Abstract. Piperlongumine (PL), a natural product ofPiper longum, inhibits multiple malignant phenotypes. Therefore, the present study examined whether PL suppresses cancer stemness in oral cancer. The cellular effects of PL were determined by examining alterations in tumor sphere formation, cell migration, invasion, proliferation ability, chemosensitivity and radiosensitivity. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed in order to determine molecular expression levels. The present study revealed that PL inhibited cancer stem cell-forming ability and suppressed the expression of the stemness-related transcription factors SRY-Box 2, POU class 5 homeobox 1, and Nanog homeobox. However, it increased the expression of the differentiation marker cytokeratin 18. PL also suppressed cell migration and invasion, resulting in the elimination of the epithelial-mesenchymal transition. Furthermore, PL increased chemo-and radiosensitivity and suppressed tumor growth in vitro and in vivo. The results of the present study suggested that PL inhibits malignant phenotypes via the suppression of cancer stemness in oral cancer. Thus, PL may serve as an effective therapeutic agent for oral cancer.
In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV (P = 0.0057) and CATV (P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness (P = 0.001), RTV (P = 0.042), and preoperative clinical nodal status (P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion (P = 0.008) and pathological nodal status (P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.
The purpose of this study was to develop an ultrasound image tracking algorithm (UITA) for extracting the exact displacement of internal organs caused by respiratory motion. The program can track organ displacements in real time, and analyze the displacement signals associated with organ displacements via a respiration compensating system (RCS). The ultrasound imaging system is noninvasive and has a high spatial resolution and a high frame rate (around 32 frames/s), which reduces the radiation doses that patients receive during computed tomography and X-ray observations. This allows for the continuous noninvasive observation and compensation of organ displacements simultaneously during a radiation therapy session.This study designed a UITA for tracking the motion of a specific target, such as the human diaphragm. Simulated diaphragm motion driven by a respiration simulation system was observed with an ultrasound imaging system, and then the induced diaphragm displacements were calculated by our proposed UITA. These signals were used to adjust the gain of the RCS so that the amplitudes of the compensation signals were close to the target movements. The inclination angle of the ultrasound probe with respect to the surface of the abdomen affects the results of ultrasound image displacement tracking. Therefore, the displacement of the phantom was verified by a LINAC with different inclination-angle settings of the ultrasound probe. The experimental results indicate that the best inclination angle of the ultrasound probe is 40 degrees, since this results in the target displacement of the ultrasound images being close to the actual target motion. The displacement signals of the tracking phantom and the opposing displacement signals created by the RCS were compared to assess the positioning accuracy of our proposed ultrasound image tracking technique combined with the RCS.When the ultrasound probe was inclined by 40 degrees in simulated respiration experiments using sine waves, the correlation between the target displacement on the ultrasound images and the actual target displacement was around 97%, and all of the compensation rates exceeded 94% after activating the RCS. Furthermore, the diaphragm movements on the ultrasound images of three patients could be captured by our image tracking technique. The test results show that our algorithm could achieve precise point locking and tracking functions on the diaphragm. This study has demonstrated the feasibility of the proposed ultrasound image tracking technique combined with the RCS for compensating for organ displacements caused by respiratory motion.This study has shown that the proposed ultrasound image tracking technique combined with the RCS can provide real-time compensation of respiratory motion during radiation therapy, without increasing the overall treatment time. In addition, the system has modest space requirements and is easy to operate.
Background: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). Methods: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan–Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. Results: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30–60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0–65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 ( p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy10 ( p = 0.011) and a Child–Pugh score of ⩾6 ( p = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively. Conclusions: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED10 of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.
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