Gadoxetic acid-enhanced MRI and sonoelastography: non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To.

BACKGROUND: This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats. MATERIALS AND METHODS: Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot. RESULTS: According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels. CONCLUSION: Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.

Photothermolysis of glioblastoma stem-like cells targeted by carbon nanotubes conjugated with CD133 monoclonal antibody.

CD133(+) cells in glioblastoma (GBM) display cancer stem cell-like properties and have been considered as the culprit of tumor recurrence, justifying exploration of potential therapeutic modalities targeting CD133(+) cancer stem-like cells (CSCs). For photothermolysis studies, GBM-CD133(+) and GBM-CD133(-) cells mixed with various ratios were challenged with single-walled carbon nanotubes (SWNTs) conjugated with CD133 monoclonal antibody (anti-CD133) and then irradiated with near-infrared laser light. Results show that GBM-CD133(+) cells were selectively targeted and eradicated, whereas GBM-CD133(-) cells remained viable. In addition, in vitro tumorigenic and self-renewal capability of GBM-CD133(+) treated with localized hyperthermia was significantly blocked. Furthermore, GBM-CD133(+) cells pretreated with anti-CD133-SWNTs and irradiated by near-infrared laser 2 days after xenotransplantation in nude mice did not exhibit sustainability of CSC features for tumor growth. Taken altogether, our studies demonstrated that anti-CD133-SWNTs have the potential to be utilized as a thermal-coupling agent to effectively target and destroy GBM CSCs in vitro and in vivo. FROM THE CLINICAL EDITOR: Glioblastoma remains one of the most notorious cancer from the standpoint of recurrence and overall resistance to therapy. CD133+ stem cells occur among GBM cells, and may be responsible for the huge recurrence risk. This paper discusses a targeted elimination method of these cells, which may enable more efficient therapy in an effort to minimize or prevent recurrence.

Monitoring breast cancer response to neoadjuvant systemic chemotherapy using parametric contrast-enhanced MRI: a pilot study.

RATIONALE AND OBJECTIVES: Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer and a common option for primary operable disease. It is important to develop standardized imaging techniques that can monitor and quantify response to NST enabling treatment tailored to each individual patient, and facilitating surgical planning. Here we present a high spatial resolution, parametric method based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), which evaluates breast cancer response to NST. MATERIALS AND METHODS: DCE-MRI examinations were performed twice on 17 breast cancer patients, before and after treatment. Seven sets of axial breast images were sequentially recorded at 1.5 Tesla applying a three-dimensional, gradient echo at a spatial resolution approximately 2 x 1.2 x 0.6 mm(3) and temporal resolution approximately 2 minutes, using gadopentate dimeglumine (0.1 mmol/kg wt). Image analysis was based on a color-coded scheme related to physiologic perfusion parameters. RESULTS: A high Pearson correlation coefficient of 0.96 (P < .0001) was found between the histopathologic estimation of viable neoplastic tissue volume and the segmented volume of all the pixels demonstrating fast and steady state washout after NST (colored in light red and green). Segmentation of these pixels before and after NST indicated response in terms of reduced tumor volume and a parallel decrease in enhancement rate which reflects diminished transcapillary transfer of the contrast agent. CONCLUSIONS: The use of a parametric MRI technique provided a means to standardize segmentation and quantify changes in the perfusion of breast neoplastic tissue in response to NST. Whether this technique can serve to predict breast cancer recurrence and survival rates requires further clinical testing.