Search

Light quality is a common environmental factor which influences the metabolism of biochemical substances in algae and leads to the response of algal growth and development. Pyropia yezoensis is a kind of economic macroalgae that naturally grows in the intertidal zone where the light environment changes dramatically. In the present study, P. yezoensis thalli were treated under white light (control) and monochromatic lights with primary colors (blue, green, and red) for 14 days to explore their physiological response to light quality. During the first 3 days of treatment, P. yezoensis grew faster under blue light than other light qualities. In the next 11 days, it showed better adaptation to green light, with higher growth rate and photosynthetic capacity (reflected by a higher rETRmax = 61.58 and Ek = 237.78). A higher nonphotochemical quenching was observed in the treatment of red light than others for 14 days. Furthermore, the response of P. yezoensis to light quality also results in the difference of photosynthetic pigment contents. The monochromatic light could reduce the synthesis of all pigments, but the reduction degree was different, which may relate to the spectral absorption characteristics of pigments. It was speculated that P. yezoensis adapted to a specific or changing light environments by regulating the synthesis of pigments to achieve the best use of light energy in photosynthesis and premium growth and metabolism. [ABSTRACT FROM AUTHOR]

Background: Radiation proctitis is a common complication after radiotherapy for cervical cancer. Unlike simple radiation damage to other organs, radiation proctitis is a complex disease closely related to the microbiota. However, analysis of the gut microbiota is time-consuming and expensive. This study aims to mine rectal information using radiomics and incorporate it into a nomogram model for cheap and fast prediction of severe radiation proctitis prediction in postoperative cervical cancer patients. Methods: The severity of the patient's radiation proctitis was graded according to the RTOG/EORTC criteria. The toxicity grade of radiation proctitis over or equal to grade 2 was set as the model's target. A total of 178 patients with cervical cancer were divided into a training set (n = 124) and a validation set (n = 54). Multivariate logistic regression was used to build the radiomic and non-raidomic models. Results: The radiomics model [AUC=0.6855(0.5174-0.8535)] showed better performance and more net benefit in the validation set than the non-radiomic model [AUC=0.6641(0.4904-0.8378)]. In particular, we applied SHapley Additive exPlanation (SHAP) method for the first time to a radiomics-based logistic regression model to further interpret the radiomic features from case-based and feature-based perspectives. The integrated radiomic model enables the first accurate quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients, addressing the limitations of the current qualitative assessment of the plan through dose-volume parameters only. Conclusion: We successfully developed and validated an integrated radiomic model containing rectal information. SHAP analysis of the model suggests that radiomic features have a supporting role in the quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of different ultrasonic machines on the performance of radiomics models using ultrasound (US) images in the prediction of lymph node metastasis (LNM) for patients with cervical cancer (CC) preoperatively. Methods A total of 536 CC patients with confirmed histological characteristics and lymph node status after radical hysterectomy and pelvic lymphadenectomy were enrolled. Radiomics features were extracted and selected with US images acquired with ATL HDI5000, Voluson E8, MyLab classC, ACUSON S2000, and HI VISION Preirus to build radiomics models for LNM prediction using support vector machine (SVM) and logistic regression, respectively. Results There were 148 patients (training vs validation: 102:46) scanned in machine HDI5000, 75 patients (53:22) in machine Voluson E8, 100 patients (69:31) in machine MyLab classC, 110 patients (76:34) in machine ACUSON S2000, and 103 patients (73:30) in machine HI VISION Preirus, respectively. Few radiomics features were reproducible among different machines. The area under the curves (AUCs) ranged from 0.75 to 0.86, 0.73 to 0.86 in the training cohorts, and from 0.71 to 0.82, 0.70 to 0.80 in the validation cohorts for SVM and logistic regression models, respectively. The highest difference in AUCs for different machines reaches 17.8% and 15.5% in the training and validation cohorts, respectively. Conclusions The performance of radiomics model is dependent on the type of scanner. The problem of scanner dependency on radiomics features should be considered, and their effects should be minimized in future studies for US images. [ABSTRACT FROM AUTHOR]

Recent studies demonstrated a significantly increased frequency of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs). The purpose of this study is to investigate the effect of first-line and second-line EGFR-tyrosine kinase inhibitors (TKIs) in the treatment of NSCLC with MPEs harboring exon 19 deletion and L858R mutation. From 2010 to 2015, 203 NSCLC patients with MPEs harboring EGFR mutation treated with EGFR-TKIs were reviewed. The efficacy were evaluated with Pearson chisquare or Fisher's exact tests, Log-rank test and Cox proportional hazards model. The objective response rate (ORR) and disease control rate (DCR) for patients treated with first-line and second-line EGFR-TKIs were 21.9%, 91.4% and 14.7%, 85.3%, respectively. The overall median PFS and OS of enrolled NSCLC patients with MPE were 9.3 months (95% CI, 8.4-10.2 months), 20.9 months (95% CI, 18.9-22.9 months) after first-line TKIs, and 7.6 months (95% CI, 6.6-8.6 months), 15.3 months (95% CI, 13.6-15.9 months) after second-line TKIs. The exon 19 deletion arm had a longer median PFS (9.4 vs 7.1 months, p=0.003) and OS (16.8 vs 13.8 months, p=0.003) compared with the L858R mutation arm after second-line TKIs. In a conclusion, EGFR genotype was an independent predictor of PFS and OS. No significant side effects differences between the two mutation groups was observed for first or second-line EGFR-TKIs. This study demonstrated that EGFR mutations are significant predictors for advanced NSCLC patients with MPE receiving secondline EGFR-TKIs treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Acquired radioresistance during radiotherapy is considered as the most important reason for local tumor recurrence or treatment failure. Circular RNAs (circRNAs) have recently been identified as microRNA sponges and involve in various biological processes. The purpose of this study is to investigate the role of circRNAs in the radioresistance of esophageal cancer.Methods: Total RNA was isolated from human parental cell line KYSE-150 and self-established radioresistant esophageal cancer cell line KYSE-150R, and hybridized to Arraystar Human circRNA Array. Quantitative real-time PCR was used to confirm the circRNA expression profiles obtained from the microarray data. Bioinformatic tools including gene ontology (GO) analysis, KEGG pathway analysis and network analysis were done for further assessment.Results: Among the detected candidate 3752 circRNA genes, significant upregulation of 57 circRNAs and downregulation of 17 circRNAs in human radioresistant esophageal cancer cell line KYSE-150R were observed compared with the parental cell line KYSE-150 (fold change ≥2.0 and P < 0.05). There were 9 out of these candidate circRNAs were validated by real-time PCR. GO analysis revealed that numerous target genes, including most microRNAs were involved in the biological processes. There were more than 400 target genes enrichment on Wnt signaling pathway. CircRNA_001059 and circRNA_000167 were the two largest nodes in circRNA/microRNA co-expression network.Conclusions: Our study revealed a comprehensive expression and functional profile of differentially expressed circRNAs in radioresistant esophageal cancer cells, indicating possible involvement of these dysregulated circRNAs in the development of radiation resistance. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stem cells (MSCs)-based therapies have had positive outcomes in animal models of cardiovascular diseases. However, the number and function of MSCs decline with age, reducing their ability to contribute to endogenous injury repair. The potential of stem cells to restore damaged tissue in older individuals can be improved by specific pretreatment aimed at delaying senescence and improving their regenerative properties. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that modulates age-related signaling pathways, and hence is a good candidate for rejuvenative function. Methods: Bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated from young (6-month-old) or aged (24-month-old) male donor rats. Cell proliferation was measured using the CCK8 cell proliferation assay; secretion of VEGF, bFGF, HGF, and IGF was assessed by RT-qPCR and ELISA. Apoptosis was induced by hypoxia and serum deprivation (hypoxia/SD) for up to 6 hr, and examined by flow cytometry. Expression levels of AMP-activated protein kinase (AMPK) and forkhead box class O 3a (FOXO3a) were detected by Western blotting. CD74 expression was assayed using RT-qPCR, Western blotting, and immunofluorescence. Results: In this study, we found that MSCs isolated from the bone marrow of aged rats displayed reduced proliferative capacity, impaired ability to mediate paracrine signaling, and lower resistance to hypoxia/serum deprivation-induced apoptosis, when compared to younger MSCs. Interestingly, pretreatment of aged MSCs with MIF enhanced their growth, paracrine function and survival. We detected enhanced secretion of VEGF, bFGF, HGF, and IGF from MIF-treated MSCs using ELISA. Finally, we show that hypoxia/serum deprivation-induced apoptosis is inhibited in aged MSCs following MIF exposure. Next, we found that the mechanism underlying the rejuvenating function of MIF involves increased CD74-dependent phosphorylation of AMPK and FOXO3a. Furthermore, this effect was abolished when CD74, AMPK, or FOXO3a expression was silenced using small-interfering RNAs(siRNA). Conclusions: MIF can rejuvenate MSCs from a state of age-induced senescence by interacting with CD74 and subsequently activating AMPK-FOXO3a signaling pathways. Pretreatment of MSCs with MIF may have important therapeutic implications in restoration or rejuvenation of endogenous bone marrow-MSCs in aged individuals. [ABSTRACT FROM AUTHOR]

Background: Acquired radioresistance has significantly compromised the efficacy of radiotherapy for esophageal cancer. The purpose of this study is to investigate the roles of epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway in the acquirement of radioresistance during the radiation treatment of esophageal cancer. Methods: We previously established a radioresistant cell line (KYSE-150R) from the KYSE-150 cell line (a human cell line model for esophageal squamous cell carcinoma) with a gradient cumulative irradiation dose. In this study, the expression of EMT phenotypes and the Wnt/β-catenin signaling pathway proteins were examined by real-time PCR, western blot and immunofluorescence in the KYSE-150R cells. The KYSE-150R cells were then treated with a β-Catenin/Tcf inhibitor FH535. The expressions of nuclear and cytoplasmic β-catenin and EMT markers in KYSE-150R cells were assessed at both mRNA and protein level after FH535 treatment. The radiosensitization effect of FH535 on KYSE-150R was evaluated by CCK8 analysis and a colony forming assay. DNA repair capacities was detected by the neutral comet assays. Results: KYSE-150R cell line displayed obvious radiation resistance and had a stable genetic ability. EMT phenotype was presented in the KYSE-150R cells with decreased E-cadherin and increased snail and twist expressions. The up-regulated expressions of Wnt/β-catenin signaling pathway proteins (Wnt1, FZD1-4, GSK3β, CTNNB1 and Cyclin D1), the increased phosphorylation of GSK3β, and the decreased phosphorylation of β-catenin were observed in KYSE-150R cells compared with KYSE-150 cells, implicating the activation of the Wnt pathway in KYSE-150R cells. The expression of nuclear β-catenin and nuclear translocation of β-catenin from the cytoplasm was decreased after FH535 treatment. FH535 also reversed EMT phenotypes by increasing E-cadherin expression. The cell proliferation rates of KYSE-150R were dose-dependent and the radiation survival fraction was significantly decreased upon FH535 treatment. Neutral comet assays indicated that FH535 impairs DNA double stranded break repair in KYSE-150R cells. Conclusions: Acquisition of radioresistance and EMT in esophageal cancer cells is associated with the activation of the Wnt/β-catenin pathway. EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting the Wnt/β-catenin pathway with FH535 treatment. [ABSTRACT FROM AUTHOR]

Purpose To investigate the feasibility of constant dose rate volumetric modulated arc therapy (CDRVMAT) in the treatment of nasopharyngeal cancer (NPC) patients and to introduce rotational arc radiotherapy for linacs incapable of dose rate variation. Materials and methods Twelve NPC patients with various stages treated previously using variable dose rate (VDR) VMAT were enrolled in this study. CDR-VMAT, VDR-VMAT and mutlicriteria optimization (MCO) VMAT plans were generated for each patient on RayStation treatment planning system with identical objective functions and the dosimetric differences among these three planning schemes were evaluated and compared. Non dosimetric parameters of optimization time, delivery time and delivery accuracy were also evaluated. Results The planning target volume of clinical target volume (PTV-CTV) coverage of CDR-VMAT was a bit inferior to those of VDR- and MCO-VMAT. The V93 (p = 0.01) and V95 (percent volume covered by isodose line) (p = 0.04) for CDR-VMAT, VDR-VMAT and MCO-VMAT were 98.74% ± 0.31%, 99.76% ± 0.16%, 99.38% ± 0.43%, and 98.40% ± 0.48%, 99.53% ± 0.28%, 99.07% ± 0.52%, respectively.. However, the CDR-VMAT showed a better dose homogeneity index (HI) (p = 0.01) in PTV-CTV. No significant difference in other target coverage parameters was observed. There was no significant difference in OAR sparing among these three planning schemes except for a higher maximum dose (Dmax) on the brainstem for CDR-VMAT. The brainstem Dmax of CDR-VMAT, VDR-VMAT and MCOVMAT were 54.26 ± 3.21 Gy, 52.19 ± 1.65 Gy, and 52.79 ± 4.77 Gy, respectively. The average delivery time (p < 0.01) and the average percent γ passing rates (p = 0.02) of CDRVMAT, VDR-VMAT and MCO-VMAT were 7.01 ± 0.43 min, 4.75 ± 0.07 min, 4.01 ± 0.28 min, and 95.75% ± 2.57%, 97.65% ± 1.45%, 97.36% ± 2.45%, respectively. Conclusion CDR-VMAT offers an additional option of rotational arc radiotherapy for linacs incapable of dose rate variation with a lower initial cost. Its plan quality was acceptable but should be thoroughly checked compared with VDR-VMAT and MCO-VMAT in the treatment of NPC. [ABSTRACT FROM AUTHOR]

Studies have shown that bone marrow-derived cells play an important role in tumor recurrence after chemotherapy and radiotherapy. In this study, we examined the relationship between the accumulation of Gr-1+CD11b+ cells and tumor recurrence after irradiation in tumor-bearing mice. By transplanting bone marrow cells into whole body-irradiated mice depleted of bone marrow, we assessed the role of Gr-1+CD11b+ cells in lung carcinoma models after local irradiation (LI). 20 Gy local irradiation could recruit CD11b+CXCR4+ cells into the irradiated tissues, and the recruited CD11b+CXCR4+ cells could promote tumor recurrence. Further 6 Gy whole body irradiation (WBI6Gy) could decrease tumor recurrence by inhibiting the accumulation of Gr-1+CD11b+ cells and then suppressing tumor vasculogenesis and angiogenesis. Our results suggest that the accumulation of CD11b+Gr-1+ cells promote tumor re-growth after local irradiation by enhancing tumor neovascularization, and low dose of whole body irradiation or irradiation of enlarged spleen may provide a new alternative for anti-angiogenesis therapies. [ABSTRACT FROM AUTHOR]

Objective To investigate the anatomic and dosimetric variations of volumetric modulated arc therapy (VMAT) in the treatment of nasopharyngeal cancer (NPC) patients based on weekly cone beam CT (CBCT). Materials and methods Ten NPC patients treated by VMAT with weekly CBCT for setup corrections were reviewed retrospectively. Deformed volumes of targets and organs at risk (OARs) in the CBCT were compared with those in the planning CT. Delivered doses were recalculated based on weekly CBCT and compared with the planned doses. Results No significant volumetric changes on targets, brainstem, and spinal cord were observed. The average volumes of right and left parotid measured from the fifth CBCT were about 4.4 and 4.5 cm³ less than those from the first CBCT, respectively. There were no significant dose differences between average planned and delivered doses for targets, brainstem and spinal cord. For right parotid, the delivered mean dose was 10.5 cGy higher (p = 0.004) than the planned value per fraction, and the V26 and V32 increased by 7.5% (p = 0.002) and 7.4% (p = 0.01), respectively. For the left parotid, the D50 (dose to the 50% volume) was 8.8 cGy higher (p = 0.03) than the planned values per fraction, and the V26 increased by 8.8% (p = 0.002). Conclusion Weekly CBCTs were applied directly to study the continuous volume changes and resulting dosimetric variations of targets and OARs for NPC patients undergoing VMAT. Significant volumetric and dosimetric variations were observed for parotids. Replanning after 30 Gy will benefit the protection on parotids. [ABSTRACT FROM AUTHOR]

Background: To investigate the feasibility and benefits of a modified adaptive radiotherapy (ART) by replanning in the initial CT (iCT) with new contours from a repeat CT (rCT) based on CT-CT image fusion for nasopharyngeal cancer (NPC) patients underwent volumetric modulated arc radiotherapy (VMAT).Materials and Methods: Nine NPC patients underwent VMAT treatment with a rCT at 23rd fraction were enrolled in this study. Dosimetric differences for replanning VMAT plans in the iCT and in the rCT were compared. Volumetric and dosimetric changes of gross tumor volume (GTV) and organs at risk (OARs) of this modified ART were also investigated.Results: No dosimetric differences between replanning in the iCT and in the rCT were observed. The average volume of GTV decreased from 78.83 ± 38.42 cm3 in the iCT to 71.44 ± 37.46 cm3 in the rCT, but with no significant difference (p = 0.42).The average volume of the left and right parotid decreased from 19.91 ± 4.89 cm3 and 21.58 ± 6.16 cm3 in the iCT to 11.80 ± 2.79 cm3 and 13.29 ± 4.17 cm3 in the rCT (both p < 0.01), respectively. The volume of other OARs did not shrink very much. No significant differences on PTVGTV and PTVCTV coverage were observed for replanning with this modified ART. Compared to the initial plans, the average mean dose of the left and right parotid after re-optimization were decreased by 62.5 cGy (p = 0.05) and 67.3 cGy (p = 0.02), respectively, and the V5 (the volume receiving 5 Gy) of the left and right parotids were decreased by 7.8% (p = 0.01) and 11.2% (p = 0.001), respectively. There was no significant difference on the dose delivered to other OARs.Conclusion: Patients with NPC undergoing VMAT have significant anatomic and dosimetric changes to parotids. Repeat CT as an anatomic changes reference and re-optimization in the iCT based on CT-CT image fusion was accurate enough to identify the volume changes and to ensure safe dose to parotids. [ABSTRACT FROM AUTHOR]

Radiation-associated toxicities due to sophisticated ocular anatomy and shape variability of organs at risk (OARs) are major concerns during external beam radiation therapy (EBRT) of patients with intraocular cancer. A novel two-step image registration strategy between optical coherence tomography (OCT) and computed tomography (CT) images was proposed and validated to precisely localize the target in the EBRT of patients with intraocular cancer. Specifically, multiple features from OCT and CT images were extracted automatically, then spatial transformation based on thin-plate spline function was performed iteratively to achieve feature alignment between the CT and OCT images. Finally, an exclusive OR (XOR) algorithm was applied for precise 3D registration using a 3D-mesh model generated from OCT and CT volumes. The accuracy of the proposed novel registration strategy was validated and tested in a schematic-eye phantom with an artificially introduced tumor and in ten patients with confirmed primary and/or secondary intraocular cancer. There was an average registration error and computational time of 0.21  ±  0.05° and 259  ±  5 s, together with an average Dice similarity coefficient and Hausdorff distance of 88.4  ±  0.65 and 0.89  ±  0.09, respectively. The preliminary experimental results demonstrated that the proposed novel strategy to overcome current limitations on eye modeling and to localize precisely the tumor target during EBRT of intraocular cancer is promising. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]