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https://www.readbyqxmd.com/read/28649690/enzymatic-conjugation-using-branched-linkers-for-constructing-homogeneous-antibody-drug-conjugates-with-high-potency
#1
Yasuaki Anami, Wei Xiong, Xun Gui, Mi Deng, Cheng Cheng Zhang, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama
Antibody-drug conjugates (ADCs) are emerging therapeutic agents in the treatment of cancer, and various conjugation strategies and chemical linkers have been developed to efficiently construct ADCs. Despite previous extensive efforts for improving conjugation efficiency and ADC homogeneity, most ADC linkers developed to date load only single payloads. Branched linkers that can load multiple payload molecules have yet to be fully explored. It is logical to envisage that a multi-loading strategy allows for increase in drug-to-antibody ratio (DAR) with less chemical or enzymatic modification to the antibody structure compared to traditional linear linkers, leading to efficient ADC construction, minimal destabilization of the antibody structure, and enhanced ADC efficacy...
June 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28648785/lc-ms-bioanalysis-of-trastuzumab-and-released-emtansine-using-nano-surface-and-molecular-orientation-limited-nsmol-proteolysis-and-liquid-liquid-partition-in-plasma-of-trastuzumab-emtansine-treated-breast-cancer-patients
#2
Noriko Iwamoto, Akihiko Shimomura, Kenji Tamura, Akinobu Hamada, Takashi Shimada
Antibody-drug conjugates (ADCs) consist of monoclonal antibody and cytotoxic drugs covalently attached via stable crosslinkers, and are prospective antibody drugs for cancer therapy. To cover the overall pharmacokinetic understanding of ADCs, both the antibody and the released drugs are necessary for practical clinical observation. The nano-surface and molecular-orientation limited (nSMOL) proteolysis is a universal approach for antibody bioanalysis that enable Fab-selective proteolysis, which maintains antibody sequence specificity while decreasing excess analyte peptides...
June 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28647756/role-of-coronal-high-resolution-diffusion-weighted-imaging-in-acute-optic-neuritis-a-comparison-with-axial-orientation
#3
Ping Lu, Yan Sha, Hailin Wan, Feng Wang, Guohong Tian
PURPOSE: Through a comparison with the axial orientation, we aimed to evaluate the role of coronal high-resolution diffusion-weighted imaging (DWI) in acute optic neuritis based on diagnostic accuracy and the reproducibility of apparent diffusion coefficient (ADC) measurements. METHODS: Orbital DWI, using readout-segmented, parallel imaging, and 2D navigator-based reacquisition (RESOLVE-DWI), was performed on 49 patients with acute vision loss. The coronal (thickness = 3 mm) and axial (thickness = 2 mm) diffusion images were evaluated by two neuroradiologists retrospectively...
June 24, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28646659/analysis-of-recombinant-monoclonal-antibodies-in-hydrophilic-interaction-chromatography-a-generic-method-development-approach
#4
Balázs Bobály, Valentina D'Atri, Alain Beck, Davy Guillarme, Szabolcs Fekete
Hydrophilic interaction liquid chromatography (HILIC) is a well-established technique for the separation and analysis of small polar compounds. A recently introduced widepore stationary phase expanded HILIC applications to larger molecules, such as therapeutic proteins. In this paper, we present some generic HILIC conditions adapted for a wide range of FDA and EMA approved recombinant monoclonal antibody (mAb) species and for an antibody-drug conjugate (ADC). Seven approved mAbs possessing various isoelectric point (pI) and hydrophobicity as well as a cysteine conjugated ADC were used in this study...
June 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#5
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28645458/pulmonary-3-he-magnetic-resonance-imaging-biomarkers-of-regional-airspace-enlargement-in-alpha-1-antitrypsin-deficiency
#6
Eric Lessard, Heather M Young, Anurag Bhalla, Damien Pike, Khadija Sheikh, David G McCormack, Alexei Ouriadov, Grace Parraga
RATIONALE AND OBJECTIVES: Thoracic x-ray computed tomography (CT) and hyperpolarized (3)He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (Lm) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers...
June 20, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28644999/diffusion-tensor-imaging-of-cingulum-bundle-and-corpus-callosum-in-schizophrenia-vs-bipolar-disorder
#7
Igor Nenadić, Anna Hoof, Maren Dietzek, Kerstin Langbein, Jürgen R Reichenbach, Heinrich Sauer, Daniel Güllmar
Both schizophrenia and bipolar disorder show abnormalities of white matter, as seen in diffusion tensor imaging (DTI) analyses of major brain fibre bundles. While studies in each of the two conditions have indicated possible overlap in anatomical location, there are few direct comparisons between the disorders. Also, it is unclear whether phenotypically similar subgroups (e.g. patients with bipolar disorder and psychotic features) might share white matter pathologies or be rather similar. Using region-of-interest (ROI) analysis of white matter with diffusion tensor imaging (DTI) at 3 T, we analysed fractional anisotropy (FA), radial diffusivity (RD), and apparent diffusion coefficient (ADC) of the corpus callosum and cingulum bundle in 33 schizophrenia patients, 17 euthymic (previously psychotic) bipolar disorder patients, and 36 healthy controls...
May 25, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28644061/diffusion-weighted-magnetic-resonance-imaging-in-the-assessment-of-choroid-plexus-aging
#8
Banu Alicioglu, Guliz Yilmaz, Ozgur Tosun, Nail Bulakbasi
Recent studies have pointed out dysfunction and histopathological changes of the choroid plexuses (CPs) with aging. This paper reviews apparent diffusion coefficient (ADC) values of the CPs for age-related changes. All the brain MR images of the patients between January 2013 and June 2014 in our Radiology Department were retrospectively investigated. Patients with major cranial abnormalities (brain tumors, hyperacute or acute ischemia, developmental anomalies, hemorrhage, hydrocephaly) were excluded. Diffusion-weighted images were obtained at the parameter values of b = 1000 s/mm(2) in the axial plane...
January 1, 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28643537/a-diffusion-weighted-imaging-study-of-basal-ganglia-in-schizophrenia
#9
Giuseppe Delvecchio, Alessandro Pigoni, Cinzia Perlini, Marco Barillari, Amelia Versace, Mirella Ruggeri, A Carlo Altamura, Marcella Bellani, Paolo Brambilla
OBJECTIVES: Several magnetic resonance imaging (MRI) studies provided evidence of selective brain abnormalities in schizophrenia, both in cortical and subcortical structures. Basal ganglia are of particular interest, given not only the high concentration of dopaminergic neurons and receptors, but also for their crucial role in cognitive functions, commonly impaired in schizophrenia. To date, very few studies explored basal ganglia using diffusion imaging, which is sensitive to microstructural organization in brain tissues...
June 23, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28642480/haralick-texture-features-from-apparent-diffusion-coefficient-adc-mri-images-depend-on-imaging-and-pre-processing-parameters
#10
Patrik Brynolfsson, David Nilsson, Turid Torheim, Thomas Asklund, Camilla Thellenberg Karlsson, Johan Trygg, Tufve Nyholm, Anders Garpebring
In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28640538/whole-lesion-histogram-analysis-of-the-apparent-diffusion-coefficient-evaluation-of-the-correlation-with-subtypes-of-mucinous-breast-carcinoma
#11
Yuan Guo, Qing-Cong Kong, Ye-Qing Zhu, Zhen-Zhen Liu, Ling-Rong Peng, Wen-Jie Tang, Rui-Meng Yang, Jia-Jun Xie, Chun-Ling Liu
PURPOSE: To evaluate the utility of the whole-lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC. MATERIALS AND METHODS: This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC-A (20 cases) and PMBC-B (17 cases) groups...
June 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28640531/apparent-diffusion-coefficient-in-estrogen-receptor-positive-and-lymph-node-negative-invasive-breast-cancers-at-3-0t-dw-mri-a-potential-predictor-for-an-oncotype-dx-test-recurrence-score
#12
Sunitha B Thakur, Manuela Durando, Soledad Milans, Gene Y Cho, Lucas Gennaro, Elizabeth J Sutton, Dilip Giri, Elizabeth A Morris
PURPOSE: To measure the apparent diffusion coefficient (ADC) values in estrogen receptor-positive (ER+) and axillary lymph node-negative (LN-) invasive breast cancer and investigate the correlation of ADC with Oncotype Dx test recurrence scores (ODxRS). MATERIALS AND METHODS: This was a Health Insurance Portability and Accountability Act (HIPAA)-compliant single-site retrospective study. Patients underwent preoperative 3.0T MRI scans with additional diffusion-weighted imaging sequential scans (b = 0, 600 and b = 0, 1000 s/mm(2) ) from January 2011 to 2013...
June 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28640476/histogram-analyses-of-diffusion-kurtosis-indices-and-apparent-diffusion-coefficient-in-assessing-liver-regeneration-after-alpps-and-a-comparative-study-with-portal-vein-ligation
#13
Ruo-Fan Sheng, He-Qing Wang, Kai-Pu Jin, Li Yang, Hao Liu, Yuan Ji, Cai-Xia Fu, Meng-Su Zeng
PURPOSE: To investigate the value of diffusion kurtosis imaging (DKI) histogram analysis in assessing liver regeneration and the microstructure basis after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), in comparison with portal vein ligation (PVL). MATERIALS AND METHODS: Thirty rats were divided into the ALPPS, PVL, and control groups. Histograms of DKI using a 3T magnetic resonance imaging (MRI) scanner were performed for corrected apparent diffusion (D), kurtosis (K), and apparent diffusion coefficient (ADC)...
June 22, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28639338/registration-strategies-for-multi-modal-whole-body-mri-mosaicing
#14
Jakub Ceranka, Mathias Polfliet, Frédéric Lecouvet, Nicolas Michoux, Johan de Mey, Jef Vandemeulebroucke
PURPOSE: To test and compare different registration approaches for performing whole-body diffusion-weighted (wbDWI) image station mosaicing, and its alignment to corresponding anatomical T1 whole-body image. METHODS: Four different registration strategies aiming at mosaicing of diffusion-weighted image stations, and their alignment to the corresponding whole-body anatomical image, were proposed and evaluated. These included two-step approaches, where diffusion-weighted stations are first combined in a pairwise (Strategy 1) or groupwise (Strategy 2) manner and later non-rigidly aligned to the anatomical image; a direct pairwise mapping of DWI stations onto the anatomical image (Strategy 3); and simultaneous mosaicing of DWI and alignment to the anatomical image (Strategy 4)...
June 21, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28639049/multiparametric-voxel-based-analyses-of-standardized-uptake-values-and-apparent-diffusion-coefficients-of-soft-tissue-tumours-with-a-positron-emission-tomography-magnetic-resonance-system-preliminary-results
#15
Koji Sagiyama, Yuji Watanabe, Ryotaro Kamei, Sungtak Hong, Satoshi Kawanami, Yoshihiro Matsumoto, Hiroshi Honda
OBJECTIVES: To investigate the usefulness of voxel-based analysis of standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) for evaluating soft-tissue tumour malignancy with a PET/MR system. METHODS: Thirty-five subjects with either ten low/intermediate-grade tumours or 25 high-grade tumours were prospectively enrolled. Zoomed diffusion-weighted and fluorodeoxyglucose ((18)FDG)-PET images were acquired along with fat-suppressed T2-weighted images (FST2WIs)...
June 20, 2017: European Radiology
https://www.readbyqxmd.com/read/28639047/apparent-diffusion-coefficient-maps-obtained-from-high-b-value-diffusion-weighted-imaging-in-the-preoperative-evaluation-of-gliomas-at-3t-comparison-with-standard-b-value-diffusion-weighted-imaging
#16
Qiang Zeng, Fei Dong, Feina Shi, Chenhan Ling, Biao Jiang, Jianmin Zhang
OBJECTIVE: To assess whether ADC maps obtained from high b value DWI were more valuable in preoperatively evaluating the grade, Ki-67 index and outcome of gliomas. METHODS: Sixty-three patients with gliomas, who underwent preoperative multi b value DWI at 3 T, were enrolled. The ADC1000, ADC2000 and ADC3000 maps were generated. Receiver operating characteristic analyses were conducted to determine the area under the curve (AUC) in differentiating high-grade gliomas (HGG) from low-grade gliomas (LGG)...
June 21, 2017: European Radiology
https://www.readbyqxmd.com/read/28638673/monitoring-of-cellular-changes-in-the-bone-marrow-following-pth-1-34-treatment-of-ovx-rats-using-a-portable-stray-field-nmr-scanner
#17
Inbar Hillel, Itzhak Binderman, Yifat Sarda, Uri Nevo
Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats...
2017: Journal of Osteoporosis
https://www.readbyqxmd.com/read/28634901/changes-in-plasma-mir-9-mir-16-mir-205-and-mir-486-levels-after-non-small-cell-lung-cancer-resection
#18
Maria Sromek, Maciej Glogowski, Magdalena Chechlinska, Mariusz Kulinczak, Lukasz Szafron, Klara Zakrzewska, Joanna Owczarek, Piotr Wisniewski, Robert Wlodarczyk, Lukasz Talarek, Maciej Turski, Jan Konrad Siwicki
PURPOSE: The majority of non-small cell lung cancer (NSCLC) patients presents with an advanced-stage disease and, consequently, exhibits a poor overall survival rate. We aimed to assess changes in plasma miR-9, miR-16, miR-205 and miR-486 levels and their potential as biomarkers for the diagnosis and monitoring of NSCLC patients. METHODS: Plasma was collected from 50 healthy donors and from NSCLC patients before surgery (n = 61), 1 month after surgery (n = 37) and 1 year after surgery (n = 14)...
June 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28634318/evaluation-and-validation-of-the-diagnostic-value-of-the-apparent-diffusion-coefficient-for-differentiating-early-stage-endometrial-carcinomas-from-benign-mimickers-at-3t-mri
#19
Xue Wang, Yu Zhao, Yumin Hu, Yongjin Zhou, Xinjian Ye, Kun Liu, Guanghui Bai, Anna Guo, Meimei Du, Lezhen Jiang, Jinhong Wang, Zhihan Yan
Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634047/the-study-of-the-intervertebral-disc-microstructure-in-matured-rats-with-diffusion-kurtosis-imaging
#20
Li Li, Wenzhen Zhu, Weiwei Chen, Jicheng Fang, Jing Li
OBJECTIVES: The aim of this study was to use DKI to detect the microstructural change of the discs in matured normal rats. METHODS: Total 24 normal SD rats (12 males/12 females) underwent DWI/DKI and T2 sequences with a 3T MRI scanner to get the values of ADC, FA, MD, Da, Dr, MK, Ka and Kr. The discs were categorized using a five-grade degeneration grading system in the T2-images. The height of the discs and the parameters in DWI/DKI were measured to compare between the different grades and sexes...
June 17, 2017: Magnetic Resonance Imaging
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