cancer-research

Adam PJ, Terrett JA, Steers G, Stockwin L, Loader JA, Fletcher GC, Lu LS, Leach BI, Mason S, Stamps AC, Boyd RS, Pezzella F, Gatter KC, Harris AL (2006) CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding. Br J Cancer 95(3):298-306. doi: 10.1038/sj.bjc.6603222

Summary: Renal cell carcinoma (RCC) is usually resistant to chemotherapy. Using a proteomics approach, the authors found a potential target for immunotherapy in RCC. An antibody against CD70, a type II transmembrane receptor, was combined with Hum-ZAP (Cat. #IT-22). The complex was then added to an RCC-derived cell-line in vitro. The aCD70/Hum-ZAP complex demonstrated significant killing at several different concentrations. This work suggests that CD70 is a potential target antigen for RCC therapy.

Related Products: Hum-ZAP (Cat. #IT-22)

Foehr ED, Lorente G, Kuo J, Ram R, Nikolich K, Urfer R (2006) Targeting of the receptor protein tyrosine phosphatase beta with a monoclonal antibody delays tumor growth in a glioblastoma model. Cancer Res 66(4):2271-2278. doi: 10.1158/0008-5472.CAN-05-1221

Summary: The receptor protein tyrosine phosphatase ß (RPTPß) is overexpressed in astrocytomas, and is a potential target for tumor therapy. After testing antibodies against an extracellular domain of RPTPß in vitro with Mab-ZAP (Cat. #IT-04), two custom conjugates, 7E4B11-SAP and 7A9B5-SAP, were created by Advanced Targeting Systems. The authors tested the custom conjugates, using anti-DAT-SAP (Cat. #IT-25) as a positive control, and mouse IgG-SAP (Cat. #IT-18) as a negative control. The 7E4B11-SAP conjugate displayed significant antitumor activity in mice engrafted with U87 glioma cells.

Related Products: Mab-ZAP (Cat. #IT-04), Anti-DAT-SAP (Cat. #IT-25), Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Vera-Portocarrero LP, Xie Y, King T, Lai J, Porreca F (2005) Facilitatory influences from the rostral ventromedial medulla (RVM) are required for pancreatic nociception. Neuroscience 2005 Abstracts 623.18. Society for Neuroscience, Washington, DC.

Summary: Pain is a frequent complaint of patients with pancreatitis or pancreatic cancer. An animal model of pancreatitis induced by dibutyltin dichloride (DBTC) is characterized by abdominal hypersensitivity to mechanical stimuli that appears by day 3 after induction of pancreatitis and persists for at least 10 days. We have used this model to evaluate the role of descending pain modulatory pathways from the RVM in the processing of visceral pain. Pancreatitis was induced in rats by a single tail vein injection of DBTC. Animals were monitored for mechanical sensitivity of the abdominal area as an index of pancreatic nociception using von Frey hairs applied to the surface of the abdomen and recording the frequency of withdrawals from stimulation. Six days after DBTC injection, when mechanical hypersensitivity was fully developed, lidocaine, or saline, was microinjected into the RVM. Lidocaine, but not saline, given into the RVM produced a time-related reversal of mechanical hypersensitivity which peaked by 20 min after injection in animals with pancreatitis. RVM lidocaine had no effect on rats without pancreatitis. A second group of rats received a single microinjection of the cytotoxin dermorphin-saporin into the RVM in order to ablate mu opioid receptor expressing cells that have been proposed to drive descending pain facilitation. 28 days later, the rats received DBTC and their response to mechanical stimulation was monitored daily. These rats showed mechanical hypersensitivity on day 3 after DBTC, but the sensory threshold reverted to normal level by day 6, while rats that had been pretreated with dermorphin, saporin, or water exhibited persistent mechanical hypersensitivity after DBTC out to day 10. These data suggest that a blockade of the descending input from the RVM by lidocaine is sufficient to block the pancreatitis-induced visceral pain, and that the mu opioid receptor expressing cells in the RVM are critical for the persistent pain state.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Gilley D, Tanaka H, Herbert BS (2005) Telomere dysfunction in aging and cancer. Int J Biochem Cell Biol 37(5):1000-1013. doi: 10.1016/j.biocel.2004.09.003 PMID: 15743674

Related Products: TRF1 Mouse Monoclonal (Cat. #AB-37)

Duxbury MS, Ito H, Ashley SW, Whang EE (2004) CEACAM6 as a novel target for indirect type 1 immunotoxin-based therapy in pancreatic adenocarcinoma. Biochem Biophys Res Commun 317(3):837-843. doi: 10.1016/j.bbrc.2004.03.128

Summary: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a cell-surface molecule that is overexpressed in a variety of human cancers. Here, the authors investigate the efficacy of a biotinylated antibody that recognizes CEACAM6 bound to streptavidin-ZAP (Cat. #IT-27) in elimination of tumor cells in vitro and in vivo. Treatment of cultured tumor cells induced significant specific cytotoxicity, while tumor growth was suppressed in a mouse xenograft model. These results indicate targeting of CEACAM6 may be a viable therapeutic strategy.

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

Luger NM, Sabino MC, Schwei MJ, Rogers SD, Pomonis JD, Keyser CP, Mach DB, Salak-Johnson J, Clohisy DR, Mantyh PW (2001) Intrathecal infusion of substance P-saporin ablates substance p receptor expressing neurons in the dorsal horn of the spinal cord and attenuates bone cancer pain. Neuroscience 2001 Abstracts 55.4. Society for Neuroscience, San Diego, CA.

Summary: Over 75% of advanced cancer patients must cope with chronic cancer pain. Interestingly, bone cancer pain is the most common and difficult to control. While current therapies are effective in alleviating many aspects of bone cancer pain, they are often accompanied by significant unwanted side effects. To better understand the population of spinal cord neurons that are involved in conveying bone cancer pain and to determine the efficacy of a novel therapeutic modality, we ablated substance P receptor (SPR)+ neurons in the spinal cord using intrathecal infusion of substance P-Saporin (SP-SAP). SP-SAP is a suicide ligand which consists of the ribosomal inactivating factor saporin conjugated to substance P, a peptidergic neurotransmitter involved in nociception. SP-SAP selectively ablates SPR+ neurons located in lamina I and III-V of the spinal cord. C3H male mice received intrathecal SP-SAP treatment 30 days prior to injection of 2472 osteosarcoma cells into the intramedulary space of a femur. Following injection, osteolytic sarcoma cells were confined within the femur by an amalgam plug. Mice were behaviorally tested 17 days post-tumor implantation and both ongoing and movement-evoked pain assessed. Ablation of SPR+ neurons in the dorsal spinal cord coincided with attenuation of both spontaneous and movement-evoked pain behaviors. These results suggest that SPR expressing neurons are involved in the development and progression of the bone cancer pain state and SP-SAP may serve as a useful therapy to treat this debilitating condition. Supported by NIH & VA.

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

Murray GI, Duncan ME, Arbuckle E, Melvin WT, Fothergill JE (1998) Matrix metalloproteinases and their inhibitors in gastric cancer. Gut 43:791-797. doi: 10.1136/gut.43.6.791 PMID: 9824606

Related Products: MMP-9 Mouse Monoclonal (Cat. #AB-32)

Flavell DJ, Noss A, Pulford KA, Ling N, Flavell SU (1997) Systemic therapy with 3BIT, a triple combination cocktail of anti-CD19, -CD22, and -CD38-saporin immunotoxins, is curative of human B-cell lymphoma in severe combined immunodeficient mice. Cancer Res 57(21):4824-4829. PMID: 9354445

Wiley RG (1996) Targeting toxins to neural antigens and receptors. Semin Cancer Biol 7(2):71-77. doi: 10.1006/scbi.1996.0011 PMID: 8740562

Davol P, Beitz JG, Mohler M, Ying W, Cook J, Lappi DA, Frackelton AR Jr (1995) Saporin toxins directed to basic fibroblast growth factor receptors effectively target human ovarian teratocarcinoma in an animal model. Cancer 76(1):79-85. doi: 10.1002/1097-0142(19950701)76:1<79::aid-cncr2820760111>3.0.co;2-g PMID: 8630880

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