The invasion status of lymphovascular space and lymph nodes in cervical cancer assessed by mono-exponential and bi-exponential DWI-related parameters.

AIM: To investigate whether mono-exponential and bi-exponential diffusion-weighted imaging (DWI)-related parameters of the primary tumour can evaluate the status of lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) in patients with cervical carcinoma preoperatively. MATERIALS AND METHODS: Eighty patients with cervical carcinoma were enrolled, who underwent preoperative multi b-value DWI and radical hysterectomy. They were classified into LVSI(+) versus LVSI(-) and LNM(+) versus LNM(-) according to postoperative pathology. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) were calculated from the whole tumour (_whole) and tumour margin (_margin). All parameters were compared between LVSI(+) and LVSI(-) and between LNM(+) and LNM(-). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic performance of these parameters. RESULTS: f_margin and D∗_whole showed significant differences in differentiating LVSI(+) from LVSI(-) tumours (p=0.002, 0.008, respectively), while LNM(+) tumours presented with significantly higher ADC_margin than that of LNM(-) tumours (p=0.009). The other parameters were not independent related factors with the status of LVSI or LNM according to logistic regression analysis (p>0.05). The area under the ROC curve of f_margin combined with D∗_whole in discriminating LVSI(+) from LVSI(-) was 0.826 (95% confidence interval [CI]: 0.691-0.961), while ADC_margin in differentiating LNM(+) from LNM(-) was 0.788 (95% CI: 0.648-0.928). CONCLUSIONS: The parameters generated from mono-exponential and bi-exponential DWI of the primary cervical carcinoma could help discriminate its status regarding LVSI (f_margin and D∗_whole) and LNM (ADC_margin).

Apparent diffusion coefficient measurement in luminal breast cancer: will tumour shrinkage patterns affect its efficacy of evaluating the pathological response?

AIM: To determine which region of interest (ROI) placement method of apparent diffusion coefficient (ADC) measurement has the best performance for predicting pathological complete response (PCR) at two cycles of neoadjuvant chemotherapy (NAC) according to different tumour shrinkage patterns of luminal breast cancer and to assess the evaluative accuracy of ADC value combined with other clinicopathological indicators. MATERIALS AND METHODS: Sixty-one patients who underwent NAC for histopathologically confirmed breast cancer were enrolled in this retrospective study. The ADC values of different shrinkage patterns (concentric shrinkage, nest or dendritic shrinkage, and mixed shrinkage) for tumours shown by diffusion-weighted imaging (DWI) were measured independently using three ROI placement methods (single-round, three-round, and freehand). Intraclass correlation coefficients (ICCs) were used to assess the interobserver variability in the ADC values. Multivariate logistic regression analysis was performed to identify the independent predictors of PCR. RESULTS: The best placement method found was single-round ROI in all the patients (AUC=0.863). When analysed separately, the effectiveness results differed: the single-round method was optimal for concentrically shrinking tumours (AUC=0.970); the freehand method was optimal for nest or dendritically shrinking tumours (AUC=0.714); and the three-round method was optimal for mixed shrinking tumours (AUC=0.975). Multivariate logistic analysis showed that oestrogen receptor (ER), ΔADC% and tumour diameter reduction (ΔD%) were independent factors in evaluating the PCR. CONCLUSION: The methods for measuring ADC values vary across different shrinkage patterns of luminal tumours. ΔADC%, ER and ΔD% were independent factors for evaluating the PCR.

Correlation between dual-energy spectral CT imaging parameters and pathological grades of non-small cell lung cancer.

AIM: To investigate the correlation between pathological grades of non-small cell lung cancers (NSCLCs) and quantitative parameters generated in dual-energy spectral computed tomography (CT). MATERIALS AND METHODS: Fifty-three patients with NSCLCs who underwent preoperative dual-energy spectral CT imaging and surgical resection were evaluated retrospectively. These patients were divided into a low-grade group and a high-grade group based on their histopathological differentiation. In the arterial phase (AP) and venous phase (VP), iodine concentration (IC) in cancers was measured in iodine-based material decomposition images, and normalised to the IC in the aorta to calculate the normalised iodine concentration (NIC), the spectral CT curve was generated from the monochromatic images to calculate the slope of the spectral curve (λHU). Differences in quantitative parameters (NIC and λHU) were compared using the two-sample t-test. The correlations between spectral CT parameters and tumour grades were evaluated using the Spearman rank correlation analysis. Receiver operating characteristic (ROC) curves were generated to calculate their diagnostic efficacies. RESULTS: The NIC and λHU in the low-grade NSCLC group were significantly higher than those in the high-grade NSCLC group both in AP and VP (all p<0.001). There was a significant negative correlation between spectral CT parameters and pathological grades by the Spearman rank correlation (all p<0.001). ROC analysis indicated that λHU in VP provided the best diagnostic performance in distinguishing high-grade cancers from low-grade cancers (area under the ROC curve [AUC], 0.914; sensitivity, 85.7%; specificity, 84.4%). CONCLUSION: The quantitative parameters in dual-energy spectral CT imaging provide useful information to differentiate the pathological grades of NSCLCs.

Utility of apparent diffusion coefficient as an imaging biomarker for assessing the proliferative potential of invasive ductal breast cancer.

AIM: To determine the clinical utility of apparent diffusion coefficient (ADC) metrics for the non-invasive assessment of tumour proliferation indicated by Ki-67 labelling index (LI) in invasive ductal breast cancer. MATERIALS AND METHODS: Eighty patients with 80 histopathologically proven invasive ductal breast cancers underwent diffusion-weighted imaging with b-values of 0 and 800 s/mm2 at a 3-T system. ADC metrics including ADCmean, ADCmedian, ADCmin, ADCmax, and ΔADC (ADCmax-ADCmin) were recorded from the entire tumour volume on ADC maps, and correlated with the Ki-67 LI. Ki-67 staining of ≥14% was considered to indicate high proliferation and <14% was considered to indicate low proliferation. RESULTS: ADCmin, ADCmax, and ΔADC showed significant correlations with the Ki-67 LI (for all tumours, r=-0.311, 0.436, and 0.551, respectively; for luminal/human epidermal growth factor receptor 2 (HER2)-negative group, r=-0.437, 0.512, and 0.639, respectively; all p<0.01), whereas ADCmean and ADCmedian showed no significant correlation (both p>0.05). Receiver operating characteristic (ROC) curve analysis for the differentiation of high- from low-proliferation groups showed that ΔADC yielded the highest area under the ROC curve for the whole tumour population (0.825; 95% confidence interval [CI]: 0.724, 0.901), as well as for the luminal/HER2-negative group (0.844; 95% CI: 0.692, 0.940). CONCLUSION: ΔADC may serve as a promising imaging biomarker for the prediction of Ki-67 proliferation status in invasive ductal breast cancer.

[Study on apoptosis, cytochrome C and mitochondrial membrane potential in CD71(+) nucleated erythrocytes in patients with chronic mountain sickness].

Objective: To investigate the changes of CD71(+) nucleated erythrocyte apoptosis, cytochrome C (Cyt-C) and mitochondrial membrane potential (MMP) in bone marrow of chronic mountain sickness (CMS). Methods: 14 patients with CMS and 15 patients with simple old fracture were divided into CMS group and control group, respectively.Bone marrow mononuclear cells (BMMNC) were separated, marked with CD71 monoclonal antibody and stained with Annexin V-FITC/PI.Then the apoptotic index of CD71(+) nucleated erythrocytes was determined by flow cytometry.CD71(+) nucleated erythrocytes were sorted out by magnetic column separation, and Cyt-C mRNA was detected by RT-qPCR, MMP was detected by JC-1 staining flow cytometry. Results: The apoptotic index of CD71(+) nucleated erythrocytes was (1.9±1.4)% in the CMS group, and was (3.2±1.5)% in the control group, with significant difference between the two groups (P<0.05). The expression of Cyt-C mRNA was (0.72±0.14) in the CMS group, and was (1.00±0.15) in the control group, with significant difference between the two groups (P<0.01). The MMP was (5.0±2.2) in the CMS group, and was (3.3±0.9) in the control group, with significant difference between the two groups (P<0.05). The apoptotic index of CD71(+) nucleated erythrocytes was negatively correlated with hemoglobin in CMS group (r=-0.569, P=0.034). But there was no significant correlation among apoptosis index, MMP and Cyt-C mRNA. Conclusions: The apoptosis index of CD71(+) nucleated erythrocytes decreased in CMS patients, which was negatively correlated with the level of hemoglobin, indicating that the decline of apoptosis index of CD71(+) nucleated erythrocytes may be related to the accumulation of red blood cells in CMS.The MMP increased and Cyt-C mRNA expression decreased in CD71(+) nucleated erythrocytes of CMS patients, which suggests that the change of mitochondrial pathway of apoptosis might be involved in the down-regulation of CD71(+) nucleated erythrocytes apoptosis in CMS patients.But there was no significant correlation among CD71(+) nucleated erythrocyte apoptosis index, MMP and Cyt-C mRNA levels, which indicates that the mechanism of CD71(+) nucleated erythrocytes apoptosis is complex in CMS.

T2* relaxation time in the detection and assessment of aggressiveness of peripheral zone cancer in comparison with diffusion-weighted imaging.

AIM: To investigate the feasibility of T2* relaxation time for distinguishing benign from malignant regions, as well as tumour aggressiveness, within the peripheral zone (PZ) of the prostate in comparison with diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Fifty-eight patients with prostate cancer underwent 3 T magnetic resonance imaging using multi-echo T2* and DWI (maximum b-value, 2000 s/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC) and T2* values. Two radiologists reviewed these maps and measured ADC and T2* values in sextants positive for cancer at biopsy. Data were analysed using mixed-model analysis of variance and receiver operating characteristic curves. RESULTS: Ninety-three sextants exhibited a Gleason score of 6; 59 exhibited a Gleason score of 7 or 8. The T2* value was significantly lower in cancerous sextants than in the benign PZ (48.69+0.60 versus 74.14+0.56, p<0.001), as well as in cancerous sextants with higher rather than lower Gleason scores (43.18+0.89 versus 52.18+0.55, p<0.001). The T2* value showed significantly greater specificity for differentiating cancerous sextants from benign PZ than ADC (93.1% versus 89.7%, p<0.001), with equal sensitivity (82.8% versus 81%, p>0.05). The T2* value exhibited significantly greater sensitivity and specificity for differentiating sextants with low- and high-grade cancer than ADC (79.6% versus 64.5% and 81.4% versus 72.9%, respectively; p<0.05). The T2* value had a significantly greater area under the receiver operating characteristic curve for differentiating sextants with low- and high-grade cancer than ADC (0.77 versus 0.71, p<0.01). CONCLUSION: Preliminary findings suggest that the T2* relaxation time has increased diagnostic value compared with DWI in prostate PZ cancer assessment.

Apparent diffusion coefficient measurements of bilateral kidneys at 3 T MRI: effects of age, gender, and laterality in healthy adults.

AIM: To investigate the effects of age and gender on apparent diffusion coefficient (ADC) measurements of bilateral kidneys at 3 T MRI, and compare the ADC values of left and right kidneys. MATERIALS AND METHODS: In all, 137 healthy participants (mean age 42.8 ± 14.7 years; age range 16-75 years) comprising 68 male and 69 female participants were enrolled. Three Tesla echo-planar diffusion-weighted imaging (DWI) of bilateral kidneys was performed and ADC values were measured in the cortex, medulla, and whole parenchyma. Pearson correlation analysis and linear regression were performed to determine the associations between the ADC values in each region and age. Effects of age and gender on ADC values were analysed using two-factor analysis of variance (ANOVA). The paired-samples t-test was established to compare the ADC values between left and right kidneys. RESULTS: ADC values were significantly higher in the young group (≤50 years) than in the old group (>50 years), and correlated inversely with the age in all regions. Male participants had higher ADC values than female participants in all regions except left medulla. Two-factor ANOVA of age × gender showed no significant interactions between the variables age and gender were found. No significant differences in ADC values between left and right kidneys were observed. CONCLUSION: Renal ADC values are age- and gender-dependent, and show no significant difference between left and right kidneys. Age- and gender-related effects should be taken into consideration in future renal DWI studies when using normal ADC values from health controls.

Knockdown of long non-coding RNA VIM-AS1 inhibits glioma cell proliferation and migration, and increases the cell apoptosis via modulation of WEE1 targeted by miR-105-5p.

OBJECTIVE: Glioma including glioblastoma is the main type of primary brain tumors worldwide. LncRNAs have participated in glioma formation. This study aims to investigate the underlying mechanism for VIM-AS1/miR-105-5p/WEE1 signaling in glioma. PATIENTS AND METHODS: The clinical tumors and adjacent tissues were collected from 24 patients with glioma in the Shang Luo Central Hospital. Then, the clinical samples were subjected to hematoxylin-eosin staining (H&E). VIM-AS1, miR-105-5p, and WEE1 levels were measured using real-time PCR. The protein levels of WEE1, Cyclin A1, PCNA, N-cadherin, Vimentin, and Bcl-2, E-cadherin, and Bax were analyzed using Western blot. The overall survival of glioma patients was evaluated using the Kaplan-Meier analysis. The interaction between VIM-AS1 and miR-105-5p was determined using RIP assay and Dual-Luciferase reporter assay, and the binding between miR-105-5p and WEE1 was also detected by Dual-Luciferase reporter assay. Cell proliferation, colony formation, cell cycle, apoptosis, and migration were confirmed using CCK-8, colony formation assay, flow cytometry, and transwell assay, respectively. RESULTS: VIM-AS1 was elevated in cancer tissues, and high level of VIM-AS1 was positively correlated with poor overall survival. Then, VIM-AS1 could bind to and downregulate miR-105-5p. Furthermore, the knockdown of VIM-AS1 significantly suppressed tumor growth in vivo. The knockdown of VIM-AS1/overexpression of miR-105-5p inhibited glioma cell growth, colony formation, and migration, and enhanced the cell apoptosis by inhibiting expression of Cyclin A1, PCNA, Vimentin, N-cadherin, and Bcl-2, and by increasing the expression of Bax and E-cadherin. Interestingly, the overexpression of VIM-AS1 reversed the tumor-suppressing role of miR-105-5p in glioma cells. Besides, the expression of WEE1 was synergistically regulated by VIM-AS1 and miR-105-5p. Consequently, VIM-AS1 promoted glioma progression via upregulating WEE1 or downregulating miR-105-5p. CONCLUSIONS: VIM-AS1/miR-105-5p/WEE1 signaling may be a promising target for glioma treatment.

[Efficacy and safety analysis of different dose idarubicin plus cytarabine regimen as induction chemotherapy for young patients with de-novo acute myeloid leukemia].

OBJECTIVE: To compare the efficacy, safety and long-term prognosis between different dose idarubicin (IDA) combined with cytarabine (IA) as induction chemotherapy in newly diagnosed young patients of acute myeloid leukemia (AML). METHODS: A total of 149 newly diagnosed young AML patients (APL excluded) between January 2009 to July 2014 was enrolled. According to the dose of IDA, the patients were divided into three groups, high standard- dose IA group (10- 12 mg · m (- 2) · d(- 1)), low standard-dose IA group (8-9 mg·m(-2)·d(-1)) and low-dose IA group (<8 mg·m(-2)·d(-1)). The efficacy, adverse effects and long- term prognosis among the three groups were compared. RESULTS: Of them, 34 patients were in high standard-dose IA group, 53 in low standard-dose IA group and 62 in low-dose IA group. After one cycle of induction chemotherapy, the complete remission (CR) rate was 79.4%, 75.5% and 46.8%, the overall response (OR) rate was 97.1%, 94.3% and 64.5%, and the overall CR rate was 85.3%, 81.1% and 54.8%, respectively. Compared with low- dose IA group, high standard- dose IA group and low standard-dose IA group had significantly better result (P<0.05), but there was no significant difference between the latter two groups (P>0.05). Multivariate analysis also showed that standard-dose IA was favorable factor for induction chemotherapy (P<0.05). The adverse effects were similar in the three group, other than the lowest count of WBC (P=0.002). Low standard-dose IA can improve the OS compared to the low-dose IA (P=0.003), but EFS, RFS was similar in the three groups. CONCLUSIONS: For the newly diagnosed young(<55) AML patients, the standard-dose IA has better CR rate. The adverse effects were similar in the three groups. High-dose IA may improve the OS compared to the low-dose IA.

The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression.

The human dopamine transporter (DAT1) gene contains a variable number of tandem repeats (VNTR) in its 3'-untranslated region (UTR). The linkage and association between the VNTR polymorphism of DAT1 and various neuropsychiatric disorders have been reported. We have determined the genomic structure of DAT1 genes containing 7-, 9-, 10-, and 11-repeat alleles and examined the effect of VNTR polymorphism in the 3'-UTR region of DAT1 on gene expression using the luciferase reporter system in COS-7 cells. Luciferase expression was significantly higher when the 3'-UTR of the DAT1 gene contained the 10-repeat allele than when it contained the 7- or 9-repeat alleles. This suggests that VNTR polymorphism affects the expression of the dopamine transporter.

Association and dissociation of the calcium-binding domains of calpain by Ca2+.

The calmodulin-like domain of calpain is important for the association of the calpain large and small subunits. We expressed the calmodulin-like domains of the large subunits of rabbit mu- and m-calpains and their small subunits in E. coli and purified them to homogeneity. Unlike the full-length subunits, the calmodulin-like domains are soluble in buffer containing Ca2+. We performed gel filtration chromatography of the purified proteins and found that all three calmodulin-like domains exist as homodimers in the absence of Ca2+ and dissociate into monomers upon the addition of Ca2+.