2018 Targeting Trends Review

Zhuravin IA, Dubrovskaya NM, Tumanova NL, Vasilev DS, Nalivaeva NN (2018) Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions. Evolutionary Physiology and Biochemistry – Advances and Perspectives: InTech 714-741. doi: 10.5772/intechopen.73666

Summary: The effectiveness of the studies of the pathogenesis of AD and search for the strategies of its prevention and treatment depend on appropriate modeling of the pathological conditions in the brain leading to AD. Traditionally, the main focus on designing animal models of AD was related to the identification of brain areas and mediator systems related to memory. One model employed injections of a monoclonal antibody against growth factor receptor conjugated with saporin (192 IgG-saporin), which also resulted in the loss of cholinergic neurons and cognitive disorder

Related Products: 192-IgG-SAP (Cat. #IT-01)

Jones I, Novikova LN, Novikov LN, Renardy M, Ullrich A, Wiberg M, Carlsson L, Kingham PJ (2018) Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury. J Tissue Eng Regen Med 12(4):e2099-e2109. doi: 10.1002/term.2642 PMID: 29327452

Objective: To determine if differentiated neural crest cells are promising supporting cell candidates to aid in peripheral nerve repair.

Summary: In this study, neural crest cells were differentiated from human embryonic stem cells. NGFR (mouse monoclonal, 1:100) Immunocytochemistry. The specificity of NGFR antibody was validated by immunocytochemical staining of both hESCs- and MACS-enriched cells.

Related Products: NGFr (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Arias-Carrion O, Ortega-Robles E, de Celis-Alonso B, Palasz A, Mendez-Rojas MA, Salas-Pacheco J, Murillo-Rodriguez E (2018) Depletion of hypocretin/orexin neurons increases cell proliferation in the adult subventricular zone. CNS Neurol Disord Drug Targets 17:106-112. doi: 10.2174/1871527317666180314115623

Objective: To establish the relationship between the depletion of orexin neurons and the number of proliferating cells in the subventricular zone.

Summary: The adult subventricular zone is affected by orexinergic signaling, the functional implication of which must be further elucidated.

Usage: 90 ng of Orexin-SAP or pyrogen-free saline was stereotaxically injected into the lateral hypothalamus (3.2 caudal, 1.7 lateral to bregma, 8.1 ventral to the skull surface) of male Wistar rats.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Wang X, Ma S, Wu H, Shen X, Xu S, Guo X, Bolick ML, Wu S, Wang F (2018) Macrophage migration inhibitory factor mediates peripheral nerve injury-induced hypersensitivity by curbing dopaminergic descending inhibition. Exp Mol Med 50(2):e445. doi: 10.1038/emm.2017.271

Objective: To investigate whether the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system.

Summary: MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.

Usage: Anti-DAT-SAP was injected i.t. or i.c.v. with ISO-1 alone or ISO-1 combined with one of the other regulators on Day 7 post-nerve injury for 14 days, and pain behaviors, including 50% withdrawal threshold, mechanical pressure and thermal withdrawal latency, were observed throughout the 70 days post nerve injury.

Related Products: Anti-DAT-SAP (Cat. #IT-25)

Yuan X, Yang M, Chen X, Zhang X, Sukhadia S, Musolino N, Bao H, Chen T, Xu C, Wang Q, Santoro S, Ricklin D, Hu J, Lin R, Yang W, Li Z, Qin W, Zhao A, Scholler N, Coukos G (2018) Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy. Cancer Immunol Immunother 67:329-339. doi: 10.1007/s00262-017-2101-0 PMID: 29313073

Objective: ScFv78 was conjugated with the ribosome-inactivating protein saporin (Streptavidin-ZAP) to evaluate whether scFv78 may be used as a vehicle for theTEM1-targeted delivery of toxins.

Summary: Site-specific, biotinylated scFv78 was conjugated with streptavidin-labeled saporin (Streptavidin-ZAP; Cat. #IT-27) by incubation at room temperature for 1h at a molar ratio of 4:1 (scFv78:ZAP).

Usage: Mouse endothelial cells (MS1) and MS1 cells transduced to express full-length human TEM1 (MS1-TEM1) were cultured in 96-well plates to 30% confluence and then incubated for 96h in the presence of 10-fold serially diluted Streptavidin-ZAP, scFv78, or scFv78-ZAP starting from 40nM down to 0.04nM. The data indicate that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has unique and favorable features that are advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Araldi D, Khomula EV, Ferrari LF, Levine JD (2018) Fentanyl induces rapid onset hyperalgesic priming: Type I at peripheral and type II at central nociceptor terminals. J Neurosci 38(9):2226-2245. doi: 10.1523/JNEUROSCI.3476-17.2018

Objective: To evaluate priming, at both nociceptor terminals, the effect of local administration of agents that reverse type I (protein translation) or type II [combination of Src and mitogen-activated protein kinase (MAPK)] priming

Summary: Fentanyl, acting at the -opioid receptor (MOR), induces hyperalgesia and hyperalgesic priming at both the central and peripheral terminal of nociceptors and this is mediated by endoplasmic reticulum Ca2 signaling. Priming in the central terminal is type II, whereas that in the peripheral terminal is type I. Our findings may provide useful information for the design of drugs with improved therapeutic profiles, selectively disrupting individual MOR signaling pathways, to maintain an adequate long-lasting control of pain.

Usage: IB4-SAP was diluted in saline and a dose of 3.2 μg in a volume of 20 μl and administered intrathecally 14 d before experiments

Related Products: IB4-SAP (Cat. #IT-10)

Kusano-Arai O, Iwanari H, Kudo S, Kikuchi C, Yui A, Akiba H, Matsusaka K, Kaneda A, Fukayama M, Tsumoto K, Hamakubo T (2018) Synergistic cytotoxic effect on gastric cancer cells of an immunotoxin cocktail in which antibodies recognize different epitopes on CDH17. Monoclon Antib Immunodiagn Immunother 37:1-11. doi: 10.1089/mab.2017.0043

Objective: To determine if an immunotoxin cocktail targeted to multiple epitopes has synergistic effects on low expression level cells, which would expand the applicable range of immunotoxin therapy for cancer.

Summary: The combination of immunotoxins with different mechanisms of action in an antibody cocktail will increase cytotoxic activities and decrease side effects.

Usage: The authors applied a monoclonal antibody (mAb) cocktail for one target protein with multiple epitopes. They generated anti-CDH17 mAbs recognizing different epitopes on CDH17 (Cadherin-17). CDH17 is expressed in gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer and has limited distribution in normal tissues. For preparation of 3 immunotoxins, Streptavidin-ZAP was mixed with biotinylated mAbs in equimolar concentrations for 30 minutes at room temperature. The study provides data to demonstrate that the cocktail of different epitope-recognizing immunotoxins has synergistic cytotoxic effects on CDH17-expressing cells.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Park HW, Kim H-L, Park YS, Kim I-B (2018) The transient intermediate plexiform layer, a plexiform layer-like structure temporarily existing in the inner nuclear layer in developing rat retina. Exp Neurobiol 27:28-33. doi: 10.5607/en.2018.27.1.28

Related Products: SSP-SAP (Cat. #IT-11)

Lee SJ, Jokiaho AJ, Sanchez-Watts G, Watts AG (2018) Catecholaminergic projections into an interconnected forebrain network control the sensitivity of male rats to diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 314(6):R811-R823. doi: 10.1152/ajpregu.00423.2017

Objective: To investigate the role of hindbrain catecholamine neuron pathways and their contribution to long-term energy homeostasis by controlling obesogenic sensitivity to a high-fat, high sucrose choice diet.

Summary: The authors show that catecholamine neurons (primarily in the VLM and NTS) convey essential feedback signals to enable long-term adaptive control of energy metabolism when animals consume a predominantly carbohydrate diet. This is the first report specifically associating this projection system with the long-term control of adiposity.

Usage: Catecholaminergic projections to the PVH and related parts of the forebrain were lesioned with bilateral injections each consisting of 42 ng/200 nL of Anti-DBH-SAP or equimolar amounts of control Mouse IgG-SAP.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Zhou H, Huang J, Zhu L, Cao Y (2018) Erythropoietin alleviates post-resuscitation myocardial dysfunction in rats potentially through increasing the expression of angiotensin II receptor type 2 in myocardial tissues. Mol Med Rep 17:5184-5192. doi: 10.3892/mmr.2018.8473 PMID: 29393490

Objective: To determine whether erythropoietin (EPO) improves post‑resuscitation myocardial dysfunction and how it affects the renin‑angiotensin system.

Summary: The present study confirmed that EPO treatment is beneficial for protecting cardiac function post‑resuscitation, and the roles of EPO in alleviating post‑resuscitation myocardial dysfunction may potentially be associated with enhanced myocardial expression of AT2R.

Usage: Western blot analysis of AT-1R (1:500) in the myocardium

Related Products: Angiotensin II receptor (AT-1R) Rabbit Polyclonal, affinity-purified (Cat. #AB-N27AP)