scholarly journals Associations among telomerase activity, p53 protein overexpression, and genetic instability in lung cancer

1999 ◽  
Vol 80 (3-4) ◽  
pp. 453-457 ◽  
Author(s):  
X Wu ◽  
B Kemp ◽  
C I Amos ◽  
S E Honn ◽  
W Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genetic Instability ◽  
P53 Protein ◽  
Telomerase Activity ◽  
Protein Overexpression

Prognostic and Predictive Importance of p53 and RAS for Adjuvant Chemotherapy in Non–Small-Cell Lung Cancer

2007 ◽  
Vol 25 (33) ◽  
pp. 5240-5247 ◽  
Author(s):  
Ming-Sound Tsao ◽  
Sarit Aviel-Ronen ◽  
Keyue Ding ◽  
Davina Lau ◽  
Ni Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
P53 Protein ◽  
P53 Gene ◽  
Small Cell ◽  
Phase Iii ◽  
Protein Overexpression ◽  
Small Cell Lung

Purpose p53 and RAS are multifunctional proteins that are critical to cell cycle regulation, apoptosis, cell survival, gene transcription, response to stress, and DNA repair. We have evaluated the prognostic and predictive value of p53 gene/protein aberrations using tumor samples from JBR.10, a North American phase III intergroup trial that randomly assigned 482 patients with completely resected stage IB and II non–small-cell lung cancer (NSCLC) to receive four cycles of adjuvant cisplatin plus vinorelbine or observation alone. Methods p53 protein expression was evaluated by immunohistochemistry. Mutations in exons 5 to 9 of the p53 gene were determined by denaturing high-performance liquid chromatography and confirmed by sequencing. RAS mutations were identified by allelic specific oligonucleotide hybridization. Results Of 253 patients, 132 (52%) were positive for p53 protein overexpression. Untreated p53-positive patients had significantly shorter overall survival than did patients with p53-negative tumors (hazard ratio [HR] = 1.89; 95% CI, 1.07 to 3.34; P = .03). However, these p53-positive patients also had a significantly greater survival benefit from adjuvant chemotherapy (HR = 0.54; P = .02) compared with patients with p53-negative tumors (HR = 1.40; P = .26; interaction P = .02). Mutations of p53 and RAS genes were found in 124 (31%) of 397 and 117 (26%) of 450 patients, respectively. Mutations in these genes were neither prognostic for survival nor predictive of a differential benefit from adjuvant chemotherapy. Conclusion p53 protein overexpression is a significant prognostic marker of shortened survival, and also a significant predictive marker for a differentially greater benefit from adjuvant chemotherapy in completely resected NSCLC patients.

scholarly journals Telomerase activity and serum levels of p53 protein as prognostic factors of survival in patients with advanced non-small cell lung cancer

2010 ◽  
Vol 104 (9) ◽  
pp. 1356-1361 ◽  
Author(s):  
Tomasz Targowski ◽  
Karina Jahnz-Rozyk ◽  
Witold Owczarek ◽  
Alicja Raczka ◽  
Pawel Janda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
P53 Protein ◽  
Serum Levels ◽  
Telomerase Activity ◽  
Small Cell ◽  
Small Cell Lung

p53 Protein Overexpression and Gene Mutation in Mixed Mullerian Tumors of the Uterus

1999 ◽  
Vol 23 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Richie Soong ◽  
Simon Knowles ◽  
Ian G. Hammond ◽  
Con Michael ◽  
Barry J. Iacopetta
Keyword(s):  
Gene Mutation ◽  
P53 Protein ◽  
Protein Overexpression

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals Myc and Human Papillomavirus Type 16 E7 Genes Cooperate To Immortalize Human Keratinocytes

2007 ◽  
Vol 81 (22) ◽  
pp. 12689-12695 ◽  
Author(s):  
Xuefeng Liu ◽  
Gary L. Disbrow ◽  
Hang Yuan ◽  
Vjekoslav Tomaić ◽  
Richard Schlegel
Keyword(s):  
Transcriptional Activation ◽  
High Efficiency ◽  
P53 Protein ◽  
Significant Proportion ◽  
Telomerase Activity ◽  
Human Papillomaviruses ◽  
Mrna Levels ◽  
Crisis Period ◽  
Cell Immortalization ◽  
Immortalized Cells

ABSTRACT The E6 protein of the oncogenic human papillomaviruses (HPVs), in combination with the E7 protein, is essential for the efficient immortalization of human foreskin keratinocytes (HFKs). Since we recently demonstrated that E6 activates the human telomerase reverse transcriptase (hTERT) promoter via a Myc-dependent mechanism, we speculated that overexpressed Myc might be able to substitute for E6 in cell immortalization. Myc (similar to E6) was unable to immortalize HFKs when transduced alone, despite inducing high levels of telomerase activity. However, when transduced with E7, Myc immortalized HFKs following a brief but detectable crisis period. In contrast to E6 + E7-immortalized cells, the Myc + E7-immortalized cells expressed high levels of p53 protein as well as two p53-regulated proteins, p21 and hdm-2. The increase in p21 and hdm-2 proteins correlated directly with their mRNA levels, suggesting transcriptional activation of the respective genes by the overexpressed p53 protein. Interestingly, a significant proportion of the p53 protein in the Myc + E7-immortalized cells was localized to the cytoplasm, potentially due to interactions with the overexpressed hdm-2 protein. Regardless, cell immortalization by the Myc + E7 genes occurred independently of p53 degradation. Since we have already observed high-efficiency cell immortalization with the hTERT + E7 or E6 mutant (p53 degradation-defective) + E7 genes (i.e., no crisis period) that proceeds in the presence of high levels of p53, we hypothesize that the crisis period in the Myc + E7 cells is due not to the levels of the p53 protein but rather to unique properties of the Myc protein. The common factor in cell immortalization by the three gene sets (E6 + E7, Myc + E7, and hTERT + E7 genes) is the induction of telomerase activity.

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