associated with the occurrence of point mutations near the replication origin of the heavy-strand of mtDNA. Interestingly, we found that 42.9% (6/14) of the HCCs without mutation in the D-loop had a reduced copy number of mtDNA, indicating that other unidentified factors involved in mitochondrial biogenesis might be defective in the tumor. The results obtained in this study strongly suggest that somatic mutations in the D-loop together with the decrease in the copy number of mtDNA may be an important event during the early phase of liver carcinogenesis.

Base Sequence↗

PubMed2003

Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. PATIENTS AND METHODS: From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m(2)/d plus fluorouracil 400 mg/m(2)/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P =.0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P =.0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for > or = 1 week for another nine patients. There were no treatment-related deaths in either arm. CONCLUSION: We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.

Adult↗

PubMed2003

Outpatient weekly 24-hour infusional adjuvant chemotherapy of cisplatin, 5-fluorouracil, and leucovorin for high-risk nasopharyngeal carcinoma.

BACKGROUND: Distant metastasis rather than locoregional recurrence is the major site of failure after adequate radiotherapy in nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the toxicity and survival of outpatient weekly 24-hour infusion adjuvant chemotherapy for NPC patients with high-risk of distant failure. METHODS: Our definition of high-risk NPC included patients with (1) 1992 AJCC staging system of N3, T4N2, or N2 with one of nodal size > 4 cm; (2) supraclavicular node metastasis; and (3) residual disease after radiotherapy or neck relapse. From August 1994 to August 1997, 41 NPC patients matching the preceding criteria agreed to receive weekly PFL (cisplatin 25 mg/m(2), 5-fluorouracil 1250 mg/m(2), and leucovorin 120 mg/m(2)) adjuvant chemotherapy for a total of 18 weeks. Clinical data of another 88 patients with similar disease status who did not receive adjuvant chemotherapy during the same period were collected and analyzed for comparison. Survival analysis was investigated by the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: A total of 700 weekly chemotherapy doses was delivered to 41 patients. The ratio of actual/planned dose delivery was 94.9%. Grade 3-4 toxicity of adjuvant chemotherapy included leucopenia (7.3%), anemia (2.4%), thrombocytopenia (2.4%), and nausea/vomiting (2.4%). After a median follow-up of 70 months, 26.8% (11 of 41) and 47.7% (42 of 88) of patients in PFL and no adjuvant chemotherapy groups had distant metastasis (p =.0247). The 5-year metastasis-free survival rates were 71.9% for the PFL group compared with 48.4% for no adjuvant chemotherapy patients (p =.0187). The 5-year overall survival rates were 53.7% (PFL group) and 38.3% (no adjuvant chemotherapy group), respectively (p =.0666). Multivariate Cox analysis showed PFL adjuvant chemotherapy was the independent factor that predicted metastasis-free survival after adjustment for other variables. CONCLUSIONS: Outpatient weekly 24-hour continuous infusion PFL adjuvant chemotherapy is a well-tolerated regimen with promising results in high-risk NPC patients and merits investigation in phase III studies.

Adolescent↗

PubMed2002

A novel p53 mutant retained functional activity in lung carcinomas.

The gene p53 is a critical tumor suppressor that can respond to multiple signals of cellular gatekeepers for growth and division. The mdm2 gene is one of the downstream target genes for transcriptional activation by the product of p53 tumor suppressor gene. Transactivation of mdm2 gene is represented by the presence of a functional P53 protein. To understand the biological function of mutant p53 in tumorigenesis, we constructed a number of p53 mutants by site-directed mutagenesis (H179Y, L194R, S240R, R249S, A276D, E286Q), followed by characterization of each P53 mutant's ability to transactivate mdm2, bax and p21waf. The transactivation properties of p53 mutants were compared by co-transfection with pGL-3-mdm2, pGL-3-bax and pGL-3-p21waf into the P53 null cell line H1299 derived from a non-small cell lung carcinoma. Among them mt p53 S240R and E286Q were shown to have enhanced transactivating activity of pGL3-mdm2, at about 43.2 and 28.2% of the wt p53 vector, respectively, while the remaining four had nearly the same level of activity as the negative control did. Furthermore, data indicated that mt p53 S240R had as high an ability to suppress the growth of the p53 null cell line H1299 as wild type p53. Therefore, mutant p53 alone is an insufficient indicator of poor prognosis. Instead, functional p53 may affect lung cancer prognosis.

Apoptosis↗

PubMed2002

Evaluation of cytokeratin-19 mRNA as a tumor marker in the peripheral blood of nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy.

The reverse transcriptase-polymerase chain reaction (RT-PCR) technique is a tool capable of detecting minute quantities of circulating tumor cell-derived transcripts. Nasopharyngeal carcinoma (NPC) is a rapidly growing tumor of epithelial origin and high metastatic potential. The aim of our study is to investigate the clinical value of circulating cytokeratin-19 (CK-19) mRNA detection in NPC patients. Between June 1997 and March 1999, 57 previously untreated, advanced NPC patients without distant metastasis were uniformly treated by concurrent chemoradiotherapy. Peripheral blood samples were collected prospectively before treatment and subjected to a nested RT-PCR assay. Measures were taken to prevent contamination and pseudogene interference. PCR products of positive results were verified by restriction enzyme Hae II and direct sequencing. Under our nested RT-PCR experimental conditions, 33.3% (19/57) clinically nonmetastatic NPC patients had CK-19 mRNA in their blood. The positive detection rates of CK-19 mRNA in the peripheral blood for different stages were 20.0% for stage II, 31.6% stage III and 43.5% stage IV (p = 0.1335). After a median follow-up time of 35 months, 2 patients had recurrences of their primary tumors and 14 developed distant metastases without locoregional recurrence. Nine of 19 (47.4%) CK-19 mRNA-positive patients and 5 of 38 (13.2%) CK-19 mRNA-negative patients developed distant metastasis (p = 0.00826). The 3-year metastasis-free survival rates were 49.9% for patients with detectable CK-19 and 85.9% for those with undetectable CK-19 (p = 0.0089, log-rank test). Our data suggest that the presence of CK-19 mRNA in the peripheral blood may be a potential marker of micrometastasis for NPC.

Adult↗

PubMed2002

PCR detection of circulating tumor cells in nasopharyngeal carcinoma patients with distant metastasis: effect of enzyme and sampling.

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a high potential to develop distant metastasis after radiotherapy. Cytokeratin 19 (CK-19) mRNA has been frequently used as a marker in the detection of circulating tumor cells of epithelial origin, but has rarely been investigated in NPC. This study was performed to evaluate the effect of blood sampling and different Taq DNA polymerase on the results of nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: Peripheral blood samples from a total of 37 NPC patients with well-documented distant metastasis (M1) were collected before treatment. Eighteen patients had more than one blood sampling. Five different Taq DNA polymerases were used to test the blood from 17 patients. Peripheral blood of 37 nonmetastatic (M0) NPC patients was tested by the same nested RT-PCR system using multiple Taq DNA polymerases to evaluate the impact of multienzyme assay in the prediction of subsequent distant metastasis. RESULTS: Among M1 NPC patients, the accumulative positive rates of CK-19 mRNA were 22.2%, 44.4%, 70.6%, 75.0%, and 80.0% when one, two, three, four, or five blood sampling were taken, respectively. The accumulative positive rates increased as the numbers of different enzymes increased-from 35.5% by one enzyme to 82.4% by five enzymes. Six of 37 M0 patients had distant metastasis develop after a median follow-up time of 20 months. The detection sensitivity for four-enzyme test (5 of 6 = 83.3%) is better than that of one-enzyme test (2 of 6 = 33.3%). CONCLUSIONS: Our data demonstrate that multiple blood sampling or using multiple enzymes for nested RT-PCR assay significantly enhances the sensitivity in the molecular diagnosis of NPC metastasis.

Adolescent↗

PubMed2002

Consistent sequence variation of Epstein-Barr virus nuclear antigen 1 in primary tumor and peripheral blood cells of patients with nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) has been proven as a cancer associated with Epstein-Barr virus (EBV). This study was performed to examine sequence variations of the EBV nuclear antigen 1 gene (EBNA-1) in primary tumor and peripheral-blood cells of NPC patients from Taiwan. EXPERIMENTAL DESIGN: DNA extracted from freshly frozen tumor tissues and corresponding peripheral-blood cells of 13 previously untreated NPC patients were subjected to PCR and direct sequencing using EBNA-1-specific primers. We compared the sequence data and analyzed the clinical outcomes. RESULTS: We obtained a 100% positive-detection rate of EBV DNA in the primary tumors of all patients irrespective of the degree of differentiation. The EBNA-1 gene of all tumor samples was the "V-val" strain, showing the same clustered point mutations. They included 21 nucleotide exchanges, leading to 14 amino-acid mutations and 6 silent exchanges, relative to B95-8 cell line. Two of 13 tumors exhibited an additional point mutation at codon 585. EBV DNA was also detected in peripheral-blood cells of 9 of 13 patients under our experimental conditions. Direct-sequencing data showed match alterations of EBNA-1 gene between the primary tumor and peripheral-blood cells. Tumor relapse was observed in four of nine patients with detectable EBNA-1 DNA in their peripheral-blood cells, whereas none of the four patients without detectable EBNA-1 DNA in their peripheral-blood cells developed tumor relapse. CONCLUSIONS: Results of the current study represents the first demonstration of consistent sequence variation of EBNA-1 in primary tumors and peripheral-blood cells. Clinical observations support that the presence of EBV DNA in the peripheral-blood cells may arise from disseminated cancer cells, resulting in a higher relapse rate and poor prognosis.

Carcinoma↗

PubMedDate not supplied

Endoscopic sinus surgery for the treatment of chronic rhinosinusitis in patients with postirradiated nasopharyngeal carcinoma.

PURPOSE: Our purpose was to evaluate the efficacy and safety of endoscopic sinus surgery (ESS) in patients with nasopharyngeal carcinoma (NPC) after irradiation. MATERIALS AND METHODS: A retrospective study of postirradiated NPC patients who received ESS for the treatment of chronic rhinosinusitis in Taichung Veterans General Hospital. Symptoms, endoscopic findings, and computed tomography were used to evaluate the efficacy of ESS in these patients, and the safety was evaluated by intraoperative findings and complications. RESULTS: Since 1996, 10 postirradiated NPC patients with chronic rhinosinusitis have been treated by ESS and followed up for at least 2 years. The interval between radiotherapy and ESS was from 4 months to 16 years. After surgery, 7 patients felt improved except for one patient who died of tumor recurrence and computed tomography scores changed from 6.6 to 3.7, although prolonged nasal crusting was observed in most patients by endoscopy. One patient was complicated with cerebrospinal fluid leakage and the dura defect was immediately repaired without any sequelae. CONCLUSIONS: This study shows that ESS is effective for the treatment of chronic rhinosinusitis in postirradiated NPC patients if they failed medical treatment.

Adolescent↗