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High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies.
Ha K, Bidlingmaier S, Zhang Y, Su Y, Liu B (2014) High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies. Mol Cell Proteomics 13:3320-3331. doi: 10.1074/mcp.M114.039768
Summary: Macropinocytosis, the internalization of large endocytic vesicles called macropinosomes, is upregulated in Ras-transformed cancers. To date, large-scale antibody generation strategies have not incorporated a selection method for antibodies. In this work the authors demonstrate screening and validation of the antibodies that utilize the macropinosome pathway. One method used was to biotinylate the antibodies and combine them with Streptavidin-ZAP (Cat. #IT-27) at a 1:1 ratio. The conjugate was applied to cells in a concentration curve starting at 200 nM in order to demonstrate internalization and cell killing.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization.
Bostad M, Kausberg M, Weyergang A, Olsen C, Berg K, Høgset A, Selbo P (2014) Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization. Mol Pharm 11:2764-2776. doi: 10.1021/mp500129t
Summary: CD44 is known as a common cancer stem cell (CSC) marker. Given that CSC’s seem to have the ability to resist many therapeutic agents, the authors investigated the use of photochemical internalization (PCI) while targeting CD44-expressing CSC’s. An immunotoxin was constructed by biotinylating a pan CD44 antibody and combining it with Streptavidin-ZAP (Cat. #IT-27) at a 4:1 biotinylated antibody to Streptavidin-ZAP molar ratio. Various cancer cell lines were incubated with the toxin at a concentration of 0.825 nM. The toxin showed specific cytotoxicity to CD44-expressing cell lines, demonstrating the efficacy of PCI in conjunction with targeted toxins to treat some cancers
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD44-SAP (Cat. #IT-72)
Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase.
Zheng X, Zhai B, Koivunen P, Shin S, Lu G, Liu J, Geisen C, Chakraborty A, Moslehi J, Smalley D, Wei X, Chen X, Chen Z, Beres J, Zhang J, Tsao J, Brenner M, Zhang Y, Fan C, DePinho R, Paik J, Gygi S, Kaelin W, Zhang Q (2014) Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes Dev 28:1429-1444. doi: 10.1101/gad.242131.114 PMID: 24990963
Summary: Members of the FOXO family are thought to act as tumor suppressor genes. In this work the authors investigated the hydroxylation of FOXO3a by EglN2. This hydroxylation pushes FOXO3a toward a protosomal degradation pathway. Loss of FOXO3a in turn allows the accumulation of Cyclin D1, which has been found to be overexpressed in some breast cancers. Some of the data were generated using immunoblots with anti-transhydroxylated proline (Cat. #AB-T044).
Usage: Western blot
Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)
Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy.
Cordier D, Gerber A, Kluba C, Bauman A, Hutter G, Mindt TL, Mariani L (2014) Expression of different neurokinin-1 receptor (NK1R) isoforms in glioblastoma multiforme: potential implications for targeted therapy. Cancer Biother Radiopharm 29(5):221-226. doi: 10.1089/cbr.2013.1588
Summary: The neurokinin-1 receptor (NK1r) has been found to be consistently over-expressed in gliomas, making it a potential target for therapeutic strategies. However, treatments with therapies utilizing substance P (SP), the ligand for the NK1r, have at best yielded uneven results. In this work the authors investigated factors that may predict the response to therapies directed at NK1r gliomas. SSP-SAP (Cat. #IT-11) was used at a concentration of 1 nM in cytotoxicity assays on several different glioma cell lines. Using this and other data it was shown that only the cell line with the most full-length NK1r RNA transcripts displayed high levels of binding, internalization, and cell killing necessary for NK1r to be a therapeutic target using SP.
Related Products: SSP-SAP (Cat. #IT-11)
Ribosome-inactivating proteins in cancer treatment
Lappi DA, Stirpe F (2014) Ribosome-inactivating proteins in cancer treatment. (eds. F. Stirpe, D.A. Lappi). In: Ribosome-inactivating Proteins 244-252. doi: 10.1002/9781118847237.ch16 PMID: 909090
The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines.
Lund K, Bostad M, Skarpen E, Braunagel M, Krauss S, Duncan A, Hogset A, Selbo P (2014) The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs 6(4):1038-1050. doi: 10.4161/mabs.28207
Summary: The epithelial cell adhesion molecule (EpCAM) is an attractive diagnostic and therapeutic target for a wide range of human carcinomas. It has also been found on cancer stem cells, increasing the interest in targeting and eliminating cells that express it. The authors have created a monoclonal antibody that binds EpCAM, and use several assays to demonstrate the antibody’s potential as an oncology tool. In one series of assays the biotinylated antibody was combined with streptavidin-ZAP (Cat. #IT-27), and in conjunction with photochemical internalization was shown to have specific cytotoxicity on several different cancer cell lines over a range of concentrations.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma.
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.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain.
Brown DC, Agnello K (2013) Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185. doi: 10.1097/ALN.0b013e3182a95188
Summary: This work demonstrates the use of naturally occurring bone cancer in dogs as a model for pain therapy. Companion dogs with bone cancer received 20-60 μg intrathecal injections of SP-SAP (currently in human clinical trials) depending on the size of the dog. Significantly more dogs in the control group required unblinding and adjustment of pain care than in the SP-SAP group, indicating the efficacy of SP-SAP in pain control. This study also demonstrates the validity of the dog model for testing analgesic protocols.
Related Products: SP-SAP (Cat. #IT-07)
Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?
Hayashida K (2013) Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?. Anesthesiology 119(5):999-1000. doi: 10.1097/ALN.0b013e3182a951a2
Summary: This editorial describes the SP-SAP papers in this latest issue of Anesthesiology. The results of the paper are discussed, and the potential in using companion dogs for pain models is emphasized. While most pain models have been rodent-based, companion dogs provide models for chronic pain due to natural causes such as cancer and arthritis, along with frequent opportunity for behavioral assessments by the owner. Such assessments can be done without stress to the animal.
Related Products: SP-SAP (Cat. #IT-07)
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