The success of adoptive T cell-based immunotherapy (ACT) in cancer is limited in part by the accumulation of myeloid-derived suppressor cells (MDSC), which block several T cell functions, including T cell proliferation and the expression of various cytotoxic mediators. Paradoxically, the inhibition of CD8+ T cell differentiation into cytotoxic populations increased their efficacy after ACT into tumor-bearing hosts. Therefore, we aimed to test the impact of conditioning CD8+ T cells with MDSC on their differentiation potential and ACT efficacy. Our results indicate that MDSC impaired the progression of CD8+ T cells into effector populations, without altering their activation status, production of IL-2, or signaling through the T cell receptor. In addition, culture of CD8+ T cells with MDSC resulted in an increased ACT anti-tumor efficacy, which correlated with a higher frequency of the transferred T cells and elevated IFNγ production. Interestingly, activated CD62L+ CD8+ Tcells were responsible for the enhanced anti-tumor activity showed by MDSC-exposed T cells. Additional results showed a decreased protein synthesis rate and lower activity of the mammalian/mechanistic target of rapamycin (mTOR) in T cells conditioned with MDSC. Silencing of the negative mTOR regulator tuberous sclerosis complex-2 in T cells co-cultured with MDSC restored mTOR activity, but resulted in T cell apoptosis. These results indicate that conditioning of T cells with MDSC induces stress survival pathways mediated by a blunted mTOR signaling, which regulated T cell differentiation and ACT efficacy. Continuation of this research will enable the development of better strategies to increase ACT responses in cancer.

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Hybrid imaging with integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) combines the advantages of the high-resolution anatomic data from MRI and functional imaging data from PET, and has the potential to improve the diagnostic evaluation of various types of cancers. The clinical oncologic applications of this newest hybrid imaging technology are evolving and substantial efforts are underway to define the role of PET/MRI in routine clinical use. The current published literature suggests that PET/MRI may play an important role in the evaluation of patients with certain types of malignancies, involving anatomic locations such as the pelvis and the liver. The purpose of this article is to review the current published PET/MRI literature in specific body oncologic applications. In addition, PET/MRI protocols and some of the technical issues of this hybrid imaging will be briefly discussed. J. Magn. Reson. Imaging 2016.
© 2016 Wiley Periodicals, Inc.

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Widely distributed osteosclerosis is an unusual radiographic finding with multiple causes. A 42-year-old pre-menopausal Spanish woman gradually acquired dense bone diffusely affecting her axial skeleton and focally affecting her proximal long bones. Systemic lupus erythematosus diagnosed in adolescence had been well controlled. She had not fractured or received antiresorptive therapy, and was hepatitis C virus antibody negative. Family members had low bone mass. Lumbar spine BMD measured by dual-photon absorptiometry at age 17 years, while receiving glucocorticoids, was 79% the average value of age-matched controls. From ages 30 to 37 years, DXA BMD z-scores steadily increased in her lumbar spine from +3.8 to +7.9, and femoral neck from -1.4 to -0.7. Serum calcium and phosphorus levels were consistently normal, 25OHD <20 ng/mL, and PTH sometimes slightly increased. Her reduced eGFR was 38-55 mls/min. Hypocalciuria likely reflected positive mineral balance. During increasing BMD, turnover markers (serum bone-ALP, PINP, osteocalcin, and CTX, and urinary NTX) were 1.6- to 2.8-fold above the reference limits. Those of bone formation seemed increased more than those of resorption. FGF-23 was slightly elevated, perhaps from kidney disease. Serum OPG and TGFβ1 levels were normal, but sclerostin (SOST) and RANKL were elevated. Serum multiplex biomarker profiling confirmed a high level of SOST and RANKL, whereas DKK-1 seemed low. Matrix metalloproteinases-3 and -7 were elevated. Iliac crest biopsy revealed tetracycline labels, no distinction between thick trabeculae and cortical bone, absence of peritrabecular fibrosis, few osteoclasts, and no mastocytosis. Then, for the past three years, BMD z-scores steadily decreased. Skeletal fluorosis, mastocytosis, myelofibrosis, hepatitis C-associated osteosclerosis, multiple myeloma, and aberrant phosphate homeostasis did not explain her osteosclerosis. Mutation analysis of the LRP5, LRP4, SOST, and osteopetrosis genes was negative. Microarray showed no notable copy number variation. Perhaps her osteosclerosis reflected an interval of autoimmune-mediated resistance to SOST and/or RANKL. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.

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Whole-body (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard of care for lymphoma. Simultaneous PET/MRI (magnetic resonance imaging) is a promising new modality that combines the metabolic information of PET with superior soft-tissue resolution and functional imaging capabilities of MRI while decreasing radiation dose. There is limited information on the clinical performance of PET/MRI in the pediatric setting.
This study evaluated the feasibility, dosimetry, and qualitative and quantitative diagnostic performance of simultaneous whole-body FDG-PET/MRI in children with lymphoma compared to PET/CT.
Children with lymphoma undergoing standard of care FDG-PET/CT were prospectively recruited for PET/MRI performed immediately after the PET/CT. Images were evaluated for quality, lesion detection and anatomical localization of FDG uptake. Maximum and mean standardized uptake values (SUVmax/mean) of normal organs and SUVmax of the most FDG-avid lesions were measured for PET/MRI and PET/CT. Estimation of radiation exposure was calculated using specific age-related factors.
Nine PET/MRI scans were performed in eight patients (mean age: 15.3 years). The mean time interval between PET/CT and PET/MRI was 51 ± 10 min. Both the PET/CT and PET/MRI exams had good image quality and alignment with complete (9/9) concordance in response assessment. The SUVs from PET/MRI and PET/CT were highly correlated for normal organs (SUVmean r(2): 0.88, P<0.0001) and very highly for FDG-avid lesions (SUVmax r(2): 0.94, P=0.0002). PET/MRI demonstrated an average percent radiation exposure reduction of 39% ± 13% compared with PET/CT.
Simultaneous whole-body PET/MRI is clinically feasible in pediatric lymphoma. PET/MRI performance is comparable to PET/CT for lesion detection and SUV measurements. Replacement of PET/CT with PET/MRI can significantly decrease radiation dose from diagnostic imaging in children.

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To compare diameter as a continuous variable with categorical R.E.N.A.L. nephrometry score (RNS) in predicting surgical outcomes of robotic partial nephrectomy (RPN).
We retrospectively reviewed consecutive patients receiving RPN at our institution between July 2007 and June 2014 (n = 286). Three separate multivariate analyses were performed to assess the relationship between RNS components (R = radius, E = endophyticity, N = nearness to collecting system, L = location relative to polar lines), total RNS, and diameter as a continuous variable with operating time, warm ischemia time (WIT), and estimated blood loss (EBL). Each linear regression model’s quality of fit to the data was assessed with coefficients of determination (R (2)).
Continuous tumor diameter and total RNS were each significantly correlated to operative time, EBL, and WIT (p < 0.001). Categorical R related to operative time (R = 2 vs. R = 1, p = 0.001; R = 3 vs. R = 1, p = 0.001) and WIT (R = 2 vs. R = 1, p = 0.003; R = 3 vs. R = 1, p = 0.016), but not to EBL. For each of these outcomes, diameter outperformed both R and total RNS, as assessed by R (2). Age, body mass index, Charlson Comorbidity Index, and anterior versus posterior location did not correlate with surgical outcomes.
In this series of RPN from a high-volume center, surgical outcomes more closely related to tumor diameter than RNS. While RNS provides surgeons a standardized tool for preoperative planning of renal masses, tumor size may be employed as a more familiar measurement when counseling patients on potential outcomes.

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