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Colorectal Cancer (CRC) is one of the most common cancers accounting for 1.8 million new cases worldwide every year. Therefore, the identification of new potential therapeutic targets represents a continuous challenge to improve survival and quality of CRC patient's life. We performed a microarray analysis dataset consisting of colon biopsies of healthy subjects (HS) and CRC patients. These results were further confirmed in a clinical setting evaluating a series of CRC patients to assess the expression of Resistin-Like Beta (RETNLB) and to correlate it with their clinical data. Our results showed a significant reduction of RETNLB expression in CRC biopsies compared to the HS mucosa. Furthermore, such reduction was significantly associated with the TNM grade and patients' age. Furthermore, a significantly positive correlation was found within mutated subjects for KRAS, TP53, and BRAF. In particular, patients with poor prognosis at 5 years exhibited RETNLB lower levels. In-silico analysis data were confirmed by histochemical analysis in a series of CRC patients recruited by our group. The results obtained provided that RETNLB low levels are associated with an unfavorable prognosis in CRC patients and its expression is also dependent on adjuvant therapy. Further studies are warranted in order to evaluate the molecular mechanisms underlying the role of RETNLB in CRC progression. [ABSTRACT FROM AUTHOR]

We have recently shown that covalent attachment of the NO moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity. In this study we evaluated the impact of Saq-NO on the growth of A375 human melanoma cells, as a prototype of NO-dependent cancer model. The novel compound strongly affected the in vitro and in vivo progression of A375 melanoma cell growth. The mechanism of antimelanoma action comprised dual drug activity-induction of apoptotic cell death and acquisition of melanoma cell responsiveness to TRAIL. Saq-NO-triggered apoptosis was dependent on transient AKT up-regulation and reduced pERK and iNOS expression that were observed within the first 12 h of exposure to the drug. Thereafter, however, Saq-NO up-regulated both iNOS transcription and NO endogenous synthesis and sensitized A375 cells to TRAIL. Furthermore, reduced YY1 expression was observed after 24 h of Saq-NO exposure, which correlated with increased expression of DR5. The biological relevance of this complex and powerful action of Saq-NO was consistent with the marked drug-induced inhibition of the growth of A375 xenotransplants in nude mice. J. Cell. Physiol. 226: 1803-1812, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Summary: Over the past 2 decades the surgeon and the hospital where he or she works have been considered to play an important role in the prognosis of the rectal cancer patients. The rate of sphincter-sparing rectal resection, local recurrence and survival are the factors more frequently utilized in the literature to evaluate if surgeons are able to affect the natural history of the rectal cancer. The quantitative aspect, high volume of the surgeon, is not enough but in order to achieve better results in the treatment of rectal cancer a specific interest in colorectal surgery is more important. While retrospective studies show a positive influence of the surgeon on the prognosis of these patients, prospective studies are very few so that we need to get more data to reach valid conclusions. The high number of rectal cancer patients does not allow a centralization of these patients into specialist Units, but we should get up everywhere colorectal programmes so that every department can reach a high standard of efficiency. [Copyright &y& Elsevier]

Summary: Follow-up of surgically treated colorectal cancer patients is not supported by objectively certain data. Despite the thousands of investigations reported in the scientific literature, only six randomized prospective studies and two meta-analysis of randomized studies provide data suggesting clear conclusions. Our review of the literature revealed that intensive colorectal follow-up should be performed even if the long-term survival benefit is small. The timing and investigations conducted in follow-ups diverge. The inconsistency of follow-ups is revealed by the fact that the leading USA and European societies propose different guidelines. One datum that the literature agrees on is that pancolonoscopy performed at 3–5 year intervals in colorectal cancer surgery patients supports diagnosis of adenomatous polyps and metachronous cancers. Cost analysis have shown that intensive follow-up would certainly exceed the cut-off point level set for every additional year of good quality of life. [Copyright &y& Elsevier]