Upregulation of α enolase (ENO1) crotonylation in colorectal cancer and its promoting effect on cancer cell metastasis.

Lysine crotonylation (Kcr) is a newly identified protein translational modification and is involved in major biological processes including glycolysis, but its role in colorectal cancer (CRC) is unknown. Here, we found that the Kcr of α enolase (ENO1) was significantly elevated in human CRC tissues compared with the paratumoral tissues. CREB-binding protein (CBP) functioned as a crotonyltranferase of ENO1, and SIRT2 was involved in the decrotonylation of ENO1. Using quantitative mass spectrometry for crotonylomics analysis, we further found that K420 was the main Kcr site of ENO1 and ENO1 K420 Kcr promoted the growth, migration, and invasion of CRC cells in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes. Our study reveals an important mechanism by which ENO1 regulates CRC through crotonylation.

Assessment of 25 CYP2D6 alleles found in the Chinese population on propafenone metabolism in vitro.

Cytochrome P450 enzyme 2D6 (CYP2D6) is an important member of the cytochrome P450 enzyme superfamily, with more than 100 CYP2D6 allelic variants being previously reported. The aim of this study was to assess the catalytic characteristics of 25 alleles (CYP2D6.1 and 24 CYP2D6 variants) and their effects on the metabolism of propafenone in vitro. Twenty-five CYP2D6 alleles were expressing in 21 Spodoptera frugiperda (Sf) insect cells, and each variant was evaluated using propafenone as the substrate. Reactions were performed at 37 °C with 1-100 µmol/L propafenone for 30 min. After termination, the product 5-OH-propafenone was extracted and used for signal collection by ultra-performance liquid chromatography (UPLC). Compared with wild type CYP2D6.1, the intrinsic clearance (Vmax and Km) values of all variants were significantly altered. Three variants (CYP2D6.87, CYP2D6.90, CYP2D6.F219S) exhibited markedly increased intrinsic clearance values (129% to 165%), whereas 21 variants exhibited significantly decreased values (16% to 85%) due to increased Km and (or) decreased Vmax values. These results indicated that the majority of tested alleles had significantly altered catalytic activity towards propafenone hydroxylation in this expression system. Attention should be paid to subjects carrying these rare alleles when treated with propafenone.

[Umbilicus metastasis in patients with epithelial ovarian cancer : clinical features of 21 patients].

OBJECTIVE: To analyze the clinical features, treatments and prognosis of patients with Sister Mary Joseph's nodule of umbilicus (SMJN) from epithelial ovarian cancer (EOC) patients. METHODS: Among a total of 2642 pathologically diagnosed EOC cases, 21 cases with SMJN were histopathologically diagnosed and had an age range of 40-66 years at Sun Yat-sen University Cancer Center between January 1991 and January 2011. Their clinical data were retrospectively analyzed. RESULTS: The incidence of SMJN in EOC was 0.79 %. The 1, 2 and 5-year survival rates were 61.8%, 26.8% and 9.5% respectively. The diagnosis was confirmed via local excision biopsy, fine-needle aspiration biopsy or gross pathological diagnosis. Univariate analysis showed that patients with progressive disease or relapsing with umbilical metastasis after treatment had worse prognosis than those diagnosed at pre-treatment (22 vs 6 months, P < 0.01) . Patients with suboptimal cytoreductive surgery and/or less than 6 circles of chemotherapy or palliative treatment had worse prognosis than those with optional cytoreductive surgery during 6-8 circles of chemotherapy (21 vs. 4 months). Multivariate analysis showed that the time to diagnose and treatment regimen were independent predictors of survival (relative risk = 41.28, P < 0.01). CONCLUSIONS: SMJN is a rare manifestation of EOC. Improving the diagnostic vigilance, optimal debulking surgery plus regular chemotherapy and other new individualized postoperative treatments may arrest the progression of EOC and prolong patient survival.

Vessels that encapsulate tumor clusters (VETC) pattern predicts the efficacy of adjuvant TACE in hepatocellular carcinoma.

PURPOSE: Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit. METHODS: Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC-) was evaluated. RESULTS: The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC- patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC- , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC- ones, may be not due to the activation of HIF-1α pathway. CONCLUSION: The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients' outcomes and responses to adjuvant TACE therapy.

Usefulness of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography combined with the platelet-lymphocyte ratio in predicting the prognosis of nasopharyngeal carcinoma.

OBJECTIVES: To investigate the value of 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) combined with the platelet-lymphocyte ratio (PLR) in predicting the prognosis of nasopharyngeal carcinoma (NPC). METHODS: This was a retrospective analysis of the data of 73 patients with NPC who underwent 18F-FDG PET/CT before treatment from January 2010 to December 2014. The maximum standard uptake value (SUVmax) of NPC and the PLR within 1 week before treatment were both measured. The Mann-Whitney U-test was used to compare the differences between the SUVmax and PLR among the different clinical characteristics of patients with NPC and the 5-year progression-free survival (PFS) rate; according to the receiver operating characteristic (ROC) curve, the best cutoff values of the SUVmax and PLR were obtained and used to group patients. The Kaplan-Meier method and Log-rank test were used to conduct univariate analysis of 5-year PFS in patients with NPC, and Cox regression was used to conduct multivariate analysis; differences in the 5-year PFS of patients with different SUVmax values combined with the PLR were compared. RESULTS: The SUVmax and PLR of patients with disease progression within 5 years were higher than those of patients without disease progression (p = 0.006 and p = 0.026). SUVmax = 9.7 and PLR = 132.98 had the best prognostic diagnostic efficiency for patients. Cox multivariate analysis showed that the SUVmax and PLR are independent factors affecting the prognosis of NPC. The 5-year PFS of patients with SUVmax <9.7 was significantly higher than that of patients with SUVmax ≥9.7 in the high PLR group (PLR ≥132.98) and in the low PLR group (PLR <132.98) (59.3% vs 29.4%, p = 0.033 and 90.9% vs 42.9%, p = 0.006, respectively). For patients with SUVmax <9.7, the 5-year PFS of the high PLR group was significantly lower than the low PLR group (59.3% vs 90.9%, p = 0.016); for patients with SUVmax ≥9.7, there was no significant difference in 5-year PFS between the high PLR group and the low PLR group (29.4% vs 42.9%, p = 0.406). CONCLUSIONS: Both the SUVmax of the primary tumor and the PLR before treatment have an important influence on the prognosis of NPC. Combining the SUVmax and the PLR can more accurately predict the prognosis of patients with NPC. ADVANCES IN KNOWLEDGE: In this study, we evaluated the prognostic value of combining pretreatment tumor 18F-FDG uptake on PET/CT imaging and PLR in NPC patients. We found that both SUVmax and PLR are independent factors for the PFS of NPC patients, and a low SUVmax (SUVmax <9.7) combined with a low PLR (PLR <132.98) revealed significant PFS benefit.

Blocking the IGF2BP1-promoted glucose metabolism of colon cancer cells via direct de-stabilizing mRNA of the LDHA enhances anticancer effects.

Colorectal cancer (CRC) is a commonly diagnosed cancer with poor prognosis and high mortality rate. Hyperthermia (HT) is an adjunctive therapy to enhance the antitumor effects of traditional chemo- or radio- therapy. Here, we report that a cluster of essential regulator genes and speed-limit enzymes of glucose metabolism were significantly elevated under HT from a glucose metabolism PCR array analysis. Under low glucose supply or glucose metabolism inhibition, CRC cells displayed increased sensitivity to HT treatments. By transcript sequencing from the established HT resistant (HTR) colon cancer cell line LoVo HTR, we observed that IGF2BP1, an RNA-binding protein, was significantly upregulated in HTR cells compared with parental cells. Furthermore, LDHA mRNA was identified as an IGF2BP1 direct target. An RNA immunoprecipitation assay and RNA pull-down assay consistently illustrated IGF2BP1 specifically bonds to the 3' UTR of LDHA mRNA, leading to enhanced stability of LDHA mRNA. Finally, we demonstrated that inhibiting the IGF2BP1-promoted glycolysis sensitized colon cancer cells to HT treatment via both in vitro and in vivo experiments. Our findings suggest that targeting the IGF2BP1-LDHA-glycolysis pathway might be a promising therapeutic approach to enhance the anti-cancer effects of HT treatment.

Efficacy and safety of spironolactone for the treatment of patients with acute heart failure: A protocol for systematic review.

BACKGROUND: This study will investigate the efficacy and safety of spironolactone for the treatment of acute heart failure (AHF). METHODS: The following electronic databases will be retrieved in PUBMED, EMBASE, Cochrane Library, Web of Science, CINAHL, CBM, CNKI, and VIP database from inception through present. Two researchers will independently screen and assess the obtained literatures and extract outcome data. All study methodological quality will be assessed using Cochrane risk of bias tool, and all statistical analysis will be performed by RevMan 5.3 software. Additionally, we will undertake a narrative synthesis if it is possible. RESULTS: This study will sum-marize most recent evidence to investigate the efficacy and safety of spironolactone for the treatment of AHF. CONCLUSION: This study will seek to assess the efficacy and safety of spironolactone for treating AHF. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070053.

Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value.

Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results:BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.

[Standard uptake value of 18F-fluorine-2-deoxyglucose is correlated with the expression of estrogen receptor in duct carcinoma of breast].

OBJECTIVE: To explore the relationship between the standard uptake value (SUV) of 18F-fluorine-2-deoxyglucose (18F-FDG) and the expression of estrogen receptor (ER) in duct carcinoma of breast, as well as their correlation. METHODS: From March 2004 to November 2006, PET/CT scans were performed to 41 patients (female, mean age (55.2 +/- 9.55) years) with duct carcinoma of breast. All of the diagnoses were proved by pathology and immunohistochemical ER assays. The SUVs were calculated. RESULTS: ER positive patients comprised 43.9% of the 41 patients. The mean age of ER positive patients was (60.20 +/- 9.34) years, older than the ER negative patients ((50.32 +/- 9.33) years, P = 0.012). The SUV in the ER positive patients (2.76 +/- 1.34) was significantly less than in the ER negative patients (5.84 +/- 2.90, P = 0 004). The receiver operating characteristic (ROC) by FDG SUV for ER demonstrated that the area under curves reached 0.801 +/- 0.075, with significant implications on the expression of estrogen receptor (P = 0.002); The cut point of FDG SUV for ER was 3.135, with sensitivity of 72.2% and specificity of 73.9%. CONCLUSION: 18F-FDG SUV is significantly correlated with the expression of ER. We propose 3.135 as a threshold of SUV for the indication of expression of ER in duct carcinoma of breast.

[Genotyping of RhD-negative blood samples diagnosed by serological tests from patients waiting for kidney transplantation].

OBJECTIVE: To compare the accuracy of serological and molecular approaches to identification of RhD-negative patients waiting for kidney transplantation. METHODS: A total of 103 RhD-negative blood samples by serological test were collected from patients waiting for kidney transplantation between January, 2006 and January, 2016. Quantitative PCR and sequencing were used to verify the results of RHD genotyping, and the false negative rates of the serological and molecular methods for RhD genotyping were compared. RESULTS: Among the 103 blood samples, true RhD negativity (with all the 10 exons missing) was found in 56 samples (54.5%), and false RhD negativity (RhD positivity with loss, repetition, or missense mutation in the 10 exons) in 47 samples (45.6%). In the 47 false RhD-negative cases, weak D was detected in 1 case (2.1%), partial D in 13 cases (27.7%), and D-elution in 33 cases (70.2%). The detection rates of RhD negativity differed significantly between the serological and molecular methods (P<0.05). CONCLUSION: Serological test is associated with a high false negative rate in detecting RhD blood group, and the use of the molecular approach has important clinical significance in accurate RhD genotyping for patients waiting for renal transplantation.

[ROC curve-based evaluation of platelet parameters for predicting delayed renal graft function].

OBJECTIVE: To investigate the value of evaluating 5 platelet parameters in predicting delayed graft function (DGF) in patients following kidney transplantation. METHODS: We retrospectively analyzed the pre- and postoperative (within 2 months) data of 330 renal transplant recipients. The cases with DGF and those without were analyzed to assess the association between relationship between DGF following transplantation and the variations of blood platelet parameters including platelet count (PLT), large platelet ratio (P-LCR), mean platelet volume (MPV), platelet volume distribution width (PDW) and platelet hematocrit (PCT). RESULTS: The DGF and non-DGF cases were comparable for the platelet parameters before the operation. On postoperative day 7 when the diagnosis of DGF was made, PLT (P<0.05) and PCT (P<0.02) were significantly lower while MPV (P<0.01), PDW (P=0.036) and P-LCR (P=0.01) significantly higher in DGF group than in non-DGF group. The AUCs of P-LCR (0.611±0.047), PDW (0.603±0.048) and MPV (0.762±0.037) were significantly higher than the reference area (P<0.05) with cut-off values of 34.80%, 12.95fl and 11.55fl, respectively. MPV showed a high sensitivity, specificity and Youden index for predicting DFG; PDW and P-LCR had a high sensitivity but a low specificity for predicting DFG with a modest diagnostic value. PLT and PCT, with AUCs of were 0.37 and 0.38, respectively, did not have a predictive value for DGF. CONCLUSIONS: Significant variations in platelet parameters occur in the event of DGF in renal transplant recipients, and monitoring the postoperative changes in MPV, PDW, and P-LCR can help in early diagnosis and treatment of DGF. MPV has a moderate value (0.7-0.9) in predicting DGF, and a MPV>11.55 fl suggests the risk of DGF.

[Diagnostic value of dual-head 18F-FDG imaging in metastatic lesion with unknown primary tumour].

OBJECTIVE: To investigate the diagnostic value of dual-head (18)F-fluorodeoxyglucose ((18)F-FDG) imaging in metastatic lesion with unknown primary tumour (UPT). METHODS: Seventy patients with UPT underwent dual-head (18)F-FDG imaging after iv (18)F-FDG 1.85 MBq/kg. The primary tumour was diagnosed according to the FDG uptake and T/N value. RESULTS: Of the 70 patients, the primary tumour was identified by positive FDG imaging and finally confirmed pathologically in 58 patients (82.9%), and 12 patients had a negative FDG imaging (17.1%). Forty-two of the 58 positive patients were found to have lung cancer (72.4%). Among the 12 negative patients, their primary tumour was then identified by other diagnostic procedures in 5 patients (41.7%), in 1 patient, the primary site was detected during follow-up, however, the primary tumour was never detected in the rest 6 patients. CONCLUSION: Dual-probe (18)F-FDG imaging is a simple, quick, non-invasive and sensitive technique with an accuracy over 80% in the diagnosis of unknown primary tumour. The lung is found to be the most frequent primary site. Dual-probe (18)F-FDG imaging can be recommended as the first diagnostic choice for UPT.

Feasibility of single-beat full-volume capture real-time three-dimensional echocardiography for quantification of right ventricular volume: validation by cardiac magnetic resonance imaging.

BACKGROUND: The lack of an accurate noninvasive method for assessing right ventricular (RV) volume and function has been a major deficiency of two-dimensional (2D) echocardiography. The aim of our study was to test the feasibility of single-beat full-volume capture with real-time three-dimensional echo (3DE) imaging system for the evaluation of RV volumes and function validated by cardiac magnetic resonance imaging (CMRI). METHODS: Sixty-one subjects (16 normal subjects, 20 patients with hypertension, 16 patients with pulmonary heart disease and 9 patients with coronary heart disease) were studied. RV volume and function assessments using 3DE were compared with manual tracing with CMRI as the reference method. RESULTS: Fifty-nine of 61 patients (96.7%; 36 male, mean age, 62 ± 15 years) had adequate three-dimensional echocardiographic data sets for analysis. The mean RV end diastolic volume (EDV) was 105 ± 38 ml, end-systolic volume (ESV) was 60 ± 30 and RV ejection fraction (EF) was 44 ± 11% by CMRI; and EDV 103 ± 38 ml, ESV 60 ± 28 ml and RV EF 41 ± 13% by 3DE. The correlations and agreements between measurements estimated by two methods were acceptable. CONCLUSION: RV volumes and function can be analyzed with 3DE software in most of subjects with or without heart diseases, which is able to be estimated with single-beat full-volume capture with real-time 3DE compared with CMRI.

[Application of 99mTc-DTPA in evaluation of blood-brain barrier permeability in patients receiving whole brain irradiation].

OBJECTIVE: To study the pattern of blood-brain barrier (BBB) permeability changes during whole brain radiotherapy (WBRT) for metastatic brain tumor. METHODS: Twenty patients with metastatic brain tumors receiving WBRT by 6 MV X-ray underwent (99)mTc-DTPA brain SPECT before and during WBRT (20, 40 Gy) and at 2 weeks after the end of irradiation. A frame of transverse (99)mTc-DTPA brain SPECT image that best displayed the brain metastasis was chosen, and the regions of interest (ROI) were defined in the tumor foci (T), the contralateral normal brain tissue (N) and the background outside the soft tissues around the cranium (B). The radioactive counts of every ROI were measured and the ratios of the total counts (T/B and N/B) before and during WBRT (20 Gy, 40 Gy) and at 2 weeks after the irradiation were calculated. RESULTS: The average T/B and N/B in the 20 patients with 30 brain metastases was 142.2-/+51.1 and 82.6-/+42.3 before WBRT, 260.3-/+121.5 and 150.7-/+72.5 during 20 Gy WBRT, 251.6-/+118.3 and 161.8-/+68.4 during 40 Gy WBRT, and 250.3-/+117.2 and 158.6-/+73.5 at 2 weeks after the irradiation, respectively. The measurements during WBRT (20 and 40 Gy) and at 2 weeks after the irradiation group underwent no significant variations (P>0.05), but showed significant differences from those before WBRT (P<0.05). CONCLUSIONS: Irradiation causes direct damage of the BBB function, and the permeability of the BBB increases significantly during and within 2 weeks following 20 and 40 Gy WBRT, which provides the optimal time window for interventions with chemotherapy.