Atrazine, a pre-emergent herbicide in the chloro-s-triazine family, has been widely used in crop lands and often detected in agriculture watersheds, which is considered as a potential threat to human health. Although atrazine and its metabolites showed an elevated incidence of mammary tumors in female Sprague–Dawley (SD) rats, no molecular evidence was found relevant to its carcinogenesis in humans. This study aims to determine whether atrazine could induce the expression of DNA damage response-related proteins in normal human breast epithelial cells (MCF-10A) and to examine the cytotoxicity of atrazine at a molecular level. Our results indicate that a short-term exposure of MCF-10A to an environmentally-detectable concentration of atrazine (0.1 µg/mL) significantly increased the expression of tumor necrosis factor receptor-1 (TNFR1) and phosphorylated Rad17 in the cells. Atrazine treatment increased H2AX phosphorylation (γH2AX) and the formation of γH2AX foci in the nuclei of MCF-10A cells. Atrazine also sequentially elevated DNA damage checkpoint proteins of ATM- and RAD3-related (ATR), ATRIP and phospho-Chk1, suggesting that atrazine could induce DNA double-strand breaks and trigger the DNA damage response ATR-Chk1 pathway in MCF-10A cells. Further investigations are needed to determine whether atrazine-triggered DNA double-strand breaks and DNA damage response ATR-Chk1 pathway occur in vivo.

Background: The Internet has become one of the most important means to obtain health and medical information. It is often the first step in checking for basic information about a disease and its treatment. The search results are often useful to general users. Various search engines such as Google, Yahoo!, Bing, and Ask.com can play an important role in obtaining medical information for both medical professionals and lay people. However, the usability and effectiveness of various search engines for medical information have not been comprehensively compared and evaluated.Objective: To compare major Internet search engines in their usability of obtaining medical and health information.Methods: We applied usability testing as a software engineering technique and a standard industry practice to compare the four major search engines (Google, Yahoo!, Bing, and Ask.com) in obtaining health and medical information. For this purpose, we searched the keyword breast cancer in Google, Yahoo!, Bing, and Ask.com and saved the results of the top 200 links from each search engine. We combined nonredundant links from the four search engines and gave them to volunteer users in an alphabetical order. The volunteer users evaluated the websites and scored each website from 0 to 10 (lowest to highest) based on the usefulness of the content relevant to breast cancer. A medical expert identified six well-known websites related to breast cancer in advance as standards. We also used five keywords associated with breast cancer defined in the latest release of Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) and analyzed their occurrence in the websites.Results: Each search engine provided rich information related to breast cancer in the search results. All six standard websites were among the top 30 in search results of all four search engines. Google had the best search validity (in terms of whether a website could be opened), followed by Bing, Ask.com, and Yahoo!. The search results highly overlapped between the search engines, and the overlap between any two search engines was about half or more. On the other hand, each search engine emphasized various types of content differently. In terms of user satisfaction analysis, volunteer users scored Bing the highest for its usefulness, followed by Yahoo!, Google, and Ask.com.Conclusions: Google, Yahoo!, Bing, and Ask.com are by and large effective search engines for helping lay users get health and medical information. Nevertheless, the current ranking methods have some pitfalls and there is room for improvement to help users get more accurate and useful information. We suggest that search engine users explore multiple search engines to search different types of health information and medical knowledge for their own needs and get a professional consultation if necessary.

Developing new technologies for cancer screening and early diagnosis is a critical issue for saving cancer patients’ lives. Our recent effort has led to the first nanopore biosensor in clinical disease detection. The targets are microRNA (miRNAs), a class of short (∼18-24-nt) non-coding RNAs molecules that regulate gene expression at the post-transcriptional level. Aberrant expression of miRNAs has been found in all types of tumors. Thus miRNAs have been recognized as potential cancer biomarkers. Most notably, specific miRNAs are released from the primary tumor into blood circulation, making the detection of circulating miRNAs profile a powerful tool for noninvasive cancer detection, diagnosis, staging, and monitoring. Guided by designed programmable oligonucleotide probe, single miRNA molecules captured in the nanopore produce a signature current signal that function fingerprints, enabling us to identify a specific miRNA and quantify its concentration. The prototype of nanopore sensor has demonstrated the capability to discriminate single nucleotide difference between miRNAs (single nucleotide polymorphisms, SNPs). In clinical tests, the nanopore has shown the power to differentiate miRNA levels in blood from lung cancer patients and healthy people. This simple, sensitive, label-free technique requiring no amplification for miRNA detection as in the RT-PCR method, has the potential for noninvasive and cost-effective early diagnosis of lung cancer. If validated in clinical trial, the nanopore sensor will become a system available to monitor cancer patients and to screen high risk populations for early diagnosis of cancers which will potentially save the lives of millions.

More and more people use internet search engines, especially Google, to learn about diseases and possible treatments. We conducted a hallway testing to evaluate the effectiveness of Google in obtaining medical information. We searched 'Breast Cancer' using Google. Six volunteers scored their experience for each of the top 500 websites. Our study shows that 50 hits of Google often help lay users in getting medical information, but some highly useful websites may be buried beyond top 200. Hence, the specificity of using Google in searching for medical information is satisfactory while the sensitivity of the search has significant room for improvement.

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Background: Both cancer and pluripotent stem cell lines share the common biological properties of unlimited capacity for self-renewal and high potency for proliferation in vitro . Several research groups have shown that differentiated somatic cells derived from all three germ layers can be induced into pluripotent stem cells (iPS) by defined transcription factors, namely OCT4, SOX2, c-MYC, KLF4, NANOG, and LIN28. Overexpression of a set of 4 genes induces global epigenetic reprogramming that in turn results in eventual transition of somatic cells to phenotypic iPS cells in a few weeks. Among these genes, OCT4 and SOX2 are required for self-renewal, while c-MYC and KLF4 are known to be oncogenic. Furthermore, xenograft of iPS cells in mouse produces a teratoma. It seems that there is not clear distinction between iPS cells and tumor cells. In this study, we demonstrated that the promoter CpG islands (CGIs) of SOX2 and KLF4 are methylated in two aggressive B-cell lymphomas, diffuse large B-cell lymphoma (BLBCL) and Burkitt lymphoma (BL). The latter is the most aggressive lymphoma characterized by a t(8;14) translocation resulting in overexpression of the c-MYC protein. Materials and Methods: DLBCL (DB) and BL (Raji and Daudi) cell lines from the American Type Culture Collection were studied. We also examined DLBCL (3) and BL (2) patient samples obtained from Ellis Fischel Cancer Center, University Missouri Healthcare, with IRB approval. Genomic DNA was extracted and subjected to digestion with 4 methylation sensitive restriction enzymes. Each of the PCR target in CGI was carefully selected and hypermethylated region can be differentially amplified. Results: CGI methylation of 10 genes was tested. These genes include SOX2, KLF4, HOXD10, COX2, DLC-1, PCDHGA12A, HIN1, SLC26A, CDH1, and CD44. Dense methylation of the SOX2 gene was observed in all 3 cell lines and 1 DLBCL patient. Only weak methylation bands were seen in all other patients. KLF4 was strongly methylated in all 3 cell lines and all DLBCL patients, but not methylated in BL patients. The HOXD10, COX2, DLC-1, SLC26A, CDH1, CD44 were methylated in both DLBCL cell lines and patient samples as well as in BL cell lines, but not in BL patient samples. No methylation was seen in pooled normal control blood samples. Conclusion: Promoter CGI hypermethylation in combination with other epigenetic alterations is associated with gene silencing. Compared with DLBCL, less CGI methylation of reprogramming factors SOX2 and KLF4 and other tested genes, in conjunction with overexpression of c-MYC in Burkitt lymphoma patients may be associated with high mitotic rate and more aggressive clinical behavior in this tumor. Activity of the reprogramming factors in both tumor cells and iPS cells may shed light on the origin of tumor stem cells. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-166.