Yanji Luo

pH-Sensitive Nanomicelles for Controlled and Efficient Drug Delivery to Human Colorectal Carcinoma LoVo Cells

Background The triblock copolymers PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) of polyethylene glycol (PEG), poly(N-(N’,N’-diisopropylaminoethyl) aspartamide) (P(Asp-DIP)), and poly (lysine-cholic acid) (P(Lys-Ca)) were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES), and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. Methodology/Principal Findings The anticancer drug Paclitaxel (PTX) and hydrophilic superparamagnetic iron oxide (SPIO) were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC) LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. Conclusions/Significance These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.

Noninvasive fat quantification of the liver and pancreas may provide potential biomarkers of impaired glucose tolerance and type 2 diabetes.

AbstractThe aim of the study is to investigate if the fat content of the liver and pancreas may indicate impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). A total of 83 subjects (34 men; aged 46.5 ± 13.5 years) were characterized as T2DM, IGT, or normal glucose tolerant (NGT). NGT individuals were stratified as <40 or ≥40 years. Standard laboratory tests were conducted for insulin resistance and &bgr;-cell dysfunction. The magnetic resonance imaging Dixon technique was used to determine fat distribution in the liver and pancreas. Correlations among liver and pancreatic fat volume fractions (LFVFs and PFVFs, respectively) and laboratory parameters were analyzed. Among the groups, fat distribution was consistent throughout sections of the liver and pancreas, and LFVFs closely correlated with PFVFs. LFVFs correlated more closely than PFVFs with insulin resistance and &bgr;-cell function. Both the LFVFs and PFVFs were the highest in the T2DM patients, less in the IGT, and least in the NGT; all differences were significant. The PFVFs of the NGT subjects ≥40 years were significantly higher than that of those <40 years. The fat content of the liver and pancreas, particularly the liver, may be a biomarker for IGT and T2DM.

MR Quantification of Total Liver Fat in Patients with Impaired Glucose Tolerance and Healthy Subjects

Objective To explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects. Materials and Methods 56 subjects were enrolled and each of them underwent upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated. Results For all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group. Conclusions People with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus.

Functional magnetic resonance cholangiography enhanced with Gd-EOB-DTPA: Effect of liver function on biliary system visualization

To evaluate effect of liver function on biliary system visualization using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance cholangiography (CE‐MRC).

CT Evaluation of Gastroenteric Neuroendocrine Tumors: Relationship Between CT Features and the Pathologic Classification

OBJECTIVE The objective of our study was to compare the CT features of gastroenteric neuroendocrine neoplasms (GE-NENs) with the pathologic classification and to analyze the correlation between the CT features and classification of GE-NENs. MATERIALS AND METHODS Fifty-six cases of pathologically and immunohisto-chemically proven GE-NENs, including 25 cases of neuroendocrine tumors (NETs) (i.e., G1 and G2 tumors) and 31 cases of neuroendocrine carcinomas (NECs) (i.e., G3 tumors and mixed adenoneuroendocrine carcinomas) were studied. We analyzed various CT features of the primary tumor, nodal status, and metastasis and compared these features with pathologic grading. RESULTS The CT features that favor NEC over NET include larger tumor size (> 4.0 cm), transmural invasion, circumscribed tumor with both intra- and extraluminal involvement, circumferential growth, areas of cystic change or necrosis, ulceration, mesenteric fat infiltration, and lymphadenopathy, with p values of 0.044, 0.002, 0.024, 0.008, 0.002, 0.007, 0.002, and < 0.001, respectively. The CT features that do not distinguish between the two types of GE-NENs include tumor boundary, growth pattern, degree of enhancement, adjacent organ invasion, distant organ metastasis, and peritoneal seeding, with p values of 0.277, 0.153, 0.672, 1.000, 0.159, and 0.877, respectively. CONCLUSION CT can be useful in the classification of GE-NENs.

Diagnostic and post-treatment CT appearance of biopsy proven mixed Cryptococcus and Candida cholangitis.

Cryptococcus neoformans and Candida are common opportunistic pathogens of human. There is very limited literature on Cryptococcus neoformans cholangitis or Candida cholangitis in immunocompetent patient while mixed Cryptococcus neoformans and Candida cholangitis has not been reported in the literature ever before. We hereby report the imaging findings of a case of mixed Cryptococcus neoformans and Candida cholangitis in an immunocompetent boy. The CT features included nodules in the cystic duct and common bile duct, dilatation of the intra- and extrahepatic bile ducts with mural thickening, irregular hypodense mass-like lesion extending along the bile ducts from the liver hilum to the periphery which was confirmed by the presence of enlarged and confluent lymph nodes. CT characteristics can contribute to timely diagnosis and treatment of this disease.

CT evaluation of response in advanced gastroenteropancreatic neuroendocrine tumors treated with long-acting-repeatable octreotide: what is the optimal size variation threshold?

ObjectiveTo identify a reliable early indicator of deriving progression-free survival (PFS) benefit in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with octreotide long-acting repeatable (LAR).MethodsWe investigated the images of 50 patients with well-differentiated advanced GEP-NETs treated with LAR octreotide and underwent baseline and follow-up thoracic, abdominal, and pelvic computed tomography. Receiver-operating characteristic (ROC) analysis and the Kaplan-Meier method were used to identify the optimal threshold to distinguish between those with and without significant improvement of PFS.ResultsThe optimal threshold for determining a response to octreotide LAR was -10% ΔSLD, with a sensitivity and specificity of 85.7% and 80%, respectively. At this threshold, 19 patients were responders and 31 were non-responders; the median PFS was 20.2 and 7.6 months in responders and non-responders (hazard ratio, 2.66; 95% confidence interval, 1.32–5.36).ConclusionA 10% shrinkage in tumor size is an optimal early predictor of response to octreotide LAR in advanced GEP-NETs.Key points• Octreotide LAR can significantly prolong PFS among patients with well-differentiated advanced GEP-NETs.• No optimal tumor size-based response criteria are reported in GEP-NETs with octreotide.• Ten percent tumor shrinkage is a reliable indicator of the response to octreotide for advanced GEP-NETs.

Combined Volumetric and Density Analyses of Contrast-Enhanced CT Imaging to Assess Drug Therapy Response in Gastroenteropancreatic Neuroendocrine Diffuse Liver Metastasis

Objective We propose a computer-aided method to assess response to drug treatment, using CT imaging-based volumetric and density measures in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and diffuse liver metastases. Methods Twenty-five patients with GEP-NETs with diffuse liver metastases were enrolled. Pre- and posttreatment CT examinations were retrospectively analyzed. Total tumor volume (volume) and mean volumetric tumor density (density) were calculated based on tumor segmentation on CT images. The maximum axial diameter (tumor size) for each target tumor was measured on pre- and posttreatment CT images according to Response Evaluation Criteria In Solid Tumors (RECIST). Progression-free survival (PFS) for each patient was measured and recorded. Results Correlation analysis showed inverse correlation between change of volume and density (Δ(V + D)), change of volume (ΔV), and change of tumor size (ΔS) with PFS (r = −0.653, P=0.001; r = −0.617, P=0.003; r = −0.548, P=0.01, respectively). There was no linear correlation between ΔD and PFS (r = −0.226, P=0.325). Conclusion The changes of volume and density derived from CT images of all lesions showed a good correlation with PFS and may help assess treatment response.

Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation

Objective To investigate the imaging features observed in preoperative Gd-EOB-DTPA-dynamic enhanced MRI and correlated with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods 66 HCCs in 60 patients with preoperative Gd-EOB-DTPA-dynamic enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, peritumor enhancement during mid-arterial phase, peritumor hypointensity during hepatobiliary phase, signal intensity ratio on DWI and apparent diffusion coefficients (ADC), T1 relaxation times, and the reduction rate between pre- and postcontrast enhancement images were assessed. Correlation between these features and histopathological presence of MVI was analyzed to establish a prediction model. Results Histopathology confirmed that MVI were observed in 17 of 66 HCCs. Univariate analysis showed tumor size (p = 0.003), margin (p = 0.013), peritumor enhancement (p = 0.001), and hypointensity during hepatobiliary phase (p = 0.004) were associated with MVI. A multiple logistic regression model was established, which showed tumor size, margin, and peritumor enhancement were combined predictors for the presence of MVI (α = 0.1). R2 of this prediction model was 0.353, and the sensitivity and specificity were 52.9% and 93.0%, respectively. Conclusion Large tumor size, irregular tumor margin, and peritumor enhancement in preoperative Gd-EOB-DTPA-dynamic enhanced MRI can predict the presence of MVI in HCC.

Quantitative evaluation of Gd-EOB-DTPA uptake in focal liver lesions by using T1 mapping: differences between hepatocellular carcinoma, hepatic focal nodular hyperplasia and cavernous hemangioma

OBJECTIVES To investigate the difference of T1 relaxation time on Gd-EOB-DTPA-enhanced MRI in hepatocellular carcinoma (HCC), hepatic focal nodular hyperplasia (FNH) and cavernous hemangioma of liver (CHL), and to quantitatively evaluate the uptake of Gd-EOB-DTPA in these three focal liver lesions (FLLs). RESULTS The T1P of CHL was significantly higher than those of HCC and FNH (P < 0.05). Reduction of T1 relaxation time on hepatobiliary phase could be observed in all three types of lesions. There were significant differences of T1P, T1E, T1D and T1D% between FNH, CHL and HCC (P < 0.001). Spearman correlation analysis revealed that T1D% was the best indicator for diagnostic differentiation, with a correlation coefficient of 0.702. Discriminant analysis using three variables (T1P, T1E, and T1D%) showed that the classification accuracy was 88.2%. MATERIALS AND METHODS 74 patients diagnosed with focal liver lesions underwent Gd-EOB-DTPA-enhanced MRI including T1 mapping were enrolled, consisting of 51 HCCs, 10 FNHs, and 13 CHLs. T1 relaxation times of these lesions were measured on pre-contrast (T1P) and on hepatobiliary phase images at 20 minute after contrast (T1E). The reduction of T1 relaxation time on hepatobiliary (T1D) and the percentage reduction (T1D%) was calculated. The differences of T1P, T1E, T1D and T1D% in these FLLs were analyzed. The usefulness of these parameters for classification of FLLs was evaluated. CONCLUSIONS Uptake of Gd-EOB-DTPA is different between in HCC, FNH and CHL. These three lesions can be distinguished using T1 mapping.Objectives To investigate the difference of T1 relaxation time on Gd-EOB-DTPA-enhanced MRI in hepatocellular carcinoma (HCC), hepatic focal nodular hyperplasia (FNH) and cavernous hemangioma of liver (CHL), and to quantitatively evaluate the uptake of Gd-EOB-DTPA in these three focal liver lesions (FLLs). Results The T1P of CHL was significantly higher than those of HCC and FNH (P < 0.05). Reduction of T1 relaxation time on hepatobiliary phase could be observed in all three types of lesions. There were significant differences of T1P, T1E, T1D and T1D% between FNH, CHL and HCC (P < 0.001). Spearman correlation analysis revealed that T1D% was the best indicator for diagnostic differentiation, with a correlation coefficient of 0.702. Discriminant analysis using three variables (T1P, T1E, and T1D%) showed that the classification accuracy was 88.2%. Materials and Methods 74 patients diagnosed with focal liver lesions underwent Gd-EOB-DTPA-enhanced MRI including T1 mapping were enrolled, consisting of 51 HCCs, 10 FNHs, and 13 CHLs. T1 relaxation times of these lesions were measured on pre-contrast (T1P) and on hepatobiliary phase images at 20 minute after contrast (T1E). The reduction of T1 relaxation time on hepatobiliary (T1D) and the percentage reduction (T1D%) was calculated. The differences of T1P, T1E, T1D and T1D% in these FLLs were analyzed. The usefulness of these parameters for classification of FLLs was evaluated. Conclusions Uptake of Gd-EOB-DTPA is different between in HCC, FNH and CHL. These three lesions can be distinguished using T1 mapping.