Purpose: The transcription factor nuclear factor-B (NF-B) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis.Experimental Design: Electromobility gel shift assays were used to evaluate NF-B DNA binding in vitro. The functional relevance of NF-B DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-B inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-B subunit was used to determine the frequency and location of NF-B in 97 prostatectomy specimens. The amount of staining was quantified on a 0 -3؉ scale.Results: An electromobility gel shift assay confirmed the presence of NFB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-B and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1؉ and 2؉ with no 3؉ staining in benign epithelium, whereas there was only 2؉ and 3؉ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage.Conclusions: NF-B is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-B, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-B for the prevention and/or treatment of prostate cancer.

We present a versatile, mass-producible, paper-based microchip electrophoresis platform that enables rapid, affordable, decentralized hemoglobin testing at the point-of-care.

DMAPT promotes cell death by both generating ROS and inhibition of NFkappaB. Its in vivo activity supports the conduct of clinical trials in patients with castrate-resistant disease.

Dimethylaminoparthenolide (DMAPT) is a water soluble parthenolide analog with preclinical activity in hematologic malignancies. Using non-small lung cancer (NSCLC) cell lines (A549 and H522) and an immortalized human bronchial epithelial cell line (BEAS2B) and TCC cell lines (UMUC-3, HT-1197 and HT-1376) and a bladder papilloma (RT-4), we aimed to characterize DMAPT's anticancer activity in tobacco-associated neoplasms. Flow cytometric, electrophoretic mobility gel shift assays (EMSA), and Western blot studies measured generation of reactive oxygen species (ROS), inhibition of NFjB DNA binding, and changes in cell cycle distribution and apoptotic proteins. DMAPT generated ROS with subsequent JNK activation and also decreased NFjB DNA binding and antiapoptotic proteins, TRAF-2 and XIAP. DMAPT-induced apoptotic cell death and altered cell cycle distribution with upregulation of p21 and p73 levels in a cell type-dependent manner. DMAPT suppressed cyclin D1 in BEAS2B. DMAPT retained NFjB and cell cycle inhibitory activity in the presence of the tobacco carcinogen nitrosamine ketone, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Using a BrdU accumulation assay, 5-20 lM of DMAPT was shown to inhibit cellular proliferation of all cell lines by more than 95%. Oral dosing of DMAPT suppressed in vivo A549 and UMUC-3 subcutaneous xenograft growth by 54% (p 5 0.015) and 63% (p < 0.01), respectively, and A549 lung metastatic volume by 28% (p 5 0.043). In total, this data demonstrates DMAPT's novel anticancer properties in both early and late stage tobacco-associated neoplasms as well as its significant in vivo activity. The data provides support for the conduct of clinical trials in TCC and NSCLC.In the United States in 2008, over 68,000 individuals were diagnosed with bladder cancer, and more than 14,000 patients died from their disease. Transitional cell carcinoma (TCC) is the dominant histology in over 95% of cases.1 There were also more than 200,000 patients diagnosed with lung cancer with 160,390 deaths and non-small lung cancer (NSCLC) makes up more than three quarters of these cases. Tobacco smoking is a major modifiable risk factor for both bladder and NSCLCs and significant achievements in decreasing this risk factor have been made in some countries. Despite this progress, these cancers are still a major cause of the current death rate from cancer.2 Modest advances have recently been made in the treatment of NSCLC with epidermal growth factor receptor and angiogenesis inhibition. 3,4 Therefore, novel strategies are needed to prevent the progression of epithelial cells which have entered the neoplastic