Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), ...deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression.
The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility.
A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls).
Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients.
Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Background
Peripheral arterial disease caused mainly by atherosclerosis portent significant morbidity, adverse prognosis and mortality, with localized treatment approaches aiming at symptom ...alleviation and improvement of circulation. Recently, scientific interest has been shifted towards epigenomics, with microRNAs appearing as a future therapeutic target in ischemic cardiovascular diseases due to their potential in regulating angiogenesis.
Purpose
We investigated the pro-angiogenic effect of miRNA-126 mimic in an in vivo model of hind limb ischemia.
Methods
Ten-week-old male C57Bl/6 mice (n=20) were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5mg/kg (Group A, n=10) or 0.2ml normal saline (Group B, n=10) on days 1, 3 and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 7 and 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR.
Results
Following microRNA-126 mimic administration in Group A subjects, we noted a qualitative and quantitative stepwise increase in I/N hind limb perfusion ratio Day 0: 0.354 (0.276, 0.455) vs. Day 8: 0.775 (0.700, 0.844) vs. Day 28: 0.681 (0.660, 0.896), p=0.001 (Figure 1, Panels A and B). In Group B a stepwise increase of lesser magnitude was observed in I/N hind limb perfusion ratio Day 0: 0.267 (0.164, 0.383) vs. Day 8: 0.400 (0.338, 0.418) vs. Day 28: 0.539 (0.483, 0.603), p=0.074. Importantly, over time changes of I/N hind limb perfusion ratio were significantly higher in group A compared to group B (p for interaction=0.005) (Figure 1, Panel B). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p<0.001) (Figure 1, Panel C). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p<0.001) (Figure 1, Panel C). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of both Group A and B subjects whereas no correlation between microRNA-126 and VEGF was observed in the non-ischemic hind limbs of the entire study population (Figure 1, Panel D).
Conclusion
MicroRNA-126 mimic delivery in the ischemic hind limb of mice can accelerate vascular perfusion recovery via angiogenesis, which is mediated by VEGF expression.
Funding Acknowledgement
Type of funding sources: None. Figure 1
To evaluate the antitumor efficacy of Ag
Au
Trp
NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism.
...Ag
Au
Trp
NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag
Au
Trp
NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively.
In the 4T1 tumor-bearing SCID mice, Ag
Au
Trp
NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels.
Based on our results, Ag
Au
Trp
NPs express anti-tumor and anti-metastatic effects in vivo. Ag
Au
Trp
NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.
Abstract
Background
Despite the advantages in the management of ulcerative colitis (UC), much less have been achieved in the field of diagnosis and monitoring of the disease, where colonoscopy ...remains the ‘golden’ method. Established serum biomarkers while commonly used, their poor correlation with the endoscopic features and poor performance as screening tools renders them as inadequate biomarkers by themselves. Therefore, the development of novel, objective, reproducible biomarkers with good correlation with disease endoscopic activity would be of great value for the diagnosis and monitoring of UC. The objective of our study was to evaluate the correlation between leucine-rich Α-2 glycoprotein (LRG), high mobility group box 1 protein (HMGB1), Annexin A1 (ANXA1) and matrix metalloproteinase 3 (MMP3) with endoscopic activity and their role as potential serum biomarkers of UC.
Methods
Patients with UC, treated with 5-ASA undergoing colonoscopy, were selectively included in our study. Individuals undergoing preventive colonoscopy with no abnormal endoscopic features were also included as control group. A blood sample was obtained from each member of both groups and endoscopic Mayo subscore (Ms) was recorded for the UC patients. Serum LRG, HMGB1, ANXA1, and MMP3 levels were measured in the blood samples. Statistical analysis (Independent-samples t-test) was performed to compare the data collected and ROC curve analysis for the statistically significant differences recorded.
Results
Forty-two UC patients and fourteen controls were included. The patients’ and controls’ median age was 48 and 54 years old, respectively. While there were no statistically significant differences reported for HMGB1 and LRG, different results were recorded for ANXA1 and MMP3 as shown in the following table.
Abstract P203
Conclusions
ANXA1 levels were significantly different between controls and UC patients implying that it could be used as a marker for diagnosis of UC. The best cut-off value was 2.043 μg/ml (88% sensitivity, 93% specificity). MMP3 was significantly lower for Ms = 0, Ms = 0/1 vs. Ms = 1, Ms = 2/3, respectively, suggesting that it could be a marker of mucosal healing and endoscopic remission. The best cut-off values were 4.743 ng/ml for Ms = 0 vs. Ms = 1 (100% sensitivity, 67% specificity) and 6.58 ng/ml for Ms = 0/1 vs. Ms = 2/3 (89% sensitivity, 61% specificity).
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