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1.
Opt Lett ; 48(11): 2969-2972, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37262256

ABSTRACT

A multipolar silicon-based resonant meta-surface scheme is proposed and numerically presented via intercalating oblique slits into the silicon patches, leading to an ultra-sharp resonant spectrum via the excitation of electric and magnetic quadrupoles and their hybridization coupling. High-performance electro-optical modulator is demonstrated, showing a spectrally shifted modulation sensitivity up to 1.546 nm/V. Moreover, novel, to the best of our knowledge, optical sensing for ion solution concentration with the detection limitation down to 5.15 × 10-3 is demonstrated as another application. These findings provide an impressive strategy for resonant silicon-based nano-photonics and opto-electronic devices.

2.
Phys Med Biol ; 68(1)2022 12 23.
Article in English | MEDLINE | ID: mdl-36562611

ABSTRACT

Objective.Develop an anatomical model based on the statistics of the population data and evaluate the model for anatomical robust optimisation in head and neck cancer proton therapy.Approach.Deformable image registration was used to build the probability model (PM) that captured the major deformation from patient population data and quantified the probability of each deformation. A cohort of 20 nasopharynx patients was included in this retrospective study. Each patient had a planning CT and 6 weekly CTs during radiotherapy. We applied the model to 5 test patients. Each test patient used the remaining 19 training patients to build the PM and estimate the likelihood of a certain anatomical deformation to happen. For each test patient, a spot scanning proton plan was created. The PM was evaluated using proton spot location deviation and dose distribution.Main results. Using the proton spot range, the PM can simulate small non-rigid variations in the first treatment week within 0.21 ± 0.13 mm. For overall anatomical uncertainty prediction, the PM can reduce anatomical uncertainty from 4.47 ± 1.23 mm (no model) to 1.49 ± 1.08 mm at week 6. The 95% confidence interval (CI) of dose metric variations caused by actual anatomical deformations in the first week is -0.59% ∼ -0.31% for low-risk CTD95, and 0.84-3.04 Gy for parotidDmean. On the other hand, the 95% CI of dose metric variations simulated by the PM at the first week is -0.52 ∼ -0.34% for low-risk CTVD95, and 0.58 ∼ 2.22 Gy for parotidDmean.Significance.The PM improves the estimation accuracy of anatomical uncertainty compared to the previous models and does not depend on the acquisition of the weekly CTs during the treatment. We also provided a solution to quantify the probability of an anatomical deformation. The potential of the model for anatomical robust optimisation is discussed.


Subject(s)
Head and Neck Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Humans , Proton Therapy/methods , Protons , Retrospective Studies , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Uncertainty , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/methods , Organs at Risk
3.
Med Phys ; 49(12): 7683-7693, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36083223

ABSTRACT

PURPOSE: To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatment plans. METHODS: A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weekly CT. RESULTS: Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D mean $_{\text{mean}}$ ) of parotid 11.87 Gy, increase in max dose (D max $_{\text{max}}$ ) of brainstem 20.82 Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D mean $_{\text{mean}}$ by 4.88 Gy, increase in brainstem D max $_{\text{max}}$ by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-risk CTV. CONCLUSION: This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocenter shift.


Subject(s)
Head and Neck Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Humans , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Proton Therapy/methods , Retrospective Studies , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Organs at Risk
4.
Contrast Media Mol Imaging ; 2022: 4542288, 2022.
Article in English | MEDLINE | ID: mdl-36017018

ABSTRACT

Breast cancer is a highly harmful malignancy, which often causes great distress to patients and seriously affects their physical and mental health. Breast cancer causes patients to experience decreased appetite, decreased eating, and indigestion, which in turn leads to malnutrition, body wasting, resistance, immune compromise, progressive anemia, cachexia, and, as a result, severe secondary infections. To investigate the efficacy evaluation of neoadjuvant chemotherapy in breast cancer by MRI, forty-eight subjects treated at the hospital from June 2014 to August 2019 were recruited. After the neoadjuvant chemotherapy, the patients were divided into two groups based on the results of histopathological examination, namely, the ineffective group (n = 14) and the effective group (n = 34). Changes in MRI indicators were compared between the two groups before and after the neoadjuvant chemotherapy. The maximum diameter of lesions decreased significantly after the neoadjuvant chemotherapy than before. The apparent diffusion coefficient (ADC) increased considerably, and the time-intensity curve (TIC) showed a transition from type III to type II/I and from type II to type I. MRI can indicate the maximum diameter of the breast cancer lesion, ADC, and TIC type. Therefore, it can be used to evaluate the efficacy of neoadjuvant chemotherapy for breast cancer and be widely applied in clinical practice.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Neoadjuvant Therapy/methods , Treatment Outcome
5.
Radiother Oncol ; 173: 93-101, 2022 08.
Article in English | MEDLINE | ID: mdl-35667573

ABSTRACT

PURPOSE: To demonstrate predictive anatomical modelling for improving the clinical workflow of adaptive intensity-modulated proton therapy (IMPT) for head and neck cancer. METHODS: 10 radiotherapy patients with nasopharyngeal cancer were included in this retrospective study. Each patient had a planning CT, weekly verification CTs during radiotherapy and predicted weekly CTs from our anatomical model. Predicted CTs were used to create predicted adaptive plans in advance with the aim of maintaining clinically acceptable dosimetry. Adaption was triggered when the increase in mean dose (Dmean) to the parotid glands exceeded 3 Gy(RBE). We compared the accumulated dose of two adaptive IMPT strategies: 1) Predicted plan adaption: One adaptive plan per patient was optimised on a predicted CT triggered by replan criteria. 2) Standard replan: One adaptive plan was created reactively in response to the triggering weekly CT. RESULTS: Statistical analysis demonstrates that the accumulated dose differences between two adaptive strategies are not significant (p > 0.05) for CTVs and OARs. We observed no meaningful differences in D95 between the accumulated dose and the planned dose for the CTVs, with mean differences to the high-risk CTV of -1.20 %, -1.23 % and -1.25 % for no adaption, standard and predicted plan adaption, respectively. The accumulated parotid Dmean using predicted plan adaption is within 3 Gy(RBE) of the planned dose and 0.31 Gy(RBE) lower than the standard replan approach on average. CONCLUSION: Prediction-based replanning could potentially enable adaptive therapy to be delivered without treatment gaps or sub-optimal fractions, as can occur during a standard replanning strategy, though the benefit of using predicted plan adaption over the standard replan was not shown to be statistically significant with respect to accumulated dose in this study. Nonetheless, a predictive replan approach can offer advantages in improving clinical workflow efficiency.


Subject(s)
Nasopharyngeal Neoplasms , Proton Therapy , Radiotherapy, Intensity-Modulated , Humans , Nasopharyngeal Neoplasms/radiotherapy , Organs at Risk , Proton Therapy/methods , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Workflow
6.
Phys Med Biol ; 67(9)2022 04 15.
Article in English | MEDLINE | ID: mdl-35316795

ABSTRACT

Objective. We proposed two anatomical models for head and neck patients to predict anatomical changes during the course of radiotherapy.Approach. Deformable image registration was used to build two anatomical models: (1) the average model (AM) simulated systematic progressive changes across the patient cohort; (2) the refined individual model (RIM) used a patient's CT images acquired during treatment to update the prediction for each individual patient. Planning CTs and weekly CTs were used from 20 nasopharynx patients. This dataset included 15 training patients and 5 test patients. For each test patient, a spot scanning proton plan was created. Models were evaluated using CT number differences, contours, proton spot location deviations and dose distributions.Main results. If no model was used, the CT number difference between the planning CT and the repeat CT at week 6 of treatment was on average 128.9 Hounsfield Units (HU) over the test population. This can be reduced to 115.5 HU using the AM, and to 110.5 HU using the RIM3(RIM, updated at week (3). When the predicted contours from the models were used, the average mean surface distance of parotid glands can be reduced from 1.98 (no model) to 1.16 mm (AM) and 1.19 mm (RIM3) at week 6. Using the proton spot range, the average anatomical uncertainty over the test population reduced from 4.47 ± 1.23 (no model) to 2.41 ± 1.12 mm (AM), and 1.89 ± 0.96 mm (RIM3). Based on the gamma analysis, the average gamma index over the test patients was improved from 93.87 ± 2.48 % (no model) to 96.16 ± 1.84% (RIM3) at week 6.Significance. The AM and the RIM both demonstrated the ability to predict anatomical changes during the treatment. The RIM can gradually refine the prediction of anatomical changes based on the AM. The proton beam spots provided an accurate and effective way for uncertainty evaluation.


Subject(s)
Head and Neck Neoplasms , Proton Therapy , Algorithms , Cone-Beam Computed Tomography/methods , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Humans , Image Processing, Computer-Assisted/methods , Proton Therapy/methods , Protons , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods
7.
Opt Express ; 29(4): 5270-5278, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33726066

ABSTRACT

We propose and demonstrate a new kind of resonant absorber via introducing the nano-slit into a photonic film. The combination of the nano-slit cavity and the photonic waveguide provides a powerful way to manipulate the light behaviors including the spectral Q factors and the absorption efficiency. Ultra-sharp resonant absorption with the Q factors up to 579.5 is achieved, suggesting an enhancement of ∼6100% in contrast to that of the metal-dielectric flat film structure. Moreover, in comparison with the low absorption of 5.4% for the system without nano-slit, the spectral absorption is up to ∼96.6% for the nano-slit assisted photonic absorber. The high Q resonant absorption can be further manipulated via the structural parameters and the polarization state. The operation wavelengths can be tuned by the lattice constant. As the nano-slit introduced into the dielectric film, strong optical field confinement effects can be achieved by the cavity resonance via the nano-slit itself, and the guided resonant effect in the photonic waveguide cavity formed by the adjacent nano-slits. Otherwise, the photonic-plasmonic hybridization effect is simultaneously excited between the dielectric guided cavity layer and the metal substrate. These findings can be extended to other photonic nano-cavity systems and pave new insights into the high Q nano-optics devices.

8.
BMC Cancer ; 20(1): 242, 2020 Mar 23.
Article in English | MEDLINE | ID: mdl-32293320

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) ranks the third among the most common malignancies globally. It is well known that microRNAs (miRNAs) play vital roles in destabilizing mRNAs and repressing their translations in this disease. However, the mechanism of miRNA-induced mRNA cleavage remains to be investigated. METHOD: In this study, high-throughput small RNA (sRNA) sequencing was utilized to identify and profile miRNAs from six pairs of colorectal cancer tissues (CTs) and adjacent tissues (CNs). Degradome sequencing (DS) was employed to detect the cleaved target genes. The Database for Annotation, Visualization and Integrated Discovery (DAVID) software was used for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. RESULTS: In total, 1278 known miRNAs (clustered into 337 families) and 131 novel miRNAs were characterized in the CT and CN libraries, respectively. Of those, 420 known and eight novel miRNAs were defined as differentially expressed miRNAs (DEmiRNAs) by comparing the expression levels observed in the CT and CN libraries. Furthermore, through DS, 9685 and 202 potential target transcripts were characterized as target genes for 268 known and 33 novel miRNAs, respectively. It was further predicted that a total of 264 targeted genes for the 85 DEmiRNAs are involved in proteoglycans in cancer and the AMP-activated protein kinase signaling pathway. After systemic analysis of prognosis-related miRNA targets in those cancer-related signal pathways, we found that two targets ezrin (EZR) and hematopoietic cell-specific Lyn substrate 1 (HCLS1) had the potential prognostic characteristics with CRC regarding over survival (OS) or recurrence. CONCLUSION: In total, we found that endonucleolytic miRNA-directed mRNA cleavage occurs in CRC. A number of potential genes targeted by CRC-related miRNAs were identified and some may have the potential as prognosis markers of CRC. The present findings may lead to an improved better appreciation of the novel interaction mode between miRNAs and target genes in CRC.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Profiling , High-Throughput Nucleotide Sequencing/methods , MicroRNAs/genetics , RNA, Messenger/genetics , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis
9.
Medicine (Baltimore) ; 98(34): e16916, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31441872

ABSTRACT

BACKGROUND: Colorectal Cancer (CRC) is a highly heterogeneous disease. RNA profiles of bulk tumors have enabled transcriptional classification of CRC. However, such ways of sequencing can only target a cell colony and obscure the signatures of distinct cell populations. Alternatively, single-cell RNA sequencing (scRNA-seq), which can provide unbiased analysis of all cell types, opens the possibility to map cellular heterogeneity of CRC unbiasedly. METHODS: In this study, we utilized scRNA-seq to profile cells from cancer tissue of a CRC patient. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of genes within the clusters. RESULTS AND CONCLUSION: The 2824 cells were analyzed and categorized into 5 distinct clusters by scRNA-seq. For every cluster, specific cell markers can be applied, indicating each 1 of them different from another. We discovered that the tumor of CRC displayed a clear sign of heterogenicity, while genes within each cluster serve different functions. GO term analysis also stated that different cluster's relatedness towards the tumor of CRC differs. Three clusters participate in peripheral works in cells, including, energy transport, extracellular matrix generation, etc; Genes in other 2 clusters participate more in immunology processes. Lastly, trajectory plot analysis also supports the viewpoint, in that some clusters present in different states and pseudo-time, while others present in a single state or pseudo time. Our analysis provides more insight into the heterogeneity of CRC, which can provide assistance to further researches on this topic.


Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Profiling/methods , Genetic Heterogeneity , Sequence Analysis, RNA/methods , Aged , Biomarkers, Tumor/genetics , Female , Humans
10.
Cancer Manag Res ; 10: 4333-4347, 2018.
Article in English | MEDLINE | ID: mdl-30349367

ABSTRACT

Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further validation studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.

11.
Quant Imaging Med Surg ; 8(7): 637-647, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30211031

ABSTRACT

BACKGROUND: To quantify the geometrical changes of each neck nodal level (NNL) and estimate the geometric planning target volume (PTV) margin during image-guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC). METHODS: Twenty patients with locally advanced NPC underwent one planning computed tomography (CTplan) and 6 weekly repeat CT (CTrep) scans during chemoradiotherapy. Each CTrep was rigidly registered to the CTplan. All the NNLs were manually delineated in each transverse CT section. When comparing the NNL in CTrep with CTplan, their volumes, displacement of the center of the mass, and the shortest perpendicular distance (SPD) were automatically calculated. This was followed by calculation of the systematic and random errors, overlapping index (OI), and dice similarity coefficient (DSC). With PTVs isotropically expanded from NNL by 1, 2, 3, 4, and 5 mm, they were compared with NNL itself; OI >0.95 was defined as the acceptable geometrical coverage. The Mann-Whitney test was used for statistical analysis. RESULTS: All volumes, OI, and DSC of the NNLs (not including level IA) showed a linear decrease over time throughout the treatment course. The volume of NNLs decreased by 1-6% in the first week and 10-21% in the sixth week. The mean SPD was 1.3-1.7 and 1.9-3.5 mm in the first and sixth week respectively. The DSCs for nodal level IB, II, III, and IV were >0.7 and that of level V was <0.7 throughout the treatment course. For level IA and VI, DSC was <0.7 after the 2nd week. To maintain the OI >0.95, 2-5 mm was needed to expand the different NNLs. CONCLUSIONS: The geometrical changes of each NNL are substantial and the necessary margin of 2-5 mm depended on individual NNL is needed to maintain geometrical coverage throughout the course of IGRT for NPC.

12.
Chem Commun (Camb) ; 54(47): 6060-6063, 2018 Jun 08.
Article in English | MEDLINE | ID: mdl-29808876

ABSTRACT

Black phosphorus quantum dots are incorporated into liposomal bilayers to produce a drug delivery system with excellent near-infrared (NIR) photothermal properties and drug release capability controlled by light. In vitro experiments demonstrate its good biocompatibility and NIR-light-induced chemo-photothermal antitumor efficiency.


Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Lipid Bilayers/chemistry , Liposomes/chemistry , Phosphorus/chemistry , Quantum Dots/radiation effects , Animals , Cholesterol/chemistry , Cholesterol/toxicity , Drug Liberation , Heating , Humans , Infrared Rays , Lipid Bilayers/toxicity , Liposomes/toxicity , MCF-7 Cells , Mice , Microscopy, Confocal , Particle Size , Phosphatidylcholines/chemistry , Phosphatidylcholines/toxicity , Phosphorus/toxicity , Quantum Dots/chemistry , Quantum Dots/toxicity
13.
Cancer Manag Res ; 10: 447-464, 2018.
Article in English | MEDLINE | ID: mdl-29563835

ABSTRACT

BACKGROUND: Circulating endothelial cells (CECs) and their subpopulations could be potential novel biomarkers for various malignancies. However, reliable enumerable methods are warranted to further improve their clinical utility. This study aimed to optimize a flow cytometric method (FCM) assay for CECs and subpopulations in peripheral blood for patients with solid cancers. PATIENTS AND METHODS: An FCM assay was used to detect and identify CECs. A panel of 60 blood samples, including 44 metastatic cancer patients and 16 healthy controls, were used in this study. Some key issues of CEC enumeration, including sample material and anticoagulant selection, optimal titration of antibodies, lysis/wash procedures of blood sample preparation, conditions of sample storage, sufficient cell events to enhance the signal, fluorescence-minus-one controls instead of isotype controls to reduce background noise, optimal selection of cell surface markers, and evaluating the reproducibility of our method, were integrated and investigated. Wilcoxon and Mann-Whitney U tests were used to determine statistically significant differences. RESULTS: In this validation study, we refined a five-color FCM method to detect CECs and their subpopulations in peripheral blood of patients with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects (P<0.01). However, there was no significant difference in resting CEC levels between healthy subjects and cancer patients (P=0.193). CONCLUSION: We integrated and comprehensively addressed significant technical issues found in previously published assays and validated the reproducibility and sensitivity of our proposed method. Future work is required to explore the potential of our optimized method in clinical oncologic applications.

14.
Biomark Med ; 11(8): 665-676, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28597689

ABSTRACT

Angiogenesis contributes to the growth of solid tumors. Antiangiogenic agents are widely used in various cancers and considerable efforts have been made in the development of novel biomarkers that can predict the outcome of an anticancer treatment. Of those, circulating endothelial cells (CECs) and their subsets constitute a surrogate tool for monitoring disease activity. However, owing to the lack of standardization on the phenotypes and detection of CECs and their subsets, results have always been inconsistent and uninterpretable. In this review, we focus on the biological characteristics in terms of physiology, phenotypes and detection of CECs along with their subsets; review the current scenario of CEC enumeration as a surrogate biomarker in clinical oncology; and explore their future potential applications.

15.
Onco Targets Ther ; 10: 67-72, 2017.
Article in English | MEDLINE | ID: mdl-28053541

ABSTRACT

Patients with stage IV nasopharyngeal carcinoma (NPC) have a poor prognosis, even with effective chemotherapy. Target agents combined with chemotherapy may improve NPC patients' outcome. The case of a patient with NPC, who was treated by adding bevacizumab to chemotherapy after disease progression using first-line chemotherapy, is reported. Recently published literature about effects of combining bevacizumab with standard chemotherapy in NPC cell lines or patients are also reviewed and discussed. Consistent with a few preclinical trials and Phase II clinical trials, bevacizumab may reverse the drug resistance to chemotherapy, and its toxic side effects are well tolerated.

16.
Oncotarget ; 7(35): 56998-57010, 2016 Aug 30.
Article in English | MEDLINE | ID: mdl-27486770

ABSTRACT

Lung adenocarcinomas are more commonly associated with brain metastases (BM). Epidermal growth factor receptor (EGFR) mutations have been demonstrated to be both predictive and prognostic for patients with lung adenocarcinoma. We aimed to explore the potential association between EGFR mutation and the risk of BM in pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were retrospectively reviewed. A total of 108 patients had EGFR mutations in the entire cohort. Among them, 76 patients developed BM during their disease course. The incidence of BM was statistically higher in patients with EGFR mutations both at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate logistic regression analysis revealed that EGFR mutation significantly increased the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM at initial diagnosis, the accumulative rate of subsequent BM was significantly higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis identified EGFR mutation as the only independent risk factor for subsequent BM (HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our data suggest that EGFR mutation is an independent predictive and prognostic risk factor for BM and a positive predictive factor for OS in patients with BM.


Subject(s)
Adenocarcinoma/metabolism , Brain Neoplasms/metabolism , ErbB Receptors/genetics , Lung Neoplasms/metabolism , Mutation , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Brain Neoplasms/secondary , DNA Mutational Analysis , ErbB Receptors/metabolism , Exons , Female , Humans , Incidence , Kaplan-Meier Estimate , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors
17.
Quant Imaging Med Surg ; 6(2): 115-24, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27190763

ABSTRACT

BACKGROUND: Considerable geometrical change occurs during chemoradiotherapy (CRT) course of nasopharyngeal carcinoma (NPC). This aim of this study was to quantify the volumetric and surface variability of the target volumes (TV) and to estimate the expanded margin to maintain acceptable geometrical coverage. METHODS: Twenty patients with locally advanced nasopharyngeal cancer underwent one planning CT (pCT) and six weekly repeated CT (rCT) scans during the treatment course of definitive CRT. The TV included the gross tumor volume (GTV) of the primary tumor, large (shortest diameter >3.0 cm) and small (diameter >1 cm and ≤3 cm) positive neck lymph nodes, and low-risk clinical target volume (CTV_Lr) that were delineated manually on the pCT and each rCT. When comparing TV in pCT (V_pCT) and TV in rCT (V_rCT), the overlapping index (OI), Dice similarity coefficient (DSC), shortest perpendicular distance (SPD), and overall standard deviation (overall SD) were calculated to present the geometric changes. An isotropical margin was expanded outward around CTV_Lr in pCT to establish the mimic planning target volume (PTV). An OI ≥0.95 was defined as acceptable geometrical coverage. RESULTS: For all TV, DSCs decreased, and the SPDs and overall SD increased with the increasing number of fractions delivered. The DSCs of all gross TV were <70% after the third week. The mean SPDs were 1.5-2.5 mm in the first week and 5.2-6.2 mm in the last week. The OI and DSC in concurrent CRT were smaller than those in the sequential therapy; and similarly the SPD and overall SD in the concurrent therapy were larger than those in the sequential one. To maintain >95% geometrical coverage, a 2-mm additional margin could maintain the coverage throughout the treatment course and a 1-mm margin could maintain the desired coverage if there is an adaptive re-planning no later than the third week of the treatment course. CONCLUSIONS: Both volumetric coverage and surface of the tumour underwent the progressive changes during the treatment course of CRT. One to two mm as the expanded margin to establish the PTV is required to maintain >95% geometrical coverage.

18.
World J Microbiol Biotechnol ; 31(3): 477-85, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25595731

ABSTRACT

Microsclerotia (MS) formation was successfully induced in Nomuraea rileyi in liquid amended medium (AM) culture. To investigate how N. rileyi senses growth stress and regulates MS differentiation, based on transcriptome library, sho1 and sln1 genes were cloned. The transcription levels of sho1 and sln1 were upregulated in response to the changing culture conditions. To determine the functions of sho1 and sln1, gene-silencing mutants (sholi, sln1i and shol&sln1i) were generated using RNA silencing technology. The significant phenotypic changes in the mutants included reduced conidial yields by 22.72, 40.27, and 63.67 % and virulence by 24.53, 25.74, and 59.04 %, respectively. Furthermore, the mutants presented decreased MS yields by approximately 96 % under changing culture conditions. Our results confirmed the crucial role of Sho1p and Sln1p in sensing growth stress due to changing culture conditions and regulating MS differentiation.


Subject(s)
Adaptation, Physiological , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Metarhizium/physiology , Protein Kinases/metabolism , Stress, Physiological , Cloning, Molecular , Gene Expression Profiling , Gene Knockdown Techniques , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Metarhizium/growth & development , Protein Kinases/genetics , Spores, Fungal/growth & development , Transcription, Genetic
19.
Radiother Oncol ; 112(3): 413-7, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25104017

ABSTRACT

BACKGROUND AND PURPOSE: Compressed sensing (CS) based cone-beam computed tomography (CBCT) reconstruction techniques have been shown to improve image quality. This study was to investigate possible improvements of CBCTCS on manual delineation uncertainties of targets and organs-at-risk. PATIENTS AND METHODS: Eight H&N and eight breast cancer patients were selected. Each H&N or breast cancer patient had planning-CT (pCT), repeat-CT (rCT), and CBCT reconstructed by both Feldkamp (CBCTFDK) and compressed sensing methods. On each scan, targets and organs-at-risk were delineated by a radiation oncologist. The impact of reconstruction technique was quantitatively assessed by dice similarity coefficient (DSC) and the shortest perpendicular distance (SPD) between contours of two corresponding scans. RESULTS: The mean CBCTCS-to-rCT DSC was 7.2% and 8.0% bigger than the CBCTFDK-to-rCT for H&N and breast cancer patients respectively. The mean CBCTCS-to-rCT SPD was 16.6% and 25.4% smaller than CBCTFDK-to-rCT SPD. Due to anatomical changes, delineation accuracy reduced in reference to pCT, but no time trend was observed in CBCT based delineation accuracy in reference to rCT. CONCLUSION: This study demonstrated that CBCTCS has the potential to improve delineation accuracy in H&N and breast cancer patients over CBCTFDK, and CBCTCS thus has potential for adaptive radiotherapy.


Subject(s)
Breast Neoplasms/diagnostic imaging , Cone-Beam Computed Tomography/methods , Head and Neck Neoplasms/diagnostic imaging , Image Processing, Computer-Assisted/methods , Organs at Risk/diagnostic imaging , Aged , Female , Humans , Male , Middle Aged , Reproducibility of Results
20.
Onco Targets Ther ; 7: 1361-6, 2014.
Article in English | MEDLINE | ID: mdl-25114574

ABSTRACT

Paclitaxel (PTX) and/or cisplatin (CDDP), as important cytotoxic anti-cancer agents, are widely used to treat various solid tumors. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity is also occasionally reported. A patient diagnosed with nasopharyngeal cancer suffering acute ocular neurotoxicity 10 days after paclitaxel and CDDP administration at the recommended dose is described in the present case report, and PTX- and/or CDDP-induced ocular neurotoxicity are summarized according to previous reports. Possible mechanisms and the potential diagnostic, therapeutic and predictive strategies of PTX- and/or CDDP-induced ocular neurotoxicity are reviewed, to help the oncologist to take the infrequent toxicity of cytotoxic drugs into account and improve patient safety during anti-cancer therapy.

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