RESUMO
Introduction: Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Results: Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. Conclusion: These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.
RESUMO
Recently, the azepino[4,3-b]indole-1-one derivative 1 showed in vitro nanomolar inhibition against butyrylcholinesterase (BChE), the ChE isoform that plays a role in the progression and pathophysiology of Alzheimer's disease (AD), and protects against N-methyl- d-aspartate-induced neuronal toxicity. Three 9-R-substituted (R = F, Br, OMe) congeners were investigated. The 9-F derivative (2a) was found more potent as BChE inhibitors (half-maximal inhibitory concentration value = 21 nM) than 2b (9-Br) and 2c (9-OMe), achieving a residence time (38 s), assessed by surface plasmon resonance, threefold higher than that of 1. To progress in featuring the in vivo pharmacological characterization of 2a, herein the 18 F-labeled congener 2a was synthesized, by applying the aromatic 18 F-fluorination method, and its whole-body distribution in healthy mice, including brain penetration, was evaluated through positron emission tomography imaging. [18 F]2a exhibited a rapid and high brain uptake (3.35 ± 0.26% ID g-1 at 0.95 ± 0.15 min after injection), followed by a rapid clearance (t1/2 = 6.50 ± 0.93 min), showing good blood-brain barrier crossing. After a transient liver accumulation of [18 F]2a, the intestinal and urinary excretion was quantified. Finally, ex vivo pharmacological experiments in mice showed that the unlabeled 2a affects the transmitters' neurochemistry, which might be favorable to reverse cognition impairment in mild-to-moderate AD-related dementias.
Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase , Relação Estrutura-Atividade , Transporte Biológico , IndóisRESUMO
The ability to automatically estimate the pose of non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non-human primate pose estimation models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the Internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose estimation models.
RESUMO
Primatologists, psychologists and neuroscientists have long hypothesized that primate behavior is highly structured. However, delineating that structure has been impossible due to the difficulties of precision behavioral tracking. Here we analyzed a dataset consisting of continuous measures of the 3D position of two male rhesus macaques (Macaca mulatta) performing three different tasks in a large unrestrained environment over several hours. Using an unsupervised embedding approach on the tracked joints, we identified commonly repeated pose patterns, which we call postures. We found that macaques' behavior is characterized by 49 distinct postures, lasting an average of 0.6 seconds. We found evidence that behavior is hierarchically organized, in that transitions between poses tend to occur within larger modules, which correspond to identifiable actions; these actions are further organized hierarchically. Our behavioral decomposition allows us to identify universal (cross-individual and cross-task) and unique (specific to each individual and task) principles of behavior. These results demonstrate the hierarchical nature of primate behavior, provide a method for the automated ethogramming of primate behavior, and provide important constraints on neural models of pose generation.
RESUMO
BACKGROUND: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. METHODS: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. RESULTS: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival. CONCLUSION: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.
Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Estudos Prospectivos , Receptores de Estrogênio/genética , Imageamento por Ressonância Magnética , Radiografia , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/genética , Lectinas Tipo C , Proteínas de MembranaRESUMO
Precise dosimetry has gained interest for interpreting the response assessments of novel therapeutic radiopharmaceuticals, as well as for improving conventional radiotherapies such as the "one dose fits all" approach. Although radioiodine as same-element isotope theranostic pairs has been used for differentiated thyroid cancer (DTC), there are insufficient studies on the determination of its dosing regimen for personalized medicine and on extrapolating strategies for companion diagnostic radiopharmaceuticals. In this study, DTC xenograft mouse models were generated after validating iodine uptakes via sodium iodine symporter proteins (NIS) through in vitro assays, and theranostic surrogacy of companion radiopharmaceuticals was investigated in terms of single photon emission computed tomography (SPECT) imaging and voxel-level dosimetry. Following a Monte Carlo simulation, the hypothetical energy deposition/dose distribution images were produced as [123I]NaI SPECT scans with the use of 131I ion source simulation, and dose rate curves were used to estimate absorbed dose. For the tumor, a peak concentration of 96.49 ± 11.66% ID/g occurred 2.91 ± 0.42 h after [123I]NaI injection, and absorbed dose for 131I therapy was estimated as 0.0344 ± 0.0088 Gy/MBq. The absorbed dose in target/off-target tissues was estimated by considering subject-specific heterogeneous tissue compositions and activity distributions. Furthermore, a novel approach was proposed for simplifying voxel-level dosimetry and suggested for determining the minimal/optimal scan time points of surrogates for pretherapeutic dosimetry. When two scan time points were set to Tmax and 26 h and the group mean half-lives were applied to the dose rate curves, the most accurate absorbed dose estimates were determined [-22.96, 2.21%]. This study provided an experimental basis to evaluate dose distribution and is expected hopefully to improve the challenging dosimetry process for clinical use.
Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Animais , Camundongos , Radioisótopos do Iodo/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Medicina de Precisão , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Radiometria/métodos , Adenocarcinoma/tratamento farmacológicoRESUMO
Although aptamers have shown excellent target specificity in preclinical and clinical studies either by themselves or as aptamer-drug conjugates, their in vivo tissue pharmacokinetic (PK) analysis is still problematic. We aimed to examine the utility of image-based positron emission tomography (PET) to evaluate in vivo tissue PK, target specificity, and applicability of oligonucleotides. For this, fluorine-18-labeled aptamers with erb-b2 receptor tyrosine kinase 2 (ERBB2)-specific binding were synthesized by base-pair hybridization using a complementary oligonucleotide platform. To investigate the PKs and properties of in vivo tissue, usefulness of in vivo PET imaging in the development of an oligonucleotide-based drug as an assessment tool was evaluated in normal and tumor xenografted mice. ERBB2-cODN-idT-APs-[18 F]F ([18 F]1), injected intravenously showed significant and rapid uptake in most tissues except for the initial brain and muscle; the uptake was highest in the heart, followed by kidneys, liver, lungs, gall bladder, spleen, and stomach. The main route of excretion was through the renal tract ~77.8%, whereas about 8.3% was through the biliary tract of the total dose. The estimated effective dose for an adult woman was 0.00189 mGy/MBq, which might be safe. ERBB2-positive tumor could be well visualized in the KPL4 xenograft animal model by in vivo PET imaging. Consequently, the distribution in each organ including ERBB2 expression could be well determined and quantified by PET with fluorine-18-labeled aptamers. In vivo PK parameters such as terminal half-life, time to maximum concentration, area under the curve, and maximum concentration, were also successfully estimated. These results suggest that image-based PET with radioisotope-labeled aptamers could be provide valuable information on properties of oligonucleotide-based drugs in drug discovery of targeted therapeutics against various diseases.
Assuntos
Neoplasias , Oligonucleotídeos , Humanos , Camundongos , Animais , Receptor ErbB-2 , Distribuição Tecidual , Tomografia por Emissão de Pósitrons/métodos , Modelos Animais de DoençasRESUMO
A key challenge of learning a visual representation for the 3D high fidelity geometry of dressed humans lies in the limited availability of the ground truth data (e.g., 3D scanned models), which results in the performance degradation of 3D human reconstruction when applying to real-world imagery. We address this challenge by leveraging a new data resource: a number of social media dance videos that span diverse appearance, clothing styles, performances, and identities. Each video depicts dynamic movements of the body and clothes of a single person while lacking the 3D ground truth geometry. To learn a visual representation from these videos, we present a new self-supervised learning method to use the local transformation that warps the predicted local geometry of the person from an image to that of another image at a different time instant. This allows self-supervision by enforcing a temporal coherence over the predictions. In addition, we jointly learn the depths along with the surface normals that are highly responsive to local texture, wrinkle, and shade by maximizing their geometric consistency. Our method is end-to-end trainable, resulting in high fidelity depth estimation that predicts fine geometry faithful to the input real image. We further provide a theoretical bound of self-supervised learning via an uncertainty analysis that characterizes the performance of the self-supervised learning without training. We demonstrate that our method outperforms the state-of-the-art human depth estimation and human shape recovery approaches on both real and rendered images.
Assuntos
Mídias Sociais , Humanos , Algoritmos , MovimentoRESUMO
Beneficial and detrimental effect of surgical adenomyomectomy is still controversial in infertile women with severely diffuse adenomyosis. The primary objective of this study was to assess whether a novel method of fertility-preserving adenomyomectomy could improve pregnancy rates. The secondary objective was to evaluate whether it could improve dysmenorrhea and menorrhagia symptoms in infertile patients with severe adenomyosis. A prospective clinical trial was conducted between December 2007 and September 2016. Fifty women with infertility due to adenomyosis were enrolled in this study after clinical assessments by infertility experts. A novel method of fertility-preserving adenomyomectomy was performed on 45 of 50 patients. The procedure included T- or transverse H-incision of the uterine serosa followed by preparation of the serosal flap, excision of the adenomyotic tissue using argon laser under ultrasonographic monitoring, and a novel technique of suturing between the residual myometrium and serosal flap. After the adenomyomectomy, the changes in the amount of menstrual blood, relief of dysmenorrhea, pregnancy outcomes, clinical characteristics, and surgical features were recorded and analyzed. All patients obtained dysmenorrhea relief 6 months postoperatively (numeric rating scale [NRS]; 7.28â ±â 2.30 vs 1.56â ±â 1.30, Pâ <â .001). The amount of menstrual blood decreased significantly (140.44â ±â 91.68 vs 66.33â ±â 65.85 mL, Pâ <â .05). Of the 33 patients who attempted pregnancy postoperatively, 18 (54.5%) conceived either by natural means, in vitro fertilization and embryo transfer (IVF-ET), or thawing embryo transfer. Miscarriage occurred in 8 patients, while 10 (30.3%) had viable pregnancies. This novel method of adenomyomectomy resulted in improved pregnancy rates, as well as relief of dysmenorrhea and menorrhagia. This operation is effective in preserving fertility potential in infertile women with diffuse adenomyosis.
Assuntos
Adenomiose , Infertilidade Feminina , Menorragia , Feminino , Humanos , Gravidez , Adenomiose/complicações , Adenomiose/cirurgia , Dismenorreia/etiologia , Dismenorreia/cirurgia , Infertilidade Feminina/cirurgia , Infertilidade Feminina/complicações , Estudos Prospectivos , Resultado do TratamentoRESUMO
Several radiolabeled prostate-specific membrane antigen (PSMA)-targeted agents have been developed for detecting prostate cancer, using positron emission tomography imaging and targeted radionuclide therapy. Among them, [18F]PSMA-1007 has several advantages, including a comparatively long half-life, delayed renal excretion, and compatible structure with α-/ß-particle emitter-labeled therapeutics. This study aimed to characterize the preclinical pharmacokinetics and internal radiation dosimetry of [18F]PSMA-1007, as well as its repeatability and specificity for target binding using prostate tumor-bearing mice. In PSMA-positive tumor-bearing mice, the kidney showed the greatest accumulation of [18F]PSMA-1007. The distribution in the tumor attained its peak concentration of 2.8%ID/g at 112 min after intravenous injection. The absorbed doses in the tumor and salivary glands were 0.079 ± 0.010 Gy/MBq and 0.036 ± 0.006 Gy/MBq, respectively. The variance of the net influx (Ki) of [18F]PSMA-1007 to the tumor was minimal between scans performed in the same animals (within-subject coefficient of variation = 7.57%). [18F]PSMA-1007 uptake in the tumor was specifically decreased by 32% in Ki after treatment with a PSMA inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). In the present study, we investigated the in vivo preclinical characteristics of [18F]PSMA-1007. Our data from [18F]PSMA-1007 PET/computed tomography (CT) studies in a subcutaneous prostate cancer xenograft mouse model supports clinical therapeutic strategies that use paired therapeutic radiopharmaceuticals (such as [177Lu]Lu-PSMA-617), especially strategies with a quantitative radiation dose estimate for target lesions while minimizing radiation-induced toxicity to off-target tissues.
Assuntos
Neoplasias da Próstata , Compostos Radiofarmacêuticos , Masculino , Humanos , Animais , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Xenoenxertos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/tratamento farmacológico , Oligopeptídeos , Glutamato Carboxipeptidase II/metabolismo , Antígenos de Superfície/metabolismo , Linhagem Celular TumoralRESUMO
This paper presents a new large multiview dataset called HUMBI for human body expressions with natural clothing. The goal of HUMBI is to facilitate modeling view-specific appearance and geometry of five primary body signals including gaze, face, hand, body, and garment from assorted people. 107 synchronized HD cameras are used to capture 772 distinctive subjects across gender, ethnicity, age, and style. With the multiview image streams, we reconstruct the geometry of body expressions using 3D mesh models, which allows representing view-specific appearance. We demonstrate that HUMBI is highly effective in learning and reconstructing a complete human model and is complementary to the existing datasets of human body expressions with limited views and subjects such as MPII-Gaze, Multi-PIE, Human3.6M, and Panoptic Studio datasets. Based on HUMBI, we formulate a new benchmark challenge of a pose-guided appearance rendering task that aims to substantially extend photorealism in modeling diverse human expressions in 3D, which is the key enabling factor of authentic social tele-presence. HUMBI is publicly available at http://humbi-data.net.
Assuntos
Algoritmos , Benchmarking , Humanos , Corpo Humano , AprendizagemRESUMO
We aimed to compare cervical elastographic parameters based on a previous loop electrosurgical excision procedure (LEEP) and to determine whether they can predict preterm delivery in pregnant women with a history of LEEP. This multicenter prospective case-control study included 71 singleton pregnant women at 14-24 weeks of gestation with a history of LEEP and 1:2 gestational age-matched controls. We performed cervical elastography using E-cervix and compared maternal characteristics, delivery outcomes, cervical length (CL), and elastographic parameters between the two groups. The median mid-trimester CL was significantly shorter in the LEEP group. Most elastographic parameters, including internal os (IOS), external os (EOS), elasticity contrast index (ECI), and hardness ratio (HR), were significantly different in the two groups. In the LEEP group, the sPTD group compared to the term delivery (TD) group showed a higher rate of previous sPTD (50% vs. 1.7%, p < 0.001), higher IOS and ECI (IOS: 0.28 [0.12-0.37] vs. 0.19 [0.10-0.37], p = 0.029; ECI: 3.89 [1.79-4.86] vs. 2.73 [1.48-5.43], p = 0.019), and lower HR (59.97 [43.88-92.43] vs. 79.06 [36.87-95.40], p = 0.028), but there was no significant difference in CL (2.92 [2.16-3.76] vs. 3.13 [1.50-3.16], p = 0.247). In conclusion, we demonstrated that a history of LEEP was associated with a change in cervical strain measured in mid-trimester as well as with CL shortening. We also showed that cervical elastography can be useful in predicting sPTD in pregnant women with previous LEEP.
Assuntos
Colo do Útero , Técnicas de Imagem por Elasticidade , Estudos de Casos e Controles , Colo do Útero/diagnóstico por imagem , Colo do Útero/cirurgia , Eletrocirurgia , Feminino , Humanos , Recém-Nascido , Gravidez , Segundo Trimestre da Gravidez , GestantesRESUMO
For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (89Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total 89Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged 89Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free 89Zr, indicating that exosomes might be rapidly taken up by cells and tissues.
RESUMO
OBJECTIVE: To evaluate the clinical significance of soft markers for aneuploidy screening in Korean women. METHODS: We retrospectively reviewed the medical records of 5,428 singleton pregnant women who underwent sonography during the second trimester at seven institutions in South Korea. We evaluated the prevalence of the following soft markers: intracardiac echogenic focus, choroid plexus cysts, pyelectasis, echogenic bowel, and mild ventriculomegaly. We developed best-fitted regression equations for the fetal femur and humerus length using our data and defined a short femur and humerus as both long bones below the fifth centile. The results of genetic testing and postnatal outcomes were investigated in patients who had been diagnosed with aforementioned soft markers. RESULTS: The median maternal age of our study population was 33 years, and the median gestational age at the time of ultrasonographic examination was 21 weeks. We detected soft markers in 10.0% (n=540) of fetuses: 9.3% (n=504) were isolated cases and 0.7% (n=36) of cases had two or more markers. We identified only two aneuploides (trisomy 18, 46,XX,t[8;10][q22.1;p13]), of which one was clinically significant. We presented the neonatal outcomes of the fetuses with the respective soft markers. Preterm delivery, low birth weight, and small-for-gestational-age (SGA) were significantly more common in women with a shortened fetal femur (P<0.001, all). However, the presence of a shortened fetal humerus was not associated with those outcomes excluding SGA. CONCLUSION: Soft markers in second-trimester ultrasonography have limited use in screening for fetal aneuploidy in Korean women. However, these markers can be used as a screening tool for adverse outcomes other than chromosomal abnormality.
RESUMO
Understanding the behavior of primates is important for primatology, for psychology, and for biology more broadly. It is also important for biomedicine, where primates are an important model organism, and whose behavior is often an important variable of interest. Our ability to rigorously quantify behavior has, however, long been limited. On one hand, we can rigorously quantify low-information measures like preference, looking time, and reaction time; on the other, we can use more gestalt measures like behavioral categories tracked via ethogram, but at high cost and with high variability. Recent technological advances have led to a major revolution in behavioral measurement that offers affordable and scalable rigor. Specifically, digital video cameras and automated pose tracking software can provide measures of full-body position (i.e., pose) of primates over time (i.e., behavior) with high spatial and temporal resolution. Pose-tracking technology in turn can be used to infer behavioral states, such as eating, sleeping, and mating. We call this technological approach behavioral imaging. In this review, we situate the behavioral imaging revolution in the history of the study of behavior, argue for investment in and development of analytical and research techniques that can profit from the advent of the era of big behavior, and propose that primate centers and zoos will take on a more central role in relevant fields of research than they have in the past.
Assuntos
Postura , Primatas , AnimaisRESUMO
This prospective study enrolled 147 women with invasive breast cancer who underwent low-dose breast CT (80 kVp, 25 mAs, 1.01-1.38 mSv) before treatment. From each tumor, we extracted eight perfusion parameters using the maximum slope algorithm and 36 texture parameters using the filtered histogram technique. Relationships between CT parameters and histological factors were analyzed using five machine learning algorithms. Performance was compared using the area under the receiver-operating characteristic curve (AUC) with the DeLong test. The AUCs of the machine learning models increased when using both features instead of the perfusion or texture features alone. The random forest model that integrated texture and perfusion features was the best model for prediction (AUC = 0.76). In the integrated random forest model, the AUCs for predicting human epidermal growth factor receptor 2 positivity, estrogen receptor positivity, progesterone receptor positivity, ki67 positivity, high tumor grade, and molecular subtype were 0.86, 0.76, 0.69, 0.65, 0.75, and 0.79, respectively. Entropy of pre- and postcontrast images and perfusion, time to peak, and peak enhancement intensity of hot spots are the five most important CT parameters for prediction. In conclusion, machine learning using texture and perfusion characteristics of breast cancer with low-dose CT has potential value for predicting prognostic factors and risk stratification in breast cancer patients.
RESUMO
PURPOSE: To investigate potential differences in the frequency of preterm births (PTB) between pregnancies with or without prophylactic cerclage in women with a history of conization. MATERIALS AND METHODS: We identified women who had their first singleton delivery after conization between 2013 and 2018 using records in the National Health Insurance Service of Korea claims database. We only included women who had undergone a health examination and interview within 2 years before delivery. We used timing of maternal serum alpha-fetoprotein (MSAFP) tests to differentiate early (before) from late (after the MSAFP test) cerclage. The frequency of adverse pregnancy outcomes, including PTB, preterm labor and premature rupture of membranes, antibiotics and tocolytics use, cesarean delivery, and number of admissions before delivery, were compared. RESULTS: A total of 8322 women was included. Compared to the no cerclage group (n=7147), the risks of adverse pregnancy outcomes were higher in the cerclage group (n=1175). After categorizing patients with cerclage into two groups, the risk of PTB was still higher in the early cerclage group than in the no cerclage group after adjusting for baseline factors (4.48%, 30/669 vs. 2.77%, 159/5749, odds ratio 2.42, 95% confidence interval 1.49, 3.92). Other adverse pregnancy outcomes were also more frequent in the early cerclage group than the no cerclage group. CONCLUSION: Early cerclage performed before MSAFP testing does not prevent PTB in pregnancy with a history of conization, but increases the risk of adverse pregnancy outcomes, including PTB.
Assuntos
Cerclagem Cervical , Nascimento Prematuro , Estudos de Coortes , Conização , Feminino , Humanos , Recém-Nascido , Programas Nacionais de Saúde , Gravidez , Nascimento Prematuro/prevenção & controle , República da Coreia , Estudos RetrospectivosRESUMO
PURPOSE: Translocator protein 18-kDa (TSPO) positron emission tomography (PET) is a valuable tool to detect neuroinflammed areas in a broad spectrum of neurodegenerative diseases. However, the clinical application of second-generation TSPO ligands as biomarkers is limited because of the presence of human rs6971 polymorphism that affects their binding. Here, we describe the ability of a new TSPO ligand, [18F]BS224, to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism. METHODS: An in vitro competitive inhibition assay of BS224 was conducted with [3H]PK 11195 using membrane proteins isolated from 293FT cells expressing TSPO-wild type (WT) or TSPO-mutant A147T (Mut), corresponding to a high-affinity binder (HAB) and low-affinity binder (LAB), respectively. Molecular docking was performed to investigate the interaction of BS224 with the binding sites of rat TSPO-WT and TSPO-Mut. We synthesized a new 18F-labeled imidazopyridine acetamide ([18F]BS224) using boronic acid pinacol ester 6 or iodotoluene tosylate precursor 7, respectively, via aromatic 18F-fluorination. Dynamic PET scanning was performed up to 90 min after the injection of [18F]BS224 to healthy mice, and PET imaging data were obtained to estimate its absorbed doses in organs. To evaluate in vivo TSPO-specific uptake of [18F]BS224, lipopolysaccharide (LPS)-induced inflammatory and ischemic stroke rat models were used. RESULTS: BS224 exhibited a high affinity (Ki = 0.51 nM) and selectivity for TSPO. The ratio of IC50 values of BS224 for LAB to that for HAB indicated that the TSPO binding affinity of BS224 has low binding sensitivity to the rs6971 polymorphism and it was comparable to that of PK 11195, which is not sensitive to the polymorphism. Docking simulations showed that the binding mode of BS224 is not affected by the A147T mutation and consequently supported the observed in vitro selectivity of [18F]BS224 regardless of polymorphisms. With optimal radiochemical yield (39 ± 6.8%, decay-corrected) and purity (> 99%), [18F]BS224 provided a clear visible image of the inflammatory lesion with a high signal-to-background ratio in both animal models (BPND = 1.43 ± 0.17 and 1.57 ± 0.37 in the LPS-induced inflammatory and ischemic stroke rat models, respectively) without skull uptake. CONCLUSION: Our results suggest that [18F]BS224 may be a promising TSPO ligand to gauge neuroinflammatory disease-related areas in a broad range of patients irrespective of the common rs6971 polymorphism.
Assuntos
Tomografia por Emissão de Pósitrons , Receptores de GABA , Animais , Proteínas de Transporte , Humanos , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Compostos Radiofarmacêuticos , Ratos , Receptores de GABA/genética , Receptores de GABA/metabolismo , Receptores de GABA-ARESUMO
BACKGROUND: The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea. METHODS: A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002-2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan-Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose-response relationship. RESULTS: The median follow-up was 79.6 of months. Kaplan-Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691-0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577-0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605-1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547-0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064). CONCLUSIONS: The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose-response relationship in a population-based cohort study.
Assuntos
Terapia de Reposição Hormonal , Neoplasias Gástricas , Estudos de Coortes , Humanos , Menopausa , República da Coreia/epidemiologiaRESUMO
Cell adhesion receptor integrin αvß3 is a promising biomarker for developing tumor-angiogenesis targeted theranostics. In this study, we aimed to examine the therapeutic potential of peptide receptor radionuclide therapy (PRRT) with 188Re-IDA-D-[c(RGDfK)]2 (11.1 MBq). The results showed that the tumor volume was significantly decreased by 81% compared with the vehicle-treated group in U87-MG xenografts. The quantitative in vivo anti-angiogenic responses of PRRT were obtained using 99mTc-IDA-D-[c(RGDfK)]2 SPECT and corresponded to the measured tumor volume. PRRT combined with temozolomide (TMZ) resulted in a 93% reduction in tumor volume, which was markedly greater than that of each agent used individually. In addition, histopathological characterization showed that PRRT combined with TMZ was superior to PRRT or TMZ alone, even when TMZ was used at half dose. Overall, our results indicated that integrin-targeted PRRT and TMZ combined therapy might be a new medical tool for the effective treatment of glioblastoma.