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We previously found that lung tumor development was reduced in a presenilin (PS) Alzheimer’s disease (AD) mouse model. Here, we investigated whether this reducing effect could occur in a different AD mouse model. We investigated urethane-induced (1 mg/g) lung tumor development and melanoma growth in Swedish amyloid precursor protein (SwAPP) transgenic mice. The expression of chitinase-3-like-1 (Chi3L1) increased during lung tumor development and melanoma growth, which was accompanied by an increase in the activity of signal transducer and activator of transcription 3 (STAT3) and the downregulation of miRNA342-3p in wild-type mice. Like tumor development, the expression of Chi3L1 and STAT3 activity was reduced in the SwAPP mice, whereas the expression of miRNA342-3p was upregulated. In addition, Chi3L1 knockdown in the lung cancer and melanoma tissues reduced cancer cell growth and STAT3 activity but enhanced miRNA342-3p expression. However, the miRNA342-3p mimic decreased Chi3L1 expression, cancer cell growth, and STAT3 activity. Moreover, a STAT3 inhibitor reduced Chi3L1 expression and cancer cell growth but enhanced miRNA342-3p expression. These data showed that lung tumor development was reduced through the decrease of Chi3L1 expression via the STAT3-dependent upregulation of miRNA342-3p. This study indicates that lung tumor development could be reduced in SwAPP AD mice. Keywords: chitinase-3-like-1, lung tumor development, miRNA342-3p, STAT3

Abstract Background To identify whether early metabolic responses as determined using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) during radiotherapy (RT) predict outcomes in patients with esophageal cancer. Methods Twenty-one patients with esophageal cancer who received pre-treatment 18F-FDG PET/CT (PET1) and inter-fractional 18F-FDG PET/CT (PET2) after 11 fractions of RT (median 23.1 Gy, 2.1 Gy per fraction) were retrospectively reviewed. The region of interest for each calculation was delineated using “PET Edge”. We calculated PET parameters including maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The relative changes (%) were calculated using the logarithmically transformed parameter values for the PET1 and PET2 scans. Multivariate analysis of locoregional recurrence and distant failures were performed using Cox regression analysis. After identifying statistically significant PET parameters for discriminating responders from non-responders, receiver operating characteristics curve analyses were used to assess the potentials of the studied PET parameters. Results After a median follow-up of 13 months, the 1-year overall and progression-free survival rates were 79.0% and 34.4%, respectively. Four patients developed locoregional recurrences (LRRs) and 8 had distant metastases (DMs). The 1-year overall LRR-free rate was 76.9% while the DM-free rate was 60.6%. The relative changes in MTV (ΔMTV) were significantly associated with LRR (p = 0.03). Conversely, the relative changes in SUVmean (ΔSUVmean) were associated with the risk of DM (p = 0.02). An ΔMTV threshold of 1.14 yielded a sensitivity of 60%, specificity of 94%, and an accuracy of 86% for predicting an LRR. Additionally, a ΔSUVmean threshold of a 35% decrease yielded a sensitivity of 67%, specificity of 83%, and accuracy of 76% for the prediction DM. Trial registration Retrospectively registered. Conclusions Changes in tumor metabolism during RT could be used to predict treatment responses, recurrences, and prognoses in patients with esophageal cancer.

This study aims to confirm the usefulness of patient-specific quality assurance (PSQA) using three-dimensional (3D)-printed phantoms in ensuring the stability of IORT and the precision of the treatment administered. In this study, five patient-specific chest phantoms were fabricated using a 3D printer such that they were dosimetrically equivalent to the chests of actual patients in terms of organ density and shape around the given target, where a spherical applicator was inserted for breast IORT treatment via the INTRABEAM™ system. Models of lungs and soft tissue were fabricated by applying infill ratios corresponding to the mean Hounsfield unit (HU) values calculated from CT scans of the patients. The two models were then assembled into one. A 3D-printed water-equivalent phantom was also fabricated to verify the vendor-provided depth dose curve. Pieces of an EBT3 film were inserted into the 3D-printed customized phantoms to measure the doses. A 10 Gy prescription dose based on the surface of the spherical applicator was delivered and measured through EBT3 films parallel and perpendicular to the axis of the beam. The shapes of the phantoms, CT values, and absorbed doses were compared between the expected and printed ones. The morphological agreement among the five patient-specific 3D chest phantoms was assessed. The mean differences in terms of HU between the patients and the phantoms was 2.2 HU for soft tissue and −26.2 HU for the lungs. The dose irradiated on the surface of the spherical applicator yielded a percent error of −2.16% ± 3.91% between the measured and prescribed doses. In a depth dose comparison using a 3D-printed water phantom, the uncertainty in the measurements based on the EBT3 film decreased as the depth increased beyond 5 mm, and a good agreement in terms of the absolute dose was noted between the EBT3 film and the vendor data. These results demonstrate the applicability of the 3D-printed chest phantom for PSQA in breast IORT. This enhanced precision offers new opportunities for advancements in IORT.