NK-92 cells labeled with Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer.

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.

MR-guided percutaneous microwave coagulation of small breast tumors.

BACKGROUND: To evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies. METHODS: From May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin-eosin (H&E) staining region in the tumor. RESULTS: All patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients. CONCLUSION: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. CRITICAL RELEVANCE STATEMENT: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. KEY POINTS: • MR-guided PMC of small breast tumors is feasible. • PMC was successfully performed for all patients. • All patients were satisfied with the final cosmetic result.

Prognostic value of amino acid metabolism-related gene expression in invasive breast carcinoma.

BACKGROUND: An increasing number of studies indicated that metabolic reprogramming of amino acid metabolism may either promote or inhibit tumor progression. The purpose of this study was to investigate the ability of a gene risk signature associated with amino acid metabolism to predict the prognosis and immune characteristics of invasive breast carcinoma. METHODS: LASSO Cox regression analysis was performed to construct and validate the prognostic risk signature based on the expression of 9 amino acid metabolism-related genes. The predictive value of the signature, immune characteristics, and chemotherapeutic drugs was also predicted. Finally, 9 significant genes were examined in MDA-MB-231 and MCF-7 cells, and the predicted chemotherapeutic drugs were also verified. RESULTS: The prognosis of the low-risk group was better than that of the high-risk group. The areas under the curve (AUCs) at 1, 2, and 3 years were 0.852, 0.790, and 0.736, respectively. In addition, the GSEA results for KEGG and GO revealed that samples with a high-risk score exhibited a variety of highly malignant manifestations. The high-risk group was characterized by an increased number of M2 macrophages, a high level of tumor purity, low levels of APC co-stimulation, cytolytic activity, HLA, para-inflammation, and type I IFN response. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) confirmed that MDA-MB-231 and MCF-7 cells express 9 amino acid metabolism-related genes differently. In addition, cell experiments were conducted to examine the effect of cephaeline-induced on cell viability, migration ability, and protein expression of the PI3K/AKT signaling pathway and HIF-1α. CONCLUSION: We established a risk signature based on 9 amino acid metabolism-related genes for invasive breast carcinoma. Further analyses revealed that this risk signature is superior to other clinical indexes in survival prediction and that the subgroups identified by the risk signature exhibit distinct immune characteristics. Cephaeline was determined to be a superior option for patients in high-risk groups.

The Alteration of Brain Interstitial Fluid Drainage with Myelination Development.

The integrity of myelination is crucial for maintaining brain interstitial fluid (ISF) drainage in adults; however, the mechanism of ISF drainage with immature myelin in the developing brain remains unknown. In the present study, the ISF drainage from the caudate nucleus (Cn) to the ipsilateral cortex was studied at different developmental stages of the rat brain (P 10, 20, 30, 40, 60, 80, 10-80). The results show that the traced ISF drained to the cortex from Cn and to the thalamus in an opposite direction before P30. From P40, we found impeded drainage to the thalamus due to myelin maturation. This altered drainage was accompanied by enhanced cognitive and social functions, which were consistent with those in the adult rats. A significant difference in diffusion parameters was also demonstrated between the extracellular space (ECS) before and after P30. The present study revealed the alteration of ISF drainage regulated by myelin at different stages during development, indicating that a regional ISF homeostasis may be essential for mature psychological and cognitive functions.

A Review of Breast Density Implications and Breast Cancer Screening.

Breast density is an independent risk factor for breast cancer and significantly decreases the sensitivity of mammography. Assessing a woman's risk of developing breast cancer is becoming increasingly important for establishing individual screening recommendations and preventive strategies. This article reviews the factors influencing mammographic density (MD), the available methods of MD assessment, and its effect on breast cancer. Finally, we discuss the supplemental screening methods for women with dense breast tissue.

White matter impairment in type 2 diabetes mellitus with and without microvascular disease.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a serious public health problem, and the phenomenon of T2DM occurring in younger people has directed more attention to functional changes in the brain. In this study, the microstructural integrity of white matter (WM) was evaluated in three groups of middle-aged subjects: healthy controls (HCs) and T2DM patients with and without peripheral microvascular complications (T2DM-C and T2DM-NC patients, respectively). METHODS: Diffusion tensor imaging (DTI) and related clinical examinations were performed in 66 subjects, including 20 T2DM-C patients, 20 T2DM-NC patients, 26 age- and sex-matched HCs. Magnetic resonance imaging (MRI) at 3 T was used to perform DTI; then, FSL and tract-based spatial statistics (TBSS) software were used to assess differences in the fractional anisotropy (FA) and mean diffusivity (MD) among the groups. The use of the FA and MD as parameters was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in sex or age among the groups, and the clinical data of the groups met the experimental requirements. There was no significant difference in the FA values between the HCs and T2DM-NC groups. Compared with the HCs, the T2DM-C patients showed decreased FA values and increased MD values in the corpus callosum, bilateral anterior limb of the internal capsule, right retrolenticular part of the internal capsule, bilateral posterior thalamic radiation, right superior longitudinal fasciculus, bilateral superior corona radiata and left middle frontal gyrus (P < .01). Compared with the T2DM-NC patients, the T2DM-C patients showed decreased FA values and increased MD values in the corpus callosum, bilateral fornix, right retrolenticular part of the internal capsule, middle cerebral peduncle, right superior longitudinal fasciculus, right posterior thalamic radiation, and left middle frontal gyrus (P < .01). CONCLUSIONS: This study indicates that WM impairment is present in T2DM patients and may be related to microvascular complications. More importantly, this study also shows that such impairment may be diagnosed using the DTI mode of functional MRI before it can be diagnosed clinically.

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

CONTEXT: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. OBJECTIVE: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. DESIGN: Case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. INTERVENTION: None. MAIN OUTCOME MEASURES: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. RESULTS: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. CONCLUSIONS: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Use of diffusion kurtosis imaging and quantitative dynamic contrast-enhanced MRI for the differentiation of breast tumors.

BACKGROUND: Breast MRI is a sensitive imaging technique to assess breast cancer but its effectiveness still remains to be improved. PURPOSE: To evaluate the diagnostic performance of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), and quantitative dynamic contrast-enhanced (DCE)-MRI in differentiating malignant from benign breast lesions independently or jointly and to explore whether correlations exist among these parameters. STUDY TYPE: Retrospective. POPULATION: In all, 106 patients with breast lesions (47 malignant, 59 benign). SEQUENCE: DKI sequence with seven b values and quantitative DCE sequence on 3.0T MRI. ASSESSMENT: Diffusion parameters (mean diffusivity [MD], mean diffusivity [MK], and apparent diffusion coefficient [ADC]) from DKI and DWI and perfusion parameters from DCE (Ktrans , kep , ve , and vp ) were calculated by two experienced radiologists after postprocessing. Disagreement between the two observers was resolved by consensus. STATISTICAL TESTS: The parameters in benign and malignant lesions were compared by Student's t-test. The diagnostic performances of DKI and quantitative DCE, either alone or in combination, were evaluated by receiver operating characteristic (ROC) analysis. The Spearman correlation test was used to evaluate correlations among the diffusion parameters and perfusion parameters. RESULTS: MK, MD, ADC, Ktrans , and kep values were significantly different between breast cancer and benign lesions (P < 0.05). MK from DKI demonstrated the highest AUC of 0.849, which is significantly higher than ADC derived from conventional DWI (z = 3.345, P = 0.0008). The specificity of DCE-MRI-derived parameters was improved when combining diffusion parameters, such as ADC and MK. The highest diagnostic specificity (93.2%) was obtained when kep and ADC were combined. kep was correlated moderately positively with MK (r = 0.516) and moderately negatively with MD (r = -0.527). Ktrans was weakly positively correlated with MK with an r of 0.398 and weakly negatively correlated with MD with an r of -0.450. DATA CONCLUSION: DKI is more valuable than conventional DWI in distinguishing between benign and malignant breast lesions. DKI exhibits promise as a quantitative technique to augment quantitative DCE-MRI. Diffusion parameters derived from DKI were statistically correlated with perfusion parameters from quantitative DCE-MRI. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1358-1366.