75 results on '"Chen-Sung Lin"'
Search Results
2. A reappraisal of lymph node dissection in colorectal cancer during primary surgical resection
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Yen-Jen Chen, Shin-Ting Yeh, Ping-Sheng Kao, Liang-Hung Ou, and Chen-Sung Lin
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Colorectal cancer (CRC) ,lymph node dissection (LND) ,Total dissected lymph nodes (TDLNs) ,Prognosis ,Surgery ,RD1-811 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Purpose Controversy exists regarding the extent to which lymph node dissection (LND) should be performed for operable colorectal cancers (CRCs) during primary surgical resection. We reappraised the role of LND in CRCs. Methods Seventy-three CRC patients (mean age, 65.3 years; 43 males) undergoing primary surgical resection at Taipei Hospital, Ministry of Health and Welfare, Taiwan, within a 3-year period were retrospectively analyzed. Their pathological T/N/M statuses and cancer stages were defined according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. The numbers of total dissected lymph nodes (TDLNs), positive dissected lymph nodes (PDLNs), and negative dissected lymph nodes (NDLNs) for each CRC patient were recorded in detail (TDLNs = PDLNs + NDLNs). Possible prognostic variables were evaluated. Results An advanced N status (N1/N2 vs. N0; HR, 5.749/17.677 vs. 1.000; p = 0.056/0.009) and M1 status (M1 vs. M0; HR, 7.517 vs. 1.000; p = 0.010) were independent variables for a poor prognosis. For all 73 CRC patients (p = 0.030), as well as T2 CRC patients (p = 0.061), those with > 15 TDLNs tended to have more PDLNs than those with ≤ 15 TDLNs. For 42 N(+) CRC patients (p = 0.007), as well as N2 CRC patients (p = 0.011), those with > 21 TDLNs tended to have more PDLNs than those with ≤ 21 TDLNs. Conclusion For CRC patients undergoing primary surgical resection, the number of TDLNs influences the accuracy of nodal staging. A minimum of 15 TDLNs is necessary for positive lymph nodes to be identified in CRC patients, and 21 TDLNs is sufficient for the severity of the N(+) status to be distinguished in N(+) CRC patients.
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- 2020
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3. The Role of Plasma Cell-Free Mitochondrial DNA and Nuclear DNA in Systemic Lupus Erythematosus
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Hui-Ting Lee, Chen-Sung Lin, Siao-Cian Pan, Wei-Sheng Chen, Chang-Youh Tsai, and Yau-Huei Wei
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plasma cell-free mitochondrial dna (mtdnapcf) ,plasma cell-free nuclear dna (ndnapcf) ,malondialdehyde (mda) ,8-hydroxy-2'-deoxyguanosine (8-ohdg) ,c-type lectin domain family 5 member a (clec5a) ,systemic lupus erythematosus (sle) ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
Background: The roles of plasma cell-free (pcf) mitochondrial DNA (mtDNApcf) and nuclear DNA (nDNApcf) in the pathogenesis of systemic lupus erythematosus (SLE) remain unclear. We analyzed the relative copies of mtDNApcf and nDNApcf and investigated their association with the levels of plasma 8-hydroxy-2’-deoxyguanosine (8-OHdG), plasma malondialdehyde (MDA) and mRNA of leukocyte C-type lectin domain family 5 member A (CLEC5A) in SLE patients. Methods: A total of 80 SLE patients and 43 healthy controls (HCs) were enrolled. Their plasma samples were subjected to the measurements of mtDNApcf copies, nDNApcf copies, 8-OHdG and MDA, respectively. Their leukocytes were analyzed for CLEC5A mRNA expression. Results: SLE patients had higher nDNApcf copies (2.84 ± 1.99 vs. 2.00 ± 0.88, p = 0.002), lower mtDNApcf copies (4.81 ± 6.33 vs. 9.83 ± 14.20, p = 0.032), higher plasma 8-OHdG (0.227 ± 0.085 vs. 0.199 ± 0.041 ng/mL, p = 0.016), lower plasma MDA (3.02 ± 2.20 vs. 4.37 ± 2.16 μM, p = 0.001) and similar leukocyte CLEC5A mRNA expression levels (1.21 ± 1.17 vs. 1.26 ± 1.05, p = 0.870), as compared with those of HCs. Among the HCs, SLE patients with SLE Disease Activity Index (SLEDAI) ≤8, and SLE patients with SLEDAI >8, their respective mtDNApcf copies decreased stepwisely (9.83 ± 14.20 vs. 6.28 ± 7.91 vs. 3.19 ± 3.35, p = 0.054). The nDNApcf copies of HCs, SLE patients without nephritis, and SLE patients with nephritis were increased stepwisely (2.00 ± 0.88 vs. 2.63 ± 1.74 vs. 3.16 ± 2.34, p = 0.043). Among SLE patients, higher nDNApcf copies were associated with higher levels of plasma 8-OHdG (p < 0.001) but lower plasma MDA (p = 0.019). Among HCs but not SLE patients, higher nDNApcf copies (p = 0.013) or lower mtDNApcf copies (p < 0.001) were related to higher levels of leukocyte CLEC5A mRNA expression. Conclusions: Higher nDNApcf, lower mtDNApcf, increased ROS-elicited oxidative DNA damage and dysregulated leukocyte CLEC5A expression might be implicated in the pathogenesis of SLE.
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- 2022
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4. Low mitochondrial DNA copy number of resected cecum appendix correlates with high severity of acute appendicitis
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Wei-Cheng Lee, Chen-Sung Lin, Fang-Chu Ko, Wei Cheng, Mau-Hwa Lee, and Yau-Huei Wei
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Medicine (General) ,R5-920 - Abstract
Background/Purpose: The roles of mitochondrial DNA alterations in acute appendicitis (AA) remain unclear. We evaluated the alterations of mtDNA copy number and mtDNA integrity [proportion of mtDNA templates without 8-hydroxyl-2′-deoxyguanosine (8-OHdG)] of the resected cecum appendixes in clinically suspected acute appendicitis (CSAA). Methods: A total of 228 CSAA patients, including 50 harbored negative AA (NAA), 155 true AA (TAA) without rupture and 23 TAA with rupture, who underwent appendectomies were enrolled. Tissues of resected cecum appendixes from the paraffin-embedded pathological blocks were subjected to DNA extraction, and their mtDNA copy number and mtDNA integrity were determined by quantitative real-time polymerase chain reaction (Q-PCR). Results: During the progression of disease severity from NAA to TAA without rupture and further TAA with rupture, increases of white blood cell (WBC) counts (p = 0.001), positive bacterial culture rates in turbid ascites (p = 0.016) and area (p
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- 2019
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5. Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma
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Tzu-Ching Chang, Hui-Ting Lee, Siao-Cian Pan, Shih-Han Cho, Chieh Cheng, Liang-Hung Ou, Chia-I Lin, Chen-Sung Lin, and Yau-Huei Wei
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copy number ,D310 mutation ,gastric adenocarcinoma (GAC) ,metabolic reprogramming ,mitochondrial DNA (mtDNA) ,mitochondrial transcription factor A (TFAM) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We used gastric cancer cell line AGS and clinical samples to investigate the roles of mitochondrial DNA (mtDNA) alterations and mitochondrial respiratory dysfunction in gastric adenocarcinoma (GAC). A total of 131 clinical samples, including 17 normal gastric mucosa (N-GM) from overweight patients who had received sleeve gastrectomy and 57 paired non-cancerous gastric mucosae (NC-GM) and GAC from GAC patients who had undergone partial/subtotal/total gastrectomy, were recruited to examine the copy number and D310 sequences of mtDNA. The gastric cancer cell line AGS was used with knockdown (KD) mitochondrial transcription factor A (TFAM) to achieve mitochondrial dysfunction through a decrease of mtDNA copy number. Parental (PT), null-target (NT), and TFAM-KD-(A/B/C) represented the parental, control, and TFAM knocked-down AGS cells, respectively. These cells were used to compare the parameters reflecting mitochondrial biogenesis, glycolysis, and cell migration activity. The median mtDNA copy numbers of 17 N-GM, 57 NC-GM, and 57 GAC were 0.058, 0.055, and 0.045, respectively. The trend of decrease was significant (p = 0.030). In addition, GAC had a lower mean mtDNA copy number of 0.055 as compared with the paired NC-GM of 0.078 (p < 0.001). The mean mtDNA copy number ratio (mtDNA copy number of GAC/mtDNA copy number of paired NC-GM) was 0.891. A total of 35 (61.4%) GAC samples had an mtDNA copy number ratio ≤0.804 (p = 0.017) and 27 (47.4%) harbored a D310 mutation (p = 0.047), and these patients had shorter survival time and poorer prognosis. After effective knockdown of TFAM, TFAM-KD-B/C cells expressed higher levels of hexokinase II (HK-II) and v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT, but lower levels of phosphorylated pyruvate dehydrogenase (p-PDH) than did the NT/PT AGS cells. Except for a higher level of p-PDH, the expression levels of these proteins remained unchanged in TFAM-KD-A, which had a mild knockdown of TFAM. Compared to those of NT, TFAM-KD-C had not only a lower mtDNA copy number (p = 0.050), but also lower oxygen consumption rates (OCR), including basal respiration (OCRBR), ATP-coupled respiration (OCRATP), reserve capacity (OCRRC), and proton leak (OCRPL)(all with p = 0.050). In contrast, TFAM-KD-C expressed a higher extracellular acidification rate (ECAR)/OCRBR ratio (p = 0.050) and a faster wound healing migration at 6, 12, and 18 h, respectively (all with p = 0.050). Beyond a threshold, the decrease in mtDNA copy number, the mtDNA D310 mutation, and mitochondrial dysfunction were involved in the carcinogenesis and progression of GACs. Activation of PDH might be considered as compensation for the mitochondrial dysfunction in response to glucose metabolic reprogramming or to adjust mitochondrial plasticity in GAC.
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- 2022
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6. The Role of hOGG1 C1245G Polymorphism in the Susceptibility to Lupus Nephritis and Modulation of the Plasma 8-OHdG in Patients with Systemic Lupus Erythematosus
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Hui-Ting Lee, Chen-Sung Lin, Chyou-Shen Lee, Chang-Youh Tsai, and Yau-Huei Wei
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8-hydroxy-2'-deoxyguanosine (8-OHdG) ,human 8-oxoguanine glycosylase 1 (hOGG1) C1245G polymorphism ,lupus nephritis ,systemic lupus erythematosus (SLE) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We investigated whether the C1245G polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) gene confers the susceptibility to systemic lupus erythematosus (SLE) occurrence of lupus nephritis and affects the plasma level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with SLE. A total of 45 healthy controls and 85 SLE patients were recruited. The C1245G polymorphism of the hOGG1 gene was determined by direct sequencing. The frequency of occurrence of the hOGG1 1245 GG genotype in SLE patients was 31.8% (27/85), which is lower than that of healthy controls of 53.3% (24/45). Thirty-three (33/85, 38.8%) SLE patients developed lupus nephritis. Significantly, SLE patients harboring the hOGG1 1245 GG genotype had a higher incidence to develop lupus nephritis than did those harboring the hOGG1 1245 CC or CG genotype (15/27, 55.6% vs.18/58, 31.0%, p = 0.031). Divided into subgroups, SLE patients harboring the hOGG1 1245 GG genotype had the highest plasma levels of 8-OHdG among patients with all genotypes, with regard to the coexistence of lupus nephritis (p = 0.020, ANOVA), including those with nephritis harboring the hOGG1 1245 CC or CG genotypes (p = 0.037), those without nephritis harboring the hOGG1 1245 GG genotype (p = 0.050), and those without nephritis harboring the hOGG1 1245 CC or CG genotype (p = 0.054). We conclude that the C1245G polymorphism of hOGG1 may be one of the factors that confer the susceptibility to lupus nephritis and modulate the plasma level of 8-OHdG in patients with SLE.
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- 2015
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7. High Mitochondrial DNA Copy Number and Bioenergetic Function Are Associated with Tumor Invasion of Esophageal Squamous Cell Carcinoma Cell Lines
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Liang-Shun Wang, Yann-Jang Chen, Yau-Huei Wei, Yao-An Shen, Shu-Yu Lee, Hui-Ting Lee, and Chen-Sung Lin
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bioenergetic function ,esophageal squamous cell carcinoma (ESCC) ,mitochondrial DNA (mtDNA) ,invasion ,epithelial mesenchymal transition (EMT) ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We previously reported a gradual increase of relative mitochondrial DNA (mtDNA) copy number during the progression of esophageal squamous cell carcinoma (ESCC). Because mitochondria are the intracellular organelles responsible for ATP production, we investigated the associations among mtDNA copy number, mitochondrial bioenergetic function, tumor invasion and the expression levels of epithelial mesenchymal transition (EMT) markers in a series of seven ESCC cell lines, including 48T, 81T, 146T, TE1, TE2, TE6 and TE9. Among them, TE1 had the highest relative mtDNA copy number of 240.7%. The mRNA of mtDNA-encoded ND1 gene (2.80), succinate-supported oxygen consumption rate (11.21 nmol/min/106 cells), ATP content (10.7 fmol/cell), and the protein level of mitochondrial transcription factor A (TFAM) were the highest and the lactate concentration in the culture medium (3.34 mM) was the lowest in TE1. These findings indicate that TE1 exhibited the highest bioenergetic function of mitochondria. Furthermore, TE1 showed the highest trans-well migration activity of 223.0 cells/field, the highest vimentin but the lowest E-cadherin protein expression levels, which suggest that TE1 had the highest invasion capability. We then conducted a knockdown study using pLKO.1-based lentiviral particles to infect TE1 cells to suppress the expression of TFAM. Molecular analyses of the parental TE1, control TE1-NT and TFAM knockdown TE1-sh-TFAM(97) cells were performed. Interestingly, as compared to the control TE1-NT, TE1-sh-TFAM(97) exhibited lower levels of the relative mtDNA copy number (p = 0.001), mRNA of mtDNA-encoded ND1 gene (p = 0.050), succinate-supported oxygen consumption rate (p = 0.065), and ATP content (p = 0.007), but had a higher lactate concentration in the culture medium (p = 0.010) and higher protein level of lactate dehydrogenase. A decline in mitochondrial bioenergetic function was observed in TE1-sh-TFAM(97). Significantly, compared to the control TE1-NT, TE1-sh-TFAM(97) had a lower trans-well migration activity (p < 0.001), a higher E-cadherin level but a lower vimentin protein level, which indicates a decrease of invasiveness. Taken together, we suggest that high relative mtDNA copy number and bioenergetic function of mitochondria may confer an advantage for tumor invasion of ESCC.
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- 2012
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8. Leukocyte Mitochondrial DNA Alteration in Systemic Lupus Erythematosus and Its Relevance to the Susceptibility to Lupus Nephritis
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Yau-Huei Wei, Chang-Youh Tsai, Hsien-Tzung Liao, Wei-Sheng Chen, Chen-Sung Lin, and Hui-Ting Lee
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systemic lupus erythematosus ,mitochondrial DNA ,copy number ,D310 sequence variation ,heteroplasmy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The role of mitochondrial DNA (mtDNA) alterations in the pathophysiology of systemic lupus erythematosus (SLE) remains unclear. We investigated sequence variations in the D310 region and copy number change of mtDNA in 85 SLE patients and 45 normal subjects. Leukocyte DNA and RNA were extracted from leukocytes of the peripheral venous blood. The D310 sequence variations and copy number of mtDNA, and mRNA expression levels of mtDNA-encoded genes in leukocytes were determined by quantitative real-time polymerase chain reaction (Q-PCR) and PCR-based direct sequencing, respectively. We found that leukocyte mtDNA in SLE patients exhibited higher frequency of D310 heteroplasmy (69.4% vs. 48.9%, p = 0.022) and more D310 variants (2.2 vs. 1.7, p = 0.014) than those found in controls. Among normal controls and patients with low, medium or high SLE disease activity index (SLEDAI), an ever-increasing frequency of D310 heteroplasmy was observed (p = 0.021). Leukocyte mtDNA copy number tended to be low in patients of high SLEDAI group (p = 0.068), especially in those harboring mtDNA with D310 heteroplasmy (p = 0.020). Moreover, the mtDNA copy number was positively correlated with the mRNA level of mtDNA-encoded ND1 (NADH dehydrogenase subunit 1) (p = 0.041) and ATPase 6 (ATP synthase subunit 6) (p = 0.030) genes. Patients with more D310 variants were more susceptible to lupus nephritis (p = 0.035). Taken together, our findings suggest that decrease in the mtDNA copy number and increase in D310 heteroplasmy of mtDNA are related to the development and progression of SLE, and that the patients harboring more D310 variants of mtDNA are more susceptible to lupus nephritis.
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- 2012
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9. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma
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Chen-Sung Lin, Hui-Ting Lee, Ming-Huei Lee, Siao-Cian Pan, Chen-Yeh Ke, Allen Wen-Hsiang Chiu, and Yau-Huei Wei
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renal cell carcinoma ,mitochondrial DNA copy number ,mitochondrial biogenesis ,Warburg effect ,invasiveness ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0.007); and drug resistance to doxorubicin (p = 0.008) of the TFAM-KD clone were significantly higher than those of the NT clone. Bioenergetically, the TFAM-KD clone expressed lower mOCRB (p = 0.009) but higher ECARB (p = 0.037) than did the NT clone. We conclude that a reduction of mtDNA copy number and decrease of respiratory function of mitochondria in RCC might be compensated for by an increase of enzymes and factors that are involved in the upregulation of glycolysis to confer RCC more invasive and a drug-resistant phenotype in vitro.
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- 2016
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10. Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis
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Wen-Chi Wei, Chia-Ching Liaw, Keng-Chang Tsai, Chun-Tang Chiou, Yu-Hwei Tseng, Wen-Fei Chiou, Yu-Chi Lin, Chia-I Tsai, Chen-Shien Lin, Chen-Sung Lin, Kuo-Tong Liou, I-Shing Yu, Yuh-Chiang Shen, and Yi-Chang Su
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Pharmacology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Lung Injury ,Fibrosis ,COVID-19 Drug Treatment ,Toll-Like Receptor 4 ,Phosphatidylinositol 3-Kinases ,Plasminogen Activator Inhibitor 1 ,Spike Glycoprotein, Coronavirus ,von Willebrand Factor ,Cytokines ,Humans ,Angiotensin-Converting Enzyme 2 ,Pulmonary Embolism ,Chemokine CCL5 ,Pandemics ,Proto-Oncogene Proteins c-akt - Abstract
The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1β, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.
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- 2022
11. A reappraisal of lymph node dissection in colorectal cancer during primary surgical resection
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Liang-Hung Ou, Chen-Sung Lin, Shin-Ting Yeh, Ping-Sheng Kao, and Yen-Jen Chen
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Male ,Oncology ,medicine.medical_specialty ,Prognostic variable ,Colorectal cancer ,Taiwan ,lcsh:Surgery ,Kaplan-Meier Estimate ,Risk Assessment ,lcsh:RC254-282 ,Colorectal cancer (CRC) ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Lymph node ,Pathological ,Colectomy ,Total dissected lymph nodes (TDLNs) ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Research ,Cancer ,lcsh:RD1-811 ,Middle Aged ,medicine.disease ,lymph node dissection (LND) ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,Dissection ,medicine.anatomical_structure ,Lymphatic Metastasis ,Practice Guidelines as Topic ,Lymph Node Excision ,Female ,Surgery ,Lymph Nodes ,Lymph ,Colorectal Neoplasms ,business - Abstract
Purpose Controversy exists regarding the extent to which lymph node dissection (LND) should be performed for operable colorectal cancers (CRCs) during primary surgical resection. We reappraised the role of LND in CRCs. Methods Seventy-three CRC patients (mean age, 65.3 years; 43 males) undergoing primary surgical resection at Taipei Hospital, Ministry of Health and Welfare, Taiwan, within a 3-year period were retrospectively analyzed. Their pathological T/N/M statuses and cancer stages were defined according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. The numbers of total dissected lymph nodes (TDLNs), positive dissected lymph nodes (PDLNs), and negative dissected lymph nodes (NDLNs) for each CRC patient were recorded in detail (TDLNs = PDLNs + NDLNs). Possible prognostic variables were evaluated. Results An advanced N status (N1/N2 vs. N0; HR, 5.749/17.677 vs. 1.000; p = 0.056/0.009) and M1 status (M1 vs. M0; HR, 7.517 vs. 1.000; p = 0.010) were independent variables for a poor prognosis. For all 73 CRC patients (p = 0.030), as well as T2 CRC patients (p = 0.061), those with > 15 TDLNs tended to have more PDLNs than those with ≤ 15 TDLNs. For 42 N(+) CRC patients (p = 0.007), as well as N2 CRC patients (p = 0.011), those with > 21 TDLNs tended to have more PDLNs than those with ≤ 21 TDLNs. Conclusion For CRC patients undergoing primary surgical resection, the number of TDLNs influences the accuracy of nodal staging. A minimum of 15 TDLNs is necessary for positive lymph nodes to be identified in CRC patients, and 21 TDLNs is sufficient for the severity of the N(+) status to be distinguished in N(+) CRC patients.
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- 2020
12. Role of mitochondrial DNA copy number alteration in non-small cell lung cancer
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Yi-Chen Yeh, Shih-Yu Lu, Chen-Sung Lin, Siao-Cian Pan, Yau-Huei Wei, Wen-Yu Chueh, and Yann-Jang Chen
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Mitochondrial DNA ,Gene knockdown ,medicine.medical_specialty ,biology ,business.industry ,Protein subunit ,Cell ,NADH dehydrogenase ,TFAM ,Pyruvate dehydrogenase complex ,Molecular biology ,respiratory tract diseases ,Surgery ,Blot ,medicine.anatomical_structure ,biology.protein ,Medicine ,business - Abstract
Background: Mitochondrial dysfunction may involve in the progression of human non-small cell lung cancers (NSCLCs). We analyzed the mitochondrial DNA (mtDNA) copy number, the expression levels of mitochondrial biogenesis-related proteins including pyruvate dehydrogenase, mitochondrial transcription factor A (TFAM) and mtDNA-encoded peptide NADH dehydrogenase subunit 1 (ND1), and the expression level of hexokinase II (HK-II) in human NSCLCs both ex vivo and in vitro. Materials and Methods: Paired cancerous and non-cancerous pathological specimens from 20 resected NSCLCs and an NSCLC cell line, the H23, were used in this study. H23 was infected by lentiviral particles to knockdown (KD) the expression of TFAM. TFAM-Null and TFAM-KD represent the control and TFAM knocked-down H23 cells, respectively. The mtDNA copy number was measured by quantitative real-time polymerase chain reaction and the protein expression levels were measured by immunohistochemical staining and Western blotting, respectively. Results: Low TFAM expression (P = 0.066) and low mtDNA copy number of NSCLCs (P = 0.009) were poor prognostic variables in NSCLC patients. Advanced T4 NSCLCs had lower TFAM expression (P = 0.021), lower expression of mtDNA-encoded ND1 polypeptide (P = 0.049), and lower mtDNA copy number (P = 0.050) than did T1 or T2/T3 NSCLCs, respectively. TFAM-KD cells expressed lower levels of TFAM protein (P Conclusion: Mitochondrial dysfunction caused by lower levels of TFAM, mtDNA copy number, and mtDNA-encoded ND1 polypeptide may play an important role in the progression of NSCLCs.
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- 2020
13. Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma
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Tzu-Ching Chang, Hui-Ting Lee, Siao-Cian Pan, Shih-Han Cho, Chieh Cheng, Liang-Hung Ou, Chia-I Lin, Chen-Sung Lin, and Yau-Huei Wei
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Male ,DNA Copy Number Variations ,QH301-705.5 ,mitochondrial transcription factor A (TFAM) ,Adenocarcinoma ,DNA, Mitochondrial ,Catalysis ,Inorganic Chemistry ,Mitochondrial Proteins ,Cell Movement ,Gastrectomy ,Stomach Neoplasms ,copy number ,Cell Line, Tumor ,metabolic reprogramming ,Humans ,Obesity ,Biology (General) ,Physical and Theoretical Chemistry ,gastric adenocarcinoma (GAC) ,QD1-999 ,Molecular Biology ,Spectroscopy ,Aged ,Aged, 80 and over ,Organelle Biogenesis ,Organic Chemistry ,General Medicine ,Middle Aged ,mitochondrial DNA (mtDNA) ,Prognosis ,Survival Analysis ,Computer Science Applications ,Mitochondria ,D310 mutation ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Chemistry ,Case-Control Studies ,Gene Knockdown Techniques ,Female ,prognosis ,Glycolysis ,Transcription Factors - Abstract
We used gastric cancer cell line AGS and clinical samples to investigate the roles of mitochondrial DNA (mtDNA) alterations and mitochondrial respiratory dysfunction in gastric adenocarcinoma (GAC). A total of 131 clinical samples, including 17 normal gastric mucosa (N-GM) from overweight patients who had received sleeve gastrectomy and 57 paired non-cancerous gastric mucosae (NC-GM) and GAC from GAC patients who had undergone partial/subtotal/total gastrectomy, were recruited to examine the copy number and D310 sequences of mtDNA. The gastric cancer cell line AGS was used with knockdown (KD) mitochondrial transcription factor A (TFAM) to achieve mitochondrial dysfunction through a decrease of mtDNA copy number. Parental (PT), null-target (NT), and TFAM-KD-(A/B/C) represented the parental, control, and TFAM knocked-down AGS cells, respectively. These cells were used to compare the parameters reflecting mitochondrial biogenesis, glycolysis, and cell migration activity. The median mtDNA copy numbers of 17 N-GM, 57 NC-GM, and 57 GAC were 0.058, 0.055, and 0.045, respectively. The trend of decrease was significant (p = 0.030). In addition, GAC had a lower mean mtDNA copy number of 0.055 as compared with the paired NC-GM of 0.078 (p < 0.001). The mean mtDNA copy number ratio (mtDNA copy number of GAC/mtDNA copy number of paired NC-GM) was 0.891. A total of 35 (61.4%) GAC samples had an mtDNA copy number ratio ≤0.804 (p = 0.017) and 27 (47.4%) harbored a D310 mutation (p = 0.047), and these patients had shorter survival time and poorer prognosis. After effective knockdown of TFAM, TFAM-KD-B/C cells expressed higher levels of hexokinase II (HK-II) and v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT, but lower levels of phosphorylated pyruvate dehydrogenase (p-PDH) than did the NT/PT AGS cells. Except for a higher level of p-PDH, the expression levels of these proteins remained unchanged in TFAM-KD-A, which had a mild knockdown of TFAM. Compared to those of NT, TFAM-KD-C had not only a lower mtDNA copy number (p = 0.050), but also lower oxygen consumption rates (OCR), including basal respiration (OCRBR), ATP-coupled respiration (OCRATP), reserve capacity (OCRRC), and proton leak (OCRPL)(all with p = 0.050). In contrast, TFAM-KD-C expressed a higher extracellular acidification rate (ECAR)/OCRBR ratio (p = 0.050) and a faster wound healing migration at 6, 12, and 18 h, respectively (all with p = 0.050). Beyond a threshold, the decrease in mtDNA copy number, the mtDNA D310 mutation, and mitochondrial dysfunction were involved in the carcinogenesis and progression of GACs. Activation of PDH might be considered as compensation for the mitochondrial dysfunction in response to glucose metabolic reprogramming or to adjust mitochondrial plasticity in GAC.
- Published
- 2021
14. The Role of Plasma Cell-Free Mitochondrial DNA and Nuclear DNA in Systemic Lupus Erythematosus
- Author
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Yau-Huei Wei, Chang-Youh Tsai, Wei-Sheng Chen, Siao-Cian Pan, Chen-Sung Lin, and Hui-Ting Lee
- Subjects
General Immunology and Microbiology ,General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
15. RAS Mediates BET Inhibitor-Endued Repression of Lymphoma Migration and Prognosticates a Novel Proteomics-Based Subgroup of DLBCL through Its Negative Regulator IQGAP3
- Author
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Chen, Chih-Cheng, primary, Hsu, Chia-Chen, additional, Chen, Sung-Lin, additional, Lin, Po-Han, additional, Chen, Ju-Pei, additional, Pan, Yi-Ru, additional, Huang, Cih-En, additional, Chen, Ying-Ju, additional, Chen, Yi-Yang, additional, Wu, Yu-Ying, additional, and Yang, Muh-Hwa, additional
- Published
- 2021
- Full Text
- View/download PDF
16. Alterations of oxygen consumption and extracellular acidification rates by glutamine in PBMCs of SLE patients
- Author
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Hui-Ting Lee, Deh-Ming Chang, Chang-Youh Tsai, Yau-Huei Wei, Tsai-Hung Wu, Chyou-Shen Lee, Siao-Cian Pan, and Chen-Sung Lin
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Glutamine ,chemistry.chemical_element ,Mitochondrion ,Peripheral blood mononuclear cell ,Oxygen ,Impaired mitochondrial respiration ,Cohort Studies ,Disease activity ,Plasma ,03 medical and health sciences ,Basal (phylogenetics) ,Oxygen Consumption ,immune system diseases ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Molecular Biology ,Aged ,Cell Biology ,Middle Aged ,Mitochondria ,030104 developmental biology ,Endocrinology ,chemistry ,Leukocytes, Mononuclear ,Molecular Medicine ,Female ,Extracellular acidification - Abstract
We evaluated plasma glutamine levels and basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB) of peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients and healthy controls (HCs). Lower plasma glutamine levels correlated with higher SLE disease activity indexes (p=0.025). Incubated in DMEM containing 100mg/dL glucose, SLE-PBMCs displayed lower mOCRB (p=0.018) but similar ECARB (p=0.467) to those of HC-PBMCs, and their mOCRB got elevated (p
- Published
- 2019
17. Impact of the extent of negative lymph nodes in gastric adenocarcinoma undergoing primary surgical resection: An institutional report
- Author
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Chiang Ting Chien, Shin Ting Yeh, Chen Sung Lin, Yen-Jen Chen, and Liang Hung Ou
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Perineural invasion ,030204 cardiovascular system & hematology ,Adenocarcinoma ,Gastroenterology ,03 medical and health sciences ,Gastric adenocarcinoma ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,medicine ,Humans ,Lymph node ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,medicine.disease ,Dissection ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Gastrectomy ,Female ,Lymph ,Lymph Nodes ,business - Abstract
Sub-total/total gastrectomy with lymph node dissection (LND) remains an effective therapeutic strategy for resectable gastric adenocarcinomas (GACs). Despite the prognostic significance of positive lymph nodes (PLNs) defined in N-status, few have appraised the impacts of negative lymph nodes (NLNs) and the percentage of NLN (=number of NLNs/number of total lymph nodes [TLNs], %), as well as the extent of TLNs to be dissected in GACs.We retrospectively analyzed 62 GAC patients (mean age of 67.1 years; 41 men) undergoing primary sub-total/total gastrectomy from a single institute. Candidate variables, including the number of NLNs (≤9 and9) and the percentage of NLN (≤37.5, 37.5-80.6 and80.6, %), were evaluated to determine their prognostic impacts and hazard ratios (HRs).Under the multivariate Cox proportional-hazards regression model, tumor length exceeding 4 cm (p = 0.017; HR = 2.828), perineural invasion (p = 0.037; HR = 3.182), and lower percentage of NLN (p = 0.016 and p = 0.060; HRs = 1.000, 0.327, and 0.333 for subgroups ≤37.5, 37.5-80.6, and80.6, respectively) were three independent predictors with elevated HRs for poor prognosis. GAC patients with the percentage of NLN80.6 were highly related to those with NLNs9 (p0.001), and GAC patients with NLNs9 were highly related to those with TLNs15 (p0.001). For all 62 GAC or 42 N(+) GAC patients, those who underwent LND with TLNs15 tended to have more PLNs (p = 0.018, p = 0.003) and more NLNs (p0.001, p = 0.029) than did those with TLNs ≤ 15. Among the 42 GAC patients with TLNs15, a lower percentage of NLN (p = 0.026 and p = 0.015; HRs = 1.000, 0.272, and 0.180 for subgroups ≤37.5, 37.5-80.6, and80.6, respectively) remained an independent predictor of poor prognosis.The percentage of NLN could predict the prognosis of GAC patients properly. However, an accurate percentage of NLN needs a minimal requirement of TLNs15 to detect an adequate number of PLNs and sufficient number of NLNs.
- Published
- 2021
18. Cost-Effectiveness of Minimally Invasive Esophagectomy for Esophageal Squamous Cell Carcinoma
- Author
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Chih-Shiun Shih, Yuh-An Huang, Chia-Chuan Liu, Chen-Sung Lin, Chih-Tao Cheng, and Chao-Yu Liu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,Cost effectiveness ,Cost-Benefit Analysis ,medicine.medical_treatment ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Carcinoma ,Humans ,Minimally Invasive Surgical Procedures ,Medicine ,Propensity Score ,Aged ,business.industry ,Perioperative ,Middle Aged ,Vascular surgery ,medicine.disease ,Intensive care unit ,Surgery ,Esophagectomy ,030220 oncology & carcinogenesis ,Propensity score matching ,Carcinoma, Squamous Cell ,Female ,030211 gastroenterology & hepatology ,Esophageal Squamous Cell Carcinoma ,business ,Abdominal surgery - Abstract
The cost-effectiveness of minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) for esophageal squamous cell carcinoma (ESCC) has not been established. Recent cost studies have shown that MIE is associated with a higher surgical expense, which is not consistently offset by savings through expedited post-operative recovery, therefore suggesting a questionable benefit of MIE over OE from an economic point of view. In the current study, we compared the cost-effectiveness of MIE versus OE for ESCC. Between April 2000 and December 2013, a total of 251 consecutive patients undergoing MIE or OE for ESCC were enrolled. After propensity score (PS)-matching the MIE group with the OE group for clinical characteristics, 95 patients from each group were enrolled to compare the peri-operative outcomes, long-term survival, and cost. After PS-matching, the baseline characteristics were not significantly different between groups. Perioperative outcomes were similar in both groups. MIE was superior to OE with respect to a shorter intensive care unit (ICU) stay, while the complication rate (except for hoarseness) and survival were similar. Post-operative cost was significantly less in the MIE group due to a shorter ICU stay; however, reduced post-operative cost failed to offset the higher surgical expense of MIE. MIE for ESCC failed to show cost-effectiveness regarding overall expense in our study, but costs less in the postoperative care, especially for ICU care. More cost studies on MIE in other health care systems are warranted to verify the cost-effectiveness of MIE.
- Published
- 2018
19. Oxidative DNA and mitochondrial DNA change in patients with SLE
- Author
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Hui-Ting Lee, Tsai-Hung Wu, Chang-Youh Tsai, Yau-Huei Wei, Deh-Ming Chang, Chyou-Shen Lee, Chen-Sung Lin, and Siao-Cian Pan
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Mitochondrial DNA ,Chemokine ,medicine.medical_treatment ,DNA, Mitochondrial ,03 medical and health sciences ,Internal medicine ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,Dialysis ,Sequence Deletion ,Lupus erythematosus ,biology ,business.industry ,Case-control study ,Deoxyguanosine ,medicine.disease ,030104 developmental biology ,Endocrinology ,8-Hydroxy-2'-Deoxyguanosine ,Antibodies, Antinuclear ,Case-Control Studies ,Disease Progression ,biology.protein ,Cytokines ,Female ,Rituximab ,Chemokines ,Antibody ,business ,Nephritis ,medicine.drug - Abstract
We evaluated plasma IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10, MCP-1, 8-OHdG, leukocyte mtDNA, serum anti-dsDNA antibodies and disease activity index (SLEDAI) in SLE patients. 93 patients (35 nephritis, 4 under dialysis, 5 under rituximab) and 50 healthy controls were recruited. Compared with healthy controls, SLE patients had higher IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10 and MCP-1 (p
- Published
- 2017
20. Intraoperative cardiac arrest caused by air embolism during video-assisted thoracoscopic segmentectomy
- Author
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Chen-Sung Lin, Chia-Chuan Liu, Nai-Liang Li, and Chih-Hsun Shih
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Epinephrine ,Adenocarcinoma of Lung ,Heart Massage ,030204 cardiovascular system & hematology ,Air embolism ,Electrocardiography ,Intraoperative Period ,03 medical and health sciences ,0302 clinical medicine ,030202 anesthesiology ,Internal medicine ,medicine ,Embolism, Air ,Humans ,Video assisted ,Heart massage ,Pneumonectomy ,medicine.diagnostic_test ,Thoracic Surgery, Video-Assisted ,business.industry ,Intraoperative cardiac arrest ,Middle Aged ,medicine.disease ,Adrenergic Agonists ,Heart Arrest ,Treatment Outcome ,Embolism ,Cardiothoracic surgery ,Cardiology ,Female ,Surgery ,Radiology ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business - Published
- 2018
21. The pathogenesis of systemic lupus erythematosus - From the viewpoint of oxidative stress and mitochondrial dysfunction
- Author
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Hui-Ting Lee, Yau-Huei Wei, Deh-Ming Chang, Chen-Sung Lin, Tsai-Hung Wu, Chang-Youh Tsai, and Chyou-Shen Lee
- Subjects
0301 basic medicine ,medicine.medical_treatment ,Lymphocyte ,Mitochondrial disease ,Biology ,Mitochondrion ,medicine.disease_cause ,Pathogenesis ,03 medical and health sciences ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Biology ,medicine.disease ,Heteroplasmy ,Mitochondria ,Oxidative Stress ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,chemistry ,Immunology ,Molecular Medicine ,Energy Metabolism ,Reactive Oxygen Species ,Oxidative stress - Abstract
SLE is characterized by an increased production of detrimental autoantigens, exaggerated effects of pro-inflammatory cytokines, dysregulated functioning of immunocompetent cells including lymphocytes and leukocytes, and devastating tissue and organ damage. All of these derangements can be potentiated or attenuated by the abnormal energy expenditure and overproduction of reactive oxygen species (ROS). Mitochondrial heteroplasmy or dysfunction has been recognized to play a role in these abnormalities. Abnormal redox reaction, decreased functioning of biogenesis-related enzymes, increased NETosis, harmful cytokine effects, and aberrant lymphocyte behavior have been shown to be associated with the pathological state of mitochondria. There is accumulating data which support the importance of abnormal oxygen metabolism and mitochondrial disorders in the immunopathogenesis of SLE. Further laboratory as well as clinical data are required to expand our understanding of SLE pathogenesis.
- Published
- 2016
22. Impact of the extent of negative lymph nodes in gastric adenocarcinoma undergoing primary surgical resection: An institutional report.
- Author
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Yen-Jen Chen, Shin-Ting Yeh, Liang-Hung Ou, Chen-Sung Lin, and Chiang-Ting Chien
- Subjects
LYMPH nodes ,SURGICAL excision ,LYMPHADENECTOMY ,ADENOCARCINOMA - Abstract
Background: Sub-total/total gastrectomy with lymph node dissection (LND) remains an effective therapeutic strategy for resectable gastric adenocarcinomas (GACs). Despite the prognostic significance of positive lymph nodes (PLNs) defined in N-status, few have appraised the impacts of negative lymph nodes (NLNs) and the percentage of NLN (=number of NLNs/number of total lymph nodes [TLNs], %), as well as the extent of TLNs to be dissected in GACs. Methods: We retrospectively analyzed 62 GAC patients (mean age of 67.1 years; 41 men) undergoing primary sub-total/total gastrectomy from a single institute. Candidate variables, including the number of NLNs (≤9 and >9) and the percentage of NLN (≤37.5, 37.5-80.6 and >80.6, %), were evaluated to determine their prognostic impacts and hazard ratios (HRs). Results: Under the multivariate Cox proportional-hazards regression model, tumor length exceeding 4 cm (p = 0.017; HR = 2.828), perineural invasion (p = 0.037; HR = 3.182), and lower percentage of NLN (p = 0.016 and p = 0.060; HRs = 1.000, 0.327, and 0.333 for subgroups ≤37.5, 37.5-80.6, and >80.6, respectively) were three independent predictors with elevated HRs for poor prognosis. GAC patients with the percentage of NLN > 80.6 were highly related to those with NLNs > 9 (p < 0.001), and GAC patients with NLNs > 9 were highly related to those with TLNs > 15 (p < 0.001). For all 62 GAC or 42 N(+) GAC patients, those who underwent LND with TLNs>15 tended to have more PLNs (p = 0.018, p = 0.003) and more NLNs (p < 0.001, p = 0.029) than did those with TLNs ≤ 15. Among the 42 GAC patients with TLNs > 15, a lower percentage of NLN (p = 0.026 and p = 0.015; HRs = 1.000, 0.272, and 0.180 for subgroups ≤37.5, 37.5-80.6, and >80.6, respectively) remained an independent predictor of poor prognosis. Conclusion: The percentage of NLN could predict the prognosis of GAC patients properly. However, an accurate percentage of NLN needs a minimal requirement of TLNs > 15 to detect an adequate number of PLNs and sufficient number of NLNs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
23. Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUV
- Author
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Chen-Sung, Lin, Yu-Yi, Huang, Siao-Cian, Pan, Chih-Tao, Cheng, Chia-Chuan, Liu, Chih-Hsun, Shih, Hsiang-Ling, Ho, Yi-Chen, Yeh, Teh-Ying, Chou, Ming-Yuan, Lee, and Yau-Huei, Wei
- Subjects
Gene Expression Regulation, Neoplastic ,Male ,DNA Copy Number Variations ,Esophageal Neoplasms ,Fluorodeoxyglucose F18 ,Positron-Emission Tomography ,Humans ,Female ,Esophageal Squamous Cell Carcinoma ,Middle Aged ,Tumor Suppressor Protein p53 ,DNA, Mitochondrial ,Aged - Abstract
We appraised Warburg effect through analysis of mitochondrial DNA (mtDNA) copy number and maximum standard uptake value (SUV
- Published
- 2018
24. AB002. Relationship between mitochondrial DNA copy number and maximum standard uptake value of 18F-fluorodeoxyglucose positron emission tomography scan in esophageal squamous cell carcinoma
- Author
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Ming-Yuan Lee, Chih-Hsun Shih, Chen-Sung Lin, Yu-Yi Huang, Teh Ying Chou, Hsiang-Ling Ho, Yau-Huei Wei, Yi-Chen Yeh, Chia-Chuan Liu, and Siao-Cian Pan
- Subjects
Pulmonary and Respiratory Medicine ,Fluorodeoxyglucose positron emission tomography ,Mitochondrial DNA ,Basic Research ,business.industry ,Medicine ,Standardized uptake value ,business ,Nuclear medicine ,Esophageal squamous cell carcinoma ,Positron Emission Tomography Scan - Published
- 2017
25. Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma
- Author
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Kuang Liang King, Shi Chuan Chang, Chen Sung Lin, Yau-Huei Wei, Yu Ping Chung, Chien Ming Chen, Liang Hung Ou, Shoei Loong Lin, and Sophie Swen Wan Hsieh
- Subjects
Cancer Research ,Mitochondrial DNA ,DNA Copy Number Variations ,Receptor, ErbB-2 ,Estrogen receptor ,Breast Neoplasms ,medicine.disease_cause ,DNA, Mitochondrial ,law.invention ,law ,Progesterone receptor ,medicine ,Humans ,Polymerase chain reaction ,Aged ,Cell Proliferation ,Mutation ,biology ,Estrogen Receptor alpha ,General Medicine ,Middle Aged ,Cell cycle ,Prognosis ,Carcinoma, Ductal ,Gene Expression Regulation, Neoplastic ,Ki-67 Antigen ,Oncology ,Ki-67 ,biology.protein ,Cancer research ,Immunohistochemistry ,Female ,Tumor Suppressor Protein p53 ,Receptors, Progesterone - Abstract
We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.
- Published
- 2015
26. The Role of hOGG1 C1245G Polymorphism in the Susceptibility to Lupus Nephritis and Modulation of the Plasma 8-OHdG in Patients with Systemic Lupus Erythematosus
- Author
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Chang Youh Tsai, Yau-Huei Wei, Hui-Ting Lee, Chen-Sung Lin, and Chyou-Shen Lee
- Subjects
Male ,Lupus nephritis ,DNA Glycosylases ,lcsh:Chemistry ,chemistry.chemical_compound ,immune system diseases ,Genotype ,Lupus Erythematosus, Systemic ,Deoxyguanosine ,Young adult ,skin and connective tissue diseases ,lcsh:QH301-705.5 ,Spectroscopy ,systemic lupus erythematosus (SLE) ,human 8-oxoguanine glycosylase 1 (hOGG1) C1245G polymorphism ,General Medicine ,Middle Aged ,Computer Science Applications ,8-Hydroxy-2'-Deoxyguanosine ,Female ,Nephritis ,Adult ,Guanine ,8-hydroxy-2'-deoxyguanosine (8-OHdG) ,Biology ,Polymorphism, Single Nucleotide ,Article ,Catalysis ,Inorganic Chemistry ,Cytosine ,Young Adult ,medicine ,Humans ,Genetic Predisposition to Disease ,In patient ,Physical and Theoretical Chemistry ,Molecular Biology ,lupus nephritis ,Organic Chemistry ,Case-control study ,Sequence Analysis, DNA ,Plasma levels ,medicine.disease ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Case-Control Studies ,Immunology - Abstract
We investigated whether the C1245G polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) gene confers the susceptibility to systemic lupus erythematosus (SLE) occurrence of lupus nephritis and affects the plasma level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with SLE. A total of 45 healthy controls and 85 SLE patients were recruited. The C1245G polymorphism of the hOGG1 gene was determined by direct sequencing. The frequency of occurrence of the hOGG1 1245 GG genotype in SLE patients was 31.8% (27/85), which is lower than that of healthy controls of 53.3% (24/45). Thirty-three (33/85, 38.8%) SLE patients developed lupus nephritis. Significantly, SLE patients harboring the hOGG1 1245 GG genotype had a higher incidence to develop lupus nephritis than did those harboring the hOGG1 1245 CC or CG genotype (15/27, 55.6% vs.18/58, 31.0%, p = 0.031). Divided into subgroups, SLE patients harboring the hOGG1 1245 GG genotype had the highest plasma levels of 8-OHdG among patients with all genotypes, with regard to the coexistence of lupus nephritis (p = 0.020, ANOVA), including those with nephritis harboring the hOGG1 1245 CC or CG genotypes (p = 0.037), those without nephritis harboring the hOGG1 1245 GG genotype (p = 0.050), and those without nephritis harboring the hOGG1 1245 CC or CG genotype (p = 0.054). We conclude that the C1245G polymorphism of hOGG1 may be one of the factors that confer the susceptibility to lupus nephritis and modulate the plasma level of 8-OHdG in patients with SLE.
- Published
- 2015
27. Subxiphoid single-incision thoracoscopic surgery for bilateral primary spontaneous pneumothorax
- Author
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Chia-Chuan Liu, Chao-Yu Liu, and Chen-Sung Lin
- Subjects
medicine.medical_specialty ,pneumothorax ,business.industry ,Urology ,Postoperative pain ,Gastroenterology ,Obstetrics and Gynecology ,Case Report ,Primary spontaneous pneumothorax ,medicine.disease ,subxiphoid ,single-incision ,Surgery ,Pneumothorax ,Single incision ,Anesthesia ,Medicine ,Operative time ,In patient ,business - Abstract
It has been reported that single-incision thoracoscopic surgery can reduce postoperative pain without compromising the main surgical steps required for treating patients affected by primary spontaneous pneumothorax. However, all the reported thoracoscopic surgery cases with a single-incision procedure were via the intercostal route for unilateral pulmonary lesions. We present a novel single-incision thoracoscopic technique via a subxiphoid route to perform one-stage bilateral thoracoscopic surgery for bilateral spontaneous pneumothorax. Reduced postoperative pain, shorter operative time, and better cosmetic results are potential benefits of this technique in selected patients. The subxiphoid single-incision procedure may be indicated in patients with bilateral pulmonary lesions requiring surgical resections.
- Published
- 2015
28. Prognostic role of initial pan-endoscopic tumor length at diagnosis in operable esophageal squamous cell carcinoma undergoing esophagectomy with or without neoadjuvant concurrent chemoradiotherapy
- Author
-
Chih-Tao Cheng, Lun-Wei Chiou, Chia-Chuan Liu, Chih-Hsun Shih, Yu-Chen Tsai, Chen-Sung Lin, Chao-Yu Liu, and Ming-Yuan Lee
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Prognostic variable ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Tumor length ,Cancer ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,Esophageal squamous cell carcinoma ,Concurrent chemoradiotherapy ,03 medical and health sciences ,0302 clinical medicine ,Esophagectomy ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Original Article ,Stage (cooking) ,business ,Pathological - Abstract
The objective of this study was to appraise the prognostic role of initial pan-endoscopic tumor length at diagnosis within or between operable esophageal squamous cell carcinoma (ESCC) undergoing upfront esophagectomy or neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by esophagectomy.Between Jan 2001 and Dec 2013 in Koo-Foundation Sun Yat-sen Cancer Center in Taiwan, 101 ESCC patients who underwent upfront esophagectomy (surgery group) and 128 nCCRT followed by esophagectomy (nCCRT-surgery group) were retrospectively collected. Prognostic variables, including initial pan-endoscopic tumor length at diagnosis (sub-grouped ≤3, 3-5 and5 cm), status of circumferential resection margin (CRM), and pathological T/N/M-status and cancer stage, were appraised within or between surgery and nCCRT-surgery groups.Within surgery group, longer initial pan-endoscopic tumor length at diagnosis (≤3, 3-5 and5 cm; HR =1.000, 1.688 and 4.165; P=0.007) was an independent prognostic factor that correlated with advanced T/N/M-status, late cancer stage, and CRM invasion (all's P0.001). Based on the initial pan-endoscopic tumor length at diagnosis ≤3, 3-5 and5 cm, nCCRT-surgery group had a poorer (P=0.039), similar (P=0.447) and better (P0.001) survivals than did surgery group, respectively. For those with initial pan-endoscopic tumor length at diagnosis5 cm, nCCRT-surgery group had more percentage of T0/N0-status and stage 0 (all's P0.05), and fewer rate of CRM invasion (P=0.036) than did surgery group.Initial pan-endoscopic tumor length at diagnosis could be a criterion to select proper ESCC cases for nCCRT followed by esophagectomy to improve survival and reduce CRM invasion.
- Published
- 2017
29. Role of mitochondrial function in the invasiveness of human colon cancer cells
- Author
-
Liang-Hung Ou, Li-Tzu Liu, Chen-Sung Lin, Yau-Huei Wei, Siao-Cian Pan, and Chia-I Lin
- Subjects
0301 basic medicine ,Cancer Research ,Gene Dosage ,DNA, Mitochondrial ,NDUFA9 ,Mitochondrial Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,Lactate dehydrogenase ,Cell Line, Tumor ,Humans ,Neoplasm Invasiveness ,biology ,Cytochrome c oxidase subunit II ,Succinate dehydrogenase ,General Medicine ,TFAM ,Cell cycle ,Molecular biology ,Cell biology ,Mitochondria ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,chemistry ,Cell culture ,Apoptosis ,Gene Knockdown Techniques ,Colonic Neoplasms ,biology.protein ,Oligomycins ,Energy Metabolism ,Reactive Oxygen Species ,Transcription Factors - Abstract
We investigated the role of mitochondrial function in the invasiveness of human colorectal cancer (CRC) cell lines, using paired primary SW480 and metastatic SW620 cells, and appraised the clinical relevance of the alteration of mtDNA copy number in 33 pairs of CRC specimens after surgical resection. Suppression of mitochondrial function was achieved by the exposure of cells to oligomycin A (OA) or by knockdown of mitochondrial transcriptional factor A (TFAM) to evaluate their effects on energy metabolism, reactive oxygen species, protein expression levels of epithelial-mesenchymal transition (EMT) markers and invasive activity of CRC cells. We found that SW620 cells expressed higher levels of TFAM and mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) and cytochrome c oxidase subunit II (COX-II) and nuclear DNA-encoded NADH ubiquinone oxidoreductase subunit A9 (NDUFA9), iron-sulfur protein subunit B of succinate dehydrogenase (SDHB), ubiquinol‑cytochrome c reductase core protein I/II (UQCRC1/2) and cytochrome c oxidase subunit IV (COX-IV) when compared with the SW480 cells. The mtDNA copy number, ADP-triggered oxygen consumption rate (OCR) and respiratory control ratio (RCR) of succinate-supported respiration in the SW620 cells were higher than those noted in the SW480 cells. The intracellular levels of H2O2 and O2-• in the SW620 cells were lower than levels noted in the SW480 cells. Moreover, SW620 cells displayed lower protein levels of hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI) and lactate dehydrogenase (LDH), and lower lactate production rate, and expressed higher levels of EMT markers N-cadherin, vimentin and Snail, and showed higher Transwell migration and invasion activities as compared with the SW480 cells. After OA treatment, SW620 cells exhibited a decrease in OCR and RCR of succinate-supported respiration, an increase in lactate production rate and intracellular levels of H2O2 and O2-•. Moreover, the level of vimentin and Transwell migration activity of the SW620 cells were decreased. After TFAM knockdown, the protein levels of TFAM, ND6 and COX-II, and mtDNA copy number, OCR and RCR of succinate-supported respiration in the SW620-KD#4 and SW620-KD#5 cells were all lower than those noted in the SW620‑Control cells. By contrast, the protein level of HK-II, lactate production rate, the intracellular levels of H2O2 and O2-• in the SW620-KD#4 and SW620-KD#5 cells were all higher than those noted in the SW620-Control cells. Subsequently, both SW620-KD#4 and SW620-KD#5 cells had lower Transwell invasion activity than did the SW620-Control cells. Furthermore, we found that deeper invasion (P=0.025) and longer tumor length (P=0.069) were associated with higher mtDNA copy ratios in the 33 pairs of CRC specimens obtained from surgical resection. Taken together, we conclude that higher mtDNA copy number and mitochondrial function may confer an invasive advantage to CRCs.
- Published
- 2017
30. Role of mitochondrial DNA copy number alteration in non-small cell lung cancer.
- Author
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Chen-Sung Lin, Yi-Chen Yeh, Siao-Cian Pan, Shih-Yu Lu, Yann-Jang Chen, and Wen-Yu Chueh
- Abstract
Background: Mitochondrial dysfunction may involve in the progression of human non-small cell lung cancers (NSCLCs). We analyzed the mitochondrial DNA (mtDNA) copy number, the expression levels of mitochondrial biogenesis-related proteins including pyruvate dehydrogenase, mitochondrial transcription factor A (TFAM) and mtDNA-encoded peptide NADH dehydrogenase subunit 1 (ND1), and the expression level of hexokinase II (HK-II) in human NSCLCs both ex vivo and in vitro. Materials and Methods: Paired cancerous and non-cancerous pathological specimens from 20 resected NSCLCs and an NSCLC cell line, the H23, were used in this study. H23 was infected by lentiviral particles to knockdown (KD) the expression of TFAM. TFAM-Null and TFAM-KD represent the control and TFAM knocked-down H23 cells, respectively. The mtDNA copy number was measured by quantitative real-time polymerase chain reaction and the protein expression levels were measured by immunohistochemical staining and Western blotting, respectively. Results: Low TFAM expression (P = 0.066) and low mtDNA copy number of NSCLCs (P = 0.009) were poor prognostic variables in NSCLC patients. Advanced T4 NSCLCs had lower TFAM expression (P = 0.021), lower expression of mtDNA-encoded ND1 polypeptide (P = 0.049), and lower mtDNA copy number (P = 0.050) than did T1 or T2/T3 NSCLCs, respectively. TFAM-KD cells expressed lower levels of TFAM protein (P < 0.005), ND1 polypeptide (P < 0.005) and mtDNA copy number (P = 0.003), but higher level of vimentin protein (P = 0.045) and higher transwell migration activity (P = 0.003) than did TFAM-Null cells. Conclusion: Mitochondrial dysfunction caused by lower levels of TFAM, mtDNA copy number, and mtDNA-encoded ND1 polypeptide may play an important role in the progression of NSCLCs. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
31. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma
- Author
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Hui-Ting Lee, Ming Huei Lee, Siao Cian Pan, Yau-Huei Wei, Chen Yeh Ke, Chen Sung Lin, and Allen W. Chiu
- Subjects
0301 basic medicine ,renal cell carcinoma ,Pyruvate dehydrogenase kinase ,mitochondrial biogenesis ,DNA Copy Number Variations ,Cell Survival ,invasiveness ,Clone (cell biology) ,SDHA ,Mitochondrion ,Biology ,DNA, Mitochondrial ,Article ,Catalysis ,Mitochondrial Proteins ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Line, Tumor ,Lactate dehydrogenase ,Humans ,Respiratory function ,Physical and Theoretical Chemistry ,Carcinoma, Renal Cell ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Organic Chemistry ,General Medicine ,TFAM ,Molecular biology ,Kidney Neoplasms ,Computer Science Applications ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,mitochondrial DNA copy number ,chemistry ,Mitochondrial biogenesis ,lcsh:Biology (General) ,lcsh:QD1-999 ,Doxorubicin ,Gene Knockdown Techniques ,Warburg effect ,Transcription Factors - Abstract
We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XF(e)-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0.007); and drug resistance to doxorubicin (p = 0.008) of the TFAM-KD clone were significantly higher than those of the NT clone. Bioenergetically, the TFAM-KD clone expressed lower mOCRB (p = 0.009) but higher ECARB (p = 0.037) than did the NT clone. We conclude that a reduction of mtDNA copy number and decrease of respiratory function of mitochondria in RCC might be compensated for by an increase of enzymes and factors that are involved in the upregulation of glycolysis to confer RCC more invasive and a drug-resistant phenotype in vitro.
- Published
- 2016
32. Cigarette Smoking and hOGG1 Ser326Cys Polymorphism are Associated with 8-OHdG Accumulation on Mitochondrial DNA in Thoracic Esophageal Squamous Cell Carcinoma
- Author
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Hui Chen Lin, Yau-Huei Wei, Shi Chuan Chang, Shu Yu Lee, Mau Hua Lee, Wen Hu Hsu, Chen Sung Lin, Teh Ying Chou, and Liang Shun Wang
- Subjects
Male ,Mitochondrial DNA ,Guanine ,Esophageal Neoplasms ,Genotype ,Real-Time Polymerase Chain Reaction ,DNA, Mitochondrial ,Esophageal squamous cell carcinoma ,DNA Glycosylases ,Oxidative damage ,Esophagus ,Cigarette smoking ,Surgical oncology ,Humans ,Medicine ,Neoplasm Staging ,Polymorphism, Genetic ,business.industry ,Smoking ,Middle Aged ,Thoracic Neoplasms ,Prognosis ,Molecular biology ,Oncology ,DNA glycosylase ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Female ,Surgery ,business - Abstract
We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC).DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing.Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051).Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.
- Published
- 2012
33. AB001. Low mitochondrial DNA copy number is associated with low mitochondrial DNA integrity and advanced T-status in non-small cell lung cancer
- Author
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Yau-Huei Wei, Siao-Cian Pan, Jiin-Chyr Hsu, Ming-Ching Lee, and Chen-Sung Lin
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Mitochondrial DNA ,business.industry ,medicine.disease ,Oxidative damage ,03 medical and health sciences ,Basic Research ,030104 developmental biology ,Cancer research ,Medicine ,Non small cell ,business ,Lung cancer - Published
- 2017
34. Pure Red Cell Aplasia and Hypogammaglobulinemia in a Patient with Thymoma
- Author
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Teh Ying Chou, Biing Shiun Huang, Han Shui Hsu, Yuan Bin Yu, Chen Sung Lin, and Wen Hu Hsu
- Subjects
medicine.medical_specialty ,Thymoma ,hypogammaglobulinemia ,Extended thymectomy ,Pure red cell aplasia ,Red-Cell Aplasia, Pure ,urologic and male genital diseases ,Hypogammaglobulinemia ,Agammaglobulinemia ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,neoplasms ,Medicine(all) ,lcsh:R5-920 ,business.industry ,Complete remission ,Thymus Neoplasms ,General Medicine ,Perioperative ,Middle Aged ,thymoma ,Thymectomy ,medicine.disease ,Dermatology ,Myasthenia gravis ,Surgery ,surgical procedures, operative ,pure red cell aplasia ,Female ,lcsh:Medicine (General) ,business - Abstract
Both pure red cell aplasia (PRCA) and hypogammaglobulinemia are rarer conditions than myasthenia gravis (MG) in thymoma patients. Several articles have discussed the relation between PRCA and thymoma or hypogammaglobulinemia and thymoma, and their proper treatments. Instances of both PRCA and hypogammaglobulinemia in a thymoma patient are few and reported sporadically in the literature. We discuss a 46-year-old woman with thymoma and simultaneous PRCA and hypogammaglobulinemia who achieved complete remission from PRCA after perioperative steroid administration and extended thymectomy, and review the literature.
- Published
- 2009
- Full Text
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35. An ellipse-shaped with slanted slot circularly polarized monopole antenna for UHF RFID readers
- Author
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Su, Hsin-Lung, primary, Huang, Hong-Sheng, additional, Chen, Sung-Lin, additional, and Sim, Chow-Yen-Desmond, additional
- Published
- 2017
- Full Text
- View/download PDF
36. Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin
- Author
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Hao-Wei Wang, Kuang Tai Kuo, Liang Shun Wang, Chen Sung Lin, Kuan-Chih Chow, Chin Ping Lin, and Jen Hwey Chiu
- Subjects
Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,DNA Repair ,AKR1C1 ,Apoptosis ,Drug resistance ,Safingol ,Biology ,chemistry.chemical_compound ,Wogonin ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Chrysin ,20-Hydroxysteroid Dehydrogenases ,Flavonoids ,Cisplatin ,Dose-Response Relationship, Drug ,Interleukin-6 ,Kinase ,Cell Cycle ,Hydroxysteroid Dehydrogenases ,biology.organism_classification ,Endocrinology ,Oncology ,chemistry ,Doxorubicin ,Drug Resistance, Neoplasm ,Flavanones ,Cancer research ,Scutellaria baicalensis ,medicine.drug - Abstract
Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1-AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression.
- Published
- 2007
37. Radical Lymph Node Dissection in Primary Esophagectomy for Esophageal Squamous Cell Carcinoma
- Author
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Chen-Sung Lin, Ming-Yuan Lee, Chao-Yu Liu, Chia-Chuan Liu, Mu-Chi Hsiao, Chih-Hsun Shih, and Chih-Tao Cheng
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Male ,medicine.medical_specialty ,Poor prognosis ,Esophageal Neoplasms ,medicine.medical_treatment ,Improved survival ,Esophageal squamous cell carcinoma ,Internal medicine ,Medicine ,Humans ,Therapeutic strategy ,Retrospective Studies ,business.industry ,Radical Lymph Node Dissection ,Hazard ratio ,Middle Aged ,Prognosis ,Surgery ,Esophagectomy ,Carcinoma, Squamous Cell ,Lymph Node Excision ,Female ,Lymph ,Esophageal Squamous Cell Carcinoma ,Cardiology and Cardiovascular Medicine ,business - Abstract
Subtotal esophagectomy with radical lymph node dissection (RLND) remains an effective therapeutic strategy for localized esophageal squamous cell carcinoma (ESCC). However, controversy exists regarding the extent to which RLND should be performed. We reappraised the prognostic impact and accurate nodal staging of RLND in ESCC.The data from 101 ESCC patients (mean age, 57.5 years; 93 men) who underwent primary subtotal esophagectomy were retrospectively collected. Candidate variables, including the number of total dissected lymph nodes (TDLN [subgrouped into TDLN less than 13, TDLN 13 to 40, and TDLN more than 40]), were evaluated to determine their prognostic impacts and hazard ratio (HR).Fewer TDLN (p0.001; HR 9.011, 2.449, and 1.000 for TDLN less than 13, TDLN 13 to 40, and TDLN more than 40, respectively), tumor length exceeding 3.5 cm (p0.001; HR 3.321), resection margin invasion (p0.001; HR 14.493), and positive nodal status (p = 0.002; HR 2.730) were independent predictors of a poor prognosis. Considering the 54 node-negative patients, more TDLN correlated with improved survival (p = 0.001). Risk analysis demonstrated that one fewer TDLN could contribute to an increased HR of 1.047 (p = 0.014). However, RLND involving more TDLN appeared to lose the prognostic impact for the 47 node-positive patients (p = 0.072). Furthermore, the number of positive dissected lymph nodes remained at approximately 4 if the number of TDLN exceeded 20.For N-negative or N-positive ESCC patients undergoing primary surgical resection, the number of TDLN influenced their prognosis or nodal staging accuracy, respectively. At least 20 TDLN were necessary for N-positive patients.
- Published
- 2014
38. Clinicopathologic significance of cyclooxygenase-2 overexpression in esophageal squamous cell carcinoma
- Author
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Hao-Wei Wang, Wing Yin Li, Kuan Chih Chow, Liang Shun Wang, Yu Chung Wu, Chen Sung Lin, and Kuang Tai Kuo
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Pathology ,Esophageal Neoplasms ,medicine.medical_treatment ,Gene Expression Regulation, Enzymologic ,Metastasis ,Internal medicine ,medicine ,Humans ,Esophagus ,Aged ,Aged, 80 and over ,Esophageal disease ,business.industry ,Membrane Proteins ,Anatomical pathology ,Middle Aged ,Esophageal cancer ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Isoenzymes ,Survival Rate ,medicine.anatomical_structure ,Peroxidases ,Epidermoid carcinoma ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Esophagectomy ,Carcinoma, Squamous Cell ,Immunohistochemistry ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Esophageal cancer is one of the most aggressive malignancies in the world, and whether multiple therapeutic modalities could improve long-term survival remains controversial. Recent studies have shown an increase of cyclooxygenase-2 (COX-2) expression in various malignancies, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods From 1993 to 1997, tissue samples from 96 patients with ESCC who underwent esophagectomy at our institution were collected for analysis. Cyclooxygenase-2 expression was examined by immunohistochemical staining, and further confirmed by Western blot analysis on six frozen tissues. Clinicopathologic data were analyzed to verify the significance. Results Cyclooxygenase-2 immunoreactivity was detected in 59 of 96 ESCC specimens (61%), and COX-2 overexpression (COX-2 high) was observed in 49% (47 of 96) of ESCCs. Statistical differences between COX-2 high and COX-2 low were found with respect to the status of distant metastasis (M factor) ( p = 0.035) and tumor stage ( p = 0.04). The survival was not significantly different between patients with and without COX-2 overexpression ( p = 0.43). Using the Cox regression analysis, only the N factor ( p = 0.0034) and M factor ( p = 0.0325) were independent prognostic factors. Conclusions Our results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with fewer metastases and less advanced stage, but had no impact on survival. The status of local or distant lymph node metastasis was the most important prognostic factor. The biological role and pathophysiologic regulation of COX-2 overexpression in ESCC deserve further investigation.
- Published
- 2003
39. Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma
- Author
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Chin San Liu, Chen Sung Lin, Liang Shun Wang, Ming Yi Chung, Yau-Huei Wei, Shi Chuan Chang, Wen Hu Hsu, Mau Hwa Lee, and Teh Ying Chou
- Subjects
Male ,Cancer Research ,Mitochondrial DNA ,DNA Copy Number Variations ,Esophageal Neoplasms ,DNA Mutational Analysis ,Loss of Heterozygosity ,Biology ,DNA, Mitochondrial ,Loss of heterozygosity ,medicine ,Humans ,Genetic Association Studies ,Laser capture microdissection ,Analysis of Variance ,Microsatellite instability ,Cancer ,General Medicine ,Middle Aged ,Cell cycle ,medicine.disease ,Survival Analysis ,Molecular biology ,Heteroplasmy ,Oncology ,Lymphatic Metastasis ,Mutation ,Carcinoma, Squamous Cell ,Microsatellite ,Female ,Microsatellite Instability ,Tumor Suppressor Protein p53 ,Microsatellite Repeats - Abstract
We investigated the microsatellite alterations in mitochondrial DNA (mtDNA) and in TP53 in thoracic esophageal squamous cell carcinomas (TESCC). Using laser microdissection, 66 paired non-cancerous esophageal muscles, non-cancerous esophageal mucosa, cancerous TESCC nests plus 35 metastatic lymph nodes harvested from 66 resected esophagi of TESCC patients were subjected to DNA extrac- tion. D310 and D17S960 were chosen as markers to address microsatellite alterations in mtDNA, including changes in copy number and homoplasmic/heteroplasmic mutations of mtDNA, and in TP53, including loss of heterozygosity (LOH) and microsatellite instability (MI). From non-cancerous esophageal mucosa to cancerous TESCC nests and then metastatic lymph nodes, a trend of homoplasmic D310 muta- tion (10.6, 25.8, 31.4%; P=0.023), an ever increase of mtDNA copy ratios (0.892, 1.128, 1.183; P=0.018) and an elevated incidence of TP53 LOH (19.7, 34.8, 37.1%; P=0.010) were observed. From T1, T2, T3 to T4 TESCC, the incidence of TP53 LOH (12.5, 16.7, 34.8, 52.2%; P=0.011) was increased, in a stepwise fashion. Furthermore, we observed an association of TP53 LOH with an increased mtDNA copy ratio (P=0.022) and TP53 MI with heteroplasmic D310 mutation (P=0.069) in TESCC. Concurrent and associated microsatellite alterations in mtDNA and in TP53 in TESCC support the cancer clonal expansion theory and imply a possible relationship between the mitochondria and p53 in TESCC.
- Published
- 2012
40. Design of a circularly polarized antenna with parasitic square-ring strip for UHF RFID reader applications
- Author
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Su, Hsin-lung, primary and Chen, Sung-Lin, additional
- Published
- 2015
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41. Dual-radiation pattern RFID tag design for application in library management
- Author
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Chiou, Shin-Fu, primary, Lin, Shir-Kuan, additional, and Chen, Sung-Lin, additional
- Published
- 2015
- Full Text
- View/download PDF
42. Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy
- Author
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Liang-Shun Wang, Yau-Huei Wei, Chen-Sung Lin, and Chun-Ming Tsai
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Male ,Mitochondrial DNA ,medicine.medical_specialty ,Lung Neoplasms ,DNA damage ,Down-Regulation ,medicine.disease_cause ,DNA, Mitochondrial ,Deoxycytidine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lung cancer ,Pneumonectomy ,Aged ,Retrospective Studies ,Cisplatin ,business.industry ,Cancer ,Deoxyguanosine ,Middle Aged ,medicine.disease ,Gemcitabine ,Neoadjuvant Therapy ,Gene Expression Regulation, Neoplastic ,Oxidative Stress ,Treatment Outcome ,Tumor progression ,8-Hydroxy-2'-Deoxyguanosine ,Chemotherapy, Adjuvant ,Cancer cell ,Disease Progression ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress ,medicine.drug ,DNA Damage - Abstract
The decrease in the copy number of mitochondrial DNA (mtDNA) in cancer tissues might be associated with a decrease in oxidative mtDNA damage to achieve cancer immortalization and progression. Lung cancer specimens were collected from 29 patients with stage III non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgical resection. The relative mtDNA copy number and the oxidative mtDNA damage (formation of 8-OHdG in mtDNA) of each cancer tissue were measured by quantitative real-time PCR. Seven female and 22 male lung cancer patients, with a mean age of 63.5 years were evaluated. Tumors of five patients became progressive, 13 stable, and 11 partially responsive after preoperative chemotherapy. Low mtDNA copy number (P=0.089) and low degree of oxidative mtDNA damage (P=0.036) were found to associate with tumor progression. Moreover, mtDNA copy number was significantly related to the degree of oxidative mtDNA damage (P=0.031). The mtDNA copy number and oxidative mtDNA damage were lower in advanced NSCLC after chemotherapy. This finding suggests that a decrease in the content of mtDNA may result in a decrease of mitochondrial density in cancer cells, which leads to a decrease of endogenous ROS production and reduction of ROS-triggered DNA damage to achieve immortalization.
- Published
- 2008
43. Prognostic variables in thoracic esophageal squamous cell carcinoma
- Author
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Hui Chen Lin, Shi Chuan Chang, Wen Hu Hsu, Teh Ying Chou, Yau-Huei Wei, Yu Chung Wu, Liang Shun Wang, and Chen Sung Lin
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Male ,Prognostic variable ,medicine.medical_specialty ,Esophageal Neoplasms ,Thoracic Cavity ,Malignancy ,Metastasis ,Internal medicine ,medicine ,Carcinoma ,Humans ,Lymph node ,Cancer staging ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,medicine.anatomical_structure ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Lymph Node Excision ,Female ,Lymph ,Lymph Nodes ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Thoracic esophageal squamous cell carcinoma (TESCC) is an aggressive malignancy with a poor prognosis. The current American Joint Committee on Cancer (AJCC) TNM cancer staging system focusing on the effect of regional (N1) and nonregional lymph node (M1a and M1b) metastasis may need reappraisal. We investigated the role of the number of dissected and positive nodes in TESCC patients. Methods A total of 109 TESCC patients (97 men; mean age of 62.3 years) who underwent surgical resection were retrospectively analyzed. The current AJCC TNM system and other lymph node classifications were used to subgroup these patients and analyze survival differences. Previously reported prognostic factors were evaluated. Results Patients with positive lymph node metastasis had a poor prognosis ( p ω 0.001). There was a significant difference in survival among the 67 node-positive patients subdivided into subgroups with 1 to 3 and 4 or more positive nodes ( p = 0.004). Multivariable Cox proportional hazard regression analysis identified four independent prognostic factors: difficulty in swallowing ( p = 0.024), cigarette smoking ( p = 0.003), number of positive lymph nodes (0, 1 to 3, and ≥4; p ω 0.001), and gastric cardia invasion ( p = 0.012). Total dissection of at least 20 lymph nodes was the minimal requirement to achieve accurate nodal staging. Conclusions Dissection of more than 20 lymph nodes is mandatory in TESCC patients to achieve accurate staging. Positive lymph node metastasis of 4 or higher is a significant independent prognostic factor.
- Published
- 2008
44. Gastric schwannoma
- Author
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Chen-Sung, Lin, Han-Shui, Hsu, Chien-Ho, Tsai, Wing-Yin, Li, and Min-Hsiung, Huang
- Subjects
Adult ,Endoscopes, Gastrointestinal ,Stomach Neoplasms ,S100 Proteins ,Stomach ,Humans ,Female ,Stomach Ulcer ,Gastrointestinal Hemorrhage ,Tomography, X-Ray Computed ,Neurilemmoma - Abstract
Gastrointestinal mesenchymal tumors are a group of tumors originated from the mesenchymal stem cells of the gastrointestinal tract, consisting of gastrointestinal stromal tumors (GIST), leiomyomas or leiomyosarcomas or schwannomas. Gastric schwannoma is a very rare gastrointestinal mesenchymal tumor, which represents only 0.2% of all gastric tumors and 4% of all benign gastric neoplasms. We report a 24-year-old girl who suffered from an episode of upper gastrointestinal bleeding. The endoscopic examination showed a round submucosal tumor with a central ulceration and bleeding over the high body of the stomach. Surgical resection of the tumor was performed. The pathological examination revealed a picture of spindle cell tumor that was strongly positive for S-100 protein stain, and non-reactive for CD34, CD117, actin, HHF-35, desmin, melan-A and HMB-45, consistent with gastric schwannoma. The literature is reviewed.
- Published
- 2005
45. Effectiveness of short-term antibiotic prophylaxis on postoperative recovery course after pulmonary lobectomies
- Author
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Chen-Sung, Lin, Wen-Hu, Hsu, Yu-Chung, Wu, Wen-Chieh, Huang, Chien-Ying, Wang, and Min-Hsiung, Huang
- Subjects
Adult ,Aged, 80 and over ,Cefuroxime ,Lung Neoplasms ,Sputum ,Pneumonia ,Adenocarcinoma ,Antibiotic Prophylaxis ,Middle Aged ,Anti-Bacterial Agents ,Postoperative Complications ,Sisomicin ,Humans ,Neoplasms, Squamous Cell ,Pneumonectomy ,Aged - Abstract
Postoperative pneumonia is a major cause of mortality and morbidity after lung surgery. The effectiveness of prophylactic antibiotics for preventing postoperative pneumonia and the recovery course after pulmonary lobectomy is still not clarified yet. We conducted this study to evaluate the effectiveness of prophylactic antibiotics on the post-operative recovery course after pulmonary lobectomies.Forty-five cases undergoing pulmonary lobectomies between June 2002 and January 2003 were enrolled in this prospective study. Each patient received prophylactic antibiotics of cefuroxime and sisomicin. Sputum culture upon admission and swab culture from the bronchus cut-end during operation were obtained. The clinical vital signs including heart rates, respiratory rates and core body temperature in the postoperative recovery courses were analyzed.Four (8.9%) patients developed pneumonia after lobectomies, and pneumonia occurred only in patients who had positive culture results from bronchial cut-end. The organisms cultured from the sputum seemed to be controlled by prophylactic antibiotics. All the organisms cultured in the bronchus cut-end differed from those in the sputum; it denoted these pathogens were inoculated during anesthesia for surgical operation. The postoperative vital signs including tachycardia and fever improved gradually in the initial 3 days. Patients with pneumonia sustained significant higher fever than the non-pneumonic patients during postoperative course.The short-term combination of cefuroxime and sisomicin offers sufficient effectiveness in prophylaxis of pneumonia after pulmonary surgery. Positive bronchial cut-end cultures were related to the post-lobectomy pneumonia significantly. Body temperature was the most useful presenting vital sign for early detection of the postoperative pneumonia.
- Published
- 2004
46. Managements of locally advanced unresectable thymic epithelial tumors
- Author
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Chen-Sung, Lin, Kuang-Tai, Kuo, Wen-Hu, Hsu, Biing-Shiun, Huang, Yu-Chung, Wu, Han-Shui, Hsu, Min-Hsiung, Huang, and Liang-Shun, Wang
- Subjects
Adult ,Aged, 80 and over ,Male ,Thymoma ,Carcinoma ,Taiwan ,Dose-Response Relationship, Radiation ,Thymus Neoplasms ,Middle Aged ,Combined Modality Therapy ,Survival Analysis ,Treatment Outcome ,Humans ,Female ,Aged ,Neoplasm Staging ,Retrospective Studies - Abstract
Surgery is the treatment of choice for thymic epithelial tumors (TET), but the resectability is about 60-70%. For those with locally advanced unresectable TETs (LAU-TETs), some controversies about the prognostic factors and treatment modalities existed. The aims of this study are to elucidate the roles of various therapeutic options and to determine the survival and prognostic factors of LAU-TETs.Twenty-seven patients diagnosed with LAU-TETs underwent treatment in Taipei Veterans General Hospital between 1979 and 1997. Multiple treatment modalities, including surgical intervention, irradiation and chemotherapy, were advocated for these patients. The clinicopathological factors and the effects of the treatment modalities were evaluated retrospectively.Twenty seven cases of LAU-TETs, included 18 thymomas (12 at stage III and 6 at stage IVa) and 9 thymic carcinomas (4 at stage III and 5 at stage IVa), were enrolled for study. The overall 5-year and 10-year survival rates were 54.6% and 35.1%, respectively. Patients receiving debulking surgery and those with irradiation dosage higher than 4400 cGy had significantly better survivals (P = 0.021 and P = 0.016, respectively).Aggressive debulking surgery and sufficient irradiation dosage provide better survivals for patients with LAU-TETs, especially for those with thymoma.
- Published
- 2004
47. A Looped-Bowtie RFID Tag Antenna Design for Metallic Objects
- Author
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Lin, Ken-Huang, primary, Chen, Sung-Lin, additional, and Mittra, Raj, additional
- Published
- 2013
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48. A low profile RFID tag designed for metallic objects
- Author
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Chen, Sung-Lin, primary, Lin, Ken-Huang, additional, and Mittra, Raj, additional
- Published
- 2009
- Full Text
- View/download PDF
49. A triple-feed and near omni-directional (3D) RFID tag antenna design
- Author
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Chen, Sung-Lin, primary and Mittra, Raj, additional
- Published
- 2009
- Full Text
- View/download PDF
50. A METALLIC RFID TAG DESIGN FOR STEEL-BAR AND WIRE-ROD MANAGEMENT APPLICATION IN THE STEEL INDUSTRY
- Author
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Chen, Sung-Lin, primary, Kuo, Shih-Kang, additional, and Lin, Chang-Tsun, additional
- Published
- 2009
- Full Text
- View/download PDF
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