Cancer tissues reflect a greater number of pathological characteristics of cancer compared to cancer cells, so the evaluation of cancer tissues can be effective in determining cancer treatment strategies. Mass spectrometry imaging (MSI) can evaluate cancer tissues and even identify molecules while preserving spatial information. Cluster analysis of cancer tissues’ MSI data is currently used to evaluate the phenotype heterogeneity of the tissues. Interestingly, it has been reported that phenotype heterogeneity does not always coincide with genotype heterogeneity in HER2-positive breast cancer. We thus investigated the phenotype heterogeneity of luminal breast cancer, which is generally known to have few gene mutations. As a result, we identified phenotype heterogeneity based on lipidomics in luminal breast cancer tissues. Clusters were composed of phosphatidylcholine (PC), triglycerides (TG), phosphatidylethanolamine, sphingomyelin, and ceramide. It was found that mainly the proportion of PC and TG correlated with the proportion of cancer and stroma on HE images. Furthermore, the number of carbons in these lipid class varied from cluster to cluster. This was consistent with the fact that enzymes that synthesize long-chain fatty acids are increased through cancer metabolism. It was then thought that clusters containing PCs with high carbon counts might reflect high malignancy. These results indicate that lipidomics-based phenotype heterogeneity could potentially be used to classify cancer for which genetic analysis alone is insufficient for classification.
To understand the ultra-early reaction of normal organ lipids during irradiation, we investigated the response of lipids, including polyunsaturated fatty acid (PUFA) chains, which are particularly susceptible to damage by ROS, in mice’s kidneys, lungs, brains, and livers within 5 min of single high-dose irradiation. In this study, we set up three groups of C56BL/6 male mice and conducted whole-body irradiation with 0 Gy, 10 Gy, and 20 Gy single doses. Kidney, lung, brain, and liver tissues were collected within 5 min of irradiation. PUFA-targeted and whole lipidomic analyses were conducted using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The results showed that PUFA chains of kidney phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG) significantly increased within 5 min of 10 Gy and 20 Gy irradiation. The main components of increased PUFA chains in PC and PE were C18:2, C20:4, and C22:6, and in TG the main component was C18:2. The kidney lipidomes also showed significant changes from the perspective of lipid species, mainly dominated by an increase in PC, PE, TG, and signal lipids, while lipidomes of the lung, brain, and liver were slightly changed. Our results revealed that acute PUFA chains increase and other lipidomic changes in the kidney upon whole-body irradiation within 5 min of irradiation. The significantly increased lipids also showed a consistent preference for possessing PUFA chains. The lipidomic changes varied from organ to organ, which indicates that the response upon irradiation within a short time is tissue-specific.
Lessons Learned Definitive concurrent chemoradiotherapy based on oxaliplatin and endostatin was effective with the objective response rate exceeding 80%, and the treatment‐related toxicities were acceptable. The treatment compliance of the current combination was much higher, without significant reduction in survival outcomes, than historical reports. Background This phase II trial aimed at assessing the efficiency and safety of definitive concurrent chemoradiotherapy (dCRT) using oxaliplatin (OHP) and endostatin in patients with inoperable esophageal squamous cell carcinoma (ESCC). Methods Radiotherapy was delivered with a daily fraction of 2.0 Gy to a total dose of 60.0 Gy over 6 weeks. Endostatin and OHP were both intravenously administered at doses of 7.5 mg/m2 daily for 2 weeks and 135 mg/m2 on day 1, respectively, every 3 weeks. The primary endpoint was the objective response rate (ORR). Results The analysis included 37 patients. The median age was 63 years (range: 49–71 years), and all patients were stage III–IVA. Of these patients, 97.3% (36/37) completed the dCRT course with an ORR of 83.8%, including 10 (27.0%) patients with complete response and 21 (56.8%) patients with partial response. The median overall survival (OS) time was 18.5 months (95% confidence interval [CI]: 10.6–26.4) with a 2‐year OS rate of 39.6% (95% CI: 0.202–0.590). The median progression‐free survival (PFS) time was 11.5 months (95% CI: 7.6–15.4) with a 2‐year PFS rate of 20.2% (95% CI: 0.049–0.355). Grade 3 toxicities included esophagitis (five patients) and leukocytopenia (three patients). Grade 4 leukopenia was observed in one patient. Late toxicity was infrequent, and no treatment‐related death occurred. Posttreatment dysphagia scores were significantly improved when compared with baseline (p < .001). Conclusion dCRT based on OHP and endostatin resulted in high treatment compliance with manageable toxicities. This combination resulted in encouraging ORR without compromising survival outcomes. It should be validated in future clinical studies.
This study used cine-magnetic resonance imaging (cine-MRI) to evaluate the safety and efficacy of a novel airbag system combined with a shell-type body fixation system in reducing respiratory motion in normal volunteers. The airbag system consists of a six-sided polygon inflatable airbag, a same shape plate, a stiff air supply tube, an air-supply pump and a digital pressure load cell monitor. Piezoelectric sensors were installed in the plate to detect compression pressure load changes; pressure load data were transferred to the digital pressure load cell monitor through Bluetooth. Five volunteers underwent cine-MRI with and without airbag compression to detect differences in the respiratory motion of the organs. The volunteers’ physiologic signs were stable during the experiment. The maximum inspiration pressure load was 4.48 ± 0.86 kgf (range, 4.00–6.00 kgf), while the minimum expiration pressure load was 3.69 ± 0.95 kgf (range, 2.8–5.3 kgf). Under airbag compression, the right diaphragm movement was reduced from 19.50 ± 6.43 mm to 9.60 ± 3.61 mm (P < 0.05) in the coronal plane and 23.12 ± 6.30 mm to 11.00 ± 3.69 mm (P < 0.05) in the sagittal plane. The left diaphragm, pancreas and liver in the coronal plane and the right kidney and liver in the sagittal plane also showed significant movement reduction. This novel airbag abdominal compression system was found to be safe during the experiment and successful in the reduction of internal organ respiratory motion and promises to be a convenient and efficient tool for clinical radiotherapy.
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