Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients' outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02-50.92) vs 0.55 (0.07-3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00-7.85) vs 0.15 (0.01-7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.

The CXCL7/CXCR1/2 axis is a key driver in the growth of clear cell renal cell carcinoma.

Mutations in the von Hippel-Lindau gene upregulate expression of the central angiogenic factor VEGF, which drives abnormal angiogenesis in clear cell renal cell carcinomas (ccRCC). However, the overexpression of VEGF in these tumors was not found to correlate with overall survival. Here, we show that the proangiogenic, proinflammatory cytokine CXCL7 is an independent prognostic factor for overall survival in this setting. CXCL7 antibodies strongly reduced the growth of ccRCC tumors in nude mice. Conversely, conditional overexpression of CXCL7 accelerated ccRCC development. CXCL7 promoted cell proliferation in vivo and in vitro, in which expression of CXCL7 was induced by the central proinflammatory cytokine interleukin (IL)-1ß. ccRCC cells normally secrete low amounts of CXCL7; it was more highly expressed in tumors due to high levels of IL-1ß there. We found that a pharmacological inhibitor of the CXCL7 receptors CXCR1 and CXCR2 (SB225002) was sufficient to inhibit endothelial cell proliferation and ccRCC growth. Because CXCR1 and CXCR2 are present on both endothelial and ccRCC cells, their inhibition affected both the tumor vasculature and the proliferation of tumor cells. Our results highlight the CXCL7/CXCR1/CXCR2 axis as a pertinent target for the treatment of ccRCC.

Assessment of a microplate method for detection of staphylococcal secretory inhibitor of platelet microbicidal protein.

We developed a novel microplate spectrophotometric assay for the detection of staphylococcal secretory inhibitor of platelet microbicidal protein (SIPMP) in

Distribution of secretory inhibitor of platelet microbicidal protein among anaerobic bacteria isolated from stool of children with diarrhea.

AIM: To study the secretory inhibitor of platelet microbicidal protein (SIPMP) phenotypes of faecal anaerobic isolates from patients with diarrhea. METHODS: Faecal isolates of anaerobic bacteria (B. fragilis, n = 42; B. longum, n = 70; A. israelii, n = 21; E. lentum, n = 12) from children with diarrhea were tested. SIPMP production was tested by inhibition of platelet microbicidal protein (PMP) bioactivity against B. subtilis and was expressed as percentage of inhibition of PMP bactericidal activity. RESULTS: Among anaerobic isolates 80% of B. longum strains, 85.7% of A. israelii strains, 50% of E. lentum strains and 92.86% of B. fragilis strains were SIPMP-positive. The isolated anaerobic organisms demonstrated SIPMP production at a mean level of 13.8% +/- 0.7%, 14.7% +/- 1.8%, 3.9% +/- 0.9% (P < 0.05) and 26.8% +/- 7.5% (P < 0.05) for bifidobacteria, A. israelii, E. lentum and B. fragilis, respectively. CONCLUSION: Data from the present study may have significant implications in understanding the pathogenesis of microecological disorders in the intestine, as well as for future improvement in the prevention and therapy of anaerobe-associated infections.

Distribution of secretory inhibitor of platelet microbicidal protein among urethral isolates with its correlation with prostatitis.

AIM: To report the detection in vitro of secretory inhibitor of platelet microbicidal protein (SIPMP) phenotypes of urethral isolates along with a comparison with isolates from patients with or without chronic bacterial prostatitis (CBP). METHODS: Urethral isolates of Staphylococcus spp. (n=4), diphtheroids (n=28), micrococci (n=15), streptococci (n=21), Enterobacteriaceae (n=9) and Enterococcus faecalis (n=19) from patients with or without CBP were tested. SIPMP production was tested by inhibition of platelet microbicidal protein (PMP) bioactivity against Bacillus subtilis and was expressed as percentage of inhibition of PMP bactericidal activity. RESULTS: A significantly higher proportion of CBP-strains (57.78% vs. 16.67%) reduced PMP-induced killing of Bacillus subtilis than non-CBP strains did (P<0.01). SIPMP levels of staphylococci and Enterococcus faecalis from the CBP group were significantly higher than those of the control group. CONCLUSION: These results suggest that SIPMP production is associated with the CBP source. Data from the present study might have significant implications for the understanding of the pathogenesis of CBP.

Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus.

Pantethine in a dosage of 600 mg for the first 3 months, and in a dosage of 1200 mg for the second 6 months was given to 16 diabetics in whom plasma beta-thromboglobulin was raised (greater than 50 ng/ml). Plasma beta-TG levels decreased significantly with pantethine treatment for 9 months. Plasma triglyceride, total cholesterol, apo E and apo CII levels decreased significantly after 9 months. Plasma LDL-C and atherogenic index (LDL-C/HDL-C ratio or apo B/apo AI ratio) tended to decrease with treatment. It is concluded that administration of pantethine may be beneficial in the prevention of diabetic angiopathy because of its lowering effect on plasma beta-TG, lipids and apolipoproteins.

Observations on the effects of some antiaggregating drugs on platelet specific protein discharge after a very weak stimulus.

Platelet adhesion, aggregation, secretion, and survival have been shown to be changed in atherosclerosis disease and thromboembolic phenomena thus further increasing interest on antiaggregating drugs. In this paper we present some evidence that 8-chlorocarbochromen and carbochromen are significantly effective in preventing the discharge of platelet specific proteins from platelets subjects to a very weak stimulus while acetylsalicylic acid and aminophylline are ineffective in this regard.