Galiximab (anti-CD80)-induced growth inhibition and prolongation of survival in vivo of B-NHL tumor xenografts and potentiation by the combination with fludarabine

Hariharan, Kandasamy; Chu, Peter; Murphy, Tracey; Clanton, Dana; Berquist, Lisa; Molina, Arturo; Ho, Steffan N.; Vega, Mario I.; Bonavida, Benjamin

doi:10.3892/ijo.2013.1986

Cited by 8 publications

(4 citation statements)

References 22 publications

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“…Galiximab exhibits a significant inhibition of tumor growth. The anti-tumor activity of Galiximab is reinforced by the combination of Galiximab with Fludarabine, a cytotoxic chemotherapy drug 71 . Furthermore, CD20 -a surface antigen expressed on normal and malignant B cells-has been identified as a target for B-cell lymphoma treatment using Rituximab, an anti-CD20 monoclonal antibody.…”

Section: ) Tumor Microenvironment: a Novel Target For Cancer Therapiesmentioning

confidence: 99%

Role of the tumor microenvironment in regulating apoptosis and cancer progression

et al. 2016

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Apoptosis is a gene-directed program that is engaged to efficiently eliminate dysfunctional cells. Evasion of apoptosis may be an important gate to tumor initiation and therapy resistance. Like any other developmental program, apoptosis can be disrupted by several genetic aberrations driving malignant cells into an uncontrolled progression and survival. For its sustained growth, cancer develops in a complex environment, which provides survival signals and rescues malignant cells from apoptosis. Recent studies have clearly shown a wide interaction between tumor cells and their microenvironment, confirming the influence of the surrounding cells on tumor expansion and invasion. These non-malignant cells not only intensify tumor cells growth but also upgrade the process of metastasis. The strong crosstalk between malignant cells and a reactive microenvironment is mediated by soluble chemokines and cytokines, which act on tumor cells through surface receptors. Disturbing the microenvironment signaling might be an encouraging approach for patient's treatment. Therefore, the ultimate knowledge of "tumor-microenvironment" interactions facilitates the identification of novel therapeutic procedures that mobilize cancer cells from their supportive cells. This review focuses on cancer progression mediated by the dysfunction of apoptosis and by the fundamental relationship between tumor and reactive cells. New insights and valuable targets for cancer prevention and therapy are also presented.

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Section: ) Tumor Microenvironment: a Novel Target For Cancer Therapiesmentioning

confidence: 99%

Role of the tumor microenvironment in regulating apoptosis and cancer progression

et al. 2016

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“…Based on the previous studies demonstrating that i.p. administrations of F-AMP at the dose of 125 mg/kg (once daily, 5 days) and 250 mg/kg (once daily, 3 days) were well-tolerated and led to significant tumor growth suppression in murine models, we chose 60 mg/kg and 120 mg/kg regimens of F-AMP in our study (35–39). F-AMP was administered by i.p.…”

Section: Resultsmentioning

confidence: 99%

Drug Repurposing Identifies a Synergistic Combination Therapy with Imatinib Mesylate for Gastrointestinal Stromal Tumor

Pessetto

Hirst

et al. 2014

Molecular Cancer Therapeutics

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Gastrointestinal Stromal Tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor, imatinib mesylate (IM) radically improved the clinical response of patients with GIST; however, its effects are often short-lived, with GISTs demonstrating a median time to progression of approximately two years. Although many investigational drugs, approved first for other cancers, have been subsequently evaluated for the management of GIST, few have greatly impacted the overall survival of patients with advanced disease. We employed a novel, focused, drug repurposing effort for GIST including IM-resistant GIST evaluating a large library of FDA-approved drugs regardless of current indication. As a result of the drug repurposing screen, we identified eight FDA-approved drugs including fludarabine phosphate (F-AMP) that showed synergy with and/or overcame resistance to IM. F-AMP induces DNA damage, annexin V and caspase 3/7 activities as the cytotoxic effects on GIST cells, including IM-resistant GIST cells. F-AMP and IM combination treatment showed greater inhibition of GIST cell proliferation when compared to IM alone and F-AMP alone. Successful in vivo experiments confirmed the combination of IM with F-AMP enhanced the antitumor effects compared to IM alone. Our results identified F-AMP as a promising, repurposed drug therapy for the treatment of GISTs, with potential to be administered in combination with IM or for treatment of IM-refractory tumors.

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“…Animal experiments were in accordance with the Swiss legislation on animal welfare and approved by the Veterinary Office of the Canton Zurich, Switzerland. For this study, we used PET data from 7-to-10-week-old female C.B.17 SCID or CD1 nude mice (16.9–21.2 g body weight; Charles River, Sulzberg, Germany), carrying hCD80-positive Raji xenografts according to [ 16 , 22 ]. Raji cells were from DSMZ (Braunschweig, Germany).…”

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modelling with Dynamic PET Data to Study the In Vivo Effects of Transporter Inhibition on Hepatobiliary Clearance in Mice

Taddio

Keller

et al. 2018

Contrast Media & Molecular Imaging

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Physiologically based pharmacokinetic modelling (PBPK) is a powerful tool to predict in vivo pharmacokinetics based on physiological parameters and data from in vivo studies and in vitro assays. In vivo PBPK modelling in laboratory animals by noninvasive imaging could help to improve the in vivo-in vivo translation towards human pharmacokinetics modelling. We evaluated the feasibility of PBPK modelling with PET data from mice. We used data from two of our PET tracers under development, [11C]AM7 and [11C]MT107. PET images suggested hepatobiliary excretion which was reduced after cyclosporine administration. We fitted the time-activity curves of blood, liver, gallbladder/intestine, kidney, and peripheral tissue to a compartment model and compared the resulting pharmacokinetic parameters under control conditions ([11C]AM7 n = 2; [11C]MT107, n = 4) and after administration of cyclosporine ([11C]MT107, n = 4). The modelling revealed a significant reduction in [11C]MT107 hepatobiliary clearance from 35.2 ± 10.9 to 17.1 ± 5.6 μl/min after cyclosporine administration. The excretion profile of [11C]MT107 was shifted from predominantly hepatobiliary (CLH/CLR = 3.8 ± 3.0) to equal hepatobiliary and renal clearance (CLH/CLR = 0.9 ± 0.2). Our results show the potential of PBPK modelling for characterizing the in vivo effects of transporter inhibition on whole-body and organ-specific pharmacokinetics.

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Galiximab (anti-CD80)-induced growth inhibition and prolongation of survival in vivo of B-NHL tumor xenografts and potentiation by the combination with fludarabine

Cited by 8 publications

References 22 publications

Role of the tumor microenvironment in regulating apoptosis and cancer progression

Role of the tumor microenvironment in regulating apoptosis and cancer progression

Drug Repurposing Identifies a Synergistic Combination Therapy with Imatinib Mesylate for Gastrointestinal Stromal Tumor

Physiologically Based Pharmacokinetic Modelling with Dynamic PET Data to Study the In Vivo Effects of Transporter Inhibition on Hepatobiliary Clearance in Mice

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