Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract

BACKGROUND: Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS: 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. CONCLUSIONS: Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only

Preparing the E-ELT M4 optical test

The design of the interferometric test of the adaptive M4 Unit of E-ELT, a deformable six petals 2.4 m mirror, will be described. The actual baseline follows a macro-stitching approach, where each segment is separately flattened and co-phased to the other petals. The optical test setup for the single shell consists in a Newtonian system, with a 1.5 m parabolic mirror as main collimator. A 0.6 m reference flat mirror is foreseen to verify the alignment of the interferometric cavity. A Demonstration Prototype of the final M4 Unit, a 222 actuators, two shells deformable mirror, has been produced by Microgate and A.D.S. International. Results of the optical measurement campaign performed in INAF on the prototype mirror are reported

Evaluation of serum levels of TGFβ1 and VEGF during colorectal carcinogenesis.

<p>The levels of TGFβ1 (A) and VEGF (B) were measured in controls and patient groups (N: control; TA: tubular adenoma; TVA: tubulovillous adenoma; I-IV AC: malignant stages of adenocarcinoma). TGFβ1 and VEGF were detected by ELISA and values expressed as ng/ml and pg/ml serum, respectively (see materials and methods). A: dots correspond to single TGFβ1 values and black lines represent the mean values within the experimental groups. Mean values ± SEM: N 6.3±0.4; TA 7.2±0.45; TVA 6.3±0.6; IAC 6.9±0.3; IIAC 4.9±0.3; IIIAC 4.4±0.3; IVAC 5.7±0.5. *Significantly different versus control group (p<0.05). B: dots correspond to single VEGF values and black lines represent the mean values within the experimental groups. Mean values ± SEM: N 227.0±18.7; TA 215.2±31.3; TVA 221.1±36.4; IAC 216.3±34.4; IIAC 205.0±26.6; IIIAC 266.5±38.6; IVAC 295.2±70.2.</p

Evaluation of serum levels of IL-8 and IL-6 during colorectal carcinogenesis.

<p>The levels of IL-8 (A) and IL-6 (B) were measured in controls and patient groups (N: control; TA: tubular adenoma; TVA: tubulovillous adenoma; I-IV AC: malignant stages of adenocarcinoma). IL-8 and IL-6 were detected by ELISA and values expressed as pg/ml serum (see materials and methods). A: dots correspond to IL-8 single values and black lines represent the mean values within the experimental groups. Mean values ± SEM: N 17.0±2.5; TA 15.9±3.7; TVA 18.4±2.2; IAC 25.4±4.8; IIAC 38.7±5.1; IIIAC 37.2±5.7; IVAC 30.5±5.7. *Significantly different versus control group (p<0.05). B: dots correspond to single IL-6 values and black lines represent the mean values within experimental groups. Mean values ± SEM: N 247.1±55; TA 375.9±54; TVA 407.9±80; IAC 237.9±68; IIAC 472.3±89; IIIAC 521.3±152; IVAC 436.3±118. *Significantly different versus control group (p<0.05).</p