Breast cancers utilize hypoxic glycogen stores via PYGB, the brain isoform of glycogen phosphorylase, to promote metastatic phenotypes.

In breast cancer, tumor hypoxia has been linked to poor prognosis and increased metastasis. Hypoxia activates transcriptional programs in cancer cells that lead to increased motility and invasion, as well as various metabolic changes. One of these metabolic changes, an increase in glycogen metabolism, has been further associated with protection from reactive oxygen species damage that may lead to premature senescence.

Loss of PTEN promotes formation of signaling-capable clathrin-coated pits.

Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs.

Inferring Intracellular Signal Transduction Circuitry from Molecular Perturbation Experiments.

The development of network inference methodologies that accurately predict connectivity in dysregulated pathways may enable the rational selection of patient therapies. Accurately inferring an intracellular network from data remains a very challenging problem in molecular systems biology. Living cells integrate extremely robust circuits that exhibit significant heterogeneity, but still respond to external stimuli in predictable ways.

Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling.

Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC).

RhoC GTPase Is a Potent Regulator of Glutamine Metabolism and N-Acetylaspartate Production in Inflammatory Breast Cancer Cells.

Inflammatory breast cancer (IBC) is an extremely lethal cancer that rapidly metastasizes. Although the molecular attributes of IBC have been described, little is known about the underlying metabolic features of the disease. Using a variety of metabolic assays, including (13)C tracer experiments, we found that SUM149 cells, the primary in vitro model of IBC, exhibit metabolic abnormalities that distinguish them from other breast cancer cells, including elevated levels of N-acetylaspartate, a metabolite primarily associated with neuronal disorders and gliomas.

Effects of hyperbaric oxygen on aggressive periodontitis and subgingival anaerobes in Chinese patients.

Objective: To investigate the effects of hyperbaric oxygen (HBO2) on aggressive periodontitis (AgP), and subgingival obligate anaerobes in Chinese patients.

Materials And Methods: Sixty cases of Chinese patients with AgP were randomly divided into two groups -the HBO2 group (30 cases) and the control group (30 cases). Study teeth were divided into four groups -: the HBO2 therapy, the HBO2 + scaling scaling group, the scaling group and the control group.

A review on endogenous regenerative technology in periodontal regenerative medicine.

Periodontitis is a globally prevalent inflammatory disease that causes the destruction of the tooth-supporting apparatus and potentially leads to tooth loss. Currently, the methods to reconstitute lost periodontal structures (i.e.

Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers.

Background: The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis; however, their specific roles in determining cancer cell adhesion and invasion have not been elucidated.

Methods: RHOA and RHOC are highly homologous, thereby posing a major challenge to study their individual functions in cancer cells. By selectively knocking down these proteins, we have been able to alternatively inhibit RHOC and RHOA, while preserving expression of the other rho protein.

Toward delivery of multiple growth factors in tissue engineering.

Inspired by physiological events that accompany the "wound healing cascade", the concept of developing a tissue either in vitro or in vivo has led to the integration of a wide variety of growth factors (GFs) in tissue engineering strategies in an effort to mimic the natural microenvironments of tissue formation and repair. Localised delivery of exogenous GFs is believed to be therapeutically effective for replication of cellular components involved in tissue development and the healing process, thus making them important factors for tissue regeneration. However, any treatment aiming to mimic the critical aspects of the natural biological process should not be limited to the provision of a single GF, but rather should release multiple therapeutic agents at an optimised ratio, each at a physiological dose, in a specific spatiotemporal pattern.

Pomegranate fruit extract impairs invasion and motility in human breast cancer.

Purpose: Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity.

Experimental Design: The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines.

[Influence of transfection with human transforming growth factor-beta1 gene on the osteogenic potential of the cultured human gingival fibroblast].

Objective: To study the influence of transfection with human transforming growth factor-beta1 (hTGF-beta1) gene on the osteogenic potential and differentiation of the cultured human gingival fibroblast (GF).

Methods: Enzyme kinetics method was used to measure the effects of the transfection on the alkaline phosphatase (ALP) activity. Immunohistochemistry stain and image analysis were applied to evaluate the alteration of the content of osteopontin (OPN), bone sialoprotein (BSP), osteonectin (ON), osteocalcin (OC) in the GF with transfection.

[Effects of gingival fibroblasts transfected with human transform growth factor-beta1 gene on improving the periodontal tissue regeneration].

Objective: To evaluate the effects of gingival fibroblasts (GF) transfected with hTGF-beta1 gene on improving the periodontal tissue regeneration for the repair of degree II artificial furcation defects.

Methods: The gingival fibroblasts transfected with hTGF-beta1 gene was compounded to the cuttlebone-transformed nanometer hydroxyapatite (CBHA) material from the cuttlefish in vitro, the degree II furcation defects on the premolars of dogs were produced surgically, and the compound was to implanted into the defect (transfected group), and compared with the compound of periodontal ligament cells (PDLC) with nanometer HA material and the compound of untransfected GF with HA. The results were examined histologically 8 weeks after operation.

In vitro cellular responses to scaffolds containing two microencapulated growth factors.

Growth factors play an important role in the complex cascade of tissue events in periodontal regeneration, although optimal methods of delivery remain to be identified. We hypothesize that multiple delivery of growth factors, particularly via a microparticle-containing scaffold, will enhance cellular events leading to periodontal regeneration. In this study, cellular responses of periodontal ligament fibroblasts (PDLFs) in scaffolds containing microparticles (MPs) loaded with either bone morphogenetic protein (BMP)-2, insulin-like growth factor (IGF)-1, or a mixture of both MPs were evaluated, and the dual-MP-containing scaffold exhibited the release of different proteins in a sustained and independent fashion.

Gene delivery for periodontal tissue engineering: current knowledge - future possibilities.

The cellular and molecular events of periodontal healing are coordinated and regulated by an elaborate system of signaling molecules, pointing to a primary strategy for functional periodontal compartment regeneration to replicate components of the natural cellular microenvironment by providing an artificial extracellular matrix (ECM) and by delivering growth factors. However, even with optimal carriers, the localized delivery of growth factors often requires a large amount of protein to stimulate significant effects in vivo, which increases the risk and unwanted side effects. A simple and relatively new approach to bypassing this dilemma involves converting cells into protein producing factories.

Composite glycidyl methacrylated dextran (Dex-GMA)/gelatin nanoparticles for localized protein delivery.

Aim: Localized delivery of growth factors has significant potential as a future therapeutic strategy in tissue engineering and regenerative medicine. A nanoparticle vehicle was created and evaluated in this study with the intent to deliver growth factors for periodontal regeneration.

Methods: Novel composite nanoparticles based on glycidyl methacrylate derivatized dextrans (Dex-GMA) and gelatin were fabricated by a facile method without using any organic solvents.

[An animal experiment for the regeneration of periodontal defect by application of the dual-release chitosan thermosensitive hydrogel system].

Objective: To observe the effect of the self-made chitosan thermosensitive hydrogel system with dual-release bone morphogenetic protein and chlorhexidine on periodontal defects repair.

Methods: The furcation defect model was established on dog premolar. The models were divided into five groups, including three experimental groups, one control group and one blank control group.

[A study on the effect of the chitosan thermosensitive hydrogel loading recombinant human bone morphogenetic protein-2 on repairing periodontal defects].

Objective: To observe the effect of the chitosan thermosensitive hydrogel loading recombinant human bone morphogenetic protein-2 (rhBMP-2) on repairing periodontal defects.

Methods: To prepare artificial furcation defects model in the posterior area in 3 healthy male dogs, and then to inject chitosan thermosensitive hydrogel loading of rhBMP-2 after fast suturing tissue flap. The groups filled with nothing or filled only with chitosan thermosensitive hydrogel were the controls.

[Preparation of functional chitosan thermosensitive hydrogel for slow release both rhBMP-2 and chlorhexidine].

The chitosan thermosensitive hydrogel is liquid at room temperature but gels rapidly when heated to body temperature. This hydrogel are wildly used for cell encapsulation, drug delivery or tissue-engineered scaffolds. The system can sustain the release of macromolecules over a period of several hours to a few days.

Epidemiology and preventive direction of periodontology in China.

Objective: The aim of this work was to estimate the present periodontal problems of people in China, based on an epidemiological investigation of adults.

Material And Methods: The data were collected from the northwest, southwest, northeast and east regions (400 subjects from each region) of China. All subjects were over 25 years of age.

Periodontal regeneration using novel glycidyl methacrylated dextran (Dex-GMA)/gelatin scaffolds containing microspheres loaded with bone morphogenetic proteins.

The objective of this study was to evaluate the biological activity enhancement of a novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hybrid hydrogel containing microspheres loaded with bone morphogenetic proteins (BMP) as periodontal cell/tissue scaffold. Larger number of human periodontal ligament cells (PDLCs) attached was observed in scaffolds containing microspheres loaded with BMP when compared to those without microspheres. When osteogenic differentiation of PDLCs in such scaffolds was evaluated, the alkaline phosphatase (ALP) activity, osteocalcin content, and calcium deposition became maximum for the scaffold containing microspheres loaded with BMP, as compared with those without microspheres but adsorbed with the same amount of BMP aqueous solution, although both values were significantly higher than those in BMP-free scaffold.

Rho proteins and cell-matrix interactions in cancer.

Dynamic interactions and dissolution of cell-extracellular matrix contacts are required steps to support cell growth and survival during cancer cell metastasis. Malignant cells acquire the ability to remodel extracellular matrix (ECM) and to modulate the expression of ECM receptors. Integrins are cellular receptors for molecules in the extracellular matrix.

MMP-2, MMP-9 and TIMP-2 gene polymorphisms in Chinese patients with generalized aggressive periodontitis.

Background: Aggressive periodontitis (AgP) has a genetic basis. It has been reported that the functional gene polymorphisms of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) alter their expressions in transcriptional level and they are involved in the tissue destruction of periodontitis. The study was carried out to analyse the association of functional polymorphisms in MMP-2, MMP-9 and TIMP-2 with generalized AgP (G-AgP) in a Chinese population.

[Experimental study on dog's bone marrow stem cells transfected by pIRES2-EGFP-IGF-1 gene].

Objective: To establish the bone marrow stem cells (MSC) model which could highly express the insulin-like growth factor 1 (IGF-1) transfected by dog's IGF-1 gene.

Methods: pIRES2-EGFP-IGF-1 was transfected into MSC by lipofectamine. Positive clones were selected with G418.

Novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hydrogel scaffolds containing microspheres loaded with bone morphogenetic proteins: formulation and characteristics.

Novel thermomechanical hydrogel scaffolds containing our previously prepared microspheres loaded with bone morphogenetic proteins (BMP) were successfully generated by radical crosslinking and low dose gamma-irradiation from combination of two kind of biomaterials: glycidyl methacrylated dextran (Dex-GMA) and gelatin. The structure of those resulting smart hybrid hydrogels was evaluated by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) analyses, and as a function of the degree of Dex-GMA's substitution (DS), the proportion between Dex-GMA and gelatin, and the initial polyethyleneglycol (PEG) concentration used in the preparation of the hydrogels. The swelling and degradation properties and the temperature-sensitive drug release manner were determined by dynamic evaluation methods in vitro, and the gel content was also calculated.