Ravi Thakur

PURPOSE: To compare the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging with that of contrast material-enhanced (CE) MR imaging and to assess the performance of these examinations combined for the characterization of renal lesions, with MR follow-up and histopathologic analysis as the reference standards. MATERIALS AND METHODS: The institutional review board waived the requirement of informed patient consent for this retrospective HIPAA-compliant study. One hundred nine renal lesions in 64 patients (46 men, 18 women; mean age, 60.7 years) were evaluated with CE MR imaging and breath-hold DW imaging performed with various b values. Renal lesions were characterized with use of CE MR criteria, and apparent diffusion coefficients (ADCs) were measured. The ADCs of benign and malignant lesions were compared at Mann-Whitney testing. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of DW imaging and CE MR imaging in the diagnosis of renal cell carcinoma (RCC). RESULTS: The 109 renal lesions--81 benign lesions and 28 RCCs--had a mean diameter of 4.2 cm +/- 2.5 (standard deviation). The mean ADC for RCCs (1.41 x 10(-3) mm(2)/sec +/- 0.61) was significantly lower (P < .0001) than that for benign lesions (2.23 x 10(-3) mm(2)/sec +/- 0.87) at DW imaging performed with b values of 0, 400, and 800 sec/mm(2). At a cutoff ADC of less than or equal to 1.92 x 10(-3) mm(2)/sec, the area under the ROC curve (AUC), sensitivity, and specificity of DW imaging for the diagnosis of RCCs (excluding angiomyolipomas) were 0.856, 86%, and 80%, respectively. The corresponding AUC, sensitivity, and specificity of CE MR imaging were 0.944, 100%, and 89%, respectively. Combined DW and CE MR imaging had 96% specificity. The AUC for the DW imaging-based diagnosis of solid RCC versus oncocytoma was 0.854. Papillary RCCs had lower ADCs than nonpapillary RCCs. CONCLUSION: DW imaging can be used to characterize renal lesions; however, compared with CE MR imaging, it is less accurate. DW imaging can be used to differentiate solid RCCs from oncocytomas and characterize the histologic subtypes of RCC.

Cancer stem cells (CSCs) are responsible for aggressive tumor growth, metastasis and therapy resistance. In this study, we evaluated the effects of Shikonin (Shk) on breast cancer and found its anti-CSC potential. Shk treatment decreased the expression of various epithelial to mesenchymal transition (EMT) and CSC associated markers. Kinase profiling array and western blot analysis indicated that Shk inhibits STAT3, FAK and Src activation. Inhibition of these signaling proteins using standard inhibitors revealed that STAT3 inhibition affected CSCs properties more significantly than FAK or Src inhibition. We observed a significant decrease in cell migration upon FAK and Src inhibition and decrease in invasion upon inhibition of STAT3, FAK and Src. Combined inhibition of STAT3 with Src or FAK reduced the mammosphere formation, migration and invasion more significantly than the individual inhibitions. These observations indicated that the anti-breast cancer properties of Shk are due to its potential to inhibit multiple signaling proteins. Shk also reduced the activation and expression of STAT3, FAK and Src in vivo and reduced tumorigenicity, growth and metastasis of 4T1 cells. Collectively, this study underscores the translational relevance of using a single inhibitor (Shk) for compromising multiple tumor-associated signaling pathways to check cancer metastasis and stem cell load.