Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy

Lin, Cheng‐Chieh; Wang, Liang-Shun; Tsai, Chun‐Ming; Wei, Yau‐Huei

doi:10.1510/icvts.2008.177006

Cited by 99 publications

(94 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to the paired non-cancerous counterparts, a decrease in mtDNA copy number was reported in lung cancer (33), hepatocellular carcinoma (34) and gastric cancer (35). In lung cancer tissues after neoadjuvant chemotherapy, a progressive decrease in mtDNA copy number was correlated with disease progression (22). These decreases were thought to be decreases in mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

“…The sequences of primers used for nDNA amplification (18S rRNA region) were: 18SF1546, 5'-T AGAGGGACAAGTGGCGTTC-3'; and 18SR1650, 5'-CGCT GAGCCAGTCAGTGT-3' (21). The equations of standard curves set for mtDNA and nDNA quantification were set as previously described (19,20,22). Then the mtDNA and nDNA copies of the clinical samples relative to mtDNA and nDNA copies of the 143B osteosarcoma cells were calculated.…”

Section: Standard Curves For Mtdna and Ndna Quantificationsmentioning

confidence: 99%

See 1 more Smart Citation

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

Lin¹,

Chang²,

Ou³

et al. 2015

Oncology Reports

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Standard Curves For Mtdna and Ndna Quantificationsmentioning

confidence: 99%

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

Lin¹,

Chang²,

Ou³

et al. 2015

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…Its clinical significance has been reported in gastric, pulmonary and breast cancers (18)(19)(20). Based on our previous study, the copy number and D310 mutation of mtDNA in TESCC were determined by quantitative real-time PCR and direct sequencing, respectively (17,21).…”

Section: Methodsmentioning

confidence: 99%

Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma

Lin¹,

Wang²,

Chang³

et al. 2012

Oncol Rep

View full text Add to dashboard Cite

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 extraction. 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 mutation (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.

show abstract

“…Oxidized mtDNA analysis was completed by qPCR as previous report [9]. Briefly, the degree of oxidized mtDNA is reflected by the abundance of 8-OH-dG formation in mtDNA, and it is presented as ΔCt value, which is the Ct difference value with and without treatment of hOGG1, an 8-oxoguanine DNA glycosylase (New England Biolab, USA).…”

Section: Oxidized Mtdna Analysis By Qpcrmentioning

confidence: 99%

Mitochondrial Impairment Mechanism in D-galactose-induced Senescence in Experimental Fibroblast Cell Model

Ye¹,

Cao²,

Tang³

et al. 2016

Proceedings of the 2016 International Conference on Biological Sciences and Technology

View full text Add to dashboard Cite

Abstract.To establish an effective model for cellular senescence, human embryo lung fibroblast cells (MRC-5) were cultured in D-galactose (D-Gal) medium respectively, as control, same concentration of D-glucose (D-Glu) was used. Decrease in cell proliferation, increase in senescence associated β-galactosidase activity, up-expression of p21 protein, and cell cycle arrest at S-phage were observed in D-Gal-treated cells. Meanwhile, D-Gal-treated cells showed the significant increased ROS and MDA level and decreased SOD activity. Furthermore, mitochondrial impairment and decrease in efficiency of oxidative phosphorylation (OXPHOS) was induced by D-Gal as evidenced by the decreased transmembrane potential, reduction of ATP production and changes of respiration function. Additionally, the significant decrease of mitochondrial quantity, mitochondrial DNA (mtDNA) copy number and increased mtDNA damage were detected in D-Gal-treated cells. Our data demonstrate that D-Gal induces mitochondrial oxidative impairment associated with increased generation of ROS, ultimately inhibiting the ATP synthesis which contributes to premature cellular senescence.

show abstract

Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy

Cited by 99 publications

References 13 publications

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

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

Associated microsatellite alterations in mitochondrial DNA and in TP53 in thoracic esophageal squamous cell carcinoma

Mitochondrial Impairment Mechanism in D-galactose-induced Senescence in Experimental Fibroblast Cell Model

Contact Info

Product

Resources

About