Evaluation of TKTL1 as a biomarker in serum of prostate cancer patients.

Introduction: Monocyte associated transketolase-like 1 (TKTL1) as a cancer biomarker has become popular with alternative practitioners, but plays no role in conventional medicine. This investigation evaluates the potential of serum TKTL1 as a biomarker for prostate cancer.

Material And Methods: Patients (n = 66) undergoing curative radical prostatectomy (RPE) for biopsy-pro-ven PCa were included in the study.

A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma.

Background: Treatment options for sarcoma are limited. Histone deacetylase inhibitors increase the efficacy of topoisomerase II inhibitors by promoting access to chromatin and by down-regulating DNA repair. Thus, combined panobinostat and epirubicin therapy was evaluated to treat refractory sarcoma.

sE-cadherin serves as a diagnostic and predictive parameter in prostate cancer patients.

Background: Measurement of prostate-specific antigen (PSA) advanced the diagnostic and prognostic potential for prostate cancer (PCa). However, due to PSA's lack of specificity, novel biomarkers are needed to improve risk assessment and ensure optimal personalized therapy. A set of protein molecules as potential biomarkers was therefore evaluated in serum of PCa patients.

Combined histone deacetylase inhibition and tamoxifen induces apoptosis in tamoxifen-resistant breast cancer models, by reversing Bcl-2 overexpression.

Introduction: The emergence of hormone therapy resistance, despite continued expression of the estrogen receptor (ER), is a major challenge to curing breast cancer. Recent clinical studies suggest that epigenetic modulation by histone deacetylase (HDAC) inhibitors reverses hormone therapy resistance. However, little is known about epigenetic modulation of the ER during acquired hormone resistance.

Histone deacetylase regulation of ATM-mediated DNA damage signaling.

Ataxia-telangiectasia mutated (ATM) is a major regulator of the DNA damage response. ATM promotes the activation of BRCA1, CHK2, and p53 leading to the induction of response genes such as CDKN1A (p21), GADD45A, and RRM2B that promote cell-cycle arrest and DNA repair. The upregulation of these response genes may contribute to resistance of cancer cells to genotoxic therapies.

Efficacy of histone deacetylase and estrogen receptor inhibition in breast cancer cells due to concerted down regulation of Akt.

Hormonal therapy resistance remains a considerable barrier in the treatment of breast cancer. Activation of the Akt-PI3K-mTOR pathway plays an important role in hormonal therapy resistance. Our recent preclinical and clinical studies showed that the addition of a histone deacetylase inhibitor re-sensitized hormonal therapy resistant breast cancer to tamoxifen.

Group mentoring: a story of transition for undergraduate baccalaureate nursing students.

Background: Group mentoring has been endorsed as an effective method of supporting novice professionals across disciplines. In one university, faculty revised the undergraduate nursing curriculum to include a group mentoring course as a requirement of students during the four semesters they are enrolled in the nursing program.

Objectives: The purpose of this study was to explore the lived experience of undergraduate nursing students participating in a group mentoring course.

A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer.

Background: Histone deacetylases (HDACs) are crucial components of the oestrogen receptor (ER) transcriptional complex. Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points.

Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer.

Histone deacetylases (HDACs) regulate the acetylation of a variety of histone and nonhistone proteins, controlling the transcription and regulation of genes involved in cell cycle control, proliferation, survival, DNA repair and differentiation. Unsurprisingly, HDAC expression is frequently altered in hematologic and solid tumor malignancies. Two HDAC inhibitors (vorinostat and romidepsin) have been approved by the US FDA for the treatment of cutaneous T-cell lymphoma.

Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy.

Modulation of estrogen signaling is one of the most successful modalities for the treatment of estrogen receptor (ER)-positive breast cancer, yet de novo and acquired resistance are frequent. Recent data suggests that the induction of autophagy may play a considerable role in promoting tumor cell survival and resistance to anti-estrogen therapy. Hence, bypassing autophagy may offer a novel strategy to enhance the anti-tumor efficacy of anti-estrogens.

Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cells.

Unlabelled: Nanotechnology has introduced many exciting new tools for the treatment of human diseases. One of the obstacles in its application to that end is the lack of a fundamental understanding of the interaction that occurs between nanoparticles and living cells. This report describes the quantitative analysis of the kinetics and endocytic pathways involved in the uptake of anatase titanium dioxide (TiO(2)) nanoparticles into prostate cancer PC-3M cells.

Labeling TiO2 nanoparticles with dyes for optical fluorescence microscopy and determination of TiO2-DNA nanoconjugate stability.

Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO2) nanoparticles. These nanoparticles, when electronically linked to single-stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents.

Methods for assessing DNA hybridization of peptide nucleic acid-titanium dioxide nanoconjugates.

We describe the synthesis of peptide nucleic acid (PNA)-titanium dioxide (TiO(2)) nanoconjugates and several novel methods developed to investigate the DNA hybridization behaviors of these constructs. PNAs are synthetic DNA analogs resistant to degradation by cellular enzymes that hybridize to single-stranded DNA (ssDNA) with higher affinity than DNA oligonucleotides, invade double-stranded DNA (dsDNA), and form different PNA/DNA complexes. Previously, we developed a DNA-TiO(2) nanoconjugate capable of hybridizing to target DNA intracellularly in a sequence-specific manner with the ability to cleave DNA when excited by electromagnetic radiation but susceptible to degradation that may lower its intracellular targeting efficiency and retention time.

Gadolinium-conjugated TiO2-DNA oligonucleotide nanoconjugates show prolonged intracellular retention period and T1-weighted contrast enhancement in magnetic resonance images.

Nanoconjugates composed of titanium dioxide (TiO2) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone.

Intracellular distribution of TiO2-DNA oligonucleotide nanoconjugates directed to nucleolus and mitochondria indicates sequence specificity.

Deoxyribonucleic acid (DNA) oligonucleotides hybridize to matching DNA sequences in cells, as established in the literature, depending on active transcription of the target sequence and local molarity of the oligonucleotide. We investigated the intracellular distribution of nanoconjugates composed of DNA oligonucleotides attached to TiO2 nanoparticles, thus creating a locally increased concentration of the oligonucleotide. Two types of nanoconjugates, with oligonucleotides matching mitochondrial or nucleolar DNA, were specifically retained in mitochondria or nucleoli.

Nanoparticles for applications in cellular imaging.

In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also discusses factors influencing nanoparticle imaging and uptake in live cells in vitro. Due to their unique size-dependent properties nanoparticles offer numerous advantages over traditional dyes and proteins.

Connecting: perceptions of becoming a faculty mentor.

The school of nursing faculty at a liberal arts university created an innovative group-mentoring course to support students' progression through the undergraduate nursing program. The foundation of the mentoring program is the dynamic relationship between novice and expert. Students are enrolled in this one-hour course for each of their four semesters in the upper division nursing curriculum.

MCT-1 oncogene contributes to increased in vivo tumorigenicity of MCF7 cells by promotion of angiogenesis and inhibition of apoptosis.

Overexpression of a novel oncogene MCT-1 (multiple copies in a T cell malignancy) causes malignant transformation of murine fibroblasts. To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 breast cancer cells negative for endogenous MCT-1 (MCF7-MCT-1). Overexpression of MCT-1 in these cells resulted in a slight elevation of estrogen receptor-alpha, and higher rates of DNA synthesis and growth in response to estradiol compared with the empty vector control (MCF7-EV).

Absence of persistence and transfer of genetic material by recombinant Escherichia coli in conventional, antibiotic-treated mice.

Strain BST-1 is a derivative of Escherichia coli K-12 that carries a plasmid designated pURA-4 and is the expression system used by The Upjohn Company in the production of recombinant bovine somatotropin (rbSt). This plasmid also encodes an ampicillin resistance gene. The plasmidless carrier strain, BST-1C, contains a gene for tetracycline resistance which is provided by the chromosomal insertion of the transposon Tn10.

Starch hydrolysis by the ruminal microflora.

The effects of grain type and processing on ruminal starch digestion are well documented but poorly understood at the biochemical and molecular levels. Waxy grains have starches high in amylopectin and are more readily digested than nonwaxy grains. However, the composition of the endosperm cell matrix and the extent to which the starch granules are embedded within it also affect starch digestion rates.

Single-site chromosomal Tn5 insertions affect the export of pectolytic and cellulolytic enzymes in Erwinia chrysanthemi EC16.

Exponentially growing cells of Erwinia chrysanthemi EC16 usually export about 98% of their pectate lyase (PL) and protease, about 40% of their polygalacturonase (PG), and about 60% of their cellulase (endoglucanase or carboxymethyl cellulase; CL). By using the R plasmid, pJB4JI (pPH1JI::Mu::Tn5), three independent Tn5 insertion mutants were obtained that exported normal levels of protease but 10% or less of PL, PG, and CL. Physical analysis revealed that single copies of Tn5 had inserted into the E.

pULB113, an RP4::mini-Mu plasmid, mediates chromosomal mobilization and R-prime formation in Erwinia amylovora, Erwinia chrysanthemi, and subspecies of Erwinia carotovora.

The RP4::mini-Mu plasmid pULB113, transferred from Escherichia coli strain MXR, was stable and transfer proficient in Erwinia amylovora strain EA303, E. carotovora subsp. atroseptica strain ECA12, E.

Isolation and characterization of Tn5 insertion mutants of Erwinia chrysanthemi that are deficient in polygalacturonate catabolic enzymes oligogalacturonate lyase and 3-deoxy-D-glycero-2,5-hexodiulosonate dehydrogenase.

Mutants of Erwinia chrysanthemi EC16 deficient in the polygalacturonate catabolic enzymes oligogalacturonate lyase (Ogl-) and 3-deoxy-D-glycero-2,5-hexodiulosonate (ketodeoxyuronate) dehydrogenase (KduD-) were obtained by Tn5 mutagenesis using the R plasmid pJB4JI. Ogl- Exu+ (Exu+, D-galacturonate utilization) and KduD- Exu- strains macerated potato tuber tissue and utilized glucose, glycerol, and gluconate, but they did not utilize polygalacturonate, unsaturated digalacturonate, or saturated digalacturonate. Genetic and physical evidence indicated that the Ogl- mutants and a KduD- recombinant contained a single copy of Tn5 and that Tn5 (Kmr) was linked to the mutant phenotypes.