Diagnostic Accuracy and Interobserver Agreement of PI-RADS Version 2 and Version 2.1 for the Detection of Transition Zone Prostate Cancers.

BACKGROUND. PI-RADS version 2.1 (v2.1) introduced a number of key changes to the assessment of transition zone (TZ) lesions. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement and diagnostic accuracy for detecting TZ prostate cancer (PCa) and clinically significant PCa (csPCa) by use of PI-RADS v2 and PI-RADS v2.1 among radiologists with different levels of experience. METHODS. This retrospective study included 355 biopsy-naïve patients who from January 2017 to March 2020 underwent prostate MRI that showed a TZ lesion and underwent subsequent biopsy. PCa was diagnosed in 93 patients (International Society of Urological Pathology [ISUP] grade group 1, n = 34; ISUP grade group ≥ 2, n = 59) and non-cancerous lesions in 262 patients. Five radiologists with varying experience in prostate MRI scored lesions using PI-RADS v2 and PI-RADS v2.1 in sessions separated by at least 4 weeks. Interobserver agreement was evaluated with kappa and Kendall W statistics. ROC curve analysis was used to evaluate performance in detection of TZ PCa and csPCa. RESULTS. Interobserver agreement among all readers was higher for PI-RADS v2.1 than for PI-RADS v2 (mean weighted κ = 0.700 vs 0.622; Kendall W = 0.805 vs 0.728; p = .03). The pooled AUC values for detecting TZ PCa and csPCa were higher among all readers using PI-RADS v2.1 (0.866 vs 0.827 for TZ PCa; 0.929 vs 0.899 for TZ csPCa; p < .001). For detecting TZ PCa, the pooled sensitivity, specificity, and accuracy were 86.9%, 79.4%, and 75.4% among all readers for PI-RADS v2.1 compared with 79.4%, 71.8%, and 73.8% for PI-RADS v2. For detecting TZ csPCa, the pooled sensitivity, specificity, and accuracy were 84.8%, 90.9%, and 89.9% among all readers for PI-RADS v2.1 compared with 81.4%, 89.9%, and 88.5% for PI-RADS v2. Reader 1, who had the least experience, had the lowest sensitivity, specificity, and accuracy (78.0%, 89.2%, and 87.3%). Reader 5, who had the most experience, had the highest sensitivity, specificity, and accuracy (88.1%, 92.9%, and 92.1%) in detecting csPCa. CONCLUSION. PI-RADS v2.1 had better interobserver agreement and diagnostic accuracy than PI-RADS v2 for evaluating TZ lesions. Reader experience continues to affect the performance of prostate MRI interpretation with PI-RADS v2.1. CLINICAL IMPACT. PI-RADS v2.1 is more accurate and reproducible than PI-RADS v2 for the diagnosis of TZ PCa.

Differentiating Transition Zone Cancers From Benign Prostatic Hyperplasia by Histogram Analysis of Apparent Diffusion Coefficient Maps With Standard and Ultrahigh b-value Diffusion-weighted MR Imaging.

OBJECTIVE: To compare the diagnostic performance of standard and ultrahigh b-value Diffusion-weighted Imaging (DWI) using volumetric histogram analysis in differentiating transition zone (TZ) cancer from benign prostatic hyperplasia (BPH). METHODS: 57 TZ cancer and 61 BPH patients received standard (1000 s/mm) and ultrahigh b-value (2000 s/mm) DWI. The diagnostic ability of ADC histogram parameters derived from two DWI for differentiating TZ cancer from BPH was determined by receiver operating characteristic curve. RESULTS: Median, minimum, the 10th, 25th percentile ADC in both ADC1000 and ADC2000 and skewness in ADC2000 had significant differences between TZ cancer and BPH (for all, P < 0.05).The 10th percentile ADC showed highest area under the ROC curve (AUC) in both ADC1000 and ADC2000.The 10th percentile ADC of ADC2000 showed significantly higher AUC than did ADC1000 (P = 0.0385). CONCLUSIONS: The 10th percentile ADC obtained from ultrahigh b-value DWI performed better for differentiating TZ cancer from BPH.

Salivary gland function in nasopharyngeal carcinoma before and late after intensity-modulated radiotherapy evaluated by dynamic diffusion-weighted MR imaging with gustatory stimulation.

BACKGROUND: Xerostomia caused by radiation-induced salivary glands injury has a considerable impact on patients' quality of life. Nowadays, the existed different methods of evaluating xerostomia in clinical practice there are still some disadvantages and limitations. This study used diffusion-weighted magnetic resonance imaging (DW-MRI) with gustatory stimulation to assess salivary glands function after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: DW-MRI was performed in 30 NPC patients and swab method was used to calculate rest and stimulated salivary flow rates (SFR). DW sequence at rest and then repeated ten times during stimulation were obtained. Apparent diffusion coefficients (ADCs) maps of three glands were calculated. Patients before and after RT were recorded as xerostomia and non-xerostomia groups separately. Rest and stimulated ADCs, ADCs increase rates (IRs), time to maximum ADCs (Tmax), ADCs change rates (CRs), rest and stimulated SFR, SFR increase rates (IRs) and SFR change rates (CRs) before and after RT were assessed. RESULTS: The rest and stimulated ADCs of three glands after RT were higher than those before RT (p < 0.001). The rest and stimulated SFR of all salivary glands after RT were lower than those before RT (p < 0.001). A correlation existed between rest ADCs of submandibular glands and rest SFR of submandibular mixed with sublingual glands and full three glands before RT (p = 0.019, p = 0.009), stimulated ADCs and stimulated SFR in parotid glands before RT (p = 0.047). The rest ADCs of parotid glands after RT correlated to XQ scores (p = 0.037). CONCLUSIONS: The salivary glands' ADCs increased after RT both in rest and stimulated state due to the radiation injury and the ADCs correlated with SFR and XQ scores of evaluating the xerostomia in clinical practice.

[Values of magnetic resonance spectrum imaging in the diagnosis of hepatic fibrosis of rats].

OBJECTIVE: To explore the values of magnetic resonance spectrum (MRS) in early diagnosis, quantization analysis and staging of hepatic fibrosis. METHODS: A rat model of hepatic fibrosis was established by the method of carbon tetra carbon (CCl4). A total of 47 SD rats were divided into model (n = 40) and control (n = 7) groups. 1H-MRS was performed. The model rats of hepatic fibrosis were grouped according to their pathological stages. The ratio of peak height and peak area of metabolites and lipid (Cho/Lip, Glx/Lip, Lac/Lip and Cr/Lip) were calculated and compared respectively. RESULTS: The ratios of peak height of metabolites and lipid were as follows: ratio of Cho and Lip: significant differences existed between control and grades 3 and 4 model groups (P < 0.05); ratio of Glx and Lip: significant differences existed between control and grades 2, 3 and 4 model groups (P < 0.05); ratio of Cr and Lip: significant differences existed between control and grade 3 model groups (P < 0.05). The peak area ratio of main metabolites and lipid of liver were as follows: ratio of Cho and Lip: significant differences existed between control and grade 4 model groups (P < 0.05); ratio of Glx and Lip: significant differences existed between control and other groups (P < 0.05); ratio of Cr and Lip: significant differences existed between control and grade 4 model groups (P < 0.05); ratio of Lac and Lip: no significant differences existed between these groups (P > 0.05). CONCLUSION: The ratios of peak height and peak area of Cho/Lip, Glx/Lip and Cr/Lip are important for the staging of hepatic fibrosis.

[Injury repairing and magnetic resonance tracing of transplanted bone marrow stromal cells in rat liver with hepatic fibrosis].

OBJECTIVE: To explore the recurring patterns of migration and distribution of transplanted bone marrow stromal cells (BMSCs) in rat model with hepatic fibrosis and the feasibility of magnetic resonance (MR) tracing. METHODS: BMSCs labeled with 5-bromodeoxyuridine (Brdu) and super para-magnetic iron oxide (SPIO) were transplanted into rat model with hepatic fibrosis via portal vein. MR scan was performed at Hour 2, Day 3, Day 7 and Week 2 post-transplantation to analyze the hepatic features of MR signal intensity and pathohistology of BMSCs. RESULTS: Multiple hypo-intense lesions appeared in hepatic hilar region at Hour 2 and became smaller with the elapsing time. Hemosiderin and Brdu immunohistochemical stains showed that positive cells were found in portal vein of hepatic porta at Hour 2, small branches of portal vein, sinus hepaticus and around central veins of hepatic lobules at Day 3 and liver parenchyma (esp. in area of lesion) at Day 7 and Week 2. Some of transplanted BMSCs were tightly connected with liver cell to form liver cell cord. The signal intensity changes of MRI corresponded to histological findings at different timepoints. CONCLUSION: The transplanted BMSCs are gradually scattered in whole liver (esp. in lesion area) so that it may help to repair hepatic lesions. And the recurring patterns of MR signal intensity changes reflected the condition of distribution, immigration and differentiation of transplanted cells.

Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

Background: To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. Methods: A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. Results: The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. Conclusions: ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

A nomogram based on LI-RADS features, clinical indicators and quantitative contrast-enhanced MRI parameters for predicting glypican-3 expression in hepatocellular carcinoma.

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy.

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

Biparametric prostate MRI and clinical indicators predict clinically significant prostate cancer in men with "gray zone" PSA levels.

PURPOSE: To predict clinically significant prostate cancer (cs-PCa) by combining the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score based on biparametric magnetic resonance imaging (bp-MRI) and clinical indicators in men with prostate-specific antigen (PSA) levels in the gray zone of 4-10 ng/mL. METHOD: We retrospectively analyzed 364 patients with elevated PSA levels in the gray zone who had pathologically confirmed disease and had undergone MRI examinations from January 2015 to October 2019; a training group (n = 255) and validation group (n = 109) were randomly established. Multivariate logistic regression analysis of the training group was performed to identify the independent predictors for cs-PCa, thereby establishing a predictive model that was evaluated in the training and validation groups by analyzing the receiver operating characteristic (ROC) curve. RESULTS: In the training group, the PI-RADS v2 score and prostate volume (PV) were independent predictors of cs-PCa (P < 0.05). The prediction model comprising the PI-RADS v2 score and PV had a larger AUC than the other predictors alone in the training group. The diagnostic sensitivity and specificity of the prediction model were 84.1 % and 83.4 %, respectively. The prediction model was indicated to have better predictive performance in the validation group. CONCLUSIONS: The prediction model exhibits a satisfactory predictive value for cs-PCa in men with PSA levels in the gray zone. PI-RADS v2 is the strongest univariate predictor for the detection of cs-PCa in men with PSA in the gray zone, but combining this with the PV can provide superior predictive ability.

Enhanced therapeutic effects for human pancreatic cancer by application K-ras and IGF-IR antisense oligodeoxynucleotides.

AIM: To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specific to GTT point mutation at codon 12 and type I insulin-like growth factor receptor (IGF-IR) antisense oligodeoxynucleotide (IGF-IR ASODN) on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. METHODS: K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras mutation ASODN specific to K-ras point mutation at codon 12 was designed and composed. After K-ras ASODN and IGF-IR ASODN treated on Patu8988 cells respectively or cooperatively, the proliferation and morphological change of Patu8988 cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony forming assay and transmission electron microscopy; the expression of K-ras and IGF-IR mRNA and protein in the treated cells was measured by reverse-transcript polymerase chain reaction (RT-PCR) and flow cytometry respectively; apoptosis was determined by flow cytometry. The combined antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. RESULTS: The results of PCR-SSP and sequence analysis showed that the human pancreatic cancer cell line Patu8988 had point mutation at codon 12, and the mutation style was GGT-->GTT. 2-32 microg/mL K-ras ASODN and 2-32 microg/mL IGF-IR ASODN could inhibit Patu8988 cells' growth, induce apoptosis and decrease the expression of K-ras and IGF-IR mRNA and protein alone. However, there was much more effective inhibition of growth and induction of apoptosis by their combination than by each one alone. In tumor bearing mice, the combination of K-ras ASODN and IGF-IR ASODN showed a significant inhibitory effect on the growth of transplanted pancreatic cancer, resulting in a statistically significant difference compared with each alone. CONCLUSION: It has been found that K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the growth of Patu8988 cells, and induce their apoptosis via reinforcing specific down regulation of K-ras and IGF-IR mRNA and protein expression.

Comparison of elastography based on transvaginal ultrasound and MRI in assessing parametrial invasion of cervical cancer.

OBJECTIVE: The purpose of this study was to evaluate the clinical value of transvaginal elastography (TVES) combined with high-resolution transvaginal ultrasound (TVS) in the detection of parametrial invasion in cervical cancer and to compare the diagnostic performance with magnetic resonance imaging (MRI). MATERIALS AND METHODS: 52 women with histologically confirmed cervical cancer over a 2-year period were staged using International Federation of Gynecology and Obstetrics (FIGO) criteria and underwent MRI and TVES combined with TVS according to a standardized protocol before treatment. When assessing parametrial involvement with TVS, MRI, and combination of TVES and TVS, the findings were recorded and compared with histopathological results after surgery in early-stage disease (stage⩽IIa). Sensitivity, specificity accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method independently; subsequently, a matched-sample analysis was performed by using McNemar's test or chi-square test. RESULTS: Of 52 patients, 39 were early-stage disease (stage⩽IIa), and 13 were advanced-stage disease (stage⩾IIb) according to conventional FIGO staging. For the detection of parametrial infiltration, both the diagnostic sensitivity of MRI and the combination of TVS and TVES were statistically higher than alone TVS in early-stage of cervical cancer (P = 0.03 < 0.05). Both MRI and the combination of TVS and TVES had a sensitivity of 72.73%; specificity rates of 82.14% for MRI and 78.57% for the combination of TVES and TVS; and the diagnostic accuracy rates of 79.49% for MRI and 76.92% for the combination of TVES and TVS. A matched sample analysis revealed no statistically significant difference between the diagnostic performance of MRI and the combination of TVES and TVS in the assessment of parametrial invasion (all P values > 0.05). CONCLUSION: TVES combined with TVS performed by a dedicated gynecologic radiologist should be considered a promising and economic method for pre-operative work-up for cervical cancer.

Local bone interaction between renin-angiotensin system and kallikrein-kinin system in diabetic rat.

OBJECTIVE: This study was performed to investigate bone deteriorations and the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) of male rat in response to the hyperglycemia. METHODS: The biomarkers in serum and urine were measured by ELISA kit, and tibias were taken for the measurement on gene, protein expression and histological analysis, femurs were taken for the measurement on biomechanical parameters and micro-CT. RESULTS: The DM1 showed the decreased level of osteocalcin, testosterone and FGF-23, and the increased level of serum CTX as compared to those of vehicle group. The H&E staining showed remarkable bone deteriorations, including increased disconnections and separation of trabecular bone among growth plate and joint cartilage in DM1 group. Biomechanically, the maximum load, maximum stress, and strain parameter of DM1 group was significantly lower than control group. Type 1 diabetic mice displayed bone loss shown the reduction of bone volume/total volume, trabecular number, trabecular thickness and bone mineral density. The STZ injection significantly up-regulated mRNA expression of AT1R, AGT, renin, renin-receptor, and ACE, and the expression of AT2R, B1R and B2R were down-regulated in tibia of rat in hyperglycemia group. The protein expression of renin, ACE and Ang II were significantly up-regulated, and AT2R, B1R and B2R were down-regulated in DM1 group. CONCLUSIONS: The treatment of hyperglycemia was detrimental to bone as compared to the vehicle group, and the underlying mechanism was mediated, at least partially, through down-regulation of KSS activity and up-regulation of RAS activity in local bone.

In vivo evaluation of cerebral transplantation of resovist-labeled bone marrow stromal cells in Parkinson's disease rats using magnetic resonance imaging.

The effectiveness of Resovist-labeled bone marrow stem cells (BMSCs) was evaluated in vivo following their cerebral transplantation in a model of Parkinson's disease (PD) in rats using MRI, and the MRI findings were further compared with the behavior and histopathological manifestations of these rats. Forty PD rats were randomly assigned into five groups according to the cell doses injected into the rat brain site: control group (normal saline injection) and groups injected with 1 × 10(5), 1.5 × 10(5), 2 × 10(5), and 2.5 × 10(5) BMSCs. Gradient echo T2-weighted images were obtained immediately after cell transplantation and repeatedly taken 1, 4, 8, and 12 week(s) after cell transplantation. The rotational behavior of the animals was observed before and 1, 4, and 8 week(s) after transplantation. The rats were killed after the last MRI scanning, the brain tissues were analyzed by histopathology techniques, and RNAs were extracted for the expression analysis of selected genes using RT-PCR. One week following cell transplantation, all injected sites showed well-defined hypointense areas on MR images, with the most significant effect observed in rats injected with 2 × 10(5) BMSCs. These MR findings in PD rats lasted up to 12 weeks. The effectiveness of BMSC transplantation revealed by MRI was well confirmed by the behavioral and histopathological observations as well as indirectly supported by gene expression analyses. With the use of SPIO labeling, MRI techniques provided a dynamic evaluation of the spatial and temporal changes following cell transplantation and allowed the association analysis among the imaging, functions, and gene expression analysis in rats. These data also suggest the therapeutic potential of transplanted BMSCs. It is reasonable to speculate that the use of MRI in in vivo evaluation of the effect and fate of transplanted cells in various disease models will be beneficial to developing new strategies of cell-based gene therapy.

[Combinational effects of K-ras and IGF-IR antisense oligodeoxynucleotide on proliferation and apoptosis of human pancreatic cancer Patu8988 cells].

BACKGROUND & OBJECTIVE: Point mutation of K-ras gene and overexpression of insulin-like growth factor receptor type 1 (IGF-IR) may contribute to the progression and aggressiveness of pancreatic cancer. Antisense oligodeoxynucleotide (ASODN) against K-ras mRNA and IGF-IR mRNA may inhibit the proliferation of pancreatic cancer cells. This study was to investigate the combinational effects of K-ras ASODN and IGF-IR ASODN on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. METHODS: K-ras gene point mutation in Patu8988 cells was detected by polymerase chain reaction using special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras ASODN was designed and composed. K-ras ASODN and IGF-IR ASODN were transfected into Patu8988 cells alone or in combination. Cell proliferation was analyzed by MTT and colony forming assay. The morphologic changes of Patu8988 cells were assessed under transmission electron microscope. The expression of K-ras and IGF-IR mRNA and protein in Patu8988 cells was measured by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Cell apoptosis was determined by FCM. The combinational antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. RESULTS: The point mutation of K-ras gene at codon 12 was detected in Patu8988 cells, and the mutation style was GGT-->GTT. Either 2-32 microg/mL K-ras ASODN or IGF-IR ASODN inhibited proliferation and induced apoptosis of Patu8988 cells. This effect was more obvious when K-ras ASODN and IGF-IR ASODN were used in combination than used alone (P<0.01). In tumor-bearing mice, the inhibitory effect on the growth of transplanted pancreatic cancer was more obvious when K-ras ASODN and IGF-IR ASODN were used in combination than used alone (P<0.01). CONCLUSION: K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the proliferation of Patu8988 cells and induce their apoptosis via down-regulating K-ras and IGF-IR expression.

[Transplantation and magnetic resonance imaging of transplantable human glioma tissue in the brain of nude mice].

BACKGROUND & OBJECTIVE: In previous reports, orthotopic transplantation models of glioma were produced by injecting cell suspension into the brain of mice, which is complex, time-consuming, and nearly impossible to prepare in a large scale within a short period. This study was to establish human glioma orthotopic transplantation model in nude mice by transplanting tumor tissue in the brain, and investigate magnetic resonance imaging (MRI) of the transplanted tumors. METHODS: Human glioma cells were injected subcutaneously into nude mice to form human glioma. The transplantable human glioma tissues (2 mm3) were put into trocar and directly injected into the caudate nucleus of nude mice. Thirty days later, the tumors were detected by 1.5T superconduct MR machine with micro-23 coil and measured by Dicomworks (V1.35) software. Tumor morphology was observed under light microscope with HE staining. Tumor volume was measured under stereomicroscope. The feasibility of measuring tumor volume according to MRI data was evaluated. RESULTS: MRI showed that in the 15 nude mice received orthotopic transplantation in the caudate nucleus, 14 developed glioma. Under microscope, glioma tissues were found at the same sites as where MRI indicated. Tumor volume was (23.45+/-11.64) mm3 as measured by MRI and (23.19+/-10.18) mm3 as detected under stereomicroscope (P>0.05). The successful rate of tumor model preparation was 93% (14/15). The successful rate of tumor imaging by MRI was 100% (14/14). CONCLUSIONS: Tissue quantitative transplantation via trocar is simple, time-saving, and easy to construct tumor model in a large scale with high successful rate. The 1.5T MR machine with micro-23 coil can be used to observe tumor position and size of orthotopic transplantation models of human glioma in nude mice.