Upregulation of VEGFR1 in a rat model of esophagogastric anastomotic healing.

Introduction: Anastomotic leakage after gastrointestinal surgery is a significant cause of morbidity and mortality. Esophagogastric and colorectal anastomoses are vulnerable to leakage. Extended knowledge of growth factors and their receptors is needed to understand anatomic healing.

Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia.

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms.

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS(-/-) ) and interstitial cells of Cajal (W/W(v) ): Implications for achalasia?

Background And Aim: Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice.

Minimally invasive surgery for achalasia in patients >40 years: more favorable than anticipated.

Purpose: The efficacy of Heller myotomy in patients >40 years-a significant predictor suggesting a favorable response to pneumatic dilation-has been questioned. The aim of our study was to evaluate the results obtained in patients aged <40 and >40 years undergoing minimally invasive surgery (MIS) for achalasia.

Methods: In January 2008, we established the MIS technique for achalasia in our clinic.

VEGF-D correlates with metastatic disease in gastric cancer patients undergoing surgery.

Background: The present study was designed to evaluate the impact of the tyrosine kinase ligands VEGF-A/C/D, PDGF-A/B on tumor dissemination and survival in gastric cancer. This is the first study analyzing all these parameters in a homogeneous patient population undergoing surgery.

Methods: The expression pattern of VEGF-A/C/D and PDGF-A/B was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in 69 samples of human gastric adenocarcinoma and correlated with tumor stage and survival.

Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters?

Background/aims: This study was initiated in order to define the (co-)expression patterns of target receptor tyrosine kinases (RTKs) in human gastric adenocarcinoma and to correlate them with clinicopathological parameters.

Methodology: The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 was analyzed in 56 samples of human gastric adenocarcinoma and correlated with staging and survival.

Results: VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 were expressed at relevant levels in 79%, 50%, 50%, 63%, 55% and 30%, respectively.

Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.

This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation.

PDGFRalpha/beta expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategy.

As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation.

Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma--a rationale for a molecular targeting strategy?

Aim: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma.

Methods: The (co-)expression pattern of VEGFR1-3, PDGFR alpha/beta and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation.

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma.

Background: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types--squamous cell and adenocarcinoma.

Sex steroid metabolism in human peripheral blood mononuclear cells changes with aging.

Context: Dehydroepiandrosterone (DHEA) mainly exerts indirect action via downstream conversion toward sex steroids within peripheral target cells including immune cells. In vitro DHEA has been shown to enhance IL-2 release from T lymphocytes, whereas it inhibits IL-6 secretion. Conversely, aging is associated with a decline in both DHEA and IL-2, whereas IL-6 increases.