saporin

Tan HL, Yong C, Tan BZ, Fong WJ, Padmanabhan J, Chin A, Ding V, Lau A, Zheng L, Bi X, Yang Y, Choo A (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Sci Rep 8:11608. doi: 10.1038/s41598-018-30070-z

Objective: To identify and characterize an antibody raised using human embryonic stem cells with potential as a cancer therapeutic.

Summary: Antibody A19 not only binds to undifferentiated hESCs by flow cytometry, it also reacts with ovarian and breast cancer cell lines with low or no binding to normal cells.

Usage: in vitro – Number of viable cells treated showed a decrease in cell number (Hum-ZAP mixed with A19; Streptavidin-ZAP mixed with biotinylated A19). To determine if there were off-target effects, Hum-ZAP and chA19 were incubated with a non-binding cell line OVCAR10; no apparent cytotoxicity was observed. invivo – 5 x 106 SKOV3 cells were implanted s.c. in NUDE mice and Biotinylated A19-Streptavidin-ZAP (ADC), administered ip. The controls were free Saporin and naked A19. By the end of 10 weeks, mice administered with the ADC saw a 60% reduction in tumor size compared to control groups.

Related Products: Hum-ZAP (Cat. #IT-22), Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)

Naves LM, Marques SM, Mourão AA, Fajemiroye JO, Xavier CH, de Castro CH, Rebelo ACS, Rosa DA, Gomes RM, Colombari E, Pedrino GR (2018) Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats. Sci Rep 8:11276. doi: 10.1038/s41598-018-29310-z

Objective: To evaluate the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats.

Summary: The recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.

Usage: In order to achieve A1 and/or A2 neuronal lesions, Anti-DBH-SAP (100 nL, 0.105 ng·nL−1 ) was nanoinjected into the CVLM and NTS region, respectively. In sham groups, the equimolar of Saporin (100 nL, 0.022 ng·nL−1 ) was nanoinjected into the same site.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

Suarez AN, Hsu TM, Liu CM, Noble EE, Cortella AM, Nakamoto EM, Hahn JD, de Lartigue G, Kanoski SE (2018) Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181. doi: 10.1038/s41467-018-04639-1

Objective: To determine the  endogenous relevance of GIderived vagal HPC communication.

Summary: Endogenous derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem–septal pathway, thereby identifying a previously unknown role for the gut–brain axis in memory control.

Usage: A 1-µl volume of CCK-SAP (250 ng/µl) or control Saporin (250 ng/µl) was injected at two sites: 0.5 µl rostral and 0.5 µl caudal to the laryngeal nerve branch.

Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)

Patrone LGA, Biancardi V, Marques DA, Bícego KC, Gargaglioni LH (2018) Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats. J Physiol 596(15):3299-3325. doi: 10.1113/JP275731

Objective: To determine the role of the brainstem CA system in ventilatory control under normocapnic and hypercapnic conditions during different phases of development (P7-8, P14-15 and P20-21) in male and female Wistar rats.

Summary: Brainstem CA neurones produce a tonic inhibitory drive that affects breathing frequency in P7-8 rats and provide an inhibitory drive during hypercapnic conditions in both males and females at P7-8 and P14-15.

Usage: Anti-DBH-SAP (420 ng/μL – 1 μL for P0-1; 1.5 μL for P7-8; 2.0 μL for P13-14) was injected into the 4th ventricle of neonatal Wistar rats of both sexes. Control rats were injected with vehicle (PBS, 0.01 M, pH 7.4) or unconjugated saporin (Cat. #PR-01), with respective volumes for each age, as described for the Anti-DBH-SAP group. All injections were performed using a microinjector pump over a period of 5 min to allow drug diffusion.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

Potter H, Alenciks E, Frazier K, Porter A, Fraley GS (2018) Immunolesion of melanopsin neurons causes gonadal regression in Pekin drakes (Anas platyrhynchos domesticus). Gen Comp Endocrinol 256:16-22. doi: 10.1016/j.ygcen.2017.08.006

Objective: Examine effects of loss of melanopsin in drakes.

Summary: Loss of melanopsin in PMM elicits decrease in GnRH mRNA expression, gonadal regression, and sex behaviors in drakes.

Usage: To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 μl of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10).

Related Products: Melanopsin-SAP (Cat. #IT-44), Saporin (Cat. #PR-01)

Oliveira LM, Moreira TS, Takakura AC (2018) Raphe pallidus is not important to central chemoreception in a rat model of Parkinson’s disease. Neuroscience 369:350-362. doi: 10.1016/j.neuroscience.2017.11.038

Objective: To investigate if serotonin-expressing neurons in the Raphe pallidus/parapyramidal region (RPa/PPy) are also involved in the modulation of breathing during central chemoreception activation in a PD animal model.

Related Products: Anti-SERT-SAP (Cat. #IT-23), Saporin (Cat. #PR-01)

Guo Y, Hu J, Wang Y, Peng X, Min J, Wang J, Matthaiou E, Cheng Y, Sun K, Tong X, Fan Y, Zhang PJ, Kandalaft LE, Irving M, Coukos G, Li C (2018) Tumour endothelial marker 1/endosialin-mediated targeting of human sarcoma. Eur J Cancer 90:111-121. doi: 10.1016/j.ejca.2017.10.035. PMID: 29304474

Objective: Using Saporin conjugated to 78Fc, an antibody fragment directed towards endosialin a.k.a. CD248, in the treatment of human sarcomas.

Summary: Endosialin/CD248 is over-expressed in human sarcomas, and a human single-chain variable fragment -Fc fusion protein was created targeting CD248. 78Fc-SAP eliminated CD248+ cells without off-target toxicity in vivo in mice and in vitro in human sarcoma cells.

Usage: In vivo: Mice were inoculated with osteosarcoma cells. These mice received, in PBS, either 4 ug of 78Fc-SAP, 1.4 ug of free saporin [PR-01], or no drug. In vitro: At 2.2 nM nearly 100% of CD248+ human sarcoma cell lines ( SJSA-1, A673, MES-SA and HOS) were eliminated. At the same concentration with free saporin ~20% of cells were eliminated.

Related Products: Saporin (Cat. #PR-01)

Leduc-Pessah H, Weilinger N, Fan C, Burma N, Thompson R, Trang T (2017) Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance. J Neurosci 37:10154-10172.. doi: 10.1523/JNEUROSCI.0852-17.2017

Summary: By selectively ablating microglia in the spinal cord using a Mac-1-SAP the authors demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats.

Usage: Mac-1-SAP or unconjugated Saporin control (15 μg) was administered by intrathecal injection.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Capone E, Giansanti F, Ponziani S, Lamolinara A, Iezzi M, Cimini A, Angelucci F, Sorda R, Laurenzi V, Natali PG, Ippoliti R, Iacobelli S, Sala G (2017) EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma. Oncotarget 8(56):95412-95424. doi: 10.18632/oncotarget.20728 PMID: 29221137

Objective: Using EV20 (Anti-Her3)-SAP to target Her3 positive melanoma

Summary: Linking a humanized monoclonal antibody targeting Her3, named EV20, to saporin creates a powerful cytotoxic agent targeting melanoma – which overexpress the Her3 receptor. The antibody, EV20, rapidly is internalized by Her3 whether its dependent ligand is there or not. EV20-SAP demonstrated potent and specific cytotoxicity towards human melanoma cells.

Usage: At a concentration of 19 nM only 10% of the human melanoma cells 9 (SK-MEL24 melanoma cells) survived, where free saporin at the same concentration shows no/minimal cytotoxicity.

Related Products: Saporin (Cat. #PR-01)

Echeverry S, Shi XQ, Yang M, Huang H, Wu Y, Lorenzo L-E, Perez-Sanchez J, Bonin RP, De Koninck Y, Zhang J (2017) Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801.. doi: 10.1097/j.pain.0000000000000982

Summary: Selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac-1-SAP and blockade of brain derived neurotrophic factor–TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity.  To selectively deplete microglia in the spinal cord, Mac-1-SAP was injected intrathecally.  In each group, rats received either an intrathecal injection of 12 mg/7 mL of Mac-1-SAP (n = 6-8) or equal volume of 0.9% saline (n 5 6) or the inactive unconjugated toxin, Saporin (n = 6).)

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)