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2020 Targeting Trends Review

54 entries

Intracellular delivery methods using biofunctional peptide-modified extracellular vesicles

Nakase I (2020) Intracellular delivery methods using biofunctional peptide-modified extracellular vesicles. Extracell Vesicles Circ Nucleic Acids 1:44. American Society for Exosomes and Microvesicles 2020 Annual Meeting. doi: 10.20517/evcna.2020.10

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

Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity

Ringel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, Yao CH, Yoon H, Sage PT, LaFleur MW, Trombley JD, Jacobson CA, Maliga Z, Gygi SP, Sorger PK, Rabinowitz JD, Sharpe AH, Haigis MC (2020) Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183(7):1848-1866.e26. doi: 10.1016/j.cell.2020.11.009

Objective: To investigate how obesity shifts the metabolic landscape of the tumor microenvironment (TME) to inhibit T cell function and promote tumor growth.

Summary: High-fat diet – induced obesity impairs CD8+ T cell function in the murine TME, accelerating tumor growth.

Usage: Immunoprecipitation

Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044A)

Extracellular levels of the sleep homeostasis mediator, adenosine, are regulated by glutamatergic neurons during wakefulness and sleep

Sun MJ, Tang Y (2020) Extracellular levels of the sleep homeostasis mediator, adenosine, are regulated by glutamatergic neurons during wakefulness and sleep. Purinergic Signal 16(4):475-476. doi: 10.1007/s11302-020-09758-3

Summary: Blanco-Centurion et al. investigated the role of cholinergic neurons in the BF by administering 192–IgG–SAP to lesion them, but surprisingly the results indicated that adenosine from cholinergic neurons in BF are not essential to sleep induction.

See: Blanco-Centurion C et al. Adenosine and sleep homeostasis in the Basal forebrain. J Neurosci 26(31):8092-8100, 2006.

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

Differential mechanisms are required for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections.

Borkowski LF, Nichols NL (2020) Differential mechanisms are required for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections. Exp Neurol 334:113460. doi: 10.1016/j.expneurol.2020.113460

Objective: To understand the mechanism responsible for this difference in magnitude of phrenic long-term facilitation (pLTF)

Summary: pLTF in 7d CTB-SAP treated rats is elicited primarily through TrkB and PI3K/Akt-dependent mechanisms, whereas BDNF and MEK/ERK-dependent mechanisms induce pLTF in 28d CTB-SAP treated rats.

Usage: Rats received bilateral intrapleural injections of CTB-SAP; 25 μg dissolved in PBS.

Related Products: CTB-SAP (Cat. #IT-14)

Measuring attention in rats with a visual signal detection task: Signal intensity vs. signal duration

Holloway Z, Koburov R, Hawkey A, Levin ED (2020) Measuring attention in rats with a visual signal detection task: Signal intensity vs. signal duration. Pharmacol Biochem Behav 199:173069. doi: 10.1016/j.pbb.2020.173069

Summary: Drug-induced effects have been used to demonstrate the construct validity of operant attention tasks, as well as to assess the pharmacological systems that underlie cognitive processes, such as attention, short-term memory and reaction time, either by interrupting or enhancing performance.

See: McGaughy J et al. Sustained attention performance in rats with intracortical infusions of 192 IgG-saporin-induced cortical cholinergic deafferentation: effects of physostigmine and FG 7142. Behav Neurosci 112(6):1519-1525, 1998.

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

Depletion of C1 neurons attenuates the salt-induced hypertension in unanesthetized rats.

Ribeiro N, Martins Sá RW, Antunes VR (2020) Depletion of C1 neurons attenuates the salt-induced hypertension in unanesthetized rats. Brain Res 1748:147107. doi: 10.1016/j.brainres.2020.147107

Objective: To determine if the ablation of C1 neurons mitigates high blood pressure induced by high-salt intake.

Summary: Data show that hypertension induced by high-salt intake is dependent on C1 neurons.

Usage: Bilateral injections of 2.4 ng/100 nl of Anti-DBH-SAP. The total number of TH+ neurons in the AS region was reduced by 37 ± 13% in the anti-DBH-SAP group when compared to control.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Pseudomonas Exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer

Fischer A, Wolf I, Fuchs H, Masilamani AP, Wolf P (2020) Pseudomonas Exotoxin A based toxins targeting epidermal growth factor receptor for the treatment of prostate cancer. Toxins (Basel) 12(12):753. doi: 10.3390/toxins12120753

Summary: Refers to chimeric murine-human mAb cetuximab bound to Streptavidin-ZAP.

See: Yip WL et al. Targeted Delivery and Enhanced Cytotoxicity of Cetuximab-Saporin by Photochemical Internalization in EGFR-Positive Cancer Cells. Mol Pharm 4(2):241-251, 2007.

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

Reversal of object recognition memory deficit in perirhinal cortex-lesioned rats and primates and in rodent models of aging and alzheimer’s diseases.

Masmudi-Martín M, Navarro-Lobato I, López-Aranda MF, Browning PGF, Simón A-M, López-Téllez JF, Jiménez-Recuerda I, Martîn-Montañez E, Pérez-Mediavilla A, Frechilla D, Baxter MG, Khan ZU (2020) Reversal of object recognition memory deficit in perirhinal cortex-lesioned rats and primates and in rodent models of aging and alzheimer’s diseases. Neuroscience 448:287-298. doi: 10.1016/j.neuroscience.2020.08.039

Objective: To determine if Object Recognition Memory (ORM) can be restored.

Summary: Memory-deficient rats were generated by induction of lesions to the perirhinal cortex (PRh) through an injection of OX7-SAP. Expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. This treatment was sufficient for full recovery of ORM in rodent models of aging and Alzheimer’s disease.

Usage: Rats were injected with OX7-SAP (0.9 mg in 1ml) in the PRh of the brain.

Related Products: OX7-SAP (Cat. #IT-02)

Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue

Irvine KA, Sahbaie P, Ferguson AR, Clark JD (2020) Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue. Exp Neurol 333:113428. doi: 10.1016/j.expneurol.2020.113428

Objective: To confirm hypothesis that dysfunctional descending noradrenergic and serotonergic pain control circuits may contribute to the loss of diffuse noxious inhibitory control (DNIC), a critical endogenous pain control mechanism, weeks to months after traumatic brain injury (TBI).

Summary: Results suggest that TBI causes maladaptation of descending nociceptive signaling mechanisms and changes in the function of both adrenergic and serotonergic circuits. Such changes could predispose those with TBI to chronic pain.

Usage: Anti-DBH-SAP (5 μg/5 μl) was injected in the left ventricle. Lesion of the LC resulted in failure of DNIC, an effect that mimics what is observed behaviorally after chronic TBI.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Noradrenaline signaling in the LPBN mediates amylin’s and salmon calcitonin’s hypophagic effect in male rats.

Boccia L, Le Foll C, Lutz TA (2020) Noradrenaline signaling in the LPBN mediates amylin’s and salmon calcitonin’s hypophagic effect in male rats. FASEB J 34(11):15448-15461. doi: 10.1096/fj.202001456RRR

Objective: To assess the phenotype of amylin activated LPBN (lateral parabrachial nucleus) neurons, especially to confirm the CGRPergic phenotype and to uncover the specific role of NA (noradrenaline) signaling from the AP to the LPBN.

Summary: The present study confirmed the central role of the LPBN in propagating amylin’s and sCT’s hypophagic action, and particularly the importance of AP → LPBN NA signaling in the mediation of this process, through the activation of LPBN (CGRP and non-CGRP) neurons.

Usage: The neuronal pathways used to process the physiological response to amylin were investigated using 50-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the area postrema (AP) or 25 ng into the lateral parabrachial nucleus (Potes et al., 2010).

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Spinal microglia-neuron interactions in chronic pain.

Ho IHT, Chan MTV, Wu WKK, Liu X (2020) Spinal microglia-neuron interactions in chronic pain. J Leukoc Biol 108:1575-1592. doi: 10.1002/JLB.3MR0520-695R

Summary: Spinal microglial activation is initiated shortly and persisted for more than 3 mo after partial sciatic nerve ligation. Intrathecal injection of Mac1-SAP, a saporin-conjugated anti-CD11b antibody to deplete microglia, abolished cold and mechanical allodynia for 2–12 wk after injury,92 supporting the role of activated microglia for chronic pain maintenance.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

See Also:

Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis.

McCall AL, Dhindsa JS, Pucci LA, Kahn AF, Fusco AF, Biswas DD, Strickland LM, Tseng HC, ElMallah MK (2020) Respiratory pathology in the Optn-/- mouse model of Amyotrophic Lateral Sclerosis. Respir Physiol Neurobiol 282:103525. doi: 10.1016/j.resp.2020.103525

Summary: Tongue muscle weakness results in dysarthria and dysphagia leading to recurrent aspiration, choking, and aggravation of respiratory disease.

See: Lind LA et al. Hypoglossal Motor Neuron Death Via Intralingual CTB-saporin (CTB-SAP) Injections Mimic Aspects of Amyotrophic Lateral Sclerosis (ALS) Related to Dysphagia. Neuroscience 390:303-316, 2018.

Related Products: CTB-SAP (Cat. #IT-14)

Local riluzole release from a thermosensitive hydrogel rescues injured motoneurons through nerve root stumps in a brachial plexus injury rat model

Fang J, Li L, Zhai H, Qin B, Quan D, Shi E, Zhu M, Yang J, Liu X, Gu L (2020) Local riluzole release from a thermosensitive hydrogel rescues injured motoneurons through nerve root stumps in a brachial plexus injury rat model. Neurochem Res 45(11):2800-2813. doi: 10.1007/s11064-020-03120-0

Summary: The authors refer to a review by Gulino describing two rodent models of motoneuron degeneration were induced by neurotoxics including volkensin and cholera toxin-B saporin, which are able to destroy motoneurons through retrograde transportation.

See: Gulino R Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease. Neural Plast 2016:2769735, 2016.

Related Products: CTB-SAP (Cat. #IT-14)

Characterization of the renin-angiotensin system in aged cavernosal tissue and its role in penile fibrosis.

Bragina ME, Costa-Fraga F, Sturny M, Ebadi B, Ruoccolo RT, Santos RAS, Fraga-Silva RA, Stergiopulos N (2020) Characterization of the renin-angiotensin system in aged cavernosal tissue and its role in penile fibrosis. J Sex Med 17:2129–2140. doi: 10.1016/j.jsxm.2020.08.008

Objective: To investigate local regulation of the renin-angiotensin system (RAS) in age-related erectile dysfunction (ED).

Summary: Experimental results highlighted the essential role of the RAS in modulation of cavernosal fibrosis.

Usage: Immunohistochemistry (1:800)

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

Molecular genetics of kappa opioids in pain and itch sensations

Tseng PY, Hoon MA (2020) Molecular genetics of kappa opioids in pain and itch sensations. Handb Exp Pharmacol . doi: 10.1007/164_2020_397

Summary: The authors review the functions of the kappa opioid receptor (KOR) and its endogenous agonists dynorphins in modulating itch and pain. Nppb-SAP ablation of neurons expressing the Natriuretic olypeptide B receptor greatly reduced itch responses evoked by histamine or by intrathecal administration of Nppb, suggesting that these neurons transmit itch signals from Nppb primary afferents.

See: Mishra SK et al. The cells and circuitry for itch responses in mice. Science 340(6135):968-971, 2013.

Related Products: Nppb-SAP (Cat. #IT-69)

Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss

Tapa S, Wang L, Francis Stuart SD, Wang Z, Jiang Y, Habecker BA, Ripplinger CM (2020) Adrenergic supersensitivity and impaired neural control of cardiac electrophysiology following regional cardiac sympathetic nerve loss. Sci Rep 10:18801. doi: 10.1038/s41598-020-75903-y

Summary: The authors present a novel mouse model of regional cardiac sympathetic hypo-innervation utilizing Anti-DBH-SAP.

Usage: Either 5μL of 40 ng/μL Anti-DBH-SAP or Mouse IgG-SAP (control) was applied three times directly to the exposed apical/anterior surface of the heart.

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

Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor.

Gick GG, Arora K, Sequeira JM, Nakayama Y, Lai SC, Quadros EV (2020) Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor. Exp Cell Res 396(1):112256. doi: 10.1016/j.yexcr.2020.112256

Summary: The increased and sustained expression of TCblR in proliferating cells has been used to target toxins preferentially to cancer cells and can be potentially used for targeted delivery of other anti-cancer drugs. In 2010 the authors published a paper which evaluated the potential of using immunotoxins to eliminate cancer cells expressing TCblR the authors performed a series of in vitro experiments using their monoclonal antibody plus Mab-ZAP in varying concentrations. The results indicated that this is a viable therapeutic model that causes minimal peripheral damage.

Related Products: Mab-ZAP (Cat. #IT-04)

The EphA2 and cancer connection: potential for immune-based interventions

London M, Gallo E (2020) The EphA2 and cancer connection: potential for immune-based interventions. Mol Biol Rep 47(10):8037-8048. doi: 10.1007/s11033-020-05767-y

Summary: The authors review the most current mAb-based therapies against EphA2-expressing cancers currently in pre-clinical and/or clinical stages. They reference Sakamoto et al. who performed in vitro testing of two different EphA2 mAbs mixed with Mab-ZAP to discover their therapeutic potential against melanoma.

See: Sakamoto A et al. An Agonistic Antibody to EPHA2 Exhibits Antitumor Effects on Human Melanoma Cells. Anticancer Res 38:3273-3282, 2018.

Related Products: Mab-ZAP (Cat. #IT-04)

Long-term potentiation in the hippocampal CA3 to CA1 synapses may be induced in vivo by activation of septal cholinergic inputs.

Dobryakova YV, Stepanichev MY, Markevich VA, Bolshakov AP (2020) Long-term potentiation in the hippocampal CA3 to CA1 synapses may be induced in vivo by activation of septal cholinergic inputs. Int J Neurosci 23:1-7. doi: 10.1080/00207454.2020.1822834

Objective: To clarify the role of septal input in the development of long-term potentiation (LTP) in this synapse.

Summary: Elimination of septal cholinergic neurons by 192-IgG-SAP abolished LTP development in both experimental series. This suppression of LTP in animals with a cholinergic deficit was not due to loss of hippocampal neurons.

Usage: Rats received intraseptal injections of 192-IgG-SAP (1.5 μg).

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

Characterization of fever and sickness behavior regulated by cytokines during infection.

Li W, Luo S, Wan C (2020) Characterization of fever and sickness behavior regulated by cytokines during infection. Behaviour 157:855-878. doi: 10.1163/1568539X-bja10028

Summary: This study reviews the characterization of fever and sickness behavior regulated by cytokines during infection.

Usage: IL-1β-saporin or unconjugated Saporin as control (icv or ip, 1.75 μg) eliminated IL-1R1-expressing cells in the hippocampus and indicated these neurons mediate the function of peripheral IL-1β induced hypophagia.

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

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