Offersendaley0539

The cytokine IFN-γ produced by tumor-reactive T cells is a key effector molecule with pleiotropic effects during anti-tumor immune responses. While IFN-γ production is targeted at the immunological synapse, its spatiotemporal activity within the tumor remains elusive. Here, we report that while IFN-γ secretion requires local antigen recognition, IFN-γ diffuses extensively to alter the tumor microenvironment in distant areas. Using intravital imaging and a reporter for STAT1 translocation, we provide evidence that T cells mediate sustained IFN-γ signaling in remote tumor cells. Furthermore, tumor phenotypic alterations required several hours of exposure to IFN-γ, a feature that disfavored local IFN-γ activity over diffusion and bystander activity. Finally, single-cell RNA-seq data from melanoma patients also suggested bystander IFN-γ activity in human tumors. Thus, tumor-reactive T cells act collectively to create large cytokine fields that profoundly modify the tumor microenvironment.Enzyme-powered motors self-propel through the catalysis of in situ bioavailable fuels, which makes them excellent candidates for biomedical applications. However, fundamental issues like their motion in biological fluids and the understanding of the propulsion mechanism are critical aspects to be tackled before a future application in biomedicine. Herein, we investigated the physicochemical effects of ionic species on the self-propulsion of urease-powered micromotors. Results showed that the presence of PBS, NaOH, NaCl, and HEPES reduced self-propulsion of urease-powered micromotors pointing towards ion-dependent mechanisms of motion. We studied the 3D motion of urease micromotors using digital holographic microscopy to rule out any motor-surface interaction as the cause of motion decay when salts are present in the media. In order to protect and minimize the negative effect of ionic species on micromotors' performance, we coated the motors with methoxypolyethylene glycol amine (mPEG) showing higher speed compared to noncoated motors at intermediate ionic concentrations. These results provide new insights into the mechanism of urease-powered micromotors, study the effect of ionic media, and contribute with potential solutions to mitigate the reduction of mobility of enzyme-powered micromotors.

To compare hyperpolarized carbon 13 (

C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent

C MRI after injection of hyperpolarized [1-carbon 13

C]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The

C-labeled lactate-to-pyruvate ratio derived from hyperpolarized

C MRI and the pharmacokinetic parameters transfer constant (



) and washout parameter (



) derived from DCE MRI were compared before and after treatment.

Exchange of the

C label between injected hyperpolarized [1-

C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the

C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean



(132%) and mean



(31%), which could be incorrectly interpreted as a poor response to treatment.

Hyperpolarized

C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

Hyperpolarized 13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

To identify patient and tumor features that predict true-positive, false-positive, and negative breast preoperative MRI outcomes.

Using a breast MRI database from a large regional cancer center, the authors retrospectively identified all women with unilateral breast cancer who underwent preoperative MRI from January 2005 to February 2015. A total of 1396 women with complete data were included. Patient features (ie, age, breast density) and index tumor features (ie, type, grade, hormone receptor, human epidermal growth factor receptor type 2/

, Ki-67) were extracted and compared with preoperative MRI outcomes (ie, true positive, false positive, negative) using univariate (ie, Fisher exact) and multivariate machine learning approaches (ie, least absolute shrinkage and selection operator, AutoPrognosis). Overall prediction performance was summarized using the area under the receiver operating characteristic curve (AUC), calculated using internal validation techniques (bootstrap and cross-validation) to accohe use of preoperative MRI provide limited predictive value for determining preoperative MRI outcomes in women. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Grimm in this issue.

To quantify diffusion and perfusion changes in hepatocellular carcinoma (HCC) induced by yttrium 90 (

Y) radioembolization and to assess the value of dynamic contrast material-enhanced (DCE) MRI and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for predicting HCC response.

Institutional review board approval was obtained for this prospective study (clinical trial registry NCT01871545). Twenty-four participants with HCC (mean age, 69 years ± 9 [standard deviation], 18 men) underwent multiparametric MRI, including IVIM DWI and gadoxetic acid DCE MRI before (

= 24) and 6 weeks (

= 21) after radioembolization. Ravoxertinib datasheet IVIM DWI and DCE MRI histogram parameters were quantified in HCCs and liver parenchyma. HCC response was assessed by using modified Response Evaluation Criteria in Solid Tumors at 6 weeks and 6-12 months after radioembolization. Logistic regression analysis was used to evaluate the diagnostic performance of baseline MRI and clinical parameters for prediction of response.

Twenty-five HCCs were analyzed (mean size, 3.