[en] 

Background

: Numerous studies have reported the preventive and protective effects of aspirin in patients with rectal cancer. However, it is not clear whether aspirin can be used as an assistance drug in preoperative neoadjuvant chemoradiotherapy. Therefore, this study will explore the efficacy of aspirin as an adjuvant agent in rectal cancer neoadjuvant chemoradiotherapy.

Methods

: A literature search was performed using the electronic platforms to obtain relevant research studies published up to Jan 2020. The search was limited to papers published in English or Chinese language. Confidence intervals of research endpoints in each study were extracted and merged. The meta-analysis was performed using Stata12.0 software. Furthermore, we performed trial sequential analysis (TSA) to evaluate the robustness of our findings and to obtain a more conservative estimation.

Results

: A total of 5 studies including 977 patients were identified to be eligible for this meta-analysis. Compared with control group, aspirin group significantly increased pathologic complete response rate from 16.5 to 22.3% (RR 1.41, 95% CI 1.01–1.96, P = 0.041), partial remission rate from 21.8 to 45.7% (RR 1.87, 95% CI 1.37–2.54, P < 0.001), and tumor down-staging rate from 44.4 to 63.8% (RR 1.43, 95% CI 1.17–1.75, P = 0.001). Moreover, aspirin group can reduce local recurrence rate (RR 0.37, 95% CI 0.17–0.84, P = 0.017), improve 3-year survival rate (RR 1.24, 95% CI 1.12–1.36, P < 0.001), and 5-year survival rate (RR 1.29, 95% CI 1.14–1.46, P < 0.001). TSA shows that the meta-analysis results of pathologic complete response rate and local recurrence rate may be a false positive. Furthermore, the meta-analysis results of other study endpoints were further confirmed by TSA.

Conclusion

: Aspirin, as an adjuvant agent, can enhance the effect of neoadjuvant chemoradiotherapy and improve the prognosis of patients with rectal cancer. Neoadjuvant therapy combined with aspirin may be considered a better option for preoperative rectal cancer patients.

[en] Highlights: • SREBP1 is overexpressed in ccRCC cell lines and positively correlated with NF-κB activation. • SREBP1 promotes and is require for lipid desaturation in ccRCC. • SREBP1-driven lipid desaturation promotes NF-κB activation in ccRCC. • SREBP1-driven lipid desaturation and NF-κB activation is required for ccRCC cell growth. Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancers, is an incurable and lethal disease. Although great progresses have been made in understanding the mechanism of ccRCC, metabolic reprogramming in ccRCC remains largely unclear. Here, we showed that lipid desatutation might be a metabolic hallmark of ccRCC. We demonstrated sterol regulatory element-binding protein 1 (SREBP1) is overexpressed in ccRCC cell lines and positively correlated with NF-κB activation. Further, SREBP1 is required for lipid desaturation and cell growth in ccRCC. Mechanistically, we demonstrated that SREBP1-driven lipid desaturation promotes NF-κB activation. Our finding reveals a crucial roles for SREBP1 in lipid desaturation of ccRCC through regulation of NF-κB signaling, which provides not only new insights in regulatory mode of NF-κB signaling but also a novel target for potential metabolic therapies.

[en] Radiation-induced lung injury (RILI) is a severe side effect of radiotherapy (RT) for thoracic malignancies and we currently lack established methods for the early detection of RILI. In this study, we synthesized a new tracer, [${}^{18}$F]AlF-NOTA-QHY-04, targeting C-X-C-chemokine-receptor-type-4 (CXCR4) and investigated its feasibility to detect RILI. An RILI rat model was constructed and scanned with [${}^{18}$F]AlF-NOTA-QHY-04 PET/CT and [${}^{18}$F]FDG PET/CT periodically after RT. Dynamic, blocking, autoradiography, and histopathological studies were performed on the day of peak uptake. Fourteen patients with radiation pneumonia, developed during or after thoracic RT, were subjected to PET scan using [${}^{18}$F]AlF-NOTA-QHY-04. The yield of [${}^{18}$F]AlF-NOTA-QHY-04 was 28.5-43.2%, and the specific activity was 27-33 GBq/µmol. [${}^{18}$F]AlF-NOTA-QHY-04 was mainly excreted through the kidney. Significant increased [${}^{18}$F]AlF-NOTA-QHY-04 uptake in the irradiated lung compared with that in the normal lung in the RILI model was observed on day 6 post-RT and peaked on day 14 post-RT, whereas no apparent uptake of [${}^{18}$F]FDG was shown on days 7 and 15 post-RT. MicroCT imaging did not show pneumonia until 42 days post-RT. Significant intense [${}^{18}$F]AlF-NOTA-QHY-04 uptake was confirmed by autoradiography. Immunofluorescence staining demonstrated expression of CXCR4 was significantly increased in the irradiated lung tissue, which correlated with results obtained from hematoxylin-eosin and Masson's trichrome staining. In 14 patients with radiation pneumonia, maximum standardized uptake values (SUVmax) were significantly higher in the irradiated lung compared with those in the normal lung. SUVmax of patients with grade 2 RILI was significantly higher than that of patients with grade 1 RILI. This study indicated that [${}^{18}$F]AlF-NOTA-QHY-04 PET/CT imaging can detect RILI non-invasively and earlier than [${}^{18}$F]FDG PET/CT in a rat model. Clinical studies verified its feasibility, suggesting the clinical potential of [${}^{18}$F]AlF-NOTA-QHY-04 as a PET/CT tracer for early monitoring of RILI.

[en] The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. Patients with triple coronary artery disease underwent cardiac sodium [${}^{18}$F]fluoride ([${}^{18}$F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [${}^{18}$F]NaF activity (target-to-blood ratio [TBR]${}_{max}$) and the global coronary [${}^{18}$F]NaF activity (TBR${}_{global}$) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBR${}_{max}$ (odds ratio [OR] = 1.445; p = 0.011) and TBR${}_{global}$ (OR = 1.797; P = 0.018) were significant predictors of PMI. TBR${}_{max}$ > 3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBR${}_{max}$. TBR${}_{max}$ > 3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBR${}_{max}$ (hazard ratio [HR], 1.298; p = 0.004) and TBR${}_{global}$ (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. Quantification of coronary microcalcification activity via [${}^{18}$F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity.