The California collaborative network to promote data driven care and improve outcomes in early psychosis (EPI-CAL) project: rationale, background, design and methodology.

Background: A prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based "coordinated specialty care" (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California's CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure.

Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing.

Silk fibers spun by silkworms and spiders exhibit exceptional mechanical properties with a unique combination of strength, extensibility and toughness. In contrast, the mechanical properties of regenerated silk materials can be tuned through control of the fabrication process. Here we introduce a biomimetic, all-aqueous process, to obtain bulk regenerated silk-based materials for the fabrication of functionalized orthopedic devices.

Taurolidine induces epithelial-mesenchymal transition via up-regulation of the transcription factor Snail in human pancreatic cancer cell lines.

Purpose: The taurine derivative taurolidine (TRD) exerts anti-neoplastic effects in a variety of tumor models. On the other hand, TRD at low doses was shown to reduce cell-cell adhesion, a prerequisite for metastasis. The aim of this study was to elucidate the effects of low-dose TRD on pancreatic cancer.

Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium.

Purpose: Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug.

Non-invasive quantification of anti-angiogenic therapy by contrast-enhanced MRI in experimental pancreatic cancer.

Background: Currently, early changes of tumor vasculature after angiogenesis inhibition can only be evaluated by histopathology, a method not suitable in a clinical setting.

Purpose: To quantify effects of different angiogenesis inhibitors on the microvasculature of orthotopically implanted pancreatic cancers by contrast-enhanced magnetic resonance imaging (MRI) in order to establish a non-invasive technique for monitoring antiangiogenic cancer treatment.

Material And Methods: DSL-6A/C1 pancreatic cancers were implanted in the pancreas of 109 Lewis rats.

In vitro and in vivo antitumor activity of cetuximab in human gastric cancer cell lines in relation to epidermal growth factor receptor (EGFR) expression and mutational phenotype.

Background: Targeting the epidermal growth factor receptor (EGFR) pathway is an important approach for a variety of tumors. This study assessed the effect of cetuximab, an anti-EGFR monoclonal antibody, on three gastric cancer cell lines with different phenotypes in vitro and in a therapeutic orthotopic murine gastric cancer model.

Methods: Three human gastric cancer cell lines (AGS, MKN-45, NCI-N87) were evaluated for cell surface EGFR expression, and K-ras and BRAF mutations.

Gadofluorine M-enhanced magnetic resonance imaging of inflammatory bowel disease: quantitative analysis and histologic correlation in a rat model.

Objectives: : To determine the colonic mural enhancement in a rat model of inflammatory bowel disease (IBD) using gadofluorine M- and diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging, and to correlate the degree of enhancement with the histopathologic severity of the disease.

Materials And Methods: : This study was approved by our hospital's institutional animal care and use committee. A total of 44 rats with 2 grades (mild, n = 17; and severe, n = 27) of dinitrobenzene sulfonic acid (DNBS)-induced IBD and 13 rats without IBD, were examined using a 2.

Genes associated with epithelial-mesenchymal transition: possible therapeutic targets in ductal pancreatic adenocarcinoma?

Epithelial to mesenchymal transition (EMT) is a biological process that allows well-differentiated, polarized epithelial cells to undergo a conversion to motile, unpolarized mesenchymal cells. EMT plays crucial roles during implantation, embryogenesis, and organ development (Type 1 EMT), is associated with tissue regeneration and organ fibrosis (Type 2 EMT), and involved in cancer invasion, metastasis, and drug resistance (Type 3 EMT). Since aggressiveness and drug resistance are hallmarks of ductal pancreatic cancer, significant effort has been undertaken in recent years to elucidate molecular EMT mechanisms in this dismal malignancy.

A novel antiangiogenic approach for adjuvant therapy of pancreatic carcinoma.

Introduction: Surgical therapy remains the only curative option for pancreatic ductal adenocarcinoma. But even after complete resection, almost all patients suffer from local tumor recurrence. Current standard adjuvant therapy with gemcitabine does not impressively affect the recurrence rate.

Specific targeting of tumor endothelial cells by a shiga-like toxin-vascular endothelial growth factor fusion protein as a novel treatment strategy for pancreatic cancer.

Purpose: Tumor endothelial cells express vascular endothelial growth factor receptor 2 (VEGFR-2). VEGF can direct toxins to tumor vessels through VEGFR-2 for antiangiogenic therapy. This study aimed to selectively damage the VEGFR-2-overexpressing vasculature of pancreatic cancer by SLT-VEGF fusion protein comprising VEGF and the A subunit of Shiga-like toxin which inhibits protein synthesis of cells with high VEGFR-2 expression.

Association between activation of atypical NF-kappaB1 p105 signaling pathway and nuclear beta-catenin accumulation in colorectal carcinoma.

Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to beta-catenin signaling leads to the stabilization of beta-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of IkappaBalpha and activation of canonical nuclear factor-kappaB (NF-kappaB) pathway. Here, we show that the noncanonical NF-kappaB1 p105 pathway is constitutively activated in colorectal carcinoma specimens, being particularly associated with beta-catenin-mediated increased expression of CRD-BP and beta-TrCP1. In the carcinoma tissues exhibiting high levels of nuclear beta-catenin the phospho-p105 levels were increased and total p105 amounts were decreased in comparison to that of normal tissue indicating an activation of this NF-kappaB pathway.

Fluid resuscitation with human albumin or hydroxyethyl starch--are there differences in the healing of experimental intestinal anastomoses?

Objectives: Restoration of the macro- and microcirculation is important for the healing of gastrointestinal anastomoses. Colloids and crystalloids are widely used for blood volume therapy. We evaluated the effects of human albumin, hydroxyethyl starch (HES) 130/0.

Beyond epithelial to mesenchymal transition: a novel role for the transcription factor Snail in inflammation and wound healing.

Introduction: Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) during embryonic development and tumor progression, is associated with migration of cells. During inflammation and tissue injury, cell movement is also observed to provide the first line of defense against bacteria and to promote wound healing. Therefore, we studied the function of Snail in activated macrophages in a variety of inflammatory processes.

Magnetic resonance imaging of experimental inflammatory bowel disease: quantitative and qualitative analyses with histopathologic correlation in a rat model using the ultrasmall iron oxide SHU 555 C.

Objectives: To quantitatively and qualitatively characterize the MR findings of inflammatory bowel disease in a rat model after i.v. injection of the reticuloendothelial system cell specific ultrasmall iron oxide SHU 555 C.

An orthotopic nude mouse model for preclinical research of gastric cardia cancer.

Purpose: A clinically relevant animal model for cancer of the esophagogastric junction does not exist. This study aimed to establish an orthotopic mouse model for human gastric cancer of the distal stomach and the gastric cardia.

Materials And Methods: Human gastric cancer cell lines AGS, MKN-45, and NCI-N87 were injected subcutaneously into nude mice.

Intravital microscopic characterization of suramin effects in an orthotopic immunocompetent rat model of pancreatic cancer.

Objectives: We investigated the effect of suramin on tumor growth and spread in an immunocompetent, orthotopic rat model of pancreatic cancer and analyzed the tumor vasculature by intravital microscopy.

Methods And Methods: In vitro, rat ductal pancreatic cancer cells (DSL-6A) were incubated with suramin (10-800 microg/ml), and cell proliferation was assessed. In vivo, DSL-6A tumors were induced in the pancreas of Lewis rats.

Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer.

Purpose: Epithelial to mesenchymal transitions are vital for tumor growth and metastasis. Several inducers of epithelial to mesenchymal transition are transcription factors that repress E-cadherin expression, such as Snail, Slug, and Twist. In this study, we aimed to examine the expression of these transcription factors in pancreatic cancer.

Suramin inhibits not only tumor growth and metastasis but also angiogenesis in experimental pancreatic cancer.

Suramin inhibits the proliferation of several human tumors in vivo and in vitro. In this study, the effects of Suramin on proliferation and angiogenesis were investigated in human pancreatic cancer cell lines and in an orthotopic nude mouse model of human pancreatic cancer. The effects of Suramin on proliferation, viability, cell cycle, and apoptosis were studied in five human pancreatic cancer cell lines.

Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer.

The family of roundabout (Robo) proteins is related to the transmembrane receptors and plays a major role in the process of axonal guidance in neurogenesis. It has recently been shown that Robo proteins are also associated with tumor angiogenesis with Slit2 acting as the corresponding ligand. The aim of this study was to validate the differential expression by means of microarray analysis and real-time PCR and to analyze the in situ expression of Robo1 and Robo4 in colorectal cancer.

Selective inhibition of endothelin receptor A as an anti-angiogenic and anti-proliferative strategy for human pancreatic cancer.

Endothelin-1 (ET-1) plays a major role in tumor proliferation and angiogenesis of various types of cancer acting through endothelin receptors A and B (ET(R)A and ET(R)B). The aim of this study was to analyze the ET-1/ET(R) system in human pancreatic cancer cell lines and to evaluate the effect of a selective endothelin A inhibitor in vitro and in vivo in an orthotopic mouse model. Three different human pancreatic cancer cell lines, MiaPaCa-2, AsPC-1, and Panc-1, were studied.

VEGF antisense therapy inhibits tumor growth and improves survival in experimental pancreatic cancer.

Background: Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, is overexpressed in pancreatic cancer. This study evaluated VEGF production in pancreatic cancer cells and the effect of VEGF antisense on growth and angiogenesis of human pancreatic cancer in a nude mouse model.

Methods: In vitro: VEGF in cell culture supernatant of pancreatic cancer cells (AsPC-1, poorly differentiated; HPAF-2, moderately differentiated) was assessed by enzyme-linked immunosorbent assay.

Selective inhibition of cyclooxygenase-2 (COX-2) reduces prostaglandin E2 production and attenuates systemic disease sequelae in experimental pancreatitis.

Background/aims: Prostaglandins and prostaglandin-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis. COX (cyclooxygenase) is the key enzyme of prostaglandin synthesis. Whereas COX-1 produces prostaglandin mediators for physiological reactions, COX-2 is overexpressed in acute pancreatitis.

An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation.

Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation.

An orthotopic nude mouse model for evaluating pathophysiology and therapy of pancreatic cancer.

Introduction: Orthotopic, clinically relevant animal models are necessary for the study of pathophysiology and therapy for pancreatic cancer.

Aims: To develop a minimally traumatic technique of orthotopic tumor induction, to develop a scoring system to quantify local and systemic tumor spread, and to provide a model with a broad range of well-differentiated to undifferentiated pancreatic cancers.

Methodology: Orthotopic tumors were induced in nude mice by atraumatic pancreatic implantation of two fragments from subcutaneous donor tumors or intrapancreatic injection of human tumor cells (MIAPaCa-2, AsPC-1, HPAF-2, Capan-1).

Evaluation of vascular endothelial growth factor blockade and matrix metalloproteinase inhibition as a combination therapy for experimental human pancreatic cancer.

Blockade of vascular endothelial growth factor (VEGF) and inhibition of matrix metalloproteinases (MMP) are promising therapies for cancer. This study assessed the effects of a neutralizing anti-VEGF antibody (A4.6.