The integrated stress response (ISR) is critical for cancer cell survival during stress stimuli and has been implicated in the resistance to cancer therapeutics, in which the mechanism, however, is poorly understood. Here, we showed that paclitaxel, the major chemotherapy drug for breast cancer, induced ISR and phosphorylated ser51 residue of EIF2S1 by EIF2AK3 and EIF2AK4. When exposed to paclitaxel, cancer cells activated the EIF2AK3/EIF2AK4‐pEIF2S1‐ATF4 axis and maintained redox homoeostasis by inducing expression of the major antioxidant enzymes HMOX1, SHMT2 and SLC7A11. Paclitaxel‐mediated cell death was significantly increased following loss of ISR or ATF4 expression. This sensitizing effect could be partially rescued by Trolox, a ROS scavenger. We demonstrated that the alternative initiation factor EIF2A was essential for cancer cell survival after paclitaxel‐mediated ISR both in vitro and in vivo. Moreover, patients with breast cancer exhibited higher ISR after chemotherapy, and the elevated mRNA levels of HMOX1, SHMT2 and EIF2A were correlated with poor prognosis. Collectively, our findings reveal a novel mechanism for paclitaxel resistance and suggest that targeting EIF2A combined with ISR agonist may be a potential treatment regimen to overcome drug resistance for breast cancer.

Stiffness and fluidity, quantified by means of tomoelastography, a multifrequency MR elastography technique, improved the diagnostic performance of multiparametric MRI for depiction of cancer, with... Background Multiparametric MRI is used for depiction of prostate cancer (PCa) but without consideration of the mechanical alteration of prostatic tissue by cancer. Purpose To investigate the diagno...

Microvascular invasion (MVI) is regarded as one of the independent risk factors for recurrence and poor prognosis of hepatocellular carcinoma (HCC). The presence of MVI in HCCs was evaluated on the basis of pathological reports of surgical specimens and was defined as tumor within a vascular space lined by endothelium that was visible only on microscopy. The aim of the study was to investigate the usefulness of intravoxel incoherent motion (IVIM) diffusion weighted (DW) magnetic resonance (MR) imaging in predicting MVI of HCC. Preoperative IVIM DW imaging and Gd-EOB-DTPA-enhanced MRI (DCE-MRI) of 51 patients were analyzed. Standard apparent diffusion coefficient (ADC), D (the true diffusion coefficient), D* (the pseudodiffusion coefficient) and f (the perfusion fraction), relative enhancement (RE) and radiological features were evaluated and analyzed. Univariate analysis revealed that HCCs with MVI had a higher portion of an irregular tumor shape than HCCs without MVI (p = 0.009), the Standard ADC, D value were significantly lower in HCCs with MVI (p = 0.022, p = 0.007, respectively). Multivariate analysis revealed that an irregular shape (p = 0.012) and D value ≤ 1.16×10^-3mm²/sec (p = 0.048) were independent predictors for MVI. Combining the two factors of an irregular shape and D value, a sensitivity of 94.4% and specificity of 63.6% for predicting MVI was obtained. In conclusion, we found that an irregular shape and D value ≤ 1.16×10^-3mm²/sec may suggest the presence of MVI in HCCs.

Recently, radiomic texture quantification of tumors has received much attention from radiologists, scientists, and stakeholders because several results have shown the feasibility of using the technique to diagnose and manage oncological conditions. In patients with hepatocellular carcinoma, radiomics has been applied in all stages of tumor evaluation, including diagnosis and characterization of the genotypic behavior of the tumor, monitoring of treatment responses and prediction of various clinical endpoints. It is also useful in selecting suitable candidates for specific treatment strategies. However, the clinical validation of hepatocellular carcinoma radiomics is limited by challenges in imaging protocol and data acquisition parameters, challenges in segmentation techniques, dimensionality reduction, and modeling methods. Identification of the best segmentation and optimal modeling methods, as well as texture features most stable to imaging protocol variability would go a long way in harmonizing HCC radiomics for personalized patient care. This article reviews the process of HCC radiomics, its clinical applications, associated challenges, and current optimization strategies.

Positive regulation of TAZ expression by EBV-LMP1 contributes to cell proliferation and epithelial-mesenchymal transition in nasopharyngeal carcinoma