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Considerable interest has been generated from the results of recent clinical trials using smoothened (SMO) antagonists to inhibit the growth of hedgehog (HH) signaling-dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH(More)
The epidemiological history of HBV genotypes A and D and subgenotypes A2 and D3 was studied on 132 isolates drawn between 1980 and 2005 from patients living in a homogenous geographical area. Evolutionary rates and divergence dates were estimated and HBV demographic history was reconstructed by using a statistical approach based on coalescent theory. The(More)
A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of(More)
The role of Hedgehog (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the(More)
A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of(More)
We investigated the prevalence and molecular epidemiology of human T cell lymphotropic virus type 1 in Peruvian HIV-1-positive subjects, and found a 10.1% prevalence in a consecutive series of 318 HIV-1-positive patients living in Lima. Phylogenetic analysis of the long terminal repeat of 10 patient isolates showed that all of them belonged to the HTLV-1aA(More)
BACKGROUND Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the(More)
Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However,(More)
Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC) promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP) and 85% of spontaneous colorectal cancers (CRC). FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC.(More)
Treatment of HBeAg-positive chronic hepatitis B with pegylated interferon achieves HBeAg seroconversion in about 30% of patients and retreatment of nonresponders is followed by a low rate of sustained response. Alanine aminotransferase flares occurring after the introduction of interferon are considered a positive predictor of response. Here we described a(More)