circadian clock circuitry in colorectal cancer

Colorectal cancer is the most prevalent among digestive system cancers.Carcinogenesis relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and apoptosis.Cell,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery.Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer patients.Epidemiological studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift workers.In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.

Lack of association between UGT1A7,UGT1A9,ARP,SPINK1 and CFTR gene polymorphisms and pancreatic cancer in Italian patients

AIM： To investigate simultaneously UGT1A7, UGT1A9, ARP, SPINK and CFTR genes to verify whether genetic polymorphisms predispose to the development of pancreatic cancer （PC）.METHODS： Genomic DNA of 61 pancreatic cancer patients and 105 healthy controls （HC） were analyzed. UGT1A7 genotyping was determined by PCR-RFLP analysis. Specific PCR and sequencing were used to analyze genetic variants of UGT1A9, ARP, SPINK1 and CFTR genes.RESULTS： Four different alleles （^＊1：WT; ＂2： N129K and R131K; ＂3： N129K, R131K, and W208R; and ＂4： W208R） in UGT1A7 and three different alleles （^＊1：WT;^＊4： Y242X; and ^＊5： D256N） in UGT1A9 were detected. All UGT1A polymorphisms were observed at similar frequency in PC patients and HC. Seven different alleles in ARP were found in PC patients and HC at similar frequency. The SPINK1 mutations N34S and P55S occurred in five PC patients with a prevalence （4.1%） not significantly different from that observed （2.0%） in HC. The only CFTR AFS08 mutation was recognized in three PC patients with a prevalence （4.9%） similar to HC.CONCLUSION： UGT1A7, UGT1A9, ARP, SPINK1 and CFTR gene polymorphisms are not associated with PC in Italian patients.

Comparison of a monoclonal antigen stool test (Hp StAR) with the ^(13)C-urea breath test in monitoring Helicobacter pylori eradication therapy

AIM： To evaluate the agreement between a mAb-based stool test （HP STAR） and the urea breath test （UBT） in monitoring （H pylon） infection after eradication therapy. METHODS： Patients with discordant results on UBT and Hp STAR underwent endoscopy with biopsies for rapid urease test, culture, and histology to confirm H pylori status. RESULTS： Among 250 patients （50±14 years）, 240 （96.0%） had concordant UBT and Hp STAR tests with a significant correlation between DOB and A values （R = 0.87; P〈0.0001）. The remaining 10 （4.0%） patients had discordant tests （positive Hp STAR and negative UBT） with the Hp STAR inaccurate in five cases （false positive） and UBT inaccurate in the other five cases （false negative）. The “maximal expected” sensitivity, specificity, ＋PV, -PV, ＋LR, and -LR were 91%, 100%, 100%, 97.4%, ∞, and 8.2 respectively, for the UBT, and 100%, 97.4%, 91%, 100%, 38.8, and 0, respectively, for the Hp STAR. Overall accuracy for both tests was 98%. CONCLUSION： Both the UBT and the Hp StAR are equally accurate in monitoring H pylori infection. Nowadays, the choice of the “best” non-invasive H pylori test in the post-treatment setting should be done not only in terms of diagnostic accuracy but also in view of cost and local facilities.