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1.
Opt Express ; 28(14): 19808-19817, 2020 Jul 06.
Article in English | MEDLINE | ID: mdl-32680053

ABSTRACT

In this paper, we propose and experimentally demonstrate a novel multi scrolls chaotic encryption scheme for CO-OFDM-PON. We analyze the principle of 3-dimension encryption scheme and discuss its encryption complexity. Compared with the previous hyper Chen chaotic encryption scheme, the proposed encryption algorithm can realize dynamic constellation point mapping of QAM signal with lower encryption complexity. We also compare the transmission performances of the two chaotic encryption schemes. The results show that the proposed multi scrolls scheme has better BER performance because it can decrease the peak to average power ratio (PAPR) of OFDM. What is more, the proposed encryption scheme is very sensitive to the initial secure key and a tiny discrepancy as small as 10-17 would lead to a completely different sequence. The high sensibility to the initial value can effectively increase encryption level and the key space of the multi scrolls encryption scheme is 106 times of that hyper Chen. Further, to verify the effectiveness of the proposed encryption algorithm, encrypted transmission of a digital picture in 80 km SSMF is carried out.

2.
Opt Express ; 28(17): 24343-24352, 2020 Aug 17.
Article in English | MEDLINE | ID: mdl-32906976

ABSTRACT

In this paper, we propose a novel phase noise suppression method based on Gaussian basis expansion (GBE) for CO-OFDM systems. We analyze the basic phase noise suppression principle of GBE and then demonstrate it in optical OFDM transmission systems. Compared with common phase compensation (CPE), orthogonal basis expansion (OBE) and eigenvector basis expansion (EBE) schemes, the proposed GBE scheme has better phase noise fitting ability with similar computation complexity. Futhermore, no additional back to back (BTB) pre-training is needed for the GBE scheme. Performance improvements by the GBE is experimental validated in the QPSK/16-QAM OFDM system with different transmission scenarios (different number of pilots and input power). In the QPSK-OFDM system, after 160 km SSMF transmission, a Q-factor improvement of 1.7 dB and 0.5 dB are achieved compared with the CPE and OBE schemes at the optimum input power of -4 dBm, respectively. In the 16-QAM-OFDM system, the measured BER improved from 8.21×10-4 to 2.36×10-4 with the GBE scheme. To further verify the effectiveness of the GBE scheme, we change the laser linewidth and measure the long transmission distance performance by simulation, the results show that the GBE scheme can effectively increase the laser linewidth tolerance and extend transmission distance. When the linewidth is 2-MHz, the proposed GBE scheme can extend the transmission distance from 1120 km to 1540 km at the BER of 10-4. Experimental and simulation results show that the proposed GBE scheme is a promising alternative phase noise suppression for CO-OFDM system.

3.
BMC Dev Biol ; 18(1): 20, 2018 11 20.
Article in English | MEDLINE | ID: mdl-30458702

ABSTRACT

BACKGROUND: Histone modifications are critical in regulating neuronal processes. However, the impacts of individual histone modifications on learning and memory are elusive. Here, we investigated the contributions of histone H3 lysine modifications to learning and memory in Drosophila by using histone lysine-to-alanine mutants. RESULTS: Behavioural analysis indicated that compared to the H3WT group, mutants overexpressing H3K23A displayed impaired courtship learning. Chromatin immunoprecipitation analysis of H3K23A mutants showed that H3K23 acetylation (H3K23ac) levels were decreased on learning-related genes. Knockdown of CREB-binding protein (CBP) decreased H3K23ac levels, attenuated the expression of learning-related genes, led to a courtship learning defect and altered development of the mushroom bodies. A decline in courtship learning ability was observed in both larvae and adult treatments with ICG-001. Furthermore, treatment of Drosophila overexpressing mutated H3K23A with a CBP inhibitor did not aggravate the learning defect. CONCLUSIONS: H3K23ac, catalysed by the acetyltransferases dCBP, contributes to Drosophila learning, likely by controlling the expression of specific genes. This is a novel epigenetic regulatory mechanism underlying neuronal behaviours.


Subject(s)
Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Histones/metabolism , Lysine/metabolism , p300-CBP Transcription Factors/metabolism , Acetylation , Animals , Courtship , Female , Gene Expression Regulation , Gene Knockdown Techniques , Histones/genetics , Learning , Male , Mutation , Neurons/metabolism
4.
Proc Natl Acad Sci U S A ; 112(45): 13988-93, 2015 Nov 10.
Article in English | MEDLINE | ID: mdl-26508632

ABSTRACT

Dynamic regulation of chromatin structure is required to modulate the transcription of genes in eukaryotes. However, the factors that contribute to the plasticity of heterochromatin structure are elusive. Here, we report that cyclin-dependent kinase 12 (CDK12), a transcription elongation-associated RNA polymerase II (RNAPII) kinase, antagonizes heterochromatin enrichment in Drosophila chromosomes. Notably, loss of CDK12 induces the ectopic accumulation of heterochromatin protein 1 (HP1) on euchromatic arms, with a prominent enrichment on the X chromosome. Furthermore, ChIP and sequencing analysis reveals that the heterochromatin enrichment on the X chromosome mainly occurs within long genes involved in neuronal functions. Consequently, heterochromatin enrichment reduces the transcription of neuronal genes in the adult brain and results in a defect in Drosophila courtship learning. Taken together, these results define a previously unidentified role of CDK12 in controlling the epigenetic transition between euchromatin and heterochromatin and suggest a chromatin regulatory mechanism in neuronal behaviors.


Subject(s)
Chromatin Assembly and Disassembly/physiology , Cyclin-Dependent Kinases/metabolism , Drosophila/genetics , Epigenesis, Genetic/physiology , Heterochromatin/physiology , Learning/physiology , Animals , Base Sequence , Blotting, Western , Chromatin Assembly and Disassembly/genetics , Chromatin Immunoprecipitation , Drosophila/physiology , Heterochromatin/genetics , Immunoprecipitation , Molecular Sequence Data , Octoxynol , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Salivary Glands/anatomy & histology , Salivary Glands/metabolism , Sequence Alignment , Sequence Analysis, DNA
5.
J Hazard Mater ; 477: 135423, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39106721

ABSTRACT

Infection with smut fungus like Ustilago maydis decreases crop yield via inducing gall formation. However, the in vitro impact of Ustilago spp. on plant growth and stress tolerance remains elusive. This study investigated the plant growth promotion and cadmium stress mitigation mechanisms of a filamentous fungus discovered on a cultural medium containing 25 µM CdCl2. ITS sequence alignment revealed 98.7 % similarity with Ustilago bromivora, naming the strain Ustilago sp. HFJ311 (HFJ311). Co-cultivation with HFJ311 significantly enhanced the growth of various plants, including Arabidopsis, tobacco, cabbage, carrot, rice, and maize, and improved Arabidopsis tolerance to abiotic stresses like salt and metal ions. HFJ311 increased chlorophyll and Fe contents in Arabidopsis shoots and enhanced root-to-shoot Fe translocation while decreasing root Fe concentration by approximately 70 %. Concurrently, HFJ311 reduced Cd accumulation in Arabidopsis by about 60 %, indicating its potential for bioremediation in Cd-contaminated soils. Additionally, HFJ311 stimulated IAA concentration by upregulating auxin biosynthesis genes. Overexpression of the Fe transporter IRT1 negated HFJ311's growth-promotion effects under Cd stress. These results suggest that HFJ311 stimulates plant growth and inhibits Cd uptake by enhancing Fe translocation and auxin biosynthesis while disrupting Fe absorption. Our findings offer a promising bioremediation strategy for sustainable agriculture and food security.


Subject(s)
Arabidopsis , Cadmium , Indoleacetic Acids , Iron , Ustilago , Arabidopsis/metabolism , Arabidopsis/microbiology , Arabidopsis/growth & development , Cadmium/metabolism , Iron/metabolism , Ustilago/metabolism , Ustilago/growth & development , Indoleacetic Acids/metabolism , Soil Pollutants/metabolism , Biodegradation, Environmental , Plant Roots/microbiology , Plant Roots/metabolism , Plant Roots/growth & development , Biological Transport , Zea mays/microbiology , Zea mays/metabolism , Zea mays/growth & development
6.
Front Microbiol ; 14: 1190650, 2023.
Article in English | MEDLINE | ID: mdl-37588884

ABSTRACT

Exponential increase in photovoltaic installations arouses concerns regarding the impacts of large-scale solar power plants on dryland ecosystems. While the effects of photovoltaic panels on soil moisture content and plant biomass in arid ecosystems have been recognized, little is known about their influence on soil microbial communities. Here, we employed a combination of quantitative PCR, high-throughput sequencing, and soil property analysis to investigate the responses of soil microbial communities to solar panel installation. We also report on the responses of plant communities within the same solar farm. Our findings showed that soil microbial communities responded differently to the shading and precipitation-alternation effects of the photovoltaic panels in an arid ecosystem. By redirecting rainwater to the lower side, photovoltaic panels stimulated vegetation biomass and soil total organic carbon content in the middle and in front of the panels, positively contributing to carbon storage. The shade provided by the panels promoted the co-occurrence of soil microbes but inhibited the abundance of 16S rRNA gene in the soil. Increase in precipitation reduced 18S rRNA gene abundance, whereas decrease in precipitation led to decline in plant aboveground biomass, soil prokaryotic community alpha diversity, and dehydrogenase activity under the panels. These findings highlight the crucial role of precipitation in maintaining plant and soil microbial diversities in dryland ecosystems and are essential for estimating the potential risks of large-scale solar power plants on local and global climate change in the long term.

7.
J Biomater Sci Polym Ed ; 31(3): 376-393, 2020 02.
Article in English | MEDLINE | ID: mdl-31724490

ABSTRACT

Biological modifications of the silk fibroin (silk) material have broad applications in textiles, biomedical materials and other industrial materials. It is economical to incorporate nanoparticles to the biosynthesis of silk fibroin by adding them to silkworm larval diets. This strategy may result in the rapid stable production of modified silk. Glucose-coated silver nanoparticles (AgNPs) were used to improve the AgNPs' biocompatibility, and the AgNPs were efficiently incorporated into silk by feeding. Larvae fed with AgNPs produced silk with significantly improved antibacterial properties and altered silk secondary structures. Both positive and negative effects on the growth and synthesis of silk proteins were observed after different AgNPs doses. Larvae feeding with low concentration of 0.02% and medium 0.20% AgNPs have greater transfer efficiencies of AgNPs to silk compared with feeding high concentration of 2.00% AgNPs. In addition, the elongation and tensile strength of the produced silk fibers were also significantly increased, with greater mammalian cell compatibility. The appropriate AgNPs concentration in the diet of silkworms can promote the synthesis of silk proteins, enhance their mechanical properties, improve their antibacterial property and inhibit the presence of Gram-negative bacteria.


Subject(s)
Bombyx/drug effects , Diet , Fibroins/biosynthesis , Glucose/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Water/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bombyx/metabolism , Escherichia coli/drug effects , Fibroins/chemistry , Fibroins/pharmacology , Larva/drug effects , Larva/metabolism , Protein Structure, Secondary , Silver/pharmacology , Solubility , Staphylococcus aureus/drug effects , Structure-Activity Relationship
8.
Cancer Lett ; 400: 18-29, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28455245

ABSTRACT

Lung cancer is one of the most lethal cancers due to its highly metastatic spreading. The motility of lung cancer cells is regulated by paracrine factors, such as TGF-ß, in the tumor microenvironment through the induction of epithelial-to-mesenchymal transition (EMT). The stability of microtubules is reported to be associated with the EMT process and the migration of cancer cells. Here, we observed that RCC1 domain-containing protein 1 (RCCD1) is highly expressed in non-small cell lung cancer (NSCLC) patients with poor prognosis, and RCCD1 is much higher expressed in tumor tissues compared with adjacent normal tissues. Depletion of RCCD1 using siRNAs significantly inhibits the migration of lung cancer cells. Subsequent studies reveal that the loss of RCCD1 results in upregulation of acetylated α-tubulin levels and stabilizes cytoskeletal microtubules. Mechanistically, we observed that RCCD1 modulates the stability of microtubules through interacting with JMJD5. Furthermore, RCCD1 depletion significantly attenuates the TGF-ß-induced EMT process, as assessed by altered expression of epithelial and mesenchymal markers (Occludin, Vimentin and Snail), and inhibits TGF-ß-induced cell migration. Collectively, these findings support RCCD1 as a novel regulator of TGF-ß-induced EMT in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carrier Proteins/metabolism , Cell Movement , Epithelial-Mesenchymal Transition , Lung Neoplasms/metabolism , Membrane Proteins/metabolism , Microtubules/metabolism , Transforming Growth Factor beta1/metabolism , A549 Cells , Acetylation , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carrier Proteins/genetics , Cell Movement/drug effects , Computational Biology , Databases, Genetic , Down-Regulation , Epithelial-Mesenchymal Transition/drug effects , HEK293 Cells , Histone Demethylases/metabolism , Humans , Kaplan-Meier Estimate , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Membrane Proteins/genetics , Microtubules/pathology , Neoplasm Invasiveness , Prognosis , RNA Interference , Signal Transduction , Time Factors , Transfection , Transforming Growth Factor beta1/pharmacology , Tubulin/metabolism
9.
J Radiosurg SBRT ; 4(1): 21-29, 2016.
Article in English | MEDLINE | ID: mdl-29296423

ABSTRACT

PURPOSE: Stereotactic Radiosurgery (SRS) can utilize different techniques. For small target SRS, the selections of the apertures of cone or MLC field influence the treatment significantly. In this study, while the aperture of the MLC and cone field vary, the dosimetric characteristics of the two techniques are compared for SRS of small targets which are in the favor of magnifying the dosimetric effect. METHODS AND MATERIALS: An anthropomorphic phantom was used to simulate the patient with an arbitrary drawn cranial target, whose volume is equivalent to a 4 millimeter sphere. Single 360 ARC plans were generated with Eclipse external beam and cone based treatment planning system from Varian Medical System. For MLC based plan, the apertures fit to the structure with circle margins varying with 2mm, 3mm, 4mm, 5mm and 6mm. These setups were compared with the cones being selected to be 5mm, 10mm, 12mm, 14mm and 16mm in diameter. For the MLC based plan, the leaf-edge-contour meet points were selected to be in the middle. Jaw positions were used both recommend and optimize options, which are provided by the treatment planning system. Mean dose was treated as the prescription dose. Comparison of the two planning techniques was carried out using 12Gy Volume (V12Gy) from dose-volume histogram (DVH), maximum dose to the prescription dose ratio (MDPD), ratio PITV (PIV/TV), radiation conformity index (RCI), which is defined to be TVPIV/PIV, and an integrated conformity index (TVPIV2/ (TVxPIV)), where PIV is the prescription isodose surface volume, TV is target volume, and TVPIV is the intersection of TV and the PIV. RESULTS: For the apertures used for this study, while MLC and cone based plans were compared by prescribed at 20Gy, the V12Gy ranges were from 1.0cc to 5.3cc with average at 3.3cc, and 0.1cc to 3.2cc with average value at 1.5cc. The variations of MDPD were 9% with average value at 1.04, and 12% with average at 1.03. The varying ranges of PITV were 35% with average value at 0.80, and 17% with average value at 0.54. Integrated conformity index (ICI) variations were up to 45% with average value at 0.34, and at the level of the 7% with average value at 0.42. CONCLUSIONS: For small target SRS, there are larger variations in V12Gy, PITV, and ICI in MLC based plan than those of cone based plan, while the difference is not significant for MDPD in both settings at the selected aperture sizes. These information could help in decision making through sensitivity study while sufficient clinical outcome information were available. The multiple ARC treatment plan and the clinical reality of algorithm for small aperture also need further investigation.

10.
Sci Rep ; 6: 34182, 2016 Sep 27.
Article in English | MEDLINE | ID: mdl-27669995

ABSTRACT

Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations.

11.
Chemosphere ; 159: 628-637, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27348562

ABSTRACT

Silicon nanoparticles (SiNPs) have attractive potential applications in biological and medical fields, and yet their impact on animals is still controversial, and there have been no reports of their effects on hematopoiesis. In this study, the effects of SiNPs on hemocytes and hematopoiesis were investigated by administering SiNPs via a vascular injection into an invertebrate model, the silkworm. Our results show that the ability of SiNPs to enter different types of circulating hemocytes and their impact on those hemocytes differed significantly. Rapid accumulation of SiNPs was observed in granulocytes, oenocytoids, and spherulocytes, which have immune functions in the circulating hemolymph, whereas SiNPs did not easily enter prohemocytes, which can differentiate into granulocytes, oenocytoids, and spherulocytes and replenish them. The SiNPs that entered the hemocytes initiated autophagy and apoptosis via the lysosomal/mitochondrial pathway. High-dose SiNPs weakly stimulated lysosomal activity in hematopoietic organs, but did not lead to a significant increase in reactive oxygen species or severe autophagy or apoptosis in the organ tissues. We suggest that the damage caused by high-dose SiNPs to hematopoiesis is self-healing, because few SiNPs entered the hematopoietic stem cells in the circulating hemolymph, so the damage to the hematopoietic tissues was limited.


Subject(s)
Bombyx/physiology , Hematopoiesis/physiology , Hemolymph/physiology , Nanoparticles/toxicity , Silicon/toxicity , Animals , Apoptosis/drug effects , Bombyx/drug effects , Hemocytes/drug effects , Hemolymph/metabolism , Mitochondria/metabolism , Models, Animal , Reactive Oxygen Species/metabolism
12.
Med Phys ; 32(10): 3132-5, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16279066

ABSTRACT

We developed a source blocking optimization algorithm for Gamma Knife radiosurgery, which is based on tracking individual source contributions to arbitrarily shaped target and critical structure volumes. A scalar objective function and a direct search algorithm were used to produce near real-time calculation results. The algorithm allows the user to set and vary the total number of plugs for each shot to limit the total beam-on time. We implemented and tested the algorithm for several multiple-isocenter Gamma Knife cases. It was found that the use of limited number of plugs significantly lowered the integral dose to the critical structures such as an optical chiasm in pituitary adenoma cases. The main effect of the source blocking is the faster dose falloff in the junction area between the target and the critical structure. In summary, we demonstrated a useful source-plugging algorithm for improving complex multi-isocenter Gamma Knife treatment planning cases.


Subject(s)
Algorithms , Models, Biological , Radiation Protection/methods , Radiometry/methods , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Computer Simulation , Humans , Radiotherapy Dosage
13.
Med Phys ; 31(3): 507-12, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15070247

ABSTRACT

Leaf end abutment is seldom studied when delivering segmental intensity modulated radiation therapy (IMRT) fields. We developed an efficient leaf sequencing method to eliminate leaf end abutment for segmental IMRT delivery. Our method uses simple matrix and sorting operations to obtain a solution that simultaneously minimizes total monitor units and number of segments without leaf end abutment between segments. We implemented and demonstrated our method for multiple clinical cases. We compared the results of our method with the results from exhaustive search method. We found that our solution without leaf end abutment produced equivalent results to the unconstrained solutions in terms of minimum total monitor units and minimum number of leaf segments. We conclude that the leaf end abutment fields can be avoided without affecting the efficiency of segmental IMRT delivery. The major strength of our method is its simplicity and high computing speed. This potentially provides a useful means for generating segmental IMRT fields that require high spatial resolution or complex intensity distributions.


Subject(s)
Particle Accelerators , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/instrumentation , Radiotherapy, Conformal/methods , Algorithms , Humans , Models, Theoretical , Time Factors
14.
Phys Med Biol ; 49(15): 3455-63, 2004 Aug 07.
Article in English | MEDLINE | ID: mdl-15379025

ABSTRACT

We have developed an automatic critical region shielding (ACRS) algorithm for Gamma Knife radiosurgery of trigeminal neuralgia. The algorithm selectively blocks 201 Gamma Knife sources to minimize the dose to the brainstem while irradiating the root entry area of the trigeminal nerve with 70-90 Gy. An independent dose model was developed to implement the algorithm. The accuracy of the dose model was tested and validated via comparison with the Leksell GammaPlan (LGP) calculations. Agreements of 3% or 3 mm in isodose distributions were found for both single-shot and multiple-shot treatment plans. After the optimized blocking patterns are obtained via the independent dose model, they are imported into the LGP for final dose calculations and treatment planning analyses. We found that the use of a moderate number of source plugs (30-50 plugs) significantly lowered (approximately 40%) the dose to the brainstem for trigeminal neuralgia treatments. Considering the small effort involved in using these plugs, we recommend source blocking for all trigeminal neuralgia treatments with Gamma Knife radiosurgery.


Subject(s)
Brain Stem/radiation effects , Models, Biological , Radiation Protection/methods , Radiometry/methods , Radiosurgery/methods , Radiotherapy Planning, Computer-Assisted/methods , Trigeminal Neuralgia/radiotherapy , Algorithms , Body Burden , Brain Injuries/etiology , Brain Injuries/prevention & control , Brain Stem/physiopathology , Computer Simulation , Humans , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Radiosurgery/adverse effects , Radiotherapy Dosage , Reproducibility of Results , Sensitivity and Specificity , Trigeminal Nerve/physiopathology , Trigeminal Nerve/radiation effects , Trigeminal Neuralgia/physiopathology
15.
J Appl Clin Med Phys ; 5(3): 62-5, 2004.
Article in English | MEDLINE | ID: mdl-15753940

ABSTRACT

We have developed a method to improve the setup accuracy of a Varian Clinac 6/100 couch for delivering conformal arc therapy using a tertiary micro multileaf collimator (MLC) system. Several immobilization devices have been developed to improve the mechanical stability and isocenter alignment of the couch: turn-knob harnesses, double-track alignment plates, and a drop-in rod that attaches the couch to the concrete floor. These add-on components minimize the intercomponent motion of the couch's scissor elevator, which allows consistent treatment setup. The accuracy of our isocenter couch alignment is an improvement over the above devices, within 1 mm of their accuracy. The couch has been used with over 15 patients and with over 50 modulated conformal arc treatment deliveries at our institution.


Subject(s)
Immobilization/instrumentation , Radiographic Image Enhancement/instrumentation , Radiosurgery/instrumentation , Radiotherapy Planning, Computer-Assisted/instrumentation , Radiotherapy, Conformal/instrumentation , Tomography, X-Ray Computed/instrumentation , Artifacts , Equipment Design , Equipment Failure Analysis , Immobilization/methods , Motion , Radiographic Image Enhancement/methods , Radiotherapy Planning, Computer-Assisted/methods , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
16.
Cancer ; 116(21): 5093-101, 2010 Nov 01.
Article in English | MEDLINE | ID: mdl-20629080

ABSTRACT

BACKGROUND: The objectives of this study were to investigate outcome prediction by measuring absolute tumor volume and regression ratios using serial magnetic resonance imaging (MRI) during radiation therapy (RT) for cervical cancer and to develop algorithms capable of identifying patients at risk of a poor therapeutic outcome. METHODS: Eighty patients with stage IB2 through IVA cervical cancer underwent 4 MRI scans: before RT (MRI1), during RT at 2 to 2.5 weeks (MRI2) at 4 to 5 weeks (MRI3), and 1 to 2 months after RT (MRI4). The median follow-up was 6.2 years (range, 0.2-9.4 years). Tumor volumes at MRI1, MRI2, MRI3, and MRI4 (V1, V2, V3, and V4, respectively) and tumor regression ratios (V2/V1, V3/V1, and V4/V1) were measured by 3-dimensional volumetry. Predictive metrics based on tumor volume/regression parameters were correlated with ultimate clinical outcomes, including tumor local recurrence (LR) and dying of disease (DOD). Predictive power was evaluated using the Mann-Whitney test, sensitivity/specificity analyses, and Kaplan-Meier analyses. RESULTS: Both tumor volume and regression ratio were strongly correlated with LR (P=.06, P = 5×10(-4), P=1×10(-6), and P=2×10(-8) for V1, V2, V3, and V4, respectively; and P=7×10(-5), P=1×10(-6), and P=1×10(-8) for V2/V1, V3/V1, and V4/V1, respectively) and DOD (P=.015, P=.004, P=.001, and P=3×10(-4) for V1, V2, V3, and V4, respectively; and P=.03, P=.009, and P=3×10(-4) for V2/V1, V3/V1, and V4/V1, respectively). Algorithms that combined tumor volumes and regression ratios improved predictive power (sensitivity, 61%-89%; specificity, 79%-100%). The strongest predictor, pre-RT volume and regression ratio at MRI3 (V1>40 cm3 and V3/V1>20%, respectively), achieved 89% sensitivity, 87% specificity, and 88% accuracy for LR and achieved 54% sensitivity, 83% specificity, and 73% accuracy for DOD. CONCLUSIONS: The current results suggested that tumor volume/regression parameters obtained during primary therapy are useful in predicting LR and DOD. Both tumor volume and regression ratio provided important information as early outcome predictors that may guide early intervention for patients with cervical cancer who are at high risk of treatment failure.


Subject(s)
Magnetic Resonance Imaging/methods , Tumor Burden , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Middle Aged , Prognosis , Sensitivity and Specificity , Treatment Failure
17.
Am J Clin Oncol ; 33(1): 70-4, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19652578

ABSTRACT

PURPOSE: To examine the outcomes of patients with a single brain metastasis from radioresistant histologies (renal cell carcinoma and melanoma) treated with stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). METHODS AND MATERIALS: We reviewed the medical records of 27 patients treated at our institution between 2000 and 2007 with a single radioresistant brain metastasis. Patients were treated with Gamma Knife based SRS. Tumor histologies included renal cell carcinoma and melanoma. RESULTS: Patients were treated to a median marginal dose was 20 Gy (range, 15-22 Gy). At follow-up intervals ranging from 1.8 to 23.2 months, the radiographic responses were as follows: progression in 7 patients; stable in 5 patients; and shrinkage in 15 patients. Fifteen patients (56%) developed distant brain failure. Seven of the 27 patients were alive at last follow-up. The 3-, 6-, 9-, 12-, and 18-months after SRS local control rates were 82.8%, 77.9%, 69.3%, 69.3%, and 55.4%, respectively. None of the 5 patients who received WBRT developed distant brain failure although the follow-up intervals were short (range, 3.5-13.7 months; median, 5.1 months). WBRT did not appear to affect local control, progression free survival, and overall survival (P = 0.32, 0.87, 0.69). One patient developed worsening of symptoms attributable to SRS. CONCLUSIONS: Gamma Knife SRS is a safe and feasible strategy for treatment of patients with a single radioresistant brain metastasis. Radiosurgery alone is a reasonable treatment option, but may carry a greater likelihood of distant brain recurrence.


Subject(s)
Brain Neoplasms/therapy , Carcinoma, Renal Cell/therapy , Cranial Irradiation , Melanoma/therapy , Neoplasm Recurrence, Local/surgery , Radiation Tolerance , Radiosurgery , Adult , Aged , Aged, 80 and over , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/radiotherapy , Carcinoma, Renal Cell/surgery , Combined Modality Therapy , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Melanoma/radiotherapy , Melanoma/secondary , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Survival Rate , Treatment Outcome
18.
Cancer Res ; 70(2): 463-70, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-20068180

ABSTRACT

Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S(2) < 0.70 vs. S(2) > or = 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time (T(1/2) < 22 days versus T(1/2) > or = 22 days, P < 0.001). The 6-year disease-specific survival was 73% versus 41% with S(2) < 0.70 versus S(2) > or = 0.70 (P = 0.025), and 87% vs. 52% with T(1/2) < 22 days versus T(1/2) > or = 22 days (P = 0.002). Our approach illustrates the promise of volume-based tumor response modeling to improve early outcome predictions that can be used to enable personalized adaptive therapy.


Subject(s)
Models, Biological , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Treatment Outcome
19.
Int J Radiat Oncol Biol Phys ; 77(2): 502-8, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-19775824

ABSTRACT

PURPOSE: To study the temporal changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion patterns during the radiation therapy (RT) course and their influence on local control and survival in cervical cancer. METHODS AND MATERIALS: DCE-MRI was performed in 98 patients with Stage IB(2)-IVA cervical cancer before RT (pre-RT) and during early RT (20-25 Gy) and mid-RT (45-50 Gy). Signal intensity (SI) from the DCE-MRI time-SI curve was derived for each tumor voxel. The poorly perfused low-DCE tumor subregions were quantified as lower 10th percentiles of SI (SI10). Local control, disease-specific survival, and overall survival were correlated with DCE parameters at pre-RT, early RT, and mid-RT. Median follow-up was 4.9 (range, 0.2-9.0) years. RESULTS: Patients (16/98) with initial pre-RT high DCE (SI10 >or=2.1) had 100% 5-year local control, 81% disease-specific survival, and 81% overall survival, compared with only 79%, 61%, and 55%, respectively, in patients with pre-RT low DCE. Conversion from pre-RT low DCE to high DCE in early RT (28/82 patients) was associated with higher local control, disease-specific survival, and overall survival (93%, 74%, and 67%, respectively). In comparison with all other groups, outcome was worst in patients with persistently low DCE from pre-RT throughout the mid-RT phase (66%, 44%, and 43%; p = 0.003, 0.003, and 0.020; respectively). CONCLUSION: Longitudinal tumor perfusion changes during RT correlate with treatment outcome. Persistently low perfusion in pre-RT, early RT, and mid-RT indicates a high risk of treatment failure, whereas outcome is favorable in patients with initially high perfusion or subsequent improvements of initially low perfusion. These findings likely reflect reoxygenation and may have potential for noninvasive monitoring of intra-treatment radio-responsiveness and for guiding adaptive therapy.


Subject(s)
Uterine Cervical Neoplasms/blood supply , Uterine Cervical Neoplasms/radiotherapy , Adenocarcinoma/blood supply , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Disease-Free Survival , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Oxygen Consumption , Prospective Studies , Radiotherapy Dosage , Time Factors , Treatment Outcome , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
20.
Expert Rev Anticancer Ther ; 9(5): 621-35, 2009 May.
Article in English | MEDLINE | ID: mdl-19445579

ABSTRACT

The standard treatment for metastatic cancer is systemic therapy. However, in a subset of patients with limited extracranial metastases or oligometastases, local ablative therapy in combination with systemic therapy may improve treatment outcomes. Stereotactic body radiation therapy (SBRT) has emerged as a novel approach for local ablation of extracranial oligometastases. There is a good body of experience in the use of SBRT for the treatment of oligometastases in various sites including the lung, the liver and the spine with promising results. This article provides an overview of the use of SBRT in the management of extracranial oligometastases.


Subject(s)
Brain Neoplasms/surgery , Liver Neoplasms/surgery , Lung Neoplasms/surgery , Radiosurgery , Spinal Neoplasms/surgery , Brain Neoplasms/pathology , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Spinal Neoplasms/secondary
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