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1.
J Magn Reson Imaging ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220105

RESUMO

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) is a newly developed system of bladder cancer staging with multiparametric MRI (mpMRI), which can be used to predict the presence of muscle invasion for bladder cancer. PURPOSE: To evaluate the accuracy of three mpMRI series (T2 WI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced image [DCEI]) and VI-RADS for diagnosing the muscle invasive bladder cancer (MIBC). STUDY TYPE: Retrospective. POPULATION: In all, 66 pathologically proven bladder cancers in 32 patients. FIELD STRENGTH/SEQUENCE: Before the diagnostic MRI with an intramuscular antispasmodic agent, optimal bladder distension was confirmed. 3.0T MRI with T2 WI, DWI, and DCEI. ASSESSMENT: Three reviewers independently assessed and scored the bladder cancers in T2 WI, DWI, and DCEI using a five-point score system. Based on the scores in the three sequences, reviewers scored each bladder cancer with reference to VI-RADS categories. We evaluated the diagnostic performance of each of three mpMRI sequences and the final VI-RADS categorization for diagnosing MIBC. STATISTICAL TESTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of each of three sequences separately and VI-RADS categorization for diagnosing the MIBC. RESULTS: The diagnostic performances of each of the three mpMRI series and VI-RADS for diagnosing MIBC were excellent. Especially using the optimal cutoff score >3 for predicting MIBC on DWI, DCEI, and VI-RADS, the sensitivity, specificity, PPV, NPV, and AUC values were 90% (95% confidence interval [CI]: 0.56, 1.00), 100% (95% CI: 0.94, 1.00), 100% (95% CI: 0.66. 1.00), 98.3% (95% CI: 0.91, 1.00), and 0.95, respectively. DATA CONCLUSION: mpMRI based on VI-RADS can stratify patients with bladder cancer according to the presence of muscle invasion. LEVEL OF EVIDENCE: 3. TECHNICAL EFFICACY STAGE: 2.

2.
Eur Radiol ; 30(1): 66-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385051

RESUMO

OBJECTIVES: To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay. METHODS: This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated. RESULTS: Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10-3 mm2/s vs. 0.746 × 10-3 mm2/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10-3 mm2/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors. CONCLUSIONS: The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer. KEY POINTS: • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.


Assuntos
Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Algoritmos , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Genes erbB-2 , Humanos , Pessoa de Meia-Idade , Receptores Estrogênicos/metabolismo , Estudos Retrospectivos , Fatores de Risco
3.
Jpn J Radiol ; 38(2): 101-111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31848888

RESUMO

Gastrointestinal tract (GI) perforations can occur due to various causes such as trauma, iatrogenic factor, infectious condition, peptic ulcer, inflammatory disease, or a neoplasm. Because GI perforations represent an emergency and life-threatening condition, prompt diagnosis and surgical treatment are required in most cases. However, according to the underlying causes of GI perforations, additional treatment strategies may be needed. Adjuvant chemotherapy or immunotherapy may be required in various GI neoplasms such as adenocarcinoma, lymphoma or gastrointestinal stromal tumor. Inflammatory bowel disease is a chronic disease repeating cycle of intermittent, thus appropriate medical treatment and periodic follow-up are also required. Moreover, vascular intervention may have a role in some cases of mesenteric ischemia associated with mesenteric artery occlusion. Recently, computed tomography (CT) has been the first choice for patients with suspected GI perforations, because CT plays an important role in the accurate assessment of the perforation site, the pathology causing the perforation and the ensuing complications. This review will illustrate characteristic CT findings that differentiate underlying pathologies causing GI perforations to help clinicians decision-making regarding an optimal treatment plan.

4.
J Magn Reson Imaging ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664776

RESUMO

BACKGROUND: Determining if a given patient with primary pancreatic adenocarcinoma (PDA) has hepatic metastasis is important for treatment planning. Several previous studies reported on the diagnostic performance of MRI for liver metastasis in patients with PDA. But the reported data are quite variable. PURPOSE: To systematically determine the diagnostic performance of MRI for liver metastasis in patients with PDA, including comparing it with computed tomography (CT). STUDY TYPE: Systemic review and meta-analysis. SUBJECTS: In all, 457 patients from five eligible articles. FIELD STRENGTH/SEQUENCE: Conventional MR sequences with or without contrast enhancement at 1.5T and 3T. ASSESSMENT: Two reviewers independently performed the data extraction. The reviewers identified and reviewed the original articles reporting the diagnostic performance of MRI for liver metastases in patients with PDA, including those articles making comparisons with CT. STATISTICAL TESTS: Meta-analytic summary sensitivity and specificity were calculated on a per-patient basis using a bivariate random effects model. We compared the meta-analytic summary sensitivity and specificity between MRI and CT. RESULTS: The meta-analytic summary sensitivity and specificity were 85% (95% confidence interval [CI], 74-92%; I2 = 0%) and 98% (95% CI, 78-100%; I2 = 85%), respectively. In comparison with CT, MRI showed a higher sensitivity (85% vs. 75%) but similar specificity (98% vs. 94%). DATA CONCLUSION: MRI had good overall diagnostic performance for liver metastasis in patients with PDA, with a higher sensitivity than CT. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019.

5.
Food Sci Biotechnol ; 28(4): 1013-1025, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31275701

RESUMO

This study was designed to determine the nutritional profile and functional components of the NZT (New Zealand deer's tail, Cervus elaphus var. scoticus Lönnberg). Twenty-nine fatty acids, eighteen amino acids, twenty-five minerals, chondroitin, and phospholipids were detected by the auto-fatty acid analyzer, auto-amino acid analyzer, inductively coupled plasma optical emission spectrophotometer, absorbance measurements, and by weighing after separating, respectively. 7-Ketocholesterol was isolated from alcohol extract by silica gel column chromatography analysis. Four steroid hormones (androstene-3,17-dione, ß-estradiol, testosterone, and dehydroepiandrosterone), one base and seven nucleosides, and N-acetylneuraminic acid were detected by a HPLC-photodiode array and HPLC-fluorescence detector. As a result, NZT was composed of many nutritional and functional ingredients found in New Zealand deer's antler (NZA) which was one of deer co-products, and it was considered that NZT could be a novel health food resource such as NZA.

6.
J Chem Phys ; 150(16): 164905, 2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31042912

RESUMO

In synthetic chemistry and biological or biomimetic systems, polymers are often grown in cavities. Polymerizations in microemulsions, biopolymers grown in cells, or in vesicles containing artificial organelles have an influence on the shape of liquid boundaries. We consider confined grand-canonical polymers to address equilibrium properties of annealed polymers. We calculate the concentration profiles established by annealed (star-) polymers inside a confining cavity. Our emphasis is on the description of pressure fields derived from the contact theorem. We further show how the pressure field exerted by a localized annealed polymer (or pair of polymers) deforms the confining vesicle/ microemulsions droplet.

7.
J Chem Phys ; 150(17): 174907, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067869

RESUMO

We theoretically study dense polymer solutions under open (capillary and slit) and closed (box) confinement. The theory is formulated for grand-canonical polymers and corrections to the self-consistent mean-field results are discussed. In contrast to the mean-field prediction, we found that the partition function of a labeled chain is affected by confinement even under neutral von Neumann boundary conditions and the chain length distribution is biased to short chains. As the container size increases, the contribution of the transverse excited states to the free energy of a labeled chain is found to approach its bulk value nonmonotonically (through an extremum) for the box and the capillary confinement but not for the slit. So does the confinement free energy of a labeled chain. The confinement energy of the solution is well behaved for open confinement but formally diverges for a closed box in the limit that the average chain length goes to infinity. Counted per chain, the confinement energy of the dense solution is qualitatively weaker than for a single ideal chain under similarly strong confinement (by one power in transverse container size). The container boundary contributes a surface tension to the free energy, which makes the effective monomer-wall affinity more repulsive. This correction increases with the average chain length. If present, edge or vertex singularities also contribute to the grand potential of the solution.

8.
AJR Am J Roentgenol ; 213(3): 659-666, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31039013

RESUMO

OBJECTIVE. The purpose of this study was to evaluate and compare the diagnostic performance and image quality of low-dose CT performed with adaptive statistical iterative reconstruction (ASIR)-V with those of routine-dose CT with filtered back projection (FBP) in the evaluation of abdominal organ injury. MATERIALS AND METHODS. The study enrolled 197 patients with trauma who underwent multiphase abdominal CT, including routine-dose portal venous phase imaging with FBP and low-dose delayed phase imaging with 50% ASIR-V. The presence of abdominal organ injuries (liver, spleen, pancreas, kidney) was reviewed, and injuries were graded according to American Association for the Surgery of Trauma (AAST) scales. CT detection rates of organ injury and AAST grading with the two protocols were compared by McNemar test. Subjective analysis of image noise and artifacts and objective analysis of CT noise were performed by unpaired t test. RESULTS. Compared with the routine-dose protocol, the low-dose protocol enabled an mean dose reduction of 59.8%. The detection rates and diagnostic performance of AAST grading did not differ significantly between the two protocols (detection rate, p = 0.289; diagnostic performance, p > 0.999). Objective image noise was significantly less with the low-dose protocol than with the routine-dose protocol (p < 0.001). Subjective imaging artifacts were similar between the low-dose and routine-dose protocols (p = 0.539). CONCLUSION. Compared with routine-dose protocol with FBP, low-dose CT with ASIR-V was useful for assessing multiorgan abdominal injury without impairing image quality.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos
9.
Mol Cancer Ther ; 18(6): 1092-1103, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30962321

RESUMO

Cell-type-specific intracellular payload delivery is desired for antibody-based-targeted therapy development. However, tumor-specific internalizing antigens are rare to find, and even rarer for those that are expressed at uniformly high levels. We constructed a bispecific antibody that is composed of a rapidly internalizing antibody binding to a tumor-associated antigen, ephrin receptor A2 (EphA2), and a noninternalizing antibody binding to a highly expressed tumor-associated antigen, activated leukocyte cell adhesion molecule (ALCAM). We found that the overall internalization property of the bispecific is profoundly impacted by the relative surface expression level (antigen density ratio) of EphA2 versus ALCAM. When the EphA2-to-ALCAM ratio is greater than a threshold level (1:5), the amount of the bispecific taken into the tumor cell exceeds what is achieved by either the monoclonal internalizing antibody or a mixture of the two antibodies, showing a bispecific-dependent amplification effect where a small amount of the internalizing antigen EphA2 induces internalization of a larger amount of the noninternalizing antigen ALCAM. When the ratio is below the threshold, EphA2 can be rendered noninternalizing by the presence of excess ALCAM on the same cell surface. We constructed a bispecific antibody-drug conjugate (ADC) based on the above bispecific design and found that the bispecific ADC is more potent than monospecific ADCs in tumor cell killing both in vitro and in vivo Thus, the internalizing property of a cell surface antigen can be manipulated in either direction by a neighboring antigen, and this phenomenon can be exploited for therapeutic targeting.

10.
Eur Radiol ; 29(7): 3574-3583, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30993435

RESUMO

PURPOSE: We evaluated the detection rate and degree of motion artifact of the modified CAIPIRINHA-VIBE (mC-VIBE) without view-sharing and compare them with the CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) with view-sharing on multi-arterial gadoxetic acid-enhanced liver MRI in the assessment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 114 pathological-proven hepatic tumors in 114 patients with risk of HCC who underwent multi-arterial gadoxetic acid-enhanced MRI between June 2016 and June 2018. All patients underwent triple arterial phase imaging using the mC-VIBE without view-sharing (54 patients; 49 HCCs and 5 non-HCCs) or the CDT-VIBE with view-sharing (60 patients; 55 HCCs and 5 non-HCCs). We compared the detection rate of two sequences for HCC, with reference to LI-RADS.V.2017. We also compared the mean motion scores and proportions of transient severe motion (TSM) in two sequences. RESULT: For the examination using the mC-VIBE, the HCC-detection rate was significantly higher, compared with that using CDT-VIBE (93.9% [46/49] vs 80.0% [44/55], respectively; p = 0.047). For the examination with the mC-VIBE, mean motion scores were significantly lower compared with those of CDT-VIBE for all multi-arterial phases (1.21, 1.19, and 1.15 vs. 1.82, 1.85, and 1.84, respectively; p < 0.001 for all three comparisons). The proportion of TSM in the CDT-VIBE was significantly higher than that in the mC-VIBE (15.0% [9/60] vs 0.0% [0/54], respectively; p = 0.003). CONCLUSION: In multi-arterial phase gadoxetic acid-enhanced MRI, the mC-VIBE sequence without view-sharing has slightly higher HCC-detection rate and fewer motion artifacts compared with CDT-VIBE with view-sharing. KEY POINTS: • Multi-arterial phase using the mC-VIBE without view-sharing can overcome motion artifacts, resulting in providing optimal arterial phase imaging. • The HCC-detection rate is slightly higher with the mC-VIBE vs. CAIPIRINHA-Dixon-TWIST-VIBE with view-sharing (CDT-VIBE). • View-sharing of CDT-VIBE in the multi-arterial phase is associated with increased frequency of TSM.


Assuntos
Artefatos , Carcinoma Hepatocelular/diagnóstico , Gadolínio DTPA/farmacologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Imagem por Ressonância Magnética/métodos , Meios de Contraste/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
11.
Korean J Radiol ; 20(1): 94-101, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30627025

RESUMO

Objective: To investigate the efficacy of motion-correction algorithm (MCA) in improving coronary artery image quality and measurement accuracy using an anthropomorphic dynamic heart phantom and 256-detector row computed tomography (CT) scanner. Materials and Methods: An anthropomorphic dynamic heart phantom was scanned under a static condition and under heart rate (HR) simulation of 50-120 beats per minute (bpm), and the obtained images were reconstructed using conventional algorithm (CA) and MCA. We compared the subjective image quality of coronary arteries using a four-point scale (1, excellent; 2, good; 3, fair; 4, poor) and measurement accuracy using measurement errors of the minimal luminal diameter (MLD) and minimal luminal area (MLA). Results: Compared with CA, MCA significantly improved the subjective image quality at HRs of 110 bpm (1.3 ± 0.3 vs. 1.9 ± 0.8, p = 0.003) and 120 bpm (1.7 ± 0.7 vs. 2.3 ± 0.6, p = 0.006). The measurement error of MLD significantly decreased on using MCA at 110 bpm (11.7 ± 5.9% vs. 18.4 ± 9.4%, p = 0.013) and 120 bpm (10.0 ± 7.3% vs. 25.0 ± 16.5%, p = 0.013). The measurement error of the MLA was also reduced using MCA at 110 bpm (19.2 ± 28.1% vs. 26.4 ± 21.6%, p = 0.028) and 120 bpm (17.9 ± 17.7% vs. 34.8 ± 19.6%, p = 0.018). Conclusion: Motion-correction algorithm can improve the coronary artery image quality and measurement accuracy at a high HR using an anthropomorphic dynamic heart phantom and 256-detector row CT scanner.


Assuntos
Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Frequência Cardíaca/fisiologia , Coração/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Artefatos , Precisão da Medição Dimensional , Humanos , Movimento (Física) , Movimento/fisiologia , Imagens de Fantasmas
12.
Asia Pac J Clin Oncol ; 15(2): e20-e27, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29920966

RESUMO

AIMS: To assess the accuracy of multiparametric magnetic resonance imaging (mpMRI), used in conjunction with the Prostrate Imaging Reporting and Data System (PI-RADS), version 2, in the detection of prostate cancer (PCa), and to determine the extent of the efficacy of mpMRI as a screening test in biopsy-naïve patients. METHODS: Retrospective analysis was conducted in 107 patients who underwent mpMRI prior to radical prostatectomy (RP) at a single institution. The mpMRI findings were reassessed using PI-RADS, version 2. A comparison was made between the histological findings for the RP specimens and the mpMRI results. RESULTS: Unique histologically confirmed PCa foci (237) were identified in 107 patients. Overall, mpMRI sensitivity of 46% was found for PCa detection (110/237). The sensitivity, specificity and negative predictive value of mpMRI was 75.5%, 77.0% and 79.8%, respectively, for clinically significant cancer, and 75.7%, 77.7% and 79.5%, for pathological index tumors. A moderate and significant correlation was observed between a high PI-RADS score and a high pathological grade, tumor volume, index tumor status and clinically significant cancer status (all, P < 0.001, respectively). Pathological tumor volume was a significant predictor of PCa detection using mpMRI according to multivariate analysis. Using a cut-off value of 0.89 cc, the sensitivity and specificity of mpMRI for PCa detection were 0.87 and 0.65, respectively. CONCLUSION: The mpMRI, used in conjunction with PI-RADS, was useful in detecting PCa and in predicting tumor aggressiveness. However, the detection of 20% of clinically significant cancer was missed using mpMRI. Thus, its inclusion in a triage test should be limited to selected biopsy-naïve patients.


Assuntos
Imagem por Ressonância Magnética/métodos , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Estudos Retrospectivos
13.
Eur Radiol ; 29(2): 485-493, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30073498

RESUMO

OBJECTIVES: To investigate the value of the whole-lesion histogram apparent diffusion coefficient (ADC) metrics for differentiating low-risk from non-low-risk ductal carcinoma in situ (DCIS). METHODS: The authors identified 93 women with pure DCIS who had undergone preoperative MR imaging and diffusion-weighted imaging from 2013 to 2016. Histogram analysis of pixel-based ADC data of the whole tumour volume was performed by two radiologists using a software tool. The results were compared between low-risk and non-low-risk DCIS. Associations between quantitative ADC metrics and low-risk DCIS were evaluated by receiver operating characteristics (ROC) curve and logistic regression analyses. RESULTS: In whole-lesion histogram analysis, mean ADC and 5th, 50th and 95th percentiles of ADC were significantly different between low-risk and non-low-risk DCIS (1.522, 1.207, 1.536 and 1.854 × 10-3 mm2/s versus 1.270, 0.917, 1.261 and 1.657 × 10-3 mm2/s, respectively; p = .004, p = .003, p = .004 and p = .024, respectively). ROC curve analysis for differentiating low-risk DCIS revealed that 5th percentile ADC yielded the largest area under the curve (0.786) among the metrics of whole-lesion histogram, and the optimal cut-off point was 1.078 × 10-3 mm2/s (sensitivity 80%, specificity 75.9%, p = .001). Multivariate regression analysis revealed that a high 5th percentile of ADC (> 1.078× 10-3 mm2/s; odds ratio [OR] = 10.494, p = .016), small tumour size (≤ 2 cm; OR = 12.692, p = .008) and low Ki-67 status (< 14%; OR = 10.879, p = .046) were significantly associated with low-risk DCIS. CONCLUSIONS: Assessment with whole-lesion histogram analysis of the ADC could be helpful for identifying patients with low-risk DCIS. KEY POINTS: • Whole-lesion histogram ADC metrics could be helpful for differentiating low-risk from non-low-risk DCIS. • A high 5th percentile ADC was a significant factor associated with low-risk DCIS. • Risk stratification of DCIS is important for their management.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Sensibilidade e Especificidade , Carga Tumoral , Adulto Jovem
14.
JCI Insight ; 3(17)2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30185663

RESUMO

Although initially responsive to androgen signaling inhibitors (ASIs), metastatic castration-resistant prostate cancer (mCRPC) inevitably develops and is incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer (NEPC) emerges to confer ASI resistance. We have previously combined laser capture microdissection and phage antibody display library selection on human cancer specimens and identified novel internalizing antibodies binding to tumor cells residing in their tissue microenvironment. We identified the target antigen for one of these antibodies as CD46, a multifunctional protein that is best known for negatively regulating the innate immune system. CD46 is overexpressed in primary tumor tissue and CRPC (localized and metastatic; adeno and NEPC), but expressed at low levels on normal tissues except for placental trophoblasts and prostate epithelium. Abiraterone- and enzalutamide-treated mCRPC cells upregulate cell surface CD46 expression. Genomic analysis showed that the CD46 gene is gained in 45% abiraterone-resistant mCRPC patients. We conjugated a tubulin inhibitor to our macropinocytosing anti-CD46 antibody and showed that the resulting antibody-drug conjugate (ADC) potently and selectively kills both adeno and NEPC cell lines in vitro (sub-nM EC50) but not normal cells. CD46 ADC regressed and eliminated an mCRPC cell line xenograft in vivo in both subcutaneous and intrafemoral models. Exploratory toxicology studies of the CD46 ADC in non-human primates demonstrated an acceptable safety profile. Thus, CD46 is an excellent target for antibody-based therapy development, which has potential to be applicable to both adenocarcinoma and neuroendocrine types of mCRPC that are resistant to current treatment.


Assuntos
Adenocarcinoma/metabolismo , Anticorpos Monoclonais/farmacologia , Antígenos de Neoplasias/metabolismo , Proteína Cofatora de Membrana/metabolismo , Tumores Neuroendócrinos/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/imunologia , Androstenos/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antineoplásicos/imunologia , Anticorpos Antineoplásicos/farmacologia , Afinidade de Anticorpos , Antígenos de Neoplasias/imunologia , Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Macaca fascicularis , Masculino , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/imunologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/imunologia , Feniltioidantoína/análogos & derivados , Feniltioidantoína/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Proteínas Recombinantes de Fusão , Transdução de Sinais/efeitos dos fármacos , Terapêutica , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Eur Phys J E Soft Matter ; 41(7): 88, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30039228

RESUMO

Since it was first proposed in 1982, the Daoud and Cotton (DC) model for star-shaped polymers was intensively used also for self-assembled copolymers and small colloids grafted with long polymers. We try to clarify the position of the DC model and focus on the star partition function which plays a central role in self-assembly and gives access to the star-star interaction. While the predicted star-star interaction agrees with scattering data by Likos et al. (Phys. Rev. Lett. 80, 4450 (1998)), an extensive simulation by Hsu et al. (Macromolecules, 37, 4658 (2004)) does not recover the prediction for the partition function. We try to reconcile this seemingly conflicting results. We discuss star-star interactions, star free energy in θ -solvents, mixing of A/B branches in copolymer stars, within or beyond the Daoud and Cotton blob model.

16.
Soft Matter ; 14(12): 2346-2356, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29498722

RESUMO

Bio-filaments often behave in a way unexpected from the standard semi-flexible polymer chain model (WLC), when squeezed to a surface, confined in microfluidic channels or clamped by their end. This calls for the super-helical filament model, going beyond WLC, where the filament forms a helix much wider than its diameter. We study this model using Brownian dynamics simulations, focusing on filaments confined to a surface by a strong potential. We analyze shapes and shape fluctuations under tension where excited states comprising a number of inflection points (twist-kink) can be stabilized. Pulling/releasing experiments during a cycle of increasing/decreasing tension show hysteresis. We find that the excited state, once established, is long-lived and the life time grows with the filament length cubed. Twist-kink diffusion involves position (filament shape) dependent friction for which we provide analytical expression. Dynamic responses to tension are investigated via numerical simulations and several mechanisms of shape relaxation are found and rationalized.

17.
Korean J Radiol ; 19(2): 284-291, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29520186

RESUMO

Objective: Postpancreatectomy hemorrhage (PPH) is an uncommon but serious complication of Whipple surgery. To evaluate the radiologic features associated with late PPH at the first postoperative follow up CT, before bleeding. Materials and Methods: To evaluate the radiological features associated with late PPH at the first follow-up CT, two radiologists retrospectively reviewed the initial postoperative follow-up CT images of 151 patients, who had undergone Whipple surgery. Twenty patients showed PPH due to vascular problem or anastomotic ulcer. The research compared CT and clinical findings of 20 patients with late PPH and 131 patients without late PPH, including presence of suggestive feature of pancreatic fistula (presence of air at fluid along pancreaticojejunostomy [PJ]), abscess (fluid collection with an enhancing rim or gas), fluid along hepaticojejunostomy or PJ, the density of ascites, and the size of visible gastroduodenal artery (GDA) stump. Results: CT findings including pancreatic fistula, abscess, and large GDA stump were associated with PPH on univariate analysis (p ≤ 0.009). On multivariate analysis, radiological features suggestive of a pancreatic fistula, abscess, and a GDA stump > 4.45 mm were associated with PPH (p ≤ 0.031). Conclusion: Early postoperative CT findings including GDA stump size larger than 4.45 mm, fluid collection with an enhancing rim or gas, and air at fluid along PJ, could predict late PPH.


Assuntos
Pancreaticoduodenectomia/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Hepática/anormalidades , Artéria Hepática/diagnóstico por imagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias , Hemorragia Pós-Operatória/diagnóstico por imagem , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto Jovem
18.
Nucleic Acids Res ; 46(8): 4129-4137, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29584891

RESUMO

Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B-Z transition in those sequences. Due to the high junction energy, an intermediate B* state has to accumulate prior to the B-Z transition. Our study showing the stable B* state supports the active picture for the protein-induced B-Z transition that occurs under a physiological setting.


Assuntos
Adenosina Desaminase/metabolismo , DNA de Forma B/química , DNA Forma Z/química , Proteínas de Ligação a RNA/metabolismo , DNA de Forma B/metabolismo , DNA Forma Z/metabolismo , Transferência Ressonante de Energia de Fluorescência , Modelos Estatísticos
19.
Int J Clin Oncol ; 23(4): 742-748, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29340839

RESUMO

BACKGROUND: The aim of this study is to investigate the cumulative incidence and risk factors of postoperative inguinal hernia (PIH) in patients undergoing radical prostatectomy, i.e., laparoscopic prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RARP). METHODS: This study included 1124 patients who had undergone radical prostatectomy or transurethral resection of bladder tumor from 2011-2016. We compared the cumulative incidence of PIH in the radical prostatectomy groups (460; LRP 341, RARP 119) and the control group (664; transurethral resection of bladder tumor), and we then analyzed the risk factors (age, operative methods, previous abdominal operative history, thickness and width of external oblique muscle and rectus muscle, thickness of abdominal subcutaneous fat layer at Hesselbach's triangle level, body mass index, prostate-specific antigen, operative time, specimen weight, Gleason score, and pathology T-stage) of PIH in the radical prostatectomy groups. RESULTS: The median follow-up period in this study was 39.6 months. In Kaplan-Meier curve analysis, the cumulative incidence of PIH was 5.3, 4.2, and 0.5% for the LRP, RARP, and control groups, respectively (p < 0.001). Multiple logistic regressions showed that thickness of external oblique muscle and width of rectus muscle were significant risk factors (p < 0.001 and p = 0.027). CONCLUSIONS: PIH is considered to be one of the complications of LRP and RARP. Moreover, we suggest that if the thickness of the muscle is <7.3 mm, thoughtful surgical manipulation is needed for radical prostatectomy, and care should be taken to determine whether hernia occurs during follow-up.


Assuntos
Hérnia Inguinal/epidemiologia , Hérnia Inguinal/etiologia , Complicações Pós-Operatórias , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Idoso , Estudos de Casos e Controles , Humanos , Incidência , Masculino , Gradação de Tumores , Neoplasias da Próstata/patologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
20.
Sci Rep ; 8(1): 766, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29335534

RESUMO

Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/ß-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting.


Assuntos
Anticorpos Biespecíficos/metabolismo , Fatores Imunológicos/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
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