targeted-toxins

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)

Shim HS, Park H-J, Lee M-S, Ye M, Shim I (2018) The role of the supramammillary area of the hypothalamus in cognitive functions. Animal Cells and Systems 22:37-44. doi: 10.1080/19768354.2018.1427627

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

Dobryakova YV, Kasianov A, Zaichenko MI, Stepanichev MY, Chesnokova EA, Kolosov PM, Markevich VA, Bolshakov AP (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus. Front Mol Neurosci 10:429. doi: 10.3389/fnmol.2017.00429

Objective: To analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus.

Summary: Disturbance of memory-associated behavior after administration of 192-IgG-SAP is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus.

Usage: Rats received bilateral i.c.v.infusions of 192-IgG-SAP (4 mcg/site).

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

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)

Ferrari LF, Khomula EV, Araldi D, Levine JD (2018) CD44 signaling mediates high molecular weight hyaluronan-induced antihyperalgesia. J Neurosci 38(2):308-321. doi: 10.1523/JNEUROSCI.2695-17.2017

Objective: To study the role of the cognate hyaluronan receptor, CD44, signaling in anti-hyperalgesia induced by high molecular weight hyaluronan (HMWH).

Summary: These results demonstrate the central role of CD44 signaling in HMWH-induced anti-hyperalgesia, and establish it as a therapeutic target against inflammatory and neuropathic pain.

Usage: Both IB4-SAP and SSP-SAP were diluted in saline to doses previously shown to deplete nonpeptidergic (3.2 mcg/rat for IB4-SAP) and peptidergic (100 ng/rat for SSP-SAP) fibers. The toxins were administered intrathecally, in a volume of 20 mcl, 14 d before intradermal injection of LMWH on the dorsum of the hindpaw. Treatment with either conjugate, or a combination of the two, did not significantly affect mechanical nociceptive threshold.

Related Products: IB4-SAP (Cat. #IT-10), SSP-SAP (Cat. #IT-11), Anti-CD44-SAP (Cat. #IT-72)

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)

Lund K, Olsen CE, Wong JJW, Olsen PA, Solberg NT, Høgset A, Krauss S, Selbo PK (2017) 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185.. doi: 10.1186/s13046-017-0662-6

Objective: Investigate resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma.

Summary: Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and Anti-CD105-SAP was assessed using microscopy. MTS assay was used to investigate cytotoxic effects of photochemical internalization of Anti-CD105-SAP. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells using Anti-CD105-SAP in vitro. PCI-based targeting of CD105 may represent a potent anti-cancer strategy and should be further evaluated in preclinical models.

Usage: Cells were seeded (3000/well) in 96-well plates and allowed to attach overnight. The cells were incubated with the Anti-CD105-saporin (2.4 nM) or Saporin as a control (6.48 nM; Saporin was added in a molecular ratio of 2.7:1 to the immunotoxin) giving an equal ratio of Saporin to immunotoxin), with or without the photosensitizer TPCS2a (0.35 μg/ml) for 18 h.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

Zhang J, Wang H, Wu S, Liu Q, Wang N (2017) Regulation of reentrainment function is dependent on a certain minimal number of intact functional iprgcs in rd mice. J Ophthalmol 2017:6804853.. doi: 10.1155/2017/6804853

Related Products: Melanopsin-SAP (Cat. #IT-44)

Liu A, Aoki S, Wickens J (2017) A streamlined method for the preparation of gelatin embedded brains and simplified organization of sections for serial reconstructions. Bio-protocol 7(22):e2610.. doi: 10.21769/BioProtoc.2610

Related Products: Anti-ChAT-SAP (Cat. #IT-42)