cancer-research

Wiedlocha A, Haugsten EM, Zakrzewska M (2021) Roles of the FGF-FGFR signaling system in cancer development and inflammation. Cells 10(9):2231. doi: 10.3390/cells10092231 PMID: 34571880

Objective: To highlight the latest advances in understanding the role of the FGF-FGFR signaling system in the development of neoplastic diseases and in the induction and maintenance of inflammation and its sequelae.

Related Products: FGF-SAP (Cat. #IT-38)

de Almeida AS, Bernardes LB, Trevisan G (2021) TRP channels in cancer pain. Eur J Pharmacol 904:174185. doi: 10.1016/j.ejphar.2021.174185 PMID: 34015320

Objective: To describe the role of TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) involved in cancer pain mechanisms.

Summary: Several studies have revealed that the administration of TRPV1 or TRPA1 agonists/antagonists and TRPV1 or TRPA1 knockdown reduced sensitivity to nociception in cancer pain models. Thus, TRP channels are potential targets for managing cancer-related pain syndromes.

Usage: Ablation of IB4 (+) neurons.

Related Products: IB4-SAP (Cat. #IT-10)

See Also:

• Ye Y et al. IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5, 2014.

Vikan AK, Kostas M, Haugsten EM, Selbo PK, Wesche J (2021) Efficacy and selectivity of FGF2-saporin cytosolically delivered by PCI in cells overexpressing FGFR1. Cells 10(6):1476. doi: 10.3390/cells10061476

Summary: Fibroblast growth factor receptors (FGFRs) have become an attractive target in cancer research and therapy due to their implication in several cancers. The authors evaluated the efficacy and selectivity of PCI of FGF2-saporin (FGF-SAP) in cells overexpressing FGFR1. The authors conclude that to prevent off-target effects of FGF-based toxins, it will be necessary to circumvent binding to HSPGs, for example by mutating the binding site of FGF2 to HSPGs.

Related Products: FGF-SAP (Cat. #IT-38)

Iida K, Abdelhamid Ahmed AH, Nagatsuma AK, Shibutani T, Yasuda S, Kitamura M, Hattori C, Abe M, Hasegawa J, Iguchi T, Karibe T, Nakada T, Inaki K, Kamei R, Abe Y, Nomura T, Andersen JL, Santagata S, Hemming ML, George S, Doi T, Ochiai A, Demetri GD, Agatsuma T (2021) Identification and therapeutic targeting of GPR20, selectively expressed in gastrointestinal stromal tumorswith DS-6157a, a first-in-class antibody-drug conjugate. Cancer Discov 11(6):1508-1523. doi: 10.1158/2159-8290.Cd-20-1434 PMID: 33579785

Objective: Introduce DS-6157a, an anti-GPR20 antibody-drug therapeutic for gastrointestinal stromal tumors (GIST).

Summary: The only approved treatments for GIST are currently tyrosine kinase inhibitors (TKI) which can be problematic. They lead to secondary resistance mutations in KIT or PDGFRA and disease progression. The authors identified G protein-coupled receptor 20 (GPR20) as a non-tyrosine kinase target and assessed its expression in cell lines, xenografts, and clinical samples. Preclinical pharmacokinetics and safety profile support its development as a novel GIST therapy.

Usage: Internalization activity of anti-GPR20 mAbs were evaluated by using Rat-ZAP. GPR20-expressing 293T cells were plated at 2500 cells/well in 96-well plates. Cells were treated with dilutions of various anti-GPR20 and 500 ng/ml of Rat-ZAP for 3 days. The percentage of living cells were measured using a CellTiter-Glo Luminescent Cell Viability Assay.

Related Products: Rat-ZAP (Cat. #IT-26)

Chen P, Pan M, Lin QS, Lin XZ, Lin Z (2021) CSF-CN contributes to cancer-induced bone pain via the MKP-1-mediated MAPK pathway. Biochem Biophys Res Commun 547:36-43. doi: 10.1016/j.bbrc.2021.02.010

Summary: Cerebrospinal fluid-contacting nucleus (CSF–CN) has been reported to be involved in the development of neuropathic pain and inflammatory pain. This study aimed to see whether it also has a role in cancer-induced bone pain (CIBP). Targeted ablation of CSF-CN dramatically aggravated pain sensitivity.

Usage: Injection via icv of CTB-SAP was performed to “knockout” the CSF-CN.

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

Masoumi KC, Huang X, Sime W, Mirkov A, Munksgaard Thorén M, Massoumi R, Lundgren-Åkerlund E (2021) Integrin α10-antibodies reduce glioblastoma tumor growth and cell migration. Cancers (Basel) 13(5):1184. doi: 10.3390/cancers13051184

Summary: The authors investigated the treatment effect of two antibodies that have been developed to target the protein integrin 10, which is present on the surface of Glioblastoma (GB) cells. Function-blocking integrin alpha10, beta1-antibodies inhibit GB tumor growth as well as the migration of GB cells. This further validates integrin alpha10, beta1 as a promising target in GB and suggests a novel therapeutic strategy for the treatment of GB and other high-grade gliomas.

Usage: Infusions of anti-integrin α10β1-SAP or Anti-ctrl-SAP were made icv (1 µg/2 L per infusion).

See: Thorén MM et al. Integrin α10, a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration, Proliferation, and Survival. Cancers (Basel) 11(4):587, 2019.

Related Products: Custom Conjugates

Andriessen AS, Donnelly CR, Ji RR (2021) Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain. Pain Rep 6(1):e867. doi: 10.1097/PR9.0000000000000867

Summary: Current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. The authors discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain.

Usage: Microglial ablation using Mac-1-SAP (15 μg in 8.8 μl i.t.) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl), is sufficient to attenuate nerve injury-induced pain in male, but not female mice.

See: Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

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

Zheng F, Chen J, Zhang X, Wang Z, Chen J, Lin X, Huang H, Fu W, Liang J, Wu W, Li B, Yao H, Hu H, Song E (2021) The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis. Nat Commun 12(1):1341. doi: 10.1038/s41467-021-21535-3 PMID: 33637716

Objective: To investigate the contributions of HIF-1 in regulating glycolysis of cancer cells under hypoxia

Summary: HIF Antisense LncRNA (HIFAL) has a critical regulatory role in HIF-1-driven transactivation and glycolysis, identifying HIFAL as a therapeutic target of cancer treatment.

Usage: Western blot (1:500)

Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)

Marquez J, Dong J, Dong C, Tian C, Serrero G (2021) Identification of prostaglandin F2 receptor negative regulator (PTGFRN) as an internalizable target in cancer cells for antibody-drug conjugate development. PLoS One 16(1):e0246197. doi: 10.1371/journal.pone.0246197

Summary: PTGFRN is a cell-surface protein that is upregulated in certain cancer types, including head and neck and, notably, pediatric medulloblastoma, an aggressive cancer with limited therapeutic options. With the selection of the mouse monoclonal antibody 33B7, the authors identified PTGFRN as a potential therapy target, and show that it is internalized by incubation with 33B7. Purified 33B7 antibody was sent to Advanced Targeting Systems where saporin was directly conjugated to the Fc region of 33B7 using their proprietary cleavable linker.

Usage: In a 96-well plate, 2000 cells/well were plated in triplicate in 100 μL of DMEM/F12 medium supplemented with 2.5% FBS, 0.4 ug/ml 33B7 antibody, and 0.9ug/ml of Fab-ZAP mouse. As an isotype control, cells were incubated with mouse Fab IgG-SAP as control (instead of 33B7) and Fab-ZAP.

Related Products: Fab-ZAP mouse (Cat. #IT-48), Fab IgG-SAP (Cat. #IT-67), Custom Conjugates

Puente BR (2021) Chronic pain in dogs (Dolor crónico en el perro). Zaragoza Spain: Gruppo Asis Biomedia, S. L..

Summary: The author presents a thorough overview of aspects of canine chronic pain. He includes SP-SAP (Substance P-Saporin) as an experimental drug, “its use as an adjuvant analgesic in dogs with bone cancer has been studied,”

Related Products: SP-SAP (Cat. #IT-07)

See Also:

• Brown DC et al. Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185, 2013.