scholarly journals Chlorine and Chromium Elements, Proteins of Oxidative Stress and Dna Repair Pathways Are Related to Tumor Aggressiveness and Prognosis of Patients With Oral Cancer

Author(s):  
Arícia L. E. M. Assis ◽  
Anderson B. Archanjo ◽  
Raul C. Maranhão ◽  
Suzanny O. Mendes ◽  
Rafael P. de Souza ◽  
...  

Abstract BackgroundSquamous cell carcinoma (OCSCC), the most frequent cancer of the oral cavity, is extremely aggressive, the response to treatment is poor and markers for prognosis of disease are scarce. The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments with the demographic and clinical evolution data is an effective strategy scarcely explored in OCSCC studies. The aim was to analyse OCSCC tissues for trace elements and protein expression of enzymes related with oxidative stress and DNA repair that can be candidates as markers of tumor aggressiveness and prognosis. MethodsSeventy-eight tumor fragments from 78 OCSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence (μ-XRF) for trace elements. Protein expression of superoxide dismutase (SOD-1) and thioredoxin (Trx) and DNA repair-related purinic/apyrimidinic endonuclease/redox factor-1 (Ref-1) and 8-oxoguanine glycosylase (OGG1/2) was performed by immunohistochemistry. Sociodemographic, clinical and hystopathological data were obtained from 4-year follow-up records. ResultsDisease relapse was higher in patients with chlorine and chromium presence and in those with tumors with strong OGG1/2 expression. Strong expression of SOD-1, Trx and Ref-1 was determinant of larger tumor. As expected, perineural, vascular invasions and alcohol consumption were markers of greater worse prognosis. ConclusionPresence of trace elements can be markers of disease prognosis. Strong expression of enzymes related with oxidative stress or DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OCSCC patients.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aricia Leone Evangelista Monteiro de Assis ◽  
Anderson Barros Archanjo ◽  
Raul C. Maranhão ◽  
Suzanny O. Mendes ◽  
Rafael P. de Souza ◽  
...  

AbstractThe comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 65-65
Author(s):  
Carl Ceraolo ◽  
Travis A. Gerke ◽  
Piotr Zareba ◽  
Andreas Pettersson ◽  
Konrad H. Stopsack ◽  
...  

65 Background: DNA repair genes including BRCA1 are commonly altered in metastatic prostate tumors. However, mutations and copy number aberrations in these genes are rare in primary tumors. Instead, preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. Methods: We undertook a prospective study of tumor BRCA1 protein expression and lethal prostate cancer among men with clinically localized prostate cancer in the Health Professionals Follow-up Study. We performed immunohistochemical staining for BRCA1 on tumor tissue microarrays using a validated antibody and scored expression as positive or negative. We also assessed tumor proliferation by immunostaining for Ki67, angiogenesis by immunostaining for CD34, and apoptosis using a TUNEL assay. Proportional hazards regression was used to evaluate the association between BRCA1 protein expression and development of lethal prostate cancer (metastasis or cancer-specific death). Results: Ten percent of tumors (60 of 589) stained positive for the BRCA1 protein. BRCA1-positive tumors were characterized by higher Gleason scores, a higher proliferative index, and a higher apoptotic index. During a median follow-up of 14.3 years, 18 men (34%) in the BRCA1-positive group and 74 men (14%) in the BRCA1-negative group developed lethal prostate cancer. There was a strong positive association between BRCA1 protein expression and lethal prostate cancer in both unadjusted analyses (HR 2.71, 95% CI 1.73–4.26) and after adjusting for clinical factors (HR 2.00, 95% CI 1.26–3.18). The positive association with BRCA1 protein expression was also independent of proliferation index. Conclusions: Primary prostate tumors expressing the BRCA1 protein have a highly proliferative phenotype and are more likely to progress to lethal disease, independent of its higher proliferative index. Assessing tumor protein expression of BRCA1 may help elucidate the Janus-faced role of DNA repair pathways in prostate cancer progression.[Table: see text]


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10075-10075
Author(s):  
C. A. Gomez-Roca ◽  
R. Ruiz-Soto ◽  
M. Castaing ◽  
V. Marty ◽  
S. Bonvalot ◽  
...  

10075 Background: Myxoid/round cell liposarcoma (MLPS) is an uncommon soft tissue sarcoma with a relatively favorable prognosis and is considered a low grade malignancy. Methods: Retrospective analysis of 123 localized MLPS adult patients (pts) treated at our institution from 1987 to 2005 was performed. Paraffin embedded tissue was analyzed for IL6, IL6 receptor, NFkB and bcl-2 protein expression (positive (+) or negative) by tissue microarray immunostaining. Results: The median age of the 77 males and 46 females was 42 years (yr) (range 15–70). Lower extremity (LE) was the site more affected (77 pts). Median tumor size was 11 cm (range 2.5–40 cm), 87 were deep tumors and 63 were grade 1 tumors. Preoperative biopsy was carried on 38 pts. All but 2 pts underwent surgery (R0 24%, R1/R2 76%); 44 pts had a second surgery. Chemotherapy (CT) and radiation therapy were given to 30% and 52% of pts respectively. Complete remission was achieved in 98% of pts. After a median follow up of 6 yr (range 0.1–19 yr) 53 pts relapsed (43%); 37 locally, 11 distant and 5 both. Metastases occurred in 26 pts, 17 solitary and 9 multiple. The 5-yr, 10-yr and 15-yr DFS were 56%, 48% and 44% respectively. Median time to first relapse was 6.5 yr (range 0.1–16 yr). The 5-yr, 10-yr and 15-yr OS are 90%, 79% and 64% respectively. Tumor site, pre-surgical biopsy, R0 surgery and second surgery correlates with a better DFS in the multivariate analysis. So far 19 tumors have been studied for, NFkB (+) 57%, IL6 (+) 47% and Bcl2 (+) 30%, positivity. All tumors (+) for IL6 were also (+) for IL6 receptor. None of the proteins correlated to DFS and/or OS. Conclusions: Pts with localized resected MLPS require a prolonged follow-up since relapses occur after 10 yrs. PFS and OS correlate with an optimal loco-regional treatment. Half of MLPS expressed IL6, probably involving an autocrine phenomenon; whether this cytokine is involved in tumor aggressiveness, remains to be established. No significant financial relationships to disclose.


2019 ◽  
Vol 8 (5) ◽  
pp. 1756-1762 ◽  
Author(s):  
Hui Chen ◽  
Peisheng Chen ◽  
Fengfei Lin ◽  
Shunyou Chen ◽  
Jianhua Lin

2020 ◽  
Vol 41 (7) ◽  
pp. 904-908
Author(s):  
Konrad H Stopsack ◽  
Travis Gerke ◽  
Piotr Zareba ◽  
Andreas Pettersson ◽  
Dipanjan Chowdhury ◽  
...  

Abstract DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7–59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18–3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82–3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54–2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.


1968 ◽  
Vol 29 (2) ◽  
pp. 364-381 ◽  
Author(s):  
Alex D. Pokorny ◽  
Byron A. Miller ◽  
Sidney E. Cleveland

2017 ◽  
Author(s):  
Georgios Boutzios ◽  
Eleni Koukoulioti ◽  
Ioannis Papoutsis ◽  
Sotirios Athanaselis ◽  
Gerasimos Tsourouflis ◽  
...  

Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.


2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.


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