scholarly journals Black raspberry restores the expression of the tumor suppressor p120ctn in the oral cavity of mice treated with the carcinogen dibenzo[a,l]pyrene diol epoxide

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259998
Author(s):  
Douglas B. Stairs ◽  
Mary E. Landmesser ◽  
Cesar Aliaga ◽  
Kun-Ming Chen ◽  
Yuan-Wan Sun ◽  
...  

One of the major risk factors for head and neck squamous cell carcinoma (HNSCC) is tobacco smoke exposure, but the mechanisms that can account for disease development remain to be fully defined. Utilizing our HNSCC mouse model, we analyzed oral squamous cell carcinomas (OSCC) induced by the active metabolite of a common smoke constituent, dibenzo[a,l]pyrene diol-epoxide (DBPDE). Analyzing protein expression by either immunofluorescence or immunohistochemistry, we identified biologic processes that are dysregulated in premalignant and invasive cancer lesions induced by DBPDE. Interestingly, p120ctn expression is downregulated in both stages of the disease. In addition to decreased p120ctn expression, there was also increased proliferation (as measured by Ki67), inflammation (as measured by NFkB (p65) expression), neovascularization (as measured by CD31) and recruitment of Ly6G-positive immune cells as well as strong EGFR expression. We also examined the effect of the chemopreventive agent black raspberry (BRB) on p120ctn and EGFR protein expression in DBPDE treated mice. p120ctn, but not EGFR, protein expression increased in mice treated with BRB. Our results suggest that modulation of p120ctn may, in part, account for the mechanism by which BRB inhibits DBPDE induced OSCC in mice.

2007 ◽  
Vol 28 (10) ◽  
pp. 433-437 ◽  
Author(s):  
W. F. P. Heerden ◽  
T. J. P. Swart ◽  
M. B. Heerden ◽  
E. J. Rensburg ◽  
S. Engelbrecht ◽  
...  

2011 ◽  
Vol 38 (7) ◽  
pp. 570-575 ◽  
Author(s):  
Adam Hsu ◽  
Bita Esmaeli ◽  
Brent Hayek ◽  
Mohammad G. Hossain ◽  
Roman Shinder ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22010-e22010
Author(s):  
R. Lopez ◽  
E. Gallardo ◽  
A. Ruibal ◽  
L. Leon ◽  
A. Sanchez-Salmon ◽  
...  

e22010 Background: Tumor hipoxia induces the up-regulation of several genes via the hipoxia-inducible transcription factors (HIF) 1 and 2. HIF-2 alpha (HIF-2 α) and HIF-1 alpha (HIF-1α) are associated with the prognosis of operable NSCLC patients. We studied the immunohistochemical expression of HIF-1α and HIF-2 α in patients with NSCLC and the possible correlation with the maximum standardised uptake value (max SUV) of 18F-FDG as well as other biological parameters. Methods: We used a Tissue Arrayer device (Beecher Instruments. WI) to construct a TMA block, according to conventional protocols for the study of immunohistochemical expression of HIF-1α, HIF-2 α, EGFR, bcl-2, MIB1, p16, p63 and cyclins A, B1, D1 and D3. Sections were scored as positive if >10% of cells stained positively. Staining patterns were correlated to clinical variables. Results: HIF- 1α expression was observed in 84/96 patients (34/39 adenocarcinomas and 50/57 squamous cell carcinomas), however it did not correlate with clinical stage (I-II: 41/45 vs III-IV: 44/51). HIF-1α correlated positively with HIF-2 α (p:0,001) and EGFR (p:<0,001) expressions. The maxSUV values of 18F-FDG-PET were higher (p:0,039) in HIF-1α -positive (17,1±8,6) than in negative tumors (11,8±4,4). HIF-2 α expression was observed in 60/103 cases (27/42 adenocarcinomas and 33/61 squamous cell carcinomas) and it did not correlate with clinical stage ((I-II: 28/45 vs III-IV: 32/57). HIF-2 α correlated positively with HIF-1α (p:0,001), MIB1 (p:0,045) and EGFR (p:0,091) expressions. After multivariate analysis, only the clinical stage (RR: 2,2) was a prognostic factor. Conclusions: 1) HIF-1α and HIF-2 α expressions are frequent in patients with NSCLCs and it did not correlate with clinical stage; 2) maxSUVs FDG-PET values were higher in HIF1alpha positive than in HIF-1α negative patients; 3) HIF-1α was correlated with EGFR expression, while HIF-2 α was correlated with MIB1 expression. No significant financial relationships to disclose.


2004 ◽  
Vol 203 (3) ◽  
pp. 798-807 ◽  
Author(s):  
Reinhard Ullmann ◽  
Patrizia Morbini ◽  
Iris Halbwedl ◽  
Massimo Bongiovanni ◽  
Margit Gogg-Kammerer ◽  
...  

2019 ◽  
Author(s):  
Andrean L. Simons ◽  
Anand Rajan ◽  
Katherine Gibson-Corley ◽  
Georgina Ofori-Amanfo ◽  
Patrick Ten Eyck ◽  
...  

2005 ◽  
Vol 33 (2) ◽  
pp. 292-299 ◽  
Author(s):  
Luca Lambertini ◽  
Kezia Surin ◽  
Thai-Vu T. Ton ◽  
Natasha Clayton ◽  
June K. Dunnick ◽  
...  

Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet radiation (primarily UVA), called PUVA therapy, has been used to treat different chronic skin diseases but led to a significant increased risk for skin cancer. The National Toxicology Program (NTP) performed a study in mice treated with PUVA that showed a significant increase in squamous cell carcinomas of the skin. In the present study, we evaluated the protein expression of p53 and PCNA and DNA mutations of p53 and H-ras genes in both hyperplastic and neoplastic squamous cell lesions from the NTP study. By immunohistochemical staining, protein expression of both p53 and PCNA was detected in 3/16 (19%) of hyperplastic lesions and 14/17 (82%) of SCCs in groups treated with both 8-MOP and UVA. The mutation frequency of p53 in SCCs from mice administered 8-MOP plus UVA was 15/17 (88%) with a predominant distribution of mutations in exon 6 (14/15 – 93%). No H-ras mutations were detected in the hyperplastic lesions/tumors. The mutagenic effect of PUVA on the p53 tumor suppressor gene may lead to a conformational modification and inactivation of the p53 protein, which are considered critical steps in PUVA-induced skin carcinogenesis. The p53 mutational frequency and patterns from our study were different from those reported in human PUVA-type tumors.


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