Ravat Panvichian - Academia.edu (original) (raw)

Papers by Ravat Panvichian

BMC Cancer

Introduction Difference in clinical responses to cancer therapy in each patient is from several f... more Introduction Difference in clinical responses to cancer therapy in each patient is from several factors. Gastrointestinal microbiota is one of the reasons. However, this correlation remains unknown. This study aims to explore correlation between gastrointestinal microbiota profile and clinical outcomes in Thai advanced non-small cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) status. Methods We enrolled 13 patients with advanced EGFR–wild-type (WT) NSCLC who received chemotherapy and 15 patients with EGFR-mutant NSCLC who received EGFR tyrosine kinase inhibitors. We collected fecal samples at baseline and first disease evaluation and performed 16S rRNA gene sequencing by NGS to assess microbiota profile. The correlations between gastrointestinal microbiota and clinical variables were studied. Results The clinical characteristics were balanced between the cohorts, excluding significantly higher albumin levels in the EGFR-mutant group. Albumin was the onl...

Cancer Reports

Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (... more Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014-2018. BRCA mutations were detected using next-generation sequencing and con rmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain signi cance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64-6.49), P = 0.229). The stage at diagnosis was the sole factor signi cantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations.

Additional file 6: Supplement Fig. S1. The specific pairing of the qPCR primers with KIAA0101 tv1... more Additional file 6: Supplement Fig. S1. The specific pairing of the qPCR primers with KIAA0101 tv1 mRNA but not with KIAA0101 tv2 mRNA.

Additional file 5: Table S5. Source, dilution, incubation time, conditions of different biomarkers.

Additional file 4: Supplement Table S4. Cohort IHC.

Additional file 2: Supplement Table S2. Cohort qRT-PCR.

Additional file 3: Supplement Table S3. Cohort ddPCR.

Additional file 1: Figure S1. The confirmation of DNA sequences of EGFR mutation. The DNA sequenc... more Additional file 1: Figure S1. The confirmation of DNA sequences of EGFR mutation. The DNA sequences of each EGFR mutations after site-directed mutagenesis in pBabe-puro were confirmed with sequencing by Macrogen. Inc., South Korea.

Copyright © 2015 Ravat Panvichian et al. This is an open access article distributed under the Cre... more Copyright © 2015 Ravat Panvichian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatocellular carcinoma (HCC) is the leading cause of cancer death inmenworldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues andmatched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5 % of tumor tissues bu...

Background PCNA-associated factor (KIAA0101/p15PAF) is a cell-cycle regulated oncoprotein that re... more Background PCNA-associated factor (KIAA0101/p15PAF) is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101 is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101 gene amplification occurs and causally correlates with the KIAA0101 overexpression in HCC. This question is relevant to the development of the optimal test(s) for KIAA0101 and the strategies to target KIAA0101 in HCC. Methods In this study, we validated KIAA0101 mRNA expression levels by quantitative real-time PCR in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues; we then evaluated KIAA0101 gene copy numbers by droplet digital PCR (ddPCR) in 36 pairs of the tissues. Besides, KIAA0101 protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. ...

Cancer Research, 2005

1886 Functional inactivation of tumor-suppressor gene(s) is an essential step in carcinogenesis a... more 1886 Functional inactivation of tumor-suppressor gene(s) is an essential step in carcinogenesis and progression. Tumor-suppressor genes are generally inactivated by an intragenic point mutation in one allele and the subsequent loss of the corresponding (wild-type) allele, resulting in a condition known as “loss of heterozygosity”(LOH). Somatic alterations in microsatellite sequence due to a deletion or an insertion of one or more repeat units have been termed “microsatellite instabilities” (MSI). MSI is associated with defects in the DNA mismatch-repair machinery, and MSI has been detected in both hereditary and sporadic human cancer. MSI could lead to inactivation of other tumor-suppressor genes. In our previous study, using comparative genomic hybridization (CGH), it was found that primary breast cancer with metastasis (axillary node and/or distant metastasis) acquired deletion on chromosome 22q13 at higher frequency than primary breast cancer without metastasis (unpublished data)...

Cancer Research, 2006

Proc Amer Assoc Cancer Res, Volume 47, 2006 4201 The molecular carcinogenesis of hepatocellular c... more Proc Amer Assoc Cancer Res, Volume 47, 2006 4201 The molecular carcinogenesis of hepatocellular carcinoma (HCC) is largely unclear, although the major causative agents for HCC, hepatitis B virus (HBV), hepatitis C virus (HCV) and aflatoxin (AFB), are well defined. Since the majority of HCC are associated with a background of chronic liver disease, the carcinogenesis of HCC is considered to be a long-term, multi-step process that involves progression from precancerous lesion to cancerous lesion caused by multiple genetic alterations. In our previous study, using comparative genomic hybridization (CGH) to metaphase chromosomes, we compared the genomic aberrations of primary human hepatocellular carcinoma tissues with those of matched non-cancerous liver tissues. Interestingly, we found that the most frequently detected gain of DNA copy numbers in HCC tissues involved chromosome X (62.5 %), 1q (38.9%), and 8q (22%). In contrast, the gain of DNA copy numbers in the matched non-cancerous...

BMC Cancer, 2021

Background PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycl... more Background PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC. Methods KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR (qRT-PCR) in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues. KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation. The relationships betwee...

Journal of Clinical Oncology, 2006

5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal c... more 5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal carcinoma (NPC). Almost every tumor cell contains EBV genome. Correlation between prognosis, disease status and serum EBV DNA level was recently reported. Methods: We conducted a cross-sectional study to determine the correlation between the EBV DNA level from circulating tumor cells and the status of disease. The subjects were classified into 4 groups: new diagnosis, in remission, recurrent disease and control (healthy volunteers). The number of subjects/group was calculated to be at least 32, using proportion of P0 = 40%, P1 = 10% at α = 0.05 and Power = 80%. Genomic DNA was isolated from buffy coat of peripheral blood sample. Using Taqman probes for latent membrane protein 2 (LMP2) gene in EBV genome and beta actin gene as internal control, real-time quantitative PCR was performed. The LMP2 copy number was adjusted according to the beta actin copy number from the same sample. Results: ...

Cell & Bioscience, 2020

Background Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target... more Background Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target. Overexpression of EGFR is frequently observed in hepatocellular carcinoma (HCC) and EGFR activation has been proven to be a potential determinant of primary resistance of HCC cells to sorafenib. In our previous study, we found 13 missense mutations in EGFR exon 19–23 from hepatocellular carcinoma (HCC) tissues, but the functions of these mutations have not been determined. This study aims to determine the kinase activity and sensitivity to erlotinib, a 1st-generation EGFR-tyrosine kinase inhibitor (TKI), of seven HCC-derived mutants (K757E, N808S, R831C, V897A, P937L, T940A, and M947T). Results Using transduction of pBabe-puro retroviral vector with or without EGFR, we constructed and determined the function of EGFRs in NIH-3T3 cells stably harboring each of the seven mutants, as well as the erlotinib-sensitive L858R-mutant, the erlotinib-resistant T790M-mutant, and EGFR wild type (WT)...

Medical Oncology, 2018

Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hep... more Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.

Medical Oncology, 2018

Breast cancers with amplification and overexpression of human epithelial growth factor receptor 2... more Breast cancers with amplification and overexpression of human epithelial growth factor receptor 2 (HER2) are associated with poor prognosis, and targeted for anti-HER2 therapy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently the recommended methods to asses HER2 overexpression/amplification. Droplet digital PCR (ddPCR), a highly accurate method to quantify DNA copy number, is potentially a robust alternative for HER2 diagnostics. In the FISH assay and most of previous ddPCR reports, chromosome 17 centromere (CEP17) has been used as the reference control to determine HER2/CEP17 ratio. Nevertheless, miss-classification could occur when HER2 is co-amplified with CEP17. To avoid this inherent defect, in the present study, we employed ddPCR assay using the human eukaryotic translation initiation factor 2C1 (EIF2C1) gene located at chromosome 1p34.3 as the reference control to quantify HER2 copy number in 31 frozen breast cancer tissues. HER2 status of these samples had been determined by FISH and classified as HER2-amplified and HER2-non-amplified breast cancers. The results showed that HER2 determined by ddPCR using HER2/EIF2C1 ratio was in good concordance with HER2 determined by FISH using HER2/CEP17 ratio, the concordance rate 87.1% (27/31), Kappa = 0.719. The sensitivity and specificity of ddPCR assay was 90% (9/10) and 85.7% (18/21), respectively. The median HER2/EIF2C1 copy number ratio in HER2-amplified cancers (6.55, range 1.3-17.3) was significantly higher than in HER2non-amplified cancers (1.05, range 0.6-3.6, p < 0.001). This study demonstrated that ddPCR using HER2/EIF2C1 ratio could accurately assess HER2 status in frozen breast cancer tissues. Thus, our findings warrant further studies into breast cancer with HER2-equivocal by IHC/FISH.

Cancer Control, 1996

BackgroundProstate cancer is the most frequently diagnosed cancer and the second leading cause of... more BackgroundProstate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It is estimated that over 300,000 men will have been diagnosed with prostate cancer in 1996, and more than 40,000 will have died of this disease.MethodsThe authors combined their experience with a review of the literature on management of this disease to examine the effectiveness of treatments for both localized and metastatic prostate cancer.ResultsSurgery and radiation therapy are potentially curative modalities for cancer still limited to the gland. Androgen ablation therapy results in stabilization or regression of metastatic disease in most instances but is not curative. Some new approaches are described for patients with hormone-refractory prostate cancer.ConclusionsNewer tumor-biology-based combinations are promising in the treatment of hormone-refractory prostate cancer, but their effect on patient survival needs to be evaluated in large...

Journal of Clinical Oncology, 2008

14537 Background: DPD deficiency is a genetic disease caused by molecular defects in the DPD gene... more 14537 Background: DPD deficiency is a genetic disease caused by molecular defects in the DPD gene (DPYD). Cancer patients with DPD deficiency developed severe toxicity after receiving 5-FU based ch...

BMC Cancer

Introduction Difference in clinical responses to cancer therapy in each patient is from several f... more Introduction Difference in clinical responses to cancer therapy in each patient is from several factors. Gastrointestinal microbiota is one of the reasons. However, this correlation remains unknown. This study aims to explore correlation between gastrointestinal microbiota profile and clinical outcomes in Thai advanced non-small cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) status. Methods We enrolled 13 patients with advanced EGFR–wild-type (WT) NSCLC who received chemotherapy and 15 patients with EGFR-mutant NSCLC who received EGFR tyrosine kinase inhibitors. We collected fecal samples at baseline and first disease evaluation and performed 16S rRNA gene sequencing by NGS to assess microbiota profile. The correlations between gastrointestinal microbiota and clinical variables were studied. Results The clinical characteristics were balanced between the cohorts, excluding significantly higher albumin levels in the EGFR-mutant group. Albumin was the onl...

Cancer Reports

Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (... more Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014-2018. BRCA mutations were detected using next-generation sequencing and con rmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain signi cance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64-6.49), P = 0.229). The stage at diagnosis was the sole factor signi cantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations.

Additional file 6: Supplement Fig. S1. The specific pairing of the qPCR primers with KIAA0101 tv1... more Additional file 6: Supplement Fig. S1. The specific pairing of the qPCR primers with KIAA0101 tv1 mRNA but not with KIAA0101 tv2 mRNA.

Additional file 5: Table S5. Source, dilution, incubation time, conditions of different biomarkers.

Additional file 4: Supplement Table S4. Cohort IHC.

Additional file 2: Supplement Table S2. Cohort qRT-PCR.

Additional file 3: Supplement Table S3. Cohort ddPCR.

Additional file 1: Figure S1. The confirmation of DNA sequences of EGFR mutation. The DNA sequenc... more Additional file 1: Figure S1. The confirmation of DNA sequences of EGFR mutation. The DNA sequences of each EGFR mutations after site-directed mutagenesis in pBabe-puro were confirmed with sequencing by Macrogen. Inc., South Korea.

Copyright © 2015 Ravat Panvichian et al. This is an open access article distributed under the Cre... more Copyright © 2015 Ravat Panvichian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatocellular carcinoma (HCC) is the leading cause of cancer death inmenworldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues andmatched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5 % of tumor tissues bu...

Background PCNA-associated factor (KIAA0101/p15PAF) is a cell-cycle regulated oncoprotein that re... more Background PCNA-associated factor (KIAA0101/p15PAF) is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101 is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101 gene amplification occurs and causally correlates with the KIAA0101 overexpression in HCC. This question is relevant to the development of the optimal test(s) for KIAA0101 and the strategies to target KIAA0101 in HCC. Methods In this study, we validated KIAA0101 mRNA expression levels by quantitative real-time PCR in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues; we then evaluated KIAA0101 gene copy numbers by droplet digital PCR (ddPCR) in 36 pairs of the tissues. Besides, KIAA0101 protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. ...

Cancer Research, 2005

1886 Functional inactivation of tumor-suppressor gene(s) is an essential step in carcinogenesis a... more 1886 Functional inactivation of tumor-suppressor gene(s) is an essential step in carcinogenesis and progression. Tumor-suppressor genes are generally inactivated by an intragenic point mutation in one allele and the subsequent loss of the corresponding (wild-type) allele, resulting in a condition known as “loss of heterozygosity”(LOH). Somatic alterations in microsatellite sequence due to a deletion or an insertion of one or more repeat units have been termed “microsatellite instabilities” (MSI). MSI is associated with defects in the DNA mismatch-repair machinery, and MSI has been detected in both hereditary and sporadic human cancer. MSI could lead to inactivation of other tumor-suppressor genes. In our previous study, using comparative genomic hybridization (CGH), it was found that primary breast cancer with metastasis (axillary node and/or distant metastasis) acquired deletion on chromosome 22q13 at higher frequency than primary breast cancer without metastasis (unpublished data)...

Cancer Research, 2006

Proc Amer Assoc Cancer Res, Volume 47, 2006 4201 The molecular carcinogenesis of hepatocellular c... more Proc Amer Assoc Cancer Res, Volume 47, 2006 4201 The molecular carcinogenesis of hepatocellular carcinoma (HCC) is largely unclear, although the major causative agents for HCC, hepatitis B virus (HBV), hepatitis C virus (HCV) and aflatoxin (AFB), are well defined. Since the majority of HCC are associated with a background of chronic liver disease, the carcinogenesis of HCC is considered to be a long-term, multi-step process that involves progression from precancerous lesion to cancerous lesion caused by multiple genetic alterations. In our previous study, using comparative genomic hybridization (CGH) to metaphase chromosomes, we compared the genomic aberrations of primary human hepatocellular carcinoma tissues with those of matched non-cancerous liver tissues. Interestingly, we found that the most frequently detected gain of DNA copy numbers in HCC tissues involved chromosome X (62.5 %), 1q (38.9%), and 8q (22%). In contrast, the gain of DNA copy numbers in the matched non-cancerous...

BMC Cancer, 2021

Background PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycl... more Background PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC. Methods KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR (qRT-PCR) in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues. KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation. The relationships betwee...

Journal of Clinical Oncology, 2006

5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal c... more 5557 Background: Epstein-Barr virus (EBV) is the major etiology of WHO type 2, 3 nasopharyngeal carcinoma (NPC). Almost every tumor cell contains EBV genome. Correlation between prognosis, disease status and serum EBV DNA level was recently reported. Methods: We conducted a cross-sectional study to determine the correlation between the EBV DNA level from circulating tumor cells and the status of disease. The subjects were classified into 4 groups: new diagnosis, in remission, recurrent disease and control (healthy volunteers). The number of subjects/group was calculated to be at least 32, using proportion of P0 = 40%, P1 = 10% at α = 0.05 and Power = 80%. Genomic DNA was isolated from buffy coat of peripheral blood sample. Using Taqman probes for latent membrane protein 2 (LMP2) gene in EBV genome and beta actin gene as internal control, real-time quantitative PCR was performed. The LMP2 copy number was adjusted according to the beta actin copy number from the same sample. Results: ...

Cell & Bioscience, 2020

Background Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target... more Background Epidermal growth factor receptor (EGFR) has emerged as an important therapeutic target. Overexpression of EGFR is frequently observed in hepatocellular carcinoma (HCC) and EGFR activation has been proven to be a potential determinant of primary resistance of HCC cells to sorafenib. In our previous study, we found 13 missense mutations in EGFR exon 19–23 from hepatocellular carcinoma (HCC) tissues, but the functions of these mutations have not been determined. This study aims to determine the kinase activity and sensitivity to erlotinib, a 1st-generation EGFR-tyrosine kinase inhibitor (TKI), of seven HCC-derived mutants (K757E, N808S, R831C, V897A, P937L, T940A, and M947T). Results Using transduction of pBabe-puro retroviral vector with or without EGFR, we constructed and determined the function of EGFRs in NIH-3T3 cells stably harboring each of the seven mutants, as well as the erlotinib-sensitive L858R-mutant, the erlotinib-resistant T790M-mutant, and EGFR wild type (WT)...

Medical Oncology, 2018

Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hep... more Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.

Medical Oncology, 2018

Breast cancers with amplification and overexpression of human epithelial growth factor receptor 2... more Breast cancers with amplification and overexpression of human epithelial growth factor receptor 2 (HER2) are associated with poor prognosis, and targeted for anti-HER2 therapy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently the recommended methods to asses HER2 overexpression/amplification. Droplet digital PCR (ddPCR), a highly accurate method to quantify DNA copy number, is potentially a robust alternative for HER2 diagnostics. In the FISH assay and most of previous ddPCR reports, chromosome 17 centromere (CEP17) has been used as the reference control to determine HER2/CEP17 ratio. Nevertheless, miss-classification could occur when HER2 is co-amplified with CEP17. To avoid this inherent defect, in the present study, we employed ddPCR assay using the human eukaryotic translation initiation factor 2C1 (EIF2C1) gene located at chromosome 1p34.3 as the reference control to quantify HER2 copy number in 31 frozen breast cancer tissues. HER2 status of these samples had been determined by FISH and classified as HER2-amplified and HER2-non-amplified breast cancers. The results showed that HER2 determined by ddPCR using HER2/EIF2C1 ratio was in good concordance with HER2 determined by FISH using HER2/CEP17 ratio, the concordance rate 87.1% (27/31), Kappa = 0.719. The sensitivity and specificity of ddPCR assay was 90% (9/10) and 85.7% (18/21), respectively. The median HER2/EIF2C1 copy number ratio in HER2-amplified cancers (6.55, range 1.3-17.3) was significantly higher than in HER2non-amplified cancers (1.05, range 0.6-3.6, p < 0.001). This study demonstrated that ddPCR using HER2/EIF2C1 ratio could accurately assess HER2 status in frozen breast cancer tissues. Thus, our findings warrant further studies into breast cancer with HER2-equivocal by IHC/FISH.

Cancer Control, 1996

BackgroundProstate cancer is the most frequently diagnosed cancer and the second leading cause of... more BackgroundProstate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. It is estimated that over 300,000 men will have been diagnosed with prostate cancer in 1996, and more than 40,000 will have died of this disease.MethodsThe authors combined their experience with a review of the literature on management of this disease to examine the effectiveness of treatments for both localized and metastatic prostate cancer.ResultsSurgery and radiation therapy are potentially curative modalities for cancer still limited to the gland. Androgen ablation therapy results in stabilization or regression of metastatic disease in most instances but is not curative. Some new approaches are described for patients with hormone-refractory prostate cancer.ConclusionsNewer tumor-biology-based combinations are promising in the treatment of hormone-refractory prostate cancer, but their effect on patient survival needs to be evaluated in large...

Journal of Clinical Oncology, 2008

14537 Background: DPD deficiency is a genetic disease caused by molecular defects in the DPD gene... more 14537 Background: DPD deficiency is a genetic disease caused by molecular defects in the DPD gene (DPYD). Cancer patients with DPD deficiency developed severe toxicity after receiving 5-FU based ch...