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CD26 has been reported as a marker for colorectal cancer stem cells endowed with tumor-initiating properties and capable of colorectal cancer (CRC) metastasis. In this study, we investigated the functional effect of CD26 on CRC angiogenesis and metastasis, and the potential underlying mechanism. The functional effects of CD26 overexpression or repression were determined by a wound healing experiment, and cell migration and invasion assays in vitro and in mouse models. Differentially expressed genes regulated by CD26 were identified by genome-wide mRNA expression array and validated by quantitative PCR. CD26 functionally regulated CRC cell migration and invasion in vitro and angiogenesis and metastasis in vivo. Genome-wide mRNA expression array and qPCR showed that MMP1 was up-regulated in CD26+ subpopulation, and a subsequent experiment demonstrated the regulatory effect of CD26 on MMP1 in CRC cell lines with CD26 repression or overexpression. Furthermore, overexpression of CAV1 abrogated the CD26-regulated MMP1 induction in CRC cell lines. This study demonstrated the functional roles of CD26 in inducing CRC migration, invasion, angiogenesis and metastasis and identified the potential involvement of MMP1 and CAV1 in such process. CD26 is an attractive therapeutic target for combating tumor progression to improve the prognosis of CRC patients.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.

Background: There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients. Methods: Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin. Results: The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment. Conclusion: This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.

Anti-hypertensive drugs have been reported to demonstrate anti-inflammatory and anti-angiogenic effects. This study aims to investigate the association between anti-hypertensive drugs and the prognosis of colorectal cancer (CRC) patients. Clinical data of 1134 CRC patients with hypertensions and the prescription of anti-hypertensive drugs who had undergone curative surgery in our hospital between 2005 and 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared among different types of anti-hypertensive drugs and overall CRC patients. The 5-year overall survival for the antihypertensives-treated patients (65.2%) was higher than the CRC patients in Hong Kong (58.2%). Hydrochlorothiazide (HCTZ) group showed the best prognosis (79.1%) among different antihypertensive drug, particularly for advance stage or elderly patients, which are poor prognostic factors for overall CRC patients, demonstrated an obviously improved prognosis upon HCTZ treatment. Moreover, our data showed the recurrence rate was significantly lower for HCTZ group (18.3%) compared to non-HCTZ group (26.8%) and the reported rate (31%) of CRC patients in Hong Kong. Finally, patients with a lower pre-operative basophil level showed better overall and disease-free survival following HCTZ treatment. This study demonstrated the association of HCTZ treatment with a better prognosis of CRC patients.

Background Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it’s expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized. Methods We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC. Results MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3’UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells. Conclusion MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.

Piwi-interacting RNAs (piRNAs) represent a novel class of small non-coding RNAs (ncRNAs) that have been shown to have a deregulated expression in several cancers, although their clinical significance in colorectal cancer (CRC) remains unclear. With an aim of delineating the piRNA distribution in CRC, we conducted a systematic discovery and validation of piRNAs within two clinical cohorts. In the discovery phase, we profiled tumor and adjacent normal tissues from 18 CRC patients by deep sequencing and identified a global piRNA downregulation in CRC. Moreover, we identified piR-24000 as an unexplored piRNA that was significantly overexpressed in CRC. Using qPCR, we validated the overexpression of piR-24000 in 87 CRC patients. Additionally, we identified a significant association between a high expression of piR-24000 and an aggressive CRC phenotype including poor differentiation, presence of distant metastases, and a higher stage. Lastly, ROC analysis demonstrated a strong diagnostic power of piR-24000 in discriminating CRC patients from normal subjects. Taken together, this study provides one of the earliest large-scale reports of the global distribution of piRNAs in CRC. In addition, piR-24000 was identified as a likely oncogene in CRC that can serve as a biomarker or a therapeutic target.

Background With the increasing availability of the surgical robotic system, the young generation colorectal surgeons may learn robotic-assisted rectal surgery upfront. There are currently very limited studies evaluating the learning curve of novice rectal surgeons. Objective This study aimed to evaluate the learning curve of a surgeon who had limited experience in open and laparoscopic rectal surgery. Methods Thirty-nine consecutive robotic-assisted total mesorectal excisions were performed from March 2013 to October 2014. All cases were performed by a single surgeon whose prior experience in open or laparoscopic low rectal cancer resections was <5 cases. The learning curve was analyzed using the cumulative sum method. Results Thirty-four low anterior resections, four abdomino-perineal resections, and one Hartmann’s operation were performed. The mean total operating time was 397.2 ± 184.3 min. There was no conversion. The major complication rate was 10.3 %. When total operating time was analyzed with the CUSUM method, three phases could be identified. They are the initial eight cases, middle 17 cases, and the final 14 cases. The first phase consisted of more proximal tumors (86.3 ± 20.7 vs. 58.0 ± 34.9 mm from anal verge, p  = 0.04) and was associated with a shorter total operating time (243.5 ± 38.0 vs. 540.9 ± 133.4 min, p  = 0.000) and less estimated blood loss (81.3 ± 25.9 vs. 168.8 ± 99.5 ml, p  = 0.02) compared to the second phase. When the third phase is compared with the first and second phase, it has shorter total operating time (310.6 ± 164.5 vs. 44 5.7 ± 179.8 min, p  = 0.03). Complications rate were 12.5, 17.6, and 0 % for phase one, two, and three respectively. Conclusions In this study, the learning curve for a novice rectal surgeon was 25 cases. This is comparable to those who have already mastered the technique with laparoscopic or open approach. Surgical robotic system may have a role in shortening the learning curve for low rectal resection.

Background Resection for colon cancer in the elderly is a major undertaking. However, data on the outcome and survival of elderly patients who underwent laparoscopic resection for colon cancer are limited. This study of patients older than 75 years compared outcome and survival between those who underwent laparoscopic resection and those who had open resection for colorectal cancer. Methods From 2000 to 2009, 434 patients ages 75 years and older who underwent elective resection for colon cancer were included in the study. Patients who had rectal cancer or had undergone emergency operations were excluded. Preoperative diagnosis was determined by colonoscopy, and computed tomography scan was performed for preoperative staging. Data on the patients’ demographics, operative details, pathology results, postoperative results, and survival were collected prospectively. The patients who underwent laparoscopic surgery were compared with those who had open surgery. Results The study included 434 patients (210 men) with a median age of 80 years (range 75–95 years). Of these 434 patients, 189 underwent laparoscopic resection. Nine patients (4.8 %) required conversion to open operation. The patients did not differ in terms of age, gender, incidence of medical comorbidities, or stage of disease. The median operating time was longer in the laparoscopic group, but the blood loss was significantly less. Laparoscopic resection was associated with a lower mortality rate and a shorter hospital stay ( p  < 0.05). The open resection group had significantly more cardiac complications ( p  < 0.05). The overall 5-year survival rates were similar between the patients who had laparoscopic resections and those who had open surgery. Conclusions For patients older than 75 years, laparoscopic resection of colon is associated with less intraoperative blood loss, a shorter hospital stay, fewer cardiac complication, and a lower mortality rate than open resection. Therefore, the authors recommend laparoscopic resection of colon cancer as the treatment of choice for elderly patients.

Background Identification of molecular markers for early detection or prediction of metastasis is crucial for both management of HCC patient postoperative treatment and identify new therapeutic targets to inhibit HCC progression and metastasis. In the current study, we investigated the clinical correlation between Pin1, RhoA and RhoC and their association with HCC metastasis. Methods Using a randomized study design of primary HCC samples from 139 patients, we determined messenger RNA expression of Pin1, RhoA and RhoC and their prognostic value. Results Our findings demonstrated for the first time the clinical correlation of Pin1 in HCC metastasis. Pin1, RhoA and RhoC transcript levels were significantly higher in HCC specimens when compared with the paired adjacent non-tumorous liver. Pin1 overexpression was closely correlated with that of RhoA (R = 0.562, p  < 0.001) and RhoC (R = 0.529, p < 0.001), and their co-overexpressions correlated with metastatic HCC ( p  = 0.000012) and poor recurrence-free survival of HCC patients ( p  < 0.00001), which showed better prognostic significance than either Pin1, RhoA or RhoC overexpression alone. Co-overexpressions of Pin1 + RhoA/RhoC were also an independent factor for predicting development of metastasis after curative resection in our multivariate regression model ( p  < 0.001). Conclusion Pin1, RhoA and RhoC co-overexpressions are prognostic factor for metastatic HCC and predict poor recurrence-free survival.

Accurate assessment of unmet supportive care needs is essential for optimal cancer patient care. This study used confirmatory factor analysis (CFA) to test the known factor structures of the short form of Supportive Care Need Survey (SCNS-34) in Hong Kong and Taiwan Chinese patients diagnosed with colorectal cancer (CRC). 360 Hong Kong and 263 Taiwanese Chinese CRC patients completed the Chinese version of SCNS-SF34. Comparative measures (patient satisfaction, anxiety, depression, and symptom distress) tested convergent validity while known group differences were examined to test discriminant validity. The original 5-factor and recent 4-factor models of the SCNS demonstrated poor data fit using CFA in both Hong Kong and Taiwan samples. Subsequently a modified five-factor model with correlated residuals demonstrated acceptable fit in both samples. Correlations demonstrated convergent and divergent validity and known group differences were observed. While the five-factor model demonstrated a better fit for data from Chinese colorectal cancer patients, some of the items within its domain overlapped, suggesting item redundancy. The five-factor model showed good psychometric properties in these samples but also suggests conceptualization of unmet supportive care needs are currently inadequate.