While natural killer (NK) cell‐based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI‐guided transcatheter intra‐hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK‐based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R 2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12‐h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.
Background:Liver cancer makes up a huge percentage of cancer mortality worldwide. Irreversible electroporation (IRE) is a relatively new minimally invasive nonthermal ablation technique for tumors that applies short pulses of high frequency electrical energy to irreversibly destabilize cell membrane to induce tumor cell apoptosis.Methods:This review aims to investigate the studies regarding the use of IRE treatment in liver tumors and metastases to liver. We searched PubMed for all of IRE relevant English language articles published up to September 2016. They included clinical trials, experimental studies, observational studies, and reviews. This review manuscript is nothing with ethics issues and ethical approval is not provided.Results:In recent years, increasingly more studies in both preclinical and clinical settings have been conducted to examine the safety and efficacy of this new technique, shedding light on the crucial advantages and disadvantages that IRE possesses. Unlike the current leading thermal ablation techniques, such as radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, IRE requires shorter ablation time without damaging adjacent important vital structures.Conclusion:Although IRE has successfully claimed its valuable status in the field of hepatic cancer treatment both preclinical and clinical settings. In order to systemically test and establish its safety and efficacy for clinical applications, more studies still need to be conducted.
The purpose of the hypothesis testing is to determine that apparent diffusion coefficient (ADC) as an early biomarker can predict the metastatic lymph nodes’ (LNs) response to neoadjuvant chemotherapy in advanced gastric cancer (GC) in early stage.From March 2011 to June 2015, 106 patients with advanced GC were enrolled in the study. Patients underwent conventional magnetic resonance imaging and functional diffusion weighted imaging before and 3 days, 7 days, 30 days, and 60 days following the standard chemotherapy. After surgery, among 3034 detected LNs, the positive group was divided into complete response (CR) group, partial response (PR) group, and stable disease (SD) group in accordance to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Mean ADCs, short/long diameters of LNs before chemotherapy between the whole positive and the negative LNs were compared by t test. Changes of mean ADCs in 3 groups were analyzed by 1-way ANOVA.The mean ADC of the whole positive LNs was (1.145 ± 0.014) × 10−3 mm2/s, which was significantly lower than that of the whole negative LNs ([1.491 ± 0.010] × 10−3 mm2/s; P < 0.05). The means of both short/long diameters in the whole positive LNs were significantly longer than those in the whole negative LNs (P < 0.05). In CR, PR, and SD groups, the mean ADC of metastatic LNs on the 3rd day, 7th day, 13th day, and 16th day following the chemotherapy were all higher than that of LNs before chemotherapy, respectively (all P < 0.05). In addition, significant difference was found between mean ADCs in any 2 time points (all P < 0.05), except between mean ADCs in the 3rd day and in the 7th day of the chemotherapy.In conclusion, ADC can be used as an early biomarker to predict the metastatic LNs’ response to neoadjuvant chemotherapy in advanced GC in early stage.
Purpose To test the hypothesis that biomarkers of fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUV) was calculated 3 days after IRE. The maximum lesion diameter change (ΔD) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUV and ΔD were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUV at 3 days and ΔD (or apoptosis index) at 14 days after IRE treatment. Results ΔSUV ΔD, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUV 3 days after IRE and ΔD 14 days after IRE (R = 0.66, P = .01) and between ΔSUV 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. RSNA, 2017.
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