Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.
Gamma Rays ; Humans ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; instrumentation ; methods

Objective To evaluate the dosimetric characteristics of helical tomotherapy (HT),intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) for postoperative radiotherapy of rectal cancer.Methods Ten male patients with stage Ⅱ or Ⅲ middle or low position rectal cancer were selected retrospectively.All of the 10 patients underwent Dixon surgery and CT simulation orientation.The target volumes and normal organs were drawn in the CT images and the plans for HT,IMRT and 3D-CRT were designed.The prescribed dose was given 50 Gy in 25 fractions,covering at least 95％ of the planning target volume.Results All plans met the needs of the prescribed doses.The HT and IMRT plans met the needs of dose limit to organs at risk,however,the 3D-CRT plans failed to do that.The conformity indexes of HT,IMRT and 3D-CRT plans were 0.86,0.82 and 0.62,respectively (F =206.81,P ＜ 0.001),and the homogeneity indexes were 0.001,0.157,and 0.205,respectively (x2 =15.8,P ＜ 0.001).The 3D-CRT plans had larger volumes than the HT plans and IMRT plans in the high-dose regions such as pelvic V50,bladder V40,bowel V50 and femoral head D5 (P ＜ 0.05),but the differences between the HT plans and IMRT plans were not statistically significant (P ＞0.05).The V15 value of bowel of HT plans were higher than those of the IMRT and 3D-CRT plans (71.1％ vs.63.3％ and 67.7％,respectively).However,there was no significantly difference.Conclusions All of the HT,IMRT and 3D-CRT plans are able to meet the prescription dose requirement of the target regions of rectal cancer.The HT plans show the best dose homogeneity and target conformity,followed by the IMRT plans,and then the 3D-CRT plans.The HT plans meet the needs of all OARs slightly better than the IMRT plans.3D-CRT plans are simple and practical with poor protective ability toward the OARs.

OBJECTIVETo evaluate the image quality of megavoltage computed Tomography imaging.

METHODSThe HU uniformity and linearity, image noise, spatial resolution, low contrast resolution and spatial linearity in MVCT mode were evaluated with Catphan 600 phantom, and the factor of pitch was also evaluated. Influencing factors of image quality were also discussed.

RESULTSThe MVCT values depended linearly on the physical density of the sample. The MVCT values uniformity was good. The spatial resolution was 4 lp/cm. The use of an MV Beam for imaging results in the loss of low contrast resolution, but it is sufficient for pretreatment image guidance. The geometric accuracy was good.

CONCLUSIONSThe image quality of MVCT is less than that of KVCT, but is good enough for IGRT.

Radiotherapy Planning, Computer-Assisted ; instrumentation ; Tomography, Spiral Computed ; instrumentation