Ye Y, Bae S, Viet CT, Troob S, Bernabe D, Schmidt BL (2014) IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5. doi: 10.1186/1744-9081-10-5
Objective: To evaluate subtypes of sensory neurons involved in cancer pain and proliferation.
Summary: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.
Usage: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.
Q: How long does it take to see the cell death occurring from the use of targeted toxins using saporin? Is there a time course of hours or days?
A: The figure below illustrates the time course of cell death very effectively. Internalization and cytotoxicity of SP-SAP in primary cultures of neonatal spinal cord neurons. Confocal image of neurons where the Substance P receptor; NK1R (SPR) immunofluorescence (A, C, D) appears red, areas of concentrated SPR immunofluorescence appear yellow. (A, C, and D) SPR immunofluorescence in neurons 2 hours, 1 day, and 4 days, respectively, after treatment with SP-SAP. (B) Confocal image showing SAP immunofluorescence (yellow) 2 hours after SP-SAP treatment.
These images were projected from 14 optical sections acquired at 0.8-mm intervals with a 603 lens. Bar, 25 mm.
It is recommended that you wait for two weeks to allow for all debris to be cleared and the animal to regain normal eating and sleeping habits.
Li AJ, Wang Q, Dinh TT, Wiater MF, Eskelsen AK, Ritter S (2013) Hindbrain catecholamine neurons control rapid switching of metabolic substrate use during glucoprivation in male rats. Endocrinology 154(12):4570-4579. doi: 10.1210/en.2013-1589
Summary: Previous work has shown that corticosterone secretion in response to glucoprivation is at least in part controlled by hindbrain catecholamine neurons in the paraventricular nucleus of the hypothalamus (PVH). In this work the authors investigate the metabolic consequences of lesioning these neurons. Rats received bilateral 82-ng infusions of Anti-DBH-SAP (Cat. #IT-03) into the PVH. Saporin (Cat. #PR-01) was used as a control. Although lesioned animals had the same energy expenditure and locomotor activity as controls, they also had a higher respiratory exchange ratio, indicating a reduced ability to switch from carbohydrate to fat metabolism in response to glucoprivation.
da Silva EF, Freiria-Oliveira AH, Custodio CH, Ghedini PC, Bataus LA, Colombari E, de Castro CH, Colugnati DB, Rosa DA, Cravo SL, Pedrino GR (2013) A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats. PLoS One 8(9):e73187. doi: 10.1371/journal.pone.0073187
Summary: Using bilateral 63-ng injections of Anti-DBH-SAP (Cat. #IT-03) into two levels of the caudal ventrolateral medulla, the authors assessed several pressor responses to infusion of hypertonic saline. Saporin (Cat. #PR-01) was used as a control. The results suggest that medullary noradrenergic A1 neurons are involved in the regulation of some responses to acute changes in body fluid composition.
Chang ST, Liu YP, Huang CL, Wang PY, Tung CS (2013) Implication of cerebral dopamine-beta hydroxylase for cardiovascular and mood regulation in rats. Chin J Physiol 56(4):209-218. doi: 10.4077/CJP.2013.BAB103
Summary: The ascending fibers affected by norepinephrine are involved in a variety of processes, including emotion, anxiety, and regulation of central autonomic outflows such as cardiovascular regulation and energy balance. The authors examined whether the loss of norephinephrine would cause autonomic failure in cardiovascular regulation. Rats received a single intraventricular injection of anti-DBH-SAP (Cat. #IT-03). Saporin (Cat. #PR-01) was used as a control. The results demonstrate that norepinephrine deficits in the brain influence reduction of excitatory responses to orthostatic stress.
Shia WW, Bailey RC (2013) Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays. Anal Chem 85(2):805-810. doi: 10.1021/ac3030416 PMID: 23268548
Summary: A major hurdle to clear in the fight against bioterrorism is the ability to identify various biowarfare agents. One of the more difficult substances to identify is ricin. This work describes the use of single domain antibodies to identify ricin in a microring resonator array assay. Saporin (Cat. #PR-01) along with affinity purified chicken anti-saporin (Cat. #AB-17AP) were used as controls when constructing the assay. The results demonstrate the feasibility of using microring resonator arrays for the detection of biowarfare agents.
Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y (2013) Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 16(2):183-192. doi: 10.1038/nn.3295
Summary: Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.
Daniels-Wells TR, Helguera G, Rodriguez JA, Leoh LS, Erb MA, Diamante G, Casero D, Pellegrini M, Martinez-Maza O, Penichet ML (2013) Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231. doi: 10.1016/j.tiv.2012.10.006
Summary: The antibody-avidin fusion protein ch128.1Av has been shown to target the human transferrin receptor 1 (TfR1) and kill malignant B cells by blocking the use of iron. Combination of this construct with a mono-biotinylated saporin custom conjugate produces an iron-independent toxicity to TfR1-expressing cells, even those that are resistant to ch128.1Av alone. The saporin-containing conjugate induces a transcriptional response consistent with oxidative stress and DNA damage. The data also show that the saporin conjugate is not toxic to human hematopoeietic stem cells.
Usage: An antibody-avidin fusion protein (ch128.1Av) was mixed with MonoBiotin-ZAP to make an immunotoxin that targets the human transferrin receptor 1 (TfR1).
