Rosa Ortiz

α2,3-Sialyltransferase ST3Gal IV promotes migration and metastasis in pancreatic adenocarcinoma cells and tends to be highly expressed in pancreatic adenocarcinoma tissues.

Sialyltransferases have received much attention recently as they are frequently up-regulated in cancer cells. However, the role played by each sialyltransferase in tumour progression is still unknown. α2,3-Sialyltransferases ST3Gal III and ST3Gal IV are involved in sialyl-Lewis(x) (SLe(x)) synthesis. Given that the role of ST3Gal III in pancreatic adenocarcinoma cells has been previously reported, in this study we have focused on investigating the role of ST3Gal IV in the acquisition of adhesive, migratory and metastatic capabilities and, secondly, in analyzing the expression of ST3Gal III and ST3Gal IV in pancreatic adenocarcinoma tissues versus control tissues. ST3Gal IV overexpressing pancreatic adenocarcinoma MDAPanc-28 cell lines were generated. They showed a heterogeneous increase in SLe(x), and enhanced E-selectin adhesion and migration. Furthermore, when injected into nude mice, increased metastasis and decreased survival were found in comparison with controls. The behaviour of MDAPanc-28 ST3Gal IV overexpressing cells in these processes was similar to the already reported MDAPanc-28 ST3Gal III overexpressing cells. Furthermore, pancreatic adenocarcinoma tissues tended to express high levels of ST3Gal III and ST3Gal IV together with other fucosyltransferase genes FUT3 and FUT6, all involved in the last steps of sialyl-Lewis(x) biosynthesis. In conclusion, both α2,3-sialyltransferases are involved in key steps of pancreatic tumour progression processes and are highly expressed in most pancreatic adenocarcinoma tissues.

Papel de la ecografía intraoperatoria y la tomografía computarizada con multidetectores en la cirugía de las metástasis hepáticas: estudio prospectivo

Resumen Objetivos Estudiar el papel de la ecografia intraoperatoria en el diagnostico de nuevas metastasis hepaticas en la era de la tomografia computarizada (TC) con multidetectores y su impacto en el acto quirurgico. Pacientes y metodo Entre febrero de 2005 y abril de 2006 se estudio de forma prospectiva, en sesiones multidisciplinarias (cirujanos, radiologos y oncologos), a los pacientes con metastasis hepaticas resecables de cancer colorrectal. Los hallazgos preoperatorios de la TC se compararon con los de la ecografia intraoperatoria, su correlacion histologica y el resultado final de la intervencion quirurgica. Resultados Se estudio a 45 pacientes candidatos a cirugia curativa, con un total de 171 metastasis hepaticas. La TC detecto correctamente 115 lesiones con una sensibilidad del 67%, un valor predictivo positivo del 97%, una tasa de falsos negativos del 33% y una tasa de falsos positivos del 2%. En 5 ocasiones los hallazgos intraoperatorios condicionaron un cambio en el acto quirurgico programado: en 3 pacientes eran irresecables (tasa de resecabilidad del 93%) y 2 pacientes precisaron de resecciones mas amplias de las previamente programadas. Conclusiones La TC con multidetectores como prueba de imagen preoperatoria y las sesiones multi-disciplinarias son el factor mas importante en la toma de decisiones en la cirugia de las metastasis hepaticas y nos permiten obtener una alta tasa de resecabilidad. La ecografia intraoperatoria hepatica nos permite encontrar un mayor numero de metastasis y realizar una correcta delimitacion anatomica y, en ocasiones, condiciona un cambio en el acto quirurgico programado.

Antibody microarray‐based technology to rapidly define matrix metalloproteinase (MMP) signatures in patients undergoing resection for primary gastric carcinoma

To the Editor: Early diagnosis is likely to improve the outcome and prognosis of most solid tumors, including biologically aggressive, chemotherapy-refractory gastric carcinomas (GC). Current clinical biomarkers in GC, however, lack the sensitivity and specificity required for screening an asymptomatic population for the purpose of early detection [1]. Moreover, there is an urgent need to develop new approaches aimed to detect and measure biomarkers in tissues and/or blood as a means of identifying GC patients who are more likely to respond to conventional and novel therapies molecularly targeting GC cells and stromal factors [2]. Although the ongoing development of the three mainstream high-throughout proteomic profiling techniques (i.e., gel-based methods, gel-free mass spectrometry [MS]-based methods and surface-enhanced laser desorption/ionization [SELDI] time-offlight [TOF] MS), through application in tissue-based clinical studies, has the potential to facilitate the identification of new and better diagnostic/prognostic biomarkers for GC detection and staging, the requirement of sophisticated devices greatly limits their broad application in routine clinical practice [3–5]. Alternatively, antibody microarray-based technology is a promising tool for the field of oncoproteomics in which one the most important applications is to compare proteome expression signatures of malignant versus normal samples [6–8]. We recently envisioned that innovative, simple, flexible and costeffective antibody-based protein array systems—which can simultaneously detect expression levels of multiple proteins and combine advantages of the specificity of ELISA, sensitivity of enhancedchemiluminiscence, and high-throughout of microspot [9]—could be useful at identifying unique ‘‘oncoproteomic signatures’’ in GC. Given that: (a) GC usually shows extensive local tumor invasion and early spread to metastasis sites; (b) the crucial step in GC development and metastasis is degradation and remodeling of tumor surrounding extracellular matrix (ECM); (c) invasion of GC cells within the basement membrane depends on the balanced activities of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) [10–16]; and that (d) GC is one of the few cancers for which a significant survival benefit from therapy with a MMP inhibitor has been described [17]; we decided to characterize the profile of MMPs and TIMPs in a pilot study for GC biomarker discovery. To minimize individual variations, we simultaneously evaluated MMPs/TIMPs profiles in GC samples and corresponding non-cancerous gastric mucosae from the same GC patient. Given that MPPs and TIMPs are secreted by both tumor and stromal cells, we used whole cancer tissues including the noncancerous stromal components as starting material for MMPs/TIMPs profiling instead of analyzing pure tumor cells. Twenty paired-samples from 10 GC patients undergoing gastrectomy at our institution were included in the study. Detection of seven MMPs (MMP-1/-2/-3/-8/-9/-10/-13) and three TIMPs (TIMP-1/-2/-4) was simultaneously performed in matched pairs of tumor/normal gastric tissues using the commercially available RayBio Human Matrix Metalloproteinase Antibody Array. Fold-change values for the expression of MMPs and TIMPs were calculated upon quantification of densitometric values of individual MMPs and TIMPs spots in tumor and paired normal tissue. Figure 1A shows representative raw arrays obtained in matched pairs of gastric tumor/normal tissues from three GC patients. Figure 1B (top) summarizes the fold-changes in MMPs/ TIMPs expression obtained for all the paired-samples evaluated in this pilot study. AGC-associated ‘‘MMP/TIMP signature’’ was constructed by considering those MMPs and TIMPs significantly altered in at least 1 GC patient (Fig. 1B, bottom). Upon this approach it was noteworthy that: (a) MMP-9 and MMP-8 were found to be overexpressed ( 5-fold) in 90% (9/10) and 80% (8/10) of GC patients, respectively; (b) TIMP-1 was significantly up-regulated in 70% (7/10) of GC patients whereas TIMP-2 expression was found to be enhanced solely in 2 out of 10 (20%) GC patients; (c) there was a good correlation between the primary MMP/TIMP interactor antigen levels, that is, 75% (6/8) of GC patients co-overexpressed MMP-9 with TIMP-1 while 2 out of 8 GC patients (25%) exhibited drastically enhanced MMP-9/ TIMP-1 ratio. Given that our pilot study involving a small group of patients rapidly and accurately identified a MMP/TIMP signature similarly reported in earlier studies that used more cumbersome, time consuming and/or expensive techniques (e.g., zymography, immunohistochemistry, ELISA, quantitative bioactivity assays [BIAs]) in larger groups of GC patients [10–16], it is reasonable to suggest that antibody

Impacto de la obesidad en las características anatomopatológicas de los tumores colorrectales. Estudio observacional

BACKGROUND To asses the influence of body mass index on the tumour characteristics of patients subjected to colorectal cancer surgery. MATERIALS AND METHODS Retrospective observational study. Patients subjected to curative elective colorectal cancer surgery at Hospital Josep Trueta de Girona (Spain), from 1990 to 2001. Univariate and bivariate analyses were performed to evaluate differences in tumour characteristics with regard to body mass index. RESULTS A total of 369 patients with colorectal cancer were included into the study, 213 (57.7%) with colon cancer, and 156 (42.3%) with rectal cancer. For colon cancer patients, when the BMI was higher than 25 kg/m(2), the tumour grade was worst (P=0.011), and when BMI was above 30 kg/m(2) there were more lymph node metastasis. For rectal tumours, the higher the BMI, the more lymph node metastasis (P=0.041), and higher tumour stage (P=0.023). CONCLUSIONS Patients with a higher BMI have more lymph node metastasis when submitted to elective colorectal cancer surgery. In the case of colon cancer they also have worst tumour grades, and in the case of rectal cancer, a more advanced tumour stage.

The impact of obesity on the histopathological characteristics of colorectal tumours. An observational study

Abstract Background To asses the influence of body mass index on the tumour characteristics of patients subjected to colorectal cancer surgery. Materials and methods Retrospective observational study. Patients subjected to curative elective colorectal cancer surgery at Hospital Josep Trueta of Girona (Spain), from 1990 to 2001. Univariate and bivariate analyses were performed to evaluate differences in tumour characteristics with regard to body mass index. Results A total of 369 patients with colorectal cancer were included into the study, 213 (57.7%) with colon cancer, and 156 (42.3%) with rectal cancer. For colon cancer patients, when the BMI was higher than 25 kg/m2, the tumour grade was worst (P=.011), and when BMI was above 30 kg/m2 there were more lymph node metastasis. For rectal tumours, the higher the BMI, the more lymph node metastasis (P=.041), and higher tumour stage (P=.023). Conclusions Patients with a higher BMI have more lymph node metastasis when submitted to elective colorectal cancer surgery. In the case of colon cancer they also have worst tumour grades, and in the case of rectal cancer, a more advanced tumour stage.

Retrospective analysis of pathologic response in colorectal cancer liver-only metastases following treatment with bevacizumab.

674 Background: Recent reports have shown that pathological response predicts for better outcome (overall survival) following preoperative chemotherapy and surgical resection of colorectal cancer (CRC) liver-only metastases. The aim of this retrospective analysis was to evaluate the effect of adding bevacizumab to standard chemotherapy on pathological response in patients with CRC liver only metastases. METHODS Patients with stage IV CRC with liver metastases who received neoadjuvant chemotherapy (oxaliplatin-or irinotecan-based) at two Spanish centres were analysed retrospectively. Pathological response was evaluated as follows: complete pathological response (cPR), PR1 (25% of residual tumour), PR2 (25-50% of residual tumour), PR3 (>50% of residual tumour). cPR or PR1 was considered to be a good response, and PR2 or PR3 a poor response. RESULTS A total of 81 patients were evaluated. Of these, 43 received chemotherapy alone and 38 received chemotherapy plus bevacizumab. Baseline characteristics were as follows: median age 61.0 years (range 43.0-80.0 years); male/female (67%/33%); tumour location - colon (69%) / rectum (31%); hepatic metastases - synchronous (74%) / metachronous (26%); In terms of pathological response, 58% of patients receiving bevacizumab had a good response (cPR + PR1) compared with 28% of those receiving chemotherapy alone. At the end of the analysis, 68% of patients were still alive. CONCLUSIONS Adding bevacizumab to oxaliplatin-based chemotherapy in the neoadjuvant setting improves the pathological response of liver metastases in patients with stage IV CRC. These findings indicate that pathological response might be a good indicator of outcome for patients receiving bevacizumab in the neoadjuvant setting.