Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response.

Recent evidence supports the presence of an L-glutamyl methyltransferase(s) in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as "acidic residue methyltransferase-1" (Armt1), an enzyme that specifically targets proliferating cell nuclear antigen (PCNA) in breast cancer cells, predominately methylating glutamate side chains. Armt1 homologs share structural similarities with the SAM-dependent methyltransferases, and negative regulation of activity by automethylation indicates a means for cellular control.

Spatial prevalence and associations among respiratory diseases in Maine.

Chronic respiratory diseases rank among the leading global disease burdens. Maine's respiratory disease prevalence exceeds the US average, despite limited urbanization/industrialization. To provide insight into potential etiologic factors among this unique, rural population, we analyzed the spatial distributions of, and potential associations among asthma, COPD, pneumonia, and URI adult outpatient data (n=47,099) from all outpatient transactions (n=5,052,900) in 2009 for Maine hospitals and affiliate clinics, using spatial scan statistic, geographic weighted regression (GWR), and a Delaunay graph algorithm.

Informed consent for biobanking research: cancer patient recruitment from rural communities in Maine.

Biobanking research seeks to improve the diversity, availability, and quality of human specimens critical for translational research, including biospecimen collections from disadvantaged minorities. American rural whites are seldom represented in such initiatives as geographic isolation makes obtaining informed consent challenging. We report a case series of 83 newly diagnosed cancer patients, attending a rural community medical center, who consented to participate in cancer research.

Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low doses of arsenic.

Environmental or occupational exposure to low doses of arsenic induces a series of health problems including cancer. The molecular events in arsenic-induced carcinogenicity remain to be defined. In the NuLi-1 immortalized human lung epithelial cell line with p53 and pRb deficiency, exposure to low doses of arsenic trioxide for 72 h promoted cell proliferation and upregulated the gene transcription levels of FOXM1, CDC6, CDC25A, and cyclin D1, which are both critical cell cycle regulatory genes and proto-oncogenes.

Novel interactions between FOXM1 and CDC25A regulate the cell cycle.

FOXM1 is a critical regulator of the G1/S and G2/M cell cycle transitions, as well as of the mitotic spindle assembly. Previous studies have suggested that FOXM1 regulates CDC25A gene transcription, but the mechanism remains unknown. Here, we provide evidence that FOXM1 directly regulates CDC25A gene transcription via direct promoter binding and indirect activation of E2F-dependent pathways.

Analyzing spatial and temporal (222)Rn trends in Maine.

Prolonged radon exposure has been linked to lung cancer. Cancer registry data indicates excess risk for age-adjusted lung cancer in Maine. Maine's mean residential radon activity exceeds the EPA maximum contaminant level (MCL).

Functional ramifications for the loss of P-selectin expression on hematopoietic and leukemic stem cells.

Hematopoiesis is a tightly regulated biological process that relies upon complicated interactions between blood cells and their microenvironment to preserve the homeostatic balance of long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), multipotent progenitors (MPPs), and differentiated cells. Adhesion molecules like P-selectin (encoded by the Selp gene) are essential to hematopoiesis, and their dysregulation has been linked to leukemogenesis. Like HSCs, leukemic stem cells (LSCs) depend upon their microenvironments for survival and propagation.

Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low-dose arsenite-induced cell proliferation.

Arsenic trioxide (ATO) is a first-line anti-cancer agent for acute promyelocytic leukemia, and induces apoptosis in other solid cancer cell lines including breast cancer cells. However, as with arsenites found in drinking water and used as raw materials for wood preservatives, insecticides, and herbicides, low doses of ATO can induce carcinogenesis after long-term exposure. At 24 h after exposure, ATO (0.

Docetaxel increases antitumor efficacy of oncolytic prostate-restricted replicative adenovirus by enhancing cell killing and virus distribution.

Background: We explored multiple molecular mechanisms of the combination of docetaxel and an oncolytic prostate-restricted replication competent adenovirus (Ad) (PRRA) in advanced prostate cancer (PCa) models. The combinational therapy has potential to overcome the therapeutic limitations of poor virus distribution inside solid tumors.

Methods: We evaluated the effect of docetaxel on the antitumor efficacy and efficiency of virus transduction, transgene expression and virus distribution of PRRA in a prostate-specific antigen/prostate-specific membrane antigen-positive tumor xenograft model.

Targeted therapy of chronic myeloid leukemia.

Inhibition of BCR-ABL with kinase inhibitors has become a well-accepted strategy for targeted therapy of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML) and has been shown to be highly effective in controlling the disease. However, BCR-ABL kinase inhibitors do not efficiently kill leukemic stem cells (LSCs), indicating that this therapeutic strategy does not lead to a cure of CML. Development of curative therapies of CML require the identification of genes/pathways that play critical roles in survival and self-renewal of LSCs.