Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

Background: Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world.

Biodegradable thermogelling polymers: working towards clinical applications.

As society ages, aging medical problems such as organ damage or failure among senior citizens increases, raising the demand for organ repair technologies. Synthetic materials have been developed and applied in various parts of human body to meet the biomedical needs. Hydrogels, in particular, have found extensive applications as wound healing, drug delivery and controlled release, and scaffold materials in the human body.

Inhibition of the 26S proteasome as a possible mechanism for toxicity of heavy metal species.

In this paper we report on the synthesis of five metal complexes coordinated to the [NN'O] ligand HL(iodo) (2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol), namely [Al(III)(L(iodo))2]ClO4 (1), [Cd(II)(L(iodo))Cl]·H2O (2), [Hg(II)(L(iodo))2]·4DMSO (3), [Pb(II)(L(iodo))NO3] (4), and [Sn(IV)(L(iodo))Cl3] (5). Species 1-5 are thoroughly characterized by spectroscopic and spectrometric methods, as well as by elemental analysis. X-ray crystallography results for complex 3 indicate the presence of Hg(II) ion hexacoordinated to two facially oriented [NN'O] ligands, whereas for complex 5 an Sn(IV) ion chelates to one deprotonated ligand and three chlorido coligands.

Proteasome inhibitor patents (2010 - present).

Introduction: Over the past 3 years, numerous patents and patent applications have been submitted and published involving compounds designed to inhibit the proteasome. Proteasome inhibition has been of great interest in cancer research since disruption of proteolysis leads to a significant buildup of cytotoxic proteins and activation of apoptotic pathways, particularly in rapidly proliferating cells. The current standards in proteasome inhibition are the only FDA-approved inhibitors, bortezomib and carfilzomib.

Genetic association of IL-21 polymorphisms with dilated cardiomyopathy in a Han Chinese population.

Background: Autoimmune abnormalities appear to be major predisposing factors for dilated cardiomyopathy (DCM). Interleukin-21 (IL-21) gene polymorphisms have been previously found to be associated with autoimmune diseases. This study aimed to assess the role of IL-21 in DCM in a Han Chinese population.

Regulation of metformin response by breast cancer associated gene 2.

Adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer. Clinical trials using the United States Food and Drug Administration (FDA)-approved, AMPK-activating, antidiabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast cancer associated gene 2 (BCA2/Rabring7/RNF115), a novel Really Interesting New Gene (RING) finger ubiquitin E3 ligase, is overexpressed in >50% of breast tumors.

Gold(III)-dithiocarbamato peptidomimetics in the forefront of the targeted anticancer therapy: preclinical studies against human breast neoplasia.

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo.

Prostate tissue metal levels and prostate cancer recurrence in smokers.

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer.

Calcium channel blocker verapamil accelerates gambogic acid-induced cytotoxicity via enhancing proteasome inhibition and ROS generation.

Verapamil (Ver), an inhibitor of the multidrug resistance gene product, has been proved to be a promising combination partner with other anti-cancer agents including proteasome inhibitor bortezomib. Gambogic acid (GA) has been approved for Phase II clinical trials in cancer therapy in China. We have most recently reported that GA is a potent proteasome inhibitor, with anticancer efficiency comparable to bortezomib but much less toxicity.

Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation.

Purpose: Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML.

Genome analysis of seven species of Kengyilia (Triticeae: Poaceae) with FISH and GISH.

The genome compositions and genetic relationships of seven species of Kengyilia were assessed using a sequential fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) technique. Five species, K. kokonorica, K.

The combination of proteasome inhibitors bortezomib and gambogic acid triggers synergistic cytotoxicity in vitro but not in vivo.

The proteasome inhibitor-based combinational therapy has been reported to be an efficient cancer treatment. Our recent studies demonstrated that the natural compound gambogic acid (GA) is a tissue-specific proteasome inhibitor, comparable to bortezomib (Bor), and sensitizes malignant cells to the proteasome inhibitor MG132/MG262 both in vitro and in vivo. The aim of this study was to further extend our investigation by combining GA with the clinically used proteasome inhibitor Bor to test their combined efficacy against human hepatoma HepG2 and mouse hepatoma H22 cells.

[Effect of quaternary ammonium methacrylates incorporation into a dental adhesive on the resistance of enzymatic degradation of resin-dentine interfaces].

Objective: To evaluate the effect of quaternary ammonium methacrylates incorporation into a dental adhesive on the resistance of enzymatic degradation of resin-dentine interfaces.

Methods: Thirty caries-free extracted human third molars were randomly divided into three groups (n = 10): 2-methacryloxylethyl dodecylmethyl ammonium bromide (MAE-DB) incorporated adhesive served as the experimental group, pre-treatment with chlorhexidine (CHX) served as a positive control, Adper(TM) Single Bond 2 served as a negative control. The resin-dentin interfaces were prepared using total etch bond system.

The role of grape seed extract in the remineralization of demineralized dentine: micromorphological and physical analyses.

Objectives: Grape seed extract (GSE) is known to have a positive effect on the demineralization and/or remineralization of artificial root caries lesions. The present study aimed to investigate whether biomodification of caries-like acid-etched demineralized dentine, using proanthocyanidins-rich GSE, would promote its remineralization potential.

Designs: Dentine specimens were acid-etched for 30s, then biomodified using proanthocyanidin-based preconditioners (at different concentrations and pH values) for 2min, followed by a 15-day artificial remineralization regimen.

Chemotherapeutic inhibitors in the treatment of prostate cancer.

Introduction: Prostate cancer being the second leading cause of death in men in Western countries remains a major challenge in healthcare. Several novel agents targeting signaling pathways in prostate cancer have recently been approved by the US Food and Drug Administration (FDA) but there is still an unmet need for new treatment strategies for castration-resistant prostate cancer (CRPC).

Areas Covered: This review provides a broad overview of prostate cancer therapeutics and highlights key players in the biology of prostate cancer as well as first- and second-line treatments for CRPC.

The interplay of AMP-activated protein kinase and androgen receptor in prostate cancer cells.

AMP-activated protein kinase (AMPK) has recently emerged as a potential target for cancer therapy due to the observation that activation of AMPK inhibits tumor cell growth. It is well-known that androgen receptor (AR) signaling is a major driver for the development and progression of prostate cancer and that downregulation of AR is a critical step in the induction of apoptosis in prostate cancer cells. However, little is known about the potential interaction between AMPK and AR signaling pathways.

[Effect of casein phosphopeptide-amorphous calcium phosphate on the stability of resin-dentin bonds against pH cycling].

Objective: To investigate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on the stability of resin-dentin bonds against pH cycling.

Methods: Resin-bonded dentin specimens were prepared following manufacturers' instructions, and randomly divided into 3 groups. Among them, 2 groups experienced pH cycling, in which specimens applied CPP-ACP or distilled and deionized water (DDW) on the bonding interface, respectively.

Mimicking cellular transport mechanism in stem cells through endosomal escape of new peptide-coated quantum dots.

Protein transport is an important phenomenon in biological systems. Proteins are transported via several mechanisms to reach their destined compartment of cell for its complete function. One such mechanism is the microtubule mediated protein transport.

Targeting the ubiquitin-proteasome system for cancer therapy.

Introduction: The ubiquitin-proteasome system (UPS) degrades 80 - 90% of intracellular proteins. Cancer cells take advantage of the UPS for their increased growth and decreased apoptotic cell death. Thus, the components that make up the UPS represent a diverse group of potential anti-cancer targets.

[The study of AutoFlow role in volume controlled ventilation].

Objective: To evaluate the efficacy and safety of automatic variable flow rate (AutoFlow) for volume control ventilation through monitoring the number of ventilator alarm.

Methods: Forty-eight adult patients receiving the Drager Evita 4 ventilator with an expectation of more than 2 days duration were divided into two groups by randomly digital methods, each n=24. The patients in control group were received routinely mode with synchronized intermittent mandatory ventilation (SIMV), and the others in observation group were given SIMV and assist with AutoFlow.

Cloning and characterization of chromosomal markers in alfalfa (Medicago sativa L.).

Eleven tandemly repetitive sequences were identified from a Cot-1 library by FISH and sequence analysis of alfalfa (Medicago sativa). Five repetitive sequences (MsCR-1, MsCR-2, MsCR-3, MsCR-4, and MsCR-5) were centromeric or pericentromeric, of which three were satellite DNAs and two were minisatellite DNAs. Monomers of 144, 148, and 168 bp were identified in MsCR-1, MsCR-2, and MsCR-3, respectively, while 15 and 39 bp monomers were identified in MsCR-4 and MsCR-5, respectively.

A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol.

A new fixation method for stick-shaped specimens in microtensile tests: laboratory tests and FEA.

Purpose: To introduce a new fixation method for stick-shaped specimens for use in microtensile tests and to evaluate the effect of this new method on microtensile bond strength, failure modes, and stress distribution.

Materials And Methods: Flat mid-coronal dentin surfaces were prepared on 12 caries-free human third molars and randomly divided into two groups for testing with two dental adhesives (Adper Single Bond 2 [SB2] and Clearfil SE Bond [SEB]). Following adhesive application and composite buildups, the bonded teeth were sectioned into beams.

Organic cadmium complexes as proteasome inhibitors and apoptosis inducers in human breast cancer cells.

Although cadmium (Cd) is a widespread environmental contaminant and human carcinogen, our studies indicate an organic Cd complex to be a potent inhibitor of proteasomal chymotrypsin-like (CT-like) activity, further capable of inducing apoptosis in a cancer cell-specific manner. It has been reported that the ligands indole-3-butyric acid (L1) and indole-3-propionic acid (L2) have cancer-fighting effects when tested in a rat carcinoma model. In addition, 3, 5-diaminobenzoic acid o-vanillin Schiff bases (L3) have high antimicrobial activity and a large number of Schiff base complexes have been reported to have proteasome-inhibitory activity.

Clinical effect of sidong wubu method in treatment of closed fracture of upper limbs.

Objective: To objectively evaluate the clinically curative effect of sidong wubu method on closed fracture of upper limbs.

Methods: A single-blind randomized controlled trial was used to divide 654 patients with closed fracture of upper limbs at early stage into two groups. 298 patients in the surgical group were treated with open reduction and internal fixation and 356 patients in the treatment group with sidong wubu method for 6 months as a course of treatment.