The Neutrophil-Lymphocyte Ratio Is an Independent Prognostic Factor for Overall Survival in Hispanic Patients with Gastric Adenocarcinoma.

INTRODUCTION: High values of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are related with poor prognosis in patients with gastric cancer. However, this association has been rarely assessed in Hispanic populations that show important clinicopathological differences to Asian and Caucasian patients. In this study, we determined the prognostic value of these biomarkers in Hispanic patients from Costa Rica. MATERIALS AND METHODS: We retrieved data regarding pre-treatment NLR and PLR, as well as clinical variables from medical records of 381 consecutive gastric cancer patients treated in four major hospitals in Costa Rica between 2009 and 2012. Univariate and multiple Cox regression analyses were performed to assess the value of NLR and PLR as predictors of overall survival (OS) and disease-free survival (DFS). The best cutoff point was based on the maximization of the Log-rank test. RESULTS: Median follow-up was 13.21 months. In univariate analysis, a NLR ≥ 5 was associated with reduced DFS (hazard ratio (HR) 2.31; 95% confidence interval (CI) 1.78-3.00; p < 0.001) and poor OS (HR 2.24; 95% CI 1.72-2.92; p < 0.001). Similarly, a PLR ≥ 350 was associated with worse DFS (HR 2.28; 95% CI 1.70-3.06; p < 0.001) and poor OS (HR 2.33; 95% CI 1.73-3.13; p < 0.001). After adjustment for potential confounders, multivariate analysis revealed that only the NLR ≥ 5 was independently associated with worse DFS (HR 1.97; 95% CI 1.44-2.47) and OS (HR 1.59; 95%CI 1.15-2.28). CONCLUSIONS: NLR ≥ 5 was independently associated with worse OS and DFS in Hispanic patients with gastric cancer.

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy.

Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p = 0.01) or replacement GP (p = 0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p = 0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p = 0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p = 0.01) or pushing GP (p = 0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated.

Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes.

In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X-ray crystallography and surface plasmon resonance studies. Importantly, these structural studies also define possible druggable target sites in uPAR for small molecules and provide guidelines for the development of reporter groups applicable for non-invasive molecular imaging of uPAR expression in vivo by positron emission tomography. In this review, we will discuss recent advances in our perception of the structure-function relationships of uPAR ligation and how these may assist translational research in preclinical intervention studies of uPAR function.

Association of interleukin-1B and interleukin-1RN polymorphisms with gastric cancer in a high-risk population of Costa Rica.

Several risk factors have been associated with gastric cancer, among them Helicobacter pylori infection. This bacterium yields inflammation, the degree of which depends on the bacterial strain and the severity of the host response. The inflammatory response involves a complex cytokine network. Recently, polymorphisms of the genes coding for interleukin-1beta (IL-1B), interleukin-1Ra (ILRN) and interleukin-10 have been associated with an increased risk of gastric cancer. In order to determine the association of the IL-1B, IL-1RN and IL-10 polymorphisms with gastric cancer in a high-risk Costa Rican population, we analysed purified DNA of 58 gastric cancer patients, 99 controls and 41 patients classified as group I or II, according to the Japanese classification. Genotyping was carried out by PCR, PCR-RFLP and pyrosequencing analysis. We did not find any association of the IL-1B-31, IL-1B-511 and IL-10 polymorphisms with the risk for developing gastric cancer in the studied population. Carriers of the IL-1B+3954T/- had an increased risk for developing gastric cancer (OR 3.7; 95%CI: 1.34-10.2). Also we found an increased risk for developing gastric cancer for allele 2 heterozygotes of the IL-1RN (OR 2.94; 95%CI: 1.09-7.93). This is the first time that IL-1B+3954 has been associated with gastric cancer. This is one of the first studies trying to describe the role played by IL-1B, IL-1RN and IL-10 genetic polymorphisms in gastric cancer in one of the highest risk American countries. Further investigation on American countries is needed.