Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma.

The primary objective of the study was to evaluate the feasibility and safety of a process which would utilize genome-wide expression data from tumor biopsies to support individualized treatment decisions. Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%. Molecular profiling may provide data which will enable the practitioner to select the most appropriate therapeutic option for individual patients, thus improving outcomes.

Minimum entropy decomposition: unsupervised oligotyping for sensitive partitioning of high-throughput marker gene sequences.

Molecular microbial ecology investigations often employ large marker gene datasets, for example, ribosomal RNAs, to represent the occurrence of single-cell genomes in microbial communities. Massively parallel DNA sequencing technologies enable extensive surveys of marker gene libraries that sometimes include nearly identical sequences. Computational approaches that rely on pairwise sequence alignments for similarity assessment and de novo clustering with de facto similarity thresholds to partition high-throughput sequencing datasets constrain fine-scale resolution descriptions of microbial communities.

Disruption of the expression of a non-coding RNA significantly impairs cellular differentiation in Toxoplasma gondii.

The protozoan parasite Toxoplasma gondii is an important human and veterinary pathogen. Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing "tachyzoites" and latent "bradyzoite" tissue cysts.

Antitumor activity of nifurtimox is enhanced with tetrathiomolybdate in medulloblastoma.

Medulloblastoma, a neuroectodermal tumor arising in the cerebellum, is the most common brain tumor found in children. We recently showed that nifurtimox induces production of reactive oxygen species (ROS) and subsequent apoptosis in neuroblastoma cells both in vitro and in vivo. Tetrathiomolybdate (TM) has been shown to decrease cell proliferation by inhibition of superoxide dismutase-1 (SOD1).

Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state.

Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites.

Human progesterone receptor polymorphisms and implantation failure during in vitro fertilization.

Objective: Polymorphic variants of the human progesterone receptor gene have been described, but their potential influence on in vitro fertilization outcome have not been studied.

Study Design: DNA was available from 317 women (cases) who had >or=2 embryo transfers without a clinical pregnancy and from 288 women (control subjects) who became pregnant after 1 in vitro fertilization attempt. With protocols that were specific for H770H (C/T genotype) and +331G/A polymorphism, amplification of polymorphism fragments, digestion with restriction enzymes, and gel visualization were performed.

Multiple displacement amplification prior to single nucleotide polymorphism genotyping in epidemiologic studies.

We assessed the whole genome amplification strategy, known as multiple displacement amplification (MDA), for use with the TaqMan genotyping platform for DNA samples derived from two case-control studies nested in the Nurses' Health Study and the Physicians' Health Study. Our objectives were to (1) quantify DNA yield from samples of varying starting concentrations and (2) assess whether MDA products give an accurate representation of the original genomic sequence. Multiple displacement amplification yielded a mean 23000-fold increase in DNA quantity and genotyping results demonstrate 99.

A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk.

Excessive estrogen stimulation unopposed by progesterone strongly predisposes to endometrial cancer. Because the antiproliferative effect of progesterone requires the progesterone receptor (PR), which exists in two isoforms, PR-A and -B, we reasoned that variants in the PR gene may predispose to endometrial cancer. We found six variable sites, including four polymorphisms in the hPR gene and five common haplotypes.