AimThe study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for targeted therapy.MethodsThe study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.ResultsData analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04).ConclusionAberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.

These results suggested that pharmacist-led telephone follow-up (TFU) could help in building a close trusting rapport between the patient and caregiving pharmacist. They also demonstrated the potential usefulness of the TFU on patients' tolerability, adherence, and OS; however, further trials with a larger sample size should be encouraged to explore more pronounced results. Otherwise, the provided standard care could be considered good enough for these patients.

Background: Global DNA methylation has an impact in cancer pathogenesis and progression. This study aimed at investigating the impact of global DNA methylation in treatment outcome of Colorectal Cancer (CRC).Patients and Methods: Global DNA methylation was measured by LC/MS/MS in peripheral blood leucocytes of 102, 48, and 32 Egyptian CRC patients at baseline and after 3 and 6 months of Fluoropyrimidine (FP) therapy respectively, in addition to 32 normal healthy matched in age and sex. The genetic expressions of DNA methyl transferases (DNMTs) were determined and correlated with patients‘ survival using univariate and multivariate methods of analyses.Results: Egyptian CRC patients had significant global hypomethylation of 5mC level and 5mC % with overexpression of DNMT3A and DNMT3B. Significant higher 5mC levels were shown in patients > 45 years, male gender, T2 tumors, stage II, negative lymph nodes, and absence of metastasis. FP therapy significantly reduced DNA methylation particularly in the subgroups of patients with high DNA methylation level at baseline and good prognostic features. After 3 years of follow up, patients with 5mC % > 8.02% had significant poor overall survival (OS) while, significant better event-free survival (EFS) was found in patients with 5mC level > 0.55. High initial CEA level and presence of metastasis were significantly associated with hazards of disease progression and death.Conclusion: Global DNA methylation has a significant impact on the treatment outcome and survival of Egyptian CRC patients treated with FP- based therapy.

The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.