PD-L1 Induces Epithelial-Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway.

Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial-mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together, we found that PD-L1 overexpression confers NPC cell malignancy and aggressiveness via activating the downstream PI3K/AKT signaling. Thus, these results provide a basis for diagnosis and treatment of NPC.

Multidimensional correlation among plan complexity, quality and deliverability parameters for volumetric-modulated arc therapy using canonical correlation analysis.

A multidimensional exploratory statistical method, canonical correlation analysis (CCA), was applied to evaluate the impact of complexity parameters on the plan quality and deliverability of volumetric-modulated arc therapy (VMAT) and to determine parameters in the generation of an ideal VMAT plan. Canonical correlations among complexity, quality and deliverability parameters of VMAT, as well as the contribution weights of different parameters were investigated with 71 two-arc VMAT nasopharyngeal cancer (NPC) patients, and further verified with 28 one-arc VMAT prostate cancer patients. The average MU and MU per control point (MU/CP) for two-arc VMAT plans were 702.6 ± 55.7 and 3.9 ± 0.3 versus 504.6 ± 99.2 and 5.6 ± 1.1 for one-arc VMAT plans, respectively. The individual volume-based 3D gamma passing rates of clinical target volume (γCTV) and planning target volume (γPTV) for NPC and prostate cancer patients were 85.7% ± 9.0% vs 92.6% ± 7.8%, and 88.0% ± 7.6% vs 91.2% ± 7.7%, respectively. Plan complexity parameters of NPC patients were correlated with plan quality (P = 0.047) and individual volume-based 3D gamma indices γ(IV) (P = 0.01), in which, MU/CP and segment area (SA) per control point (SA/CP) were weighted highly in correlation with γ(IV) , and SA/CP, percentage of CPs with SA < 5 × 5 cm2 (%SA < 5 × 5 cm2) and PTV volume were weighted highly in correlation with plan quality with coefficients of 0.98, 0.68 and -0.99, respectively. Further verification with one-arc VMAT plans demonstrated similar results. In conclusion, MU, SA-related parameters and PTV volume were found to have strong effects on the plan quality and deliverability.

Dosimetric advantage of volumetric modulated arc therapy in the treatment of intraocular cancer.

OBJECTIVE: The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT). METHODS: CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared. RESULTS: The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively. CONCLUSIONS: Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients.

Dosimetric benefits of intensity-modulated radiotherapy and volumetric-modulated arc therapy in the treatment of postoperative cervical cancer patients.

As the advantage of using complex volumetric-modulated arc therapy (VMAT) in the treatment of gynecologic cancer has not yet been fully determined, the purpose of this study was to investigate the dosimetric advantages of VMAT by comparing directly with whole pelvic conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) in the treatment of 15 postoperative cervical cancer patients. Four-field CRT, seven-field IMRT, and two-arc VMAT plans were generated for each patient with identical objective functions to achieve clinically acceptable dose distribution. Target coverage and OAR sparing differences were investigated through dose-volume histogram (DVH) analysis. Nondosimtric differences between IMRT and VMAT were also compared. Target coverage presented by V95% were 88.9% ± 3.8%, 99.9% ± 0.07%, and 99.9% ± 0.1% for CRT, IMRT, and VMAT, respectively. Significant differences on conformal index (CI) and conformal number (CN) were observed with CIs of 0.37 ± 0.07, 0.55 ± 0.04, 0.61 ± 0.04, and CNs of 0.33 ± 0.06, 0.55 ± 0.04, 0.60 ± 0.04 for CRT, IMRT, and VMAT, respectively. IMRT and VMAT decreased the dose to bladder and rectum significantly compared with CRT. No significant differences on the Dmean, V45, and V30 of small bowel were observed among CRT, IMRT, and VMAT. However, VMAT (10.4 ± 4.8 vs. 19.8 ± 11.0, P = 0.004) and IMRT (12.3 ± 5.0 vs. 19.8 ± 11.0, P = 0.02) decreased V40, increased the Dmax of small bowel and the irradiation dose to femoral heads compared with CRT. VMAT irradiated less dose to bladder, rectum, small bowel and larger volume of health tissue with a lower dose (V5 and V10) compared with IMRT, although the differences were not statistical significant. In conclusion, VMAT and IMRT showed significant dosimetric advantages both on target coverage and OAR sparing compared with CRT in the treatment of postoperative cervical cancer. However, no significant difference between IMRT and VMAT was observed except for slightly better dose conformity, slightly less MU, and significant shorter delivery time achieved for VMAT.

Individual volume-based 3D gamma indices for pretreatment VMAT QA.

Although gamma analysis is still a widely accepted quantitative tool to analyze and report patient-specific QA for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT), the correlation between the 2D percentage gamma passing rate (%GP), and the clinical dosimetric difference for IMRT and VMAT has been questioned. The purpose of this study was to investigate the feasibility of individual volume-based 3D gamma indices for pretreatment VMAT QA. Percentage dosimetric errors (%DE) of dose-volume histogram metrics (includes target volumes and organ at risks) between the treatment planning system and QA-reconstructed dose distribution, %GPs for individual volume and global gamma indices, as well their correlations and sensitivities were investigated for one- and two-arc VMAT plans. The %GPs of individual volumes had a higher percent of correlation with individual 15 %DE metrics compared with global %GPs. For two-arc VMAT at 2%/2 mm, 3%/3 mm, and 4%/4 mm criteria, individual volume %GPs were correlated with 9, 12, and 9 out of 15 %DE metrics, while global %GPs were correlated with only 2 out of 15 %DE metrics, respectively. For one-arc VMAT at 2%/2 mm, 3%/3 mm, and 4%/4 mm criteria, individual volume %GPs were correlated with 18, 16, and 13 out of 23 %DE metrics, and global %GPs were correlated with 19, 12, and 1 out 23 %DE metrics, respectively. The area under curves (AUC) of individual volume %GPs were higher than those of global %GPs for two-arc VMAT plans, but with mixed results for one-arc VMAT plans. In a conclusion, the idea of individual volume %GP was created and investigated to better serve for VMAT QA and individual volume-based %GP had a higher percent of correlation with DVH 15 %DE metrics compared with global %GP for both one- and two-arc VMAT plans.

Low-dose dynamic myocardial perfusion CT image reconstruction using pre-contrast normal-dose CT scan induced structure tensor total variation regularization.

Dynamic myocardial perfusion CT (DMP-CT) imaging provides quantitative functional information for diagnosis and risk stratification of coronary artery disease by calculating myocardial perfusion hemodynamic parameter (MPHP) maps. However, the level of radiation delivered by dynamic sequential scan protocol can be potentially high. The purpose of this work is to develop a pre-contrast normal-dose scan induced structure tensor total variation regularization based on the penalized weighted least-squares (PWLS) criteria to improve the image quality of DMP-CT with a low-mAs CT acquisition. For simplicity, the present approach was termed as 'PWLS-ndiSTV'. Specifically, the ndiSTV regularization takes into account the spatial-temporal structure information of DMP-CT data and further exploits the higher order derivatives of the objective images to enhance denoising performance. Subsequently, an effective optimization algorithm based on the split-Bregman approach was adopted to minimize the associative objective function. Evaluations with modified dynamic XCAT phantom and preclinical porcine datasets have demonstrated that the proposed PWLS-ndiSTV approach can achieve promising gains over other existing approaches in terms of noise-induced artifacts mitigation, edge details preservation, and accurate MPHP maps calculation.

[An integrative bioinformatics study of DNA copy number variation and differentially expressed genes in ovarian cancer].

OBJECTIVE: To explore the pathogenesis of ovarian cancer from the perspective of molecular genetic variation and changes in mRNA expression profiles. METHOD: The data of DNA copy number and mRNA expression profiles of high-grade serious ovarian cancer were obtained from TCGA. The significant copy number variation regions were identified using the bioinformatics tool GISTIC, and the differentially expressed genes in these regions were identified using the samr package of SAM. The selected genes were subjected to bioinformatics analysis using GSEA tools. RESULTS: GISTIC analysis identified 45 significant copy number amplification regions in ovarian cancer, and SAM and Fisher's exact test found that 40 of these genes showed altered expression levels. GSEA enrichment analysis revealed that most of these genes were reported in several published studies describing genetic study of tumorigenesis. CONCLUSION: An integrative bioinformatics study of DNA copy number variation data and microarray data can identify genes involved in tumor pathogenesis. and offer new clues for studying early diagnosis and therapeutic target of ovarian cancer.