The Role of PDGFs and PDGFRs in Colorectal Cancer.

Introduction. Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Angiogenesis was reported as one important mechanism activated in colorectal carcinogenesis. Tumor microenvironment associated angiogenesis involves a large spectrum of signaling molecules and deciphering their role in colorectal carcinogenesis still represents a major challenge. The aim of our study is to point out the diagnosis and prediction role of PDGF family and their receptors in colorectal carcinogenesis. Material and Methods. A systematic search in Medline and PubMed for studies reporting the role of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in tumor biology related to CRC was made. Results. PDGFs are important growth factors for normal tissue growth and division, with an important role in blood vessel formation. PDGFs/PDGFRs signaling pathway has been demonstrated to be involved in angiogenesis mainly by targeting pericytes and vascular smooth muscle cells. High levels of PDGF-BB were reported in CRC patients compared to those with adenomas, while elevated levels of PDGFR α/ß in the stroma of CRC patients were correlated with invasion and metastasis. Moreover, PDGF-AB and PDGF-C were correlated with early diagnosis, cancer grading, and metastatic disease. Conclusions. Both PDGFs and PDGFRs families play an important role in colorectal carcinogenesis and could be considered to be investigated as useful biomarkers both for diagnosis and treatment of CRC.

Can we change our microbiome to prevent colorectal cancer development?

BACKGROUND: Colorectal cancer represents an important disease as one of the major causes of death worldwide. Although a lot of genetic and epigenetic research has been conducted, all the pieces of the puzzle of colorectal cancer carcinogenesis have not yet been identified. New recent data has highlighted that gut microbiota could have an influence on colorectal carcinogenesis. Gut microbiota represents the microbe population living in the human intestine and contains tens of trillions of microorganisms. MATERIAL AND METHODS: A systematic search in Medline and PubMed for studies reporting the influence of gut microbiota and inflammation on patients with colorectal cancer was made. RESULTS: In this review we discuss many of the specific bacteria, as well as their metabolites which may have an important role in development of colorectal cancer. Furthermore, we emphasize the molecular mechanisms modulated by gut microbiota, which promote inflammation, toxic metabolites, DNA damaging and pro-carcinogenic compounds, as support for colorectal carcinogenesis. The interrelation between microbiota and inflammation is complex because bacteria and inflammation could mutually impact upon each other. In this context, both endogenous and exogenous miRNAs may have an important role to modulate tumor-related inflammation in colorectal cancer. CONCLUSIONS: Better understanding of the role of gut microbiota in colorectal carcinogenesis could provide promising new directions to improve both prevention and treatment of colorectal cancer. Moreover, the discovery of novel biomarkers in the gut microbiome in order to detect colorectal cancer in an early stage or even in a precancerous stage is of outmost importance.

Is there a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer?

PURPOSE: The aim of this study was to evaluate whether there is a correlation between peripheral blood expression of angiogenic transcriptional factors/receptors and colorectal cancer (CRC). METHODS: Eighty six blood samples collected from patients with CRC (N=42), adenomas and/or hyperplastic polyps(AP, N=30) and individuals without colon pathology (control group/CTR, N=14) were used for this study. Twelve transcription factors and receptors were assessed by qRT-PCR in a case-control study. The molecules with a minimum of 30% differences in gene expression for CRC and AP compared to CTR were then analyzed separately for each sample. Gene expression was evaluated relatively to the CTR after normalization to the large ribosomal protein PO (RPLPO) housekeeping gene, and the differential expression between studied groups was assessed by ANOVA. RESULTS: Seven out of 12 genes presented differences in expression between 10-29% in CRC and/or AP compared to CTR. Considering the selection criteria, we further individually evaluated the levels of expression of 5 genes that had a minimum of 30% expression in the case-control study. Our data showed a significant up-regulation of platelet derived growth factor (PDGF) C in the blood of the patients with CRC compared to CTR (p=0.007). Likewise, clusterin (CLU) was significantly up-regulated both in CRC and AP groups compared to healthy subjects (p=0.01). For VEGFR1, PDGFRA and TGFB1 we didn't find significantly differential expression between any of the studied groups, even if increased levels were observed in both CRC and AP vs CTR. CONCLUSIONS: The results of our study indicated that increased blood level of PDGFC mRNA was associated with the presence of CRC (p=0.007). Additionally, high levels of circulating CLU mRNA were observed in both malignant and benign colorectal pathologies.

Systemic sclerosis-polymyositis overlap syndrome associated with autoimmune hepatitis and cerebral vasculitis.

Autoimmune hepatitis (AIH) is a chronic disorder characterized by persistent hepatocellular inflammation and necrosis. AIH overlap syndromes with other autoimmune diseases have been reported, including connective tissue diseases (CTD). Reports of AIH in systemic sclerosis (SSc), however, are scarce and have been particularly described in the limited SSc subtype. We report a case of systemic sclerosis-polymyositis overlap syndrome that developed AIH and subsequently, cerebral vasculitis. To our knowledge, this is the first report of such a complex mosaic of autoimmunity. We also review the literature regarding scleroderma-related AIH.

The long-term evolution of chronic hepatitis B acquired in childhood.

UNLABELLED: The AIM of this study was to assess the long-term evolution of chronic hepatitis B acquired in childhood. METHODS: The study was carried out in 2007 - 2008 on a group of 77 adult patients who were diagnosed with chronic hepatitis B in childhood. The actual assessment included epidemiological, clinical, biological and virological data, ultrasound examination in all patients and liver histology in 3 patients. RESULTS: From the 77 patients, 69 were HBeAg positive and the other 8 patients were anti-HBe positive when the diagnosis was made in their childhood. Thirty-seven patients from the HBeAg positive group and 2 patients from the anti-HBe group had been treated in childhood with IFN-alpha and the other 38 patients remained untreated (32 patients with HBeAg positive and 6 patients anti-HBe positive). Overall, 78.26% seroconverted to anti-HBe (87.50% untreated and 70.27% of patients treated with IFN). After a median follow-up period of 13 years, 36 patients from the HBeAg positive group (48.65% of treated patients and 56.25% of untreated ones) became inactive carriers. Seroconversion to anti-HBs, in the HBeAg positive group, occurred in 10.14% of cases (8.1% in treated patients) without statistical significance. Three patients from the whole group developed cirrhosis but none developed hepatocellular carcinoma. CONCLUSION: The long-term outcome in our patients with CHB acquired in childhood did not differ between treated and untreated patients.