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https://www.readbyqxmd.com/read/29656320/the-role-of-mesothelin-as-a-diagnostic-and-therapeutic-target-in-pancreatic-ductal-adenocarcinoma-a-comprehensive-review
#1
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
April 14, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29655990/inorganic-kernel-supported-asymmetric-hybrid-vesicles-for-targeting-delivery-of-stat3-decoy-oligonucleotides-to-overcome-anti-her2-therapeutic-resistance-of-bt474r
#2
Kai Shi, Yan Fang, Shan Gao, Dongjuan Yang, Hongshu Bi, Jianxiu Xue, Anqi Lu, Yuai Li, Liyuan Ke, Xiaojie Lin, Xuechao Jin, Min Li
As a recombinant humanized monoclonal antibody that targets the extracellular region of HER2 tyrosine kinase receptor, trastuzumab (TRAZ) has demonstrated comparable clinical efficacy and improved survival in patients with HER2-positive breast cancer. Nevertheless, the therapeutic potential of TRAZ is often limited due to its frequent resistance to anti-HER2 therapy. Therefore, we investigate the reversal effect of STAT3-specific decoy oligonucleotides (STAT3-decoy ODNs) on TRAZ resistance, which contain the consensus sequence within the targeted gene promoter of STAT3...
April 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29655914/importance-of-cynomolgus-monkeys-in-development-of-monoclonal-antibody-drugs
#3
REVIEW
Kazuhide Iwasaki, Yasuhiro Uno, Masahiro Uto, Hiroshi Yamazaki
Animal species used in the preclinical studies for development of monoclonal antibody (mAb) drugs are surveyed in this review. Relevant animal species for preclinical studies of mAb candidates are those express desired epitope of mAb candidates. Cynomolgus monkeys cross-react with mAb drugs much higher than other animal species commonly used in preclinical studies such as absorption, distribution, metabolism and excretion (ADME), efficacy, and toxicity studies, for development of new drugs. Moreover, plasma exposure of the mAb drugs in humans is predicted well from the exposure in the monkeys, and the placental transfer of immunoglobulin G (IgG, all the mAb drugs contain IgG) from mother to fetus is similar between humans and the monkeys from a viewpoint of time course and plasma level of IgG transferred...
March 20, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29655788/antibody-engineering-to-improve-manufacturability
#4
Sujeewa D Wijesuriya, Elizabeth Pongo, Milan Tomic, Fangjiu Zhang, Consuelo Garcia-Rodriquez, Fraser Conrad, Shauna Farr-Jones, James D Marks, Arnold H Horwitz
Expression variation among antibodies produced by stably transfected Chinese Hamster Ovary (CHO) cells is well established. While developing CHO-K1 cell lines, we encountered a human monoclonal antibody, mAb B-c, with severe manufacturability issues, including very poor expression and high levels of heavy chain (HC) dimer and high molecular weight aggregates. Using transient expression in CHO-K1 cells, we identified light chain (LC) as the source of the manufacturability issues for this antibody. While other antibodies achieved optimal expression at 1:1 or 2:1 LC to HC ratios, mAb B-c required up to a 6:1 LC:HC for maximal expression, which was still significantly lower than that for other tested antibodies...
April 12, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29653224/tumor-uptake-of-pegylated-diabodies-balancing-systemic-clearance-and-vascular-transport
#5
Qing Li, Jason B White, Norman C Peterson, Keith W Rickert, Christopher O Lloyd, Kevin L Allen, Kim Rosenthal, Xizhe Gao, Herren Wu, William F Dall'Acqua, M Jack Borrok, Ping Tsui
The accumulation, dissemination and clearance of monoclonal antibody-based therapeutics or imaging reagents targeting tumor associated antigens is governed by several factors including affinity, size, charge, and valency. Tumor targeting antibody fragments have distinct advantages over intact monoclonal antibodies such as enhanced penetration within the tumor and rapid accumulation but are subject to rapid clearance. Polyethylene glycol (PEG)-modified antibody fragments can provide a way to balance tumor penetration and accumulation with improved serum persistence...
April 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29653142/characterization-of-a-conjunctival-melanoma-cell-line-cm-as16-newly-established-from-a-metastatic-han-chinese-patient
#6
Yongyun Li, Qingfeng Shang, Peng Li, Jinfeng Cao, Liqi Zhu, Martine J Jager, Xianqun Fan, Shengfang Ge, Renbing Jia
Conjunctival melanoma (CM) is associated with metastases formation, can be fatal, and occurs in all different races. While cell lines are essential for experimental research, all available CM cell lines are derived from Caucasian patients. Furthermore, they are not derived from metastases. We aimed to establish a new CM cell line from a parotid metastasis in a Han Chinese patient and to depict its characteristics. The novel cell line, CM-AS16, was obtained from a surgical parotid sample and determined as a unique one with short tandem repeat (STR) analysis...
April 10, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29653006/-a-weak-d-type-59-case-identified-in-the-chinese-han-population
#7
Zhaoping Liao, Huiying Xu, Chunhua Liu, Rui Wang, Kaihua Xiang, Jie Feng, Fangjia Le, Ting Wu, Zhihua Tao
OBJECTIVE: To study a case with weak D59 phenotype identified among ethnic Han Chinese population. METHODS: Routine serological tests were used to analyze the reaction patterns, and the RhD epitopes were verified with 12 monoclonal antibodies. Sequence-specific primer PCR was applied for typing the weak RhD and RhD zygosity in the proband and his family members. RESULTS: A c.1148T>C variant was identified in the proband, for which serological test indicated a weak D phenotype...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29652548/ca125-suppresses-amatuximab-immune-effector-function-and-elevated-serum-levels-are-associated-with-reduced-clinical-response-in-first-line-mesothelioma-patients
#8
Nicholas C Nicolaides, Charles Schweizer, Elizabeth B Somers, Wenquan Wang, Shawn Fernando, Erin N Ross, Luigi Grasso, Raffit Hassan, J Bradford Kline
The tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care...
April 13, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29652061/bevacizumab-and-near-infrared-probe-conjugated-iron-oxide-nanoparticles-for-vascular-endothelial-growth-factor-targeted-mr-and-optical-imaging
#9
Run Lin, Jing Huang, Liya Wang, Yuancheng Li, Malgorzata Lipowska, Hui Wu, Jianyong Yang, Hui Mao
Vascular endothelial growth factor (VEGF) plays a pivotal role in the cascade of development and progression of cancers. Targeting this cancer hallmark is a logical strategy for imaging based cancer detection and monitoring the anti-angiogenesis treatment. Using Bevacizumab (Avastin®), which is a recombinant humanized monoclonal antibody directly against VEGF and an angiogenesis inhibitor, as a targeting ligand, a multimodal VEGF targeted molecular imaging probe was developed by conjugating near infrared dye (NIR830) labeled bevacizumab to magnetic iron oxide nanoparticles (IONP) for optical and magnetic resonance (MR) imaging of cancers over-expressing VEGF...
April 13, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29651889/how-to-conduct-research-of-rare-autoimmune-diseases
#10
Chikashi Terao
Rare autoimmune diseases are difficult to conduct researches in spite of present era with advanced scientific progress. Research using genetic approach is a promising way since genetic findings implicate causality of diseases. Still, there are multiple obstacles preventing genetic studies of rare diseases. Here, we list up the problems and propose solutions for them with detailed examples. The biggest problem is that it is difficult to collect a substantial number of DNA samples from patients with rare diseases...
April 13, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29651639/abatacept-for-treatment-of-rheumatoid-arthritis-special-focus-on-the-elderly
#11
Martin Soubrier, Clement Lahaye, Zuzana Tatar
Targeted therapies have been developed for patients with rheumatoid arthritis (RA) for whom prior treatment with traditional disease-modifying anti-rheumatic drugs has failed. The numerous different signaling pathways now targeted by various classes of monoclonal antibodies and small molecule inhibitors may complicate treatment decisions. Abatacept selectively modulates a co-stimulatory signal necessary for T-cell activation. Thus, abatacept is effective in biologic-naive patients and in those for whom biologic therapy has failed...
April 12, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29651353/a-rare-case-of-systemic-al-amyloidosis-with-muscle-involvement-a-misleading-diagnosis
#12
Fabrizio Accardi, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, Roberta Costa, Laura Notarfranchi, Benedetta Dalla Palma, Franco Aversa, Vladimiro Pietrini, Giovanna Cenacchi, Nicola Giuliani
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29651292/autoantibodies-to-chemokines-and-cytokines-participate-in-the-regulation-of-cancer-and-autoimmunity
#13
REVIEW
Nathan Karin
We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29651117/field-validation-of-recombinant-antigen-immunoassays-for-diagnosis-of-lassa-fever
#14
Matthew L Boisen, Jessica N Hartnett, Jeffrey G Shaffer, Augustine Goba, Mambu Momoh, John Demby Sandi, Mohamed Fullah, Diana K S Nelson, Duane J Bush, Megan M Rowland, Megan L Heinrich, Anatoliy P Koval, Robert W Cross, Kayla G Barnes, Anna E Lachenauer, Aaron E Lin, Mahan Nekoui, Dylan Kotliar, Sarah M Winnicki, Katherine J Siddle, Michael Gbakie, Mbalu Fonnie, Veronica J Koroma, Lansana Kanneh, Peter C Kulakosky, Kathryn M Hastie, Russell B Wilson, Kristian G Andersen, Onikepe O Folarin, Christian T Happi, Pardis C Sabeti, Thomas W Geisbert, Erica Ollmann Saphire, S Humarr Khan, Donald S Grant, John S Schieffelin, Luis M Branco, Robert F Garry
Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient's clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650949/treating-cat-allergy-with-monoclonal-igg-antibodies-that-bind-allergen-and-prevent-ige-engagement
#15
J M Orengo, A R Radin, V Kamat, A Badithe, L H Ben, B L Bennett, S Zhong, D Birchard, A Limnander, A Rafique, J Bautista, A Kostic, D Newell, X Duan, M C Franklin, W Olson, T Huang, N A Gandhi, L Lipsich, N Stahl, N J Papadopoulos, A J Murphy, G D Yancopoulos
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29650945/impact-of-regulatory-t-cells-on-innate-immune-cells-in-a-pre-sensitized-heart-transplant-model
#16
Weihua Gong, Baoqing Liu, Juntao Chen, Chen Liu, Zhonghua Shen
BACKGROUND Although our previous studies revealed the role of Tregs (regulatory T cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac transplant model, interplay between Tregs and NK cells, neutrophils, and macrophages remain undefined. MATERIAL AND METHODS Mice heart transplantation with skin pre-sensitization was performed, in which prolonged-cold ischemia time (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies), adoptive cell transfer with Tregs, and rapamycin...
April 13, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29650777/-mll-leukemia-induction-by-t-9-11-chromosomal-translocation-in-human-hematopoietic-stem-cells-using-genome-editing
#17
Corina Schneidawind, Johan Jeong, Dominik Schneidawind, In-Suk Kim, Jesús Duque-Afonso, Stephen Hon Kit Wong, Masayuki Iwasaki, Erin H Breese, James L Zehnder, Matthew Porteus, Michael L Cleary
Genome editing provides a potential approach to model de novo leukemogenesis in primary human hematopoietic stem and progenitor cells (HSPCs) through induction of chromosomal translocations by targeted DNA double-strand breaks. However, very low efficiency of translocations and lack of markers for translocated cells serve as barriers to their characterization and model development. Here, we used transcription activator-like effector nucleases to generate t(9;11) chromosomal translocations encoding MLL-AF9 and reciprocal AF9-MLL fusion products in CD34+ human cord blood cells...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29650525/flushing-disorders-associated-with-gastrointestinal-symptoms-part-1-neuroendocrine-tumors-mast-cell-disorders-and-hyperbasophila
#18
REVIEW
Vaibhav Rastogi, Devina Singh, Joseph J Mazza, Dennis Yang, Dipendra Parajuli, Steven H Yale
Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands...
April 12, 2018: Clinical Medicine & Research
https://www.readbyqxmd.com/read/29649930/pulmonary-paracoccidioidomycosis-associated-with-the-use-of-natalizumab-in-multiple-sclerosis
#19
Kelson James Almeida, Raissa Viera Barreto-Soares, Raimundo Nonato Campos-Sousa, Maria Graças Campos-Sousa, Edson Bor-Seng-Shu
BACKGROUND: Natalizumab (NTZ) is a monoclonal antibody with an immunosuppressive effect that reduces the inflammation of the central nervous system, and it has been used for the treatment of relapsing-remitting multiple sclerosis (RRMS). In patients with low cellular immune response, systemic mycosis arising from endemic areas may occur. RESULTS AND CONCLUSION: In this article, we will describe a case of paracoccidioidomycosis as a complication to treatment with NTZ in an RRMS patient...
April 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29649884/the-pharmacologic-role-and-clinical-utility-of-pcsk9-inhibitors-for-the-treatment-of-hypercholesterolemia
#20
C Michael White
In addition to monoclonal antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), vaccines against PCSK9 and smaller molecule inhibitors as well as RNA inhibitors of PCSK9 production have been created. The monoclonal antibodies against PCSK9 and the PCSK9 RNA inhibitors can reduce low-density lipoproteins (LDLs) by over 50%, non-high-density lipoprotein (HDL) cholesterol and triglycerides, and increasing HDL. Although effective in several homozygous familial hypercholesterolemia patient types, PCSK9 inhibitors does not work in all patient types...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
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