The prognostic roles of PYCR2 and ZBTB18 expression in tissues of colorectal carcinoma and non-neoplastic tissues: an immunohistochemical study

Background: It is important to detect novel biomarkers responsible for the progression and spread of colorectal cancer (CRC) to better evaluate the prognosis of the patients, provide better management, and foster the development of therapeutic targets. In humans, pyrroline-5-carboxylate reductase 2 (PYCR2) is encoded on chromosome 1q42.12, and its metabolic activity has been linked to oncogenesis in many cancers. Zinc finger and broad-complex, tramtrack, and bric-à-brac (BTB) domain-containing protein 18 (ZBTB18), a zinc finger transcriptional repressor, has been found to have a tumor-suppressor role and to be methylated in CRCs. To date, the prognostic roles of PYCR2 and ZBTB18 in CRC patients have not been thoroughly studied. Objective: To evaluate the tissue protein expression of PYCR2 and ZBTB18 in CRC and adjacent non-neoplastic intestinal tissues, to detect their roles in CRC carcinogenesis, progression and metastases. Patients and methods: After applying the inclusion criteria, 60 CRC patients were included in the study. Tissue samples from the tumor and the adjacent non-neoplastic tissues were stained with PYCR2 and ZBTB18. The patients were followed up for about 30 months (range: 10 to 36 months). We performed a correlation regarding the expression of the markers, and clinicopathological and prognostic parameters. Results Upregulation of PYCR2 and downregulation of ZBTB18 were found to be higher in CRC tissue than in the adjacent non-neoplastic colonic mucosa (p = 0.026 and p < 0.001 respectively). High expression of PYCR2 and low expression of ZBTB18 were positively correlated with large tumor size, higher tumor grade, advanced tumor stage, presence of spread to lymph nodes, and presence of distant metastases (p < 0.001). High PYCR2 and low ZBTB18 expressions were significantly associated with poor response to therapy (p = 0.008 and 0.0.17 respectively), as well as high incidence of progression and recurrence (p = 0.005), and unfavorable overall survival (OS) rates (p = 0.001). Conclusion: High expression of PYCR2 and low expression of ZBTB18 were independent predictors of CRC, progression, poor prognosis and unfavorable patient OS and progression-free survival (PFS) rates. (AU)

Hepatic Hilar and Celiac Plexus Nerve Blocks as Analgesia for Doxorubicin-Eluting Microsphere Chemoembolization Procedures for Hepatocellular Carcinoma: A Nonblinded Randomized Clinical Trial.

PURPOSE: To investigate whether hepatic hilar and celiac plexus nerve blocks provide safe and effective analgesia to patients undergoing doxorubicin-eluting embolics transarterial chemoembolization (DEE-TACE) for hepatocellular carcinoma. MATERIALS AND METHODS: In this prospective, randomized trial, 92 patients undergoing DEE-TACE for hepatocellular carcinoma were enrolled. The control group received standard intraprocedural local anesthetic, intra-arterial lidocaine, and intravenous analgesia; the study group underwent additional hepatic hilar and celiac plexus nerve blocks. Intra-arterial lidocaine, intravenous and oral narcotic and antiemetic requirements after the procedure, pain, patient satisfaction, adverse events, and hospital stay were compared. RESULTS: The nerve block group reported less pain during and after the procedure at days 1 and 7 (P < .001), although differences resolved by week 2. The control group received more intra-arterial lidocaine (P < .001) and required approximately double the amount of narcotic analgesia during and after the procedure, extending to 3 weeks after the procedure (P < .001), as well as less antiemetics (P < .001). No differences in adverse events, hospital stay, and overall patient satisfaction were noted. CONCLUSIONS: Hepatic hilar and celiac plexus nerve blocks before procedures can result in lower pain during and after procedures in patients undergoing DEE-TACE. Furthermore, nerve blocks result in lower opioid consumption and opioid-related complications for 3 weeks following procedures.

Transarterial chemoembolisation in patients with hepatocellular carcinoma: low-dose doxorubicin reduces post-embolisation syndrome without affecting survival-prospective interventional study.

BACKGROUND: No chemotherapeutic agents have been standardised for transarterial chemoembolisation (TACE). In particular, doxorubicin has no defined optimal dosage in TACE procedures. We compared low versus currently used dose of doxorubicin for TACE in patients with hepatocellular carcinoma (HCC) in terms of severity of post-embolisation syndrome (PES) and overall survival (OS). METHODS: From October 2014 to March 2018, we enrolled patients with primary HCC scheduled for TACE. Patients were randomised to receive 50 mg (group A) or 100 mg (group B) of doxorubicin. Outcomes were the rate of patients with PES; free-time-to-PES; changes in laboratory results; tumour response at 1, 3, and 6 months after TACE; and overall survival. RESULTS: Twenty-eight patients (24 males, 4 females) were enrolled, aged 58.9 ± 6.8 years (mean ± standard deviation). Fifteen of them palliated with 50 mg (group A) and 13 with 100 mg (group B) of doxorubicin for a total of 68 TACE procedures (of 28 patients who had repeated TACE procedures). Visual analogue scale (VAS) and duration of pain were significantly differently lower in group A than in group B (p < 0.001). The median duration of fever was shorter in group A than in group B (p = 0.003). No significant differences between both groups were observed for tumour response to TACE and OS. The doxorubicin dose was significantly correlated with duration of pain, fever, and VAS score. CONCLUSION: A lower dose of doxorubicin (50 mg) was associated with fewer PES symptoms compared with 100 mg, without effects on tumour response nor OS.

Angiopoietin-like protein 3 and 4 expression 4 and their serum levels in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th most common cancer and the 3rd leading cause of cancer causing death allover the world. The aim of this research to explore the clinical relevance of blood angiopoietin-like protein-3 (ANGPTL3) and ANGPTL4 expression and their proteins levels as non invasive biomarkers in cirrhotic and HCC patients and their influence on the clinicopathological features of HCC. MATERIAL AND METHODS: This work comprised 200 patients with chronic hepatitis (120 cases complicated with cirrhosis, 80 patients with primary HCC) and 100 controls. circulating ANGPTL3 and ANGPTL4 expression was estimated by real-time polymerase chain reaction (RT-PCR). ANGPTL3 and ANGPTL4 protein levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The circulating ANGPTL3 and ANGPTL 4 expression was significantly elevated in HCC cases compared to chronic hepatitis patients and controls. There were much more serum ANGPTL3 and ANGPTL4 values in HCC and chronic hepatitis patients as compared to controls, but we couldn't detect this significance between chronic hepatitis and HCC cases as regards ANGPTL4. By Multiple stepwise linear regression analysis, an increased ANGPTL3 expression, alpha-fetoprotein (AFP), serum ANGPTL 3 levels, Child-Pugh grade were significantly assosciatedassociated with increased risk of HCC. Logistic regression analysis revealed that ANGPTL 3 expression and AFP levels were the only pridectorspredictors of HCC (odd's ratio (OR)=8.9; 8.6 respectively, P=0.003). Receiver operator characteristic (ROC) demonsterated that serum ANGPTL3 and ANGPTL4 levels were usufuluseful biomarkers discriminating chronic hepatitis cases from controls (AUC=0.820,0.887, respectively P<0.001). However, they fail to discriminate HCC patients from chronic hepatitis patients (P=0.27,0.12 respectively). Moreover, ANGPTL3 and ANGPTL 4 expression were promising biomarkers discriminating chronic hepatitis cases from controls and those HCC cases from chronic hepatitis patients (P<0.001). Combined ANGPTL3 expression and serum level wasn't useful in discriminating HCC patient from chronic hepatitis (P=0.09). In contrast, combined ANGPTL4 expression and serum level was an useful biomarker discriminating HCC cases from chronic hepatitis. CONCLUSION: ANGPTL3 and ANGPTL 4 expression and serum levels can be promising non invasive biomarkers in diagnosis of chronic hepatitis and HCC especially their expression could be useful in discriminating HCC from chronic hepatitis patients.

Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women.

Obesity and diabetes are increasing in epidemic proportions globally. Lipocalin-2 (LCN-2) is an inflammatory adipocytokine and obesity-related marker of low-grade inflammation. We aimed to investigate, for first time, the possible role of LCN-2 expression and serum levels in prediction of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) among obese Egyptian women. This study included 188 obese women and 180 controls. Obese women were subdivided into three subgroups according to their fasting blood glucose, normal glucose tolerance (NGT), IGT and T2DM. Circulating LCN-2 expression levels were determined by real time polymerase chain reaction. Serum LCN-2 concentrations were assessed by ELISA. Our findings revealed that LCN-2 expression and serum levels were higher in obese women compared to lean controls. They were higher in IGT and T2DM obese cases than in NGT obese women. Receiver operating characteristic analyses revealed that LCN-2 expression level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.735 and 0.740, respectively). It was an independent predictor of IGT and T2DM among obese women. Serum LCN-2 level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.705 and 0.728, respectively). It was independent predictor of T2DM without predicting IGT among obese women. The power of combined LCN-2 serum levels and expression in discriminating between IGT from NGT and T2DM from IGT obese women was high (AUC = 0.717 and 0.741, respectively). In conclusion, LCN-2 expression and serum levels could discriminate IGT from NGT and T2DM from IGT obese women and early predicting T2DM among obese women. While, LCN-2 expression level was the independent predictor of IGT in obese women. Combination of both LCN-2 expression and serum levels improved their diagnostic value in early detection of IGT and T2DM among obese women. © 2017 IUBMB Life, 69(2):88-97, 2017.