Identification of activated pathways in lung adenocarcinoma based on network strategy.

Background: Lung adenocarcinoma has increased incidence over the past years and is the cause for almost 50% of deaths attributable to lung cancer. The objective of this paper is to identify activated pathways associated with lung adenocarcinoma based on gene co-expression network analysis.

Materials And Methods: Kyoto Encyclopedia of Genes and Genomes pathway analysis of dysregulated genes was performed based on Expression Analysis Systematic Explorer test to illuminate the biological pathways.

Recognition of linear stress fibers based on Hough transform.

Objective: To present an algorithm based on Hough transform for recognition and extraction of linear stress fibers formed on exposure to lysophosphatidic acid (LPA).

Study Design: A ridge set of head points with lower shoulders is calculated, followed by a thinning process shrinking long, narrow regions to regions of single pixel thickness, then converted into a rectangular map whose value is the number of regional points in the path of a straight line at the angle and intercept determined by two coordinates. The location of the maximum in the map is sought, and the corresponding line with an unlimited length is constructed from the paired coordinates.

The NF-κB pathway mediates lysophosphatidic acid (LPA)-induced VEGF signaling and cell invasion in epithelial ovarian cancer (EOC).

Objectives: Our previous report has implicated the involvement of VEGF-VEGFR-2 h signaling in LPA-induced EOC invasion. However, the mechanism by which LPA regulates VEGF and VEGFR-2 expression remains to be elucidated. In the present study, we systematically examined the signal transduction pathways activated by LPA and further evaluated whether LPA's effect on VEGF-VEGFR-2 signaling and EOC invasion was mediated by the activation of NF-κB pathway.

MMP-1-PAR1 axis mediates LPA-induced epithelial ovarian cancer (EOC) invasion.

Objectives: MMP-1 is over-expressed in many cancers, with high expression often associated with poor survival. In the present study, we examined the expression of MMP-1 in EOC and its role in EOC invasion. Moreover, we evaluated the role of a newly identified MMP-1-protease activated receptor (PAR)-1 axis in LPA-induced EOC invasion.

Biomarkers for ovarian cancer detection and therapy.

Despite advances in surgical technologies and the development of more effective chemotherapeutics, epithelial ovarian cancer (EOC) remains the leading cause of death in women with gynecologic malignancies. The high mortality and morbidity associated with EOC is mostly attributed to the inability to detect the disease before it is widely disseminated throughout the abdominal cavity. In the past decade, tremendous efforts have been taken to search for novel biomarkers that will detect EOC at an early stage, which may also serve as new targets for the prevention and control of metastasis.

New frontiers for ovarian cancer risk evaluation: proteomics and contrast-enhanced ultrasound.

Objective: The grim ovarian cancer statistics are attributed to the fact that most women typically present with widespread disease at the time of initial diagnosis. Our current diagnostic tools, such as pelvic examination and standard ultrasound, are inadequate to detect early-stage epithelial ovarian cancer. In recent years there has been an explosion of important advances in biomedical engineering, proteomic technologies, and computational analyses that has led to the identification of hundreds of previously unknown proteins unique to the pathophysiology of ovarian cancer, some of which are currently under clinical validation.

Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro proliferation, invasion, and matrix metalloproteinase activity.

Objectives: Lysophosphatidic acid (LPA) has potent growth-regulatory effect in many cell types and has been linked to the in vivo tumor growth and metastasis in several malignancies. The goal of this study was to assess the regulation of (EC) microenvironment by LPA through the examination of its effect on cell proliferation, migration, invasion, uPA activity, and matrix metalloproteinase (MMP) secretion/activation.

Methods: All experiments were performed in vitro using an EC cell line, HEC-1A.

Roles of LPA in ovarian cancer development and progression.

Lysophosphatidic acid (LPA), a bioactive phospholipid, stimulates survival, proliferation, adhesion, migration and invasion of ovarian cancer cells through the activation of G-protein-coupled plasma membrane receptors. LPA and its receptors are aberrantly expressed in ovarian cancer, with high levels predominantly found in malignant ascites and in the plasma of ovarian cancer patients. LPA signals multiple intracellular pathways, such as Ras/MEKK1-MAPK and PI3K/Akt, to promote growth factors and protease expression, and induce angiogenesis and tumor cell invasion through the extracellular matrix and across the basement membrane.

VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced epithelial ovarian cancer (EOC) invasion.

Background: The VEGF-VEGF receptor (VEGFR) signaling axis has emerged as a promising target for cancer therapy, attributing to its vital role in tumor angiogenesis and growth. We have previously reported the regulation of epithelial ovarian cancer (EOC) invasion and migration by VEGF and the implication of VEGF-VEGFR-2 axis in lysophosphatidic acid (LPA)-induced EOC invasion. However, the expression profile of VEGF and VEGFRs in EOC, their association with tumor aggressiveness, and their regulation by LPA remain unclear.

LPA receptor 2 mediates LPA-induced endometrial cancer invasion.

Objective: We have previously shown that lysophosphatidic acid (LPA) promotes the ovarian cancer metastatic cascade. In this study, we evaluated the role of LPA on endometrial cancer invasion.

Methods: Transient mRNA knockdown was accomplished using pre-designed siRNA duplexes against LPA receptor 2 (LPA2) and human matrix metalloproteinase-7 (MMP-7).

Lysophosphatidic acid (LPA) promotes E-cadherin ectodomain shedding and OVCA429 cell invasion in an uPA-dependent manner.

Objectives: To evaluate the role of LPA in regulating E-cadherin cell surface expression, adhesion, and invasion in epithelial ovarian carcinoma (EOC) cells.

Methods: E-cadherin mRNA expression in OVCA429 and IOSE-29 cells was evaluated by real-time RT-PCR. Immunofluorescence and Western blot analysis were performed to determine cell surface expression and shedding of E-cadherin 80-kDa soluble fragment by LPA.

Inhibition of matrilysin expression by antisense or RNA interference decreases lysophosphatidic acid-induced epithelial ovarian cancer invasion.

Our previous reports show that matrilysin [matrix metalloproteinase (MMP)-7] is overexpressed in epithelial ovarian cancer (EOC) and recombinant MMP-7 promotes EOC invasion in vitro. In the present study, we further evaluated the correlation of MMP-7 expression to EOC invasiveness and examined its role in lysophosphatidic acid (LPA)-induced invasion. By sense and antisense gene transfection in vitro, we show that overexpression of MMP-7 in all MMP-7 stably transfected DOV13 clones significantly enhanced their invasiveness, although MMP-7 antisense transfection caused a 91% decrease of MMP-7 expression (P < 0.

S1P regulation of ovarian carcinoma invasiveness.

Objectives: Within the tumor microenvironment the invasiveness of epithelial ovarian carcinoma (EOC) cells is stimulated by biologically active lipids such as lysophosphatidic acid (LPA). We tested the in vitro effect of another bioactive lysophospholipid, sphingosine-1-phosphate (S1P), on the invasiveness of EOC cells.

Methods: Dov13 EOC cells were tested for invasion through matrigel-coated chambers and for gelatinase activity using a fluorogenic assay.

Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases.

Vascular endothelial growth factor (VEGF) expression is elevated in primary ovarian tumors and metastases. We examined the effect of VEGF on epithelial ovarian cancer (EOC) in vitro invasion and migration and underlying mechanisms. Using the Matrigel invasion assay and colloidal gold phagokinetic track assay, we found that VEGF induced EOC DOV13 invasion and migration in a matrix metalloproteinase (MMP)-dependent manner.

Antitumor activity of anti-type IV collagenase monoclonal antibody and its lidamycin conjugate against colon carcinoma.

Aim: Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for mAb-directed therapy. The immunoreactivity of mAb 3G11, a mAb directed against type IV collagenase in human colorectal carcinomas, was studied by immuno-histochemical (IHC) staining. mAb 3G11 was conjugated to an antitumor antibiotic lidamycin (LDM).

LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2 (VEGF-R2).

Objective: Lysophosphatidic acid (LPA) stimulates ovarian tumor growth partially via induction of VEGF expression through transcriptional activation. Previous studies have shown that LPA induces epithelial ovarian cancer (EOC) in vitro metastasis. In this study, we examined the role of VEGF in LPA-induced EOC invasion and migration and underlying mechanisms.

Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase.

Although matrilysin (MMP-7) is overexpressed in various malignancies, few studies have evaluated its role in epithelial ovarian cancer (EOC) invasion and metastasis. We report that the secretion of MMP-7 in EOC is stimulated significantly by vascular endothelial growth factor (VEGF) and interlukin-8 (IL-8). We also examined the in vivo expression of MMP-7 in EOC and its effects on the in vitro invasion and progelatinase activation.

Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the increased expression of interleukin-8.

Objective: We previously reported that lysophosphatidic acid (LPA) stimulates cellular invasion of ovarian cancer (OVCA) cells by enhancing membrane-type-1-matrix metalloproteinase (MT1-MMP)-mediated activation of MMP2. Here, we investigate a second mechanism in which LPA enhances cellular invasion through the increased expression of IL-8, independent of the expression or activation of MMP2.

Methods: Epithelial ovarian carcinoma cells (DOV 13) were exposed to LPA (80 microM) and IL-8 (100 ng/ml) for 24 h.

[Antitumor effects of the immunoconjugate composed of lidamycin and monoclonal antibody 3G11].

Aim: To study the antitumor effects of an immunoconjugate composed of lidamycin (LDM) and monoclonal antibody 3G11 (3G11-LDM conjugate).

Methods: 3G11-LDM conjugate was prepared by using 2-iminothiolane (2-IT) and m-maleimidobenzoyl-N-hydroxy-succimide ester (MBS) as crosslinkers. The molecular weight of the conjugate was measured on non-reduced SDS-PAGE gel.

A cytotoxic diterpenoid and antifungal phenolic compounds from Frullania muscicola Steph.

A novel ent-labdane type diterpenoid, muscicolone (1), as well as two bibenzyls (2, 3) and four flavonoids (4-7) were isolated from the liverwort Frullania muscicola Steph. Their structures were established by analysis of the spectral data of IR, UV, ID-, 2D-NMR, and ORD. The stereostructure of 1 was confirmed by X-ray crystallographic analysis.