NQO1 protein expression was associated with estrogen receptor (ER) expression (P = 0.011), whereas 34.5% of NFκB-nuclear/activated tumors were ER negative (P = 0.001).
Secondary objectives were assessment of toxicity, pharmacokinetic determination of RH1 and pharmacodynamic assessment of drug effect through measurement of DNA cross linking in peripheral blood mononuclear cells (PBMCs) and tumour, DTD activity in tumour and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphism status.
We found that NQO1 was frequently up-regulated in human liver cancer, and its high expression level was correlated with the tumor stage and low survival rate of HCC patients.
Developing an effective method for detecting NQO1 activity with high sensitivity and selectivity in tumors holds a great potential for cancer diagnosis, treatment, and management.
NQO1 protein expression was assessed using immunohistochemical (IHC) staining in 160 patients with serous ovarian carcinoma, 62 patients with ovarian borderline tumors and 53 patients with benign ovarian tumors.
We show elevated NAD(P)H:quinone oxidoreductase-1 (NQO1) levels in tumors from NSCLC patients. beta-Lapachone, an effective chemotherapeutic and radiosensitizing agent, selectively killed NSCLC cells that expressed high levels of NQO1.
The rate of strong positive NQO1 protein expression was correlated with large tumor size (P=0.019), late pathologic stage (P=0.001) and the presence of lymph node metastasis (P=0.001).
Analysis of RNA indicated 20- to 50-fold higher levels of NQO1 gene expression in the liver tumors and in the tissue surrounding the tumors of patients with hepatocarcinoma than in normal individuals.
Low NQO1 mRNA and protein levels were observed in the TP53 mutated subgroup compared to others tumors (p < .05) and in silico analyses of The Cancer Genome Atlas data further indicated that NQO1 mRNA levels were lower in serous compared to endometrioid copy-number high EC.
The FANCD2-associated survival effect was most pronounced in hormone receptor positive, HER2-negative tumors, and in tumors with above-median NQO1 expression.
Additionally, the NQO1 expression rate was positively correlated with tumor size, serosal invasion, tumor stage, and both disease-free survival and 5-year survival rates.
These results support the ideas that reductive activation of MMC by DTD may be important in the cytotoxicity of MMC and that polymerase chain reaction may be a useful technique for quantitating the relative expression of genes in human tumors.
A broad spectrum of NQO1 protein expression existed in tumours genotyped as NQO1*1 and NQO1*1/*2 although tumours with NQO1*1 typically expressed higher NQO1 protein.
Here, we present a treatment strategy that makes BER inhibition tumor-selective and NQO1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer.
Agents, such as β-lapachone, that target the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce programmed necrosis in solid tumors have shown great promise, but more potent tumor-selective compounds are needed.
Protection from tumor formation is associated with elevation of Phase II enzymes, including glutathione (GSH) transferase and NAD(P)H:quinone oxidoreductase (DT-diaphorase) in experimental carcinogenesis models in vivo.