scholarly journals Antitumor activity of IHL-305, a novel pegylated liposome containing irinotecan, in human xenograft models

2011 ◽  
Author(s):  
Akimitsu Takagi
Keyword(s):  
Antitumor Activity ◽  
Pegylated Liposome ◽  
Xenograft Models ◽  
Human Xenograft Models

scholarly journals Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models

mAbs ◽  
2014 ◽  
Vol 6 (2) ◽  
pp. 556-566 ◽  
Author(s):  
Kathleen R Whiteman ◽  
Holly A Johnson ◽  
Michele F Mayo ◽  
Charlene A Audette ◽  
Christina N Carrigan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Antitumor Activity ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antibody Drug Conjugate ◽  
Xenograft Models ◽  
Antibody Drug ◽  
Human Xenograft Models

156 POSTER Antitumor activity of IHL-305, a novel PEGylated liposome containing irinotecan, in huan xenograft models

2006 ◽  
Vol 4 (12) ◽  
pp. 50
Author(s):  
A. Takagi ◽  
T. Matsuzaki ◽  
T. Furuta ◽  
S. Ueno ◽  
G. Nohara ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Pegylated Liposome ◽  
Xenograft Models

Preclinical Results of the Camptothecin-Polymer Conjugate IT-101 in Multiple Human Lymphoma Xenografts.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1376-1376
Author(s):  
Tontanai Numbenjapon ◽  
Jianyi Wang ◽  
David Colcher ◽  
Thomas Schluep ◽  
Mark E. Davis ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Water Soluble ◽  
Lymphoma Cell ◽  
Type I ◽  
Human Lymphoma ◽  
Relapsed Lymphoma ◽  
Xenograft Models ◽  
Human Xenograft Models

Abstract Camptothecin (CPT), a natural alkaloid isolated from Camptotheca acuminata, has potent broad spectrum antitumor activity by inhibiting type I DNA topoisomerase. It has not been used clinically because it is water-insoluble and highly toxic. As a result, irinotecan (CPT-11), a water-soluble analogue of CPT, has been developed and used as salvage chemotherapy in patients with refractory/relapsed lymphoma, but with only modest activity. For intravenous administration, we have developed IT-101, a ca. 40 nm diameter nanoparticle that is an assembly of cyclodextrin-based polymer conjugates of 20-(S)-CPT. The purpose of this study is to compare the preclinical efficacy of IT-101 with CPT-11 both in vitro and in vivo. Fluorescence microscopy studies demonstrated that incubation of a human lymphoma cell line with IT-101 resulted in the uptake and intracellular accumulation of CPT. Based on the demonstration of in vitro cytotoxity of IT-101 against multiple human lymphoma cell lines, we initiated experiments in xenograft models of lymphoma. In subcutaneous human xenograft models, a single cycle of three weekly doses of intravenous IT-101 at 10 mg/kg (CPT equivalents) showed significantly potent antitumor activity against Daudi, Karpas 299, and L540 cell lines compared to three weekly doses of intraperitoneal CPT-11 at its maximum tolerated dose in mouse of 100 mg/kg (P < 0.0001, P = 0.0072, and P < 0.0001, respectively). In the same animal models, IT-101 led to pathologically complete remissions in 78%, 44%, and 78% of animals inoculated with Daudi, Karpas 299, and L540 cell lines, respectively. In disseminated human xenograft models, IT-101, administered using the same dosing schedule, significantly prolonged the survival of animals intravenously injected with either Daudi or Karpas 299 cell lines when compared to CPT-11 (P < 0.0001 and P = 0.0049, respectively). The promising present results in a variety of lymphomas provide the basis for a phase I/II clinical trial in patients with refractory/relapsed lymphoma.

Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor xenograft models

2004 ◽  
Vol 55 (5) ◽  
pp. 411-419 ◽  
Author(s):  
Michael H. Woo ◽  
Jennifer K. Peterson ◽  
Catherine Billups ◽  
Hua Liang ◽  
Mary-Ann Bjornsti ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumor ◽  
Tumor Xenograft ◽  
Pediatric Solid Tumor ◽  
Xenograft Models

scholarly journals APTO-253 Induces KLF4 to Promote Potent in Vitro Pro-Apoptotic Activity in Hematologic Cancer Cell Lines and Antitumor Efficacy As a Single Agent and in Combination with Azacitidine in Animal Models of Acute Myelogenous Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4813-4813 ◽  
Author(s):  
William G Rice ◽  
Avanish Vellanki ◽  
Yoon Lee ◽  
Jeff Lightfoot ◽  
Robert Peralta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Animal Models ◽  
Antitumor Activity ◽  
Single Agent ◽  
Xenograft Model ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Xenograft Models

Abstract APTO-253, a small molecule that mediates anticancer activity through induction of the Krüppel-like factor 4 (KLF4) tumor suppressor, is being developed clinically for the treatment of acute myelogenous leukemia (AML) and high risk myelodysplastic syndromes (MDS). APTO-253 was well tolerated in a Phase I study in patients with solid tumors using a dosing schedule of days 1, 2, 15, 16 of a 28 day cycle (2T-12B-2T-12B), but recent scientific observations guided APTO-253 toward AML and high risk MDS. Indeed, suppression of KLF4 was reported as a key driver in the leukemogenesis of AML and subsets of other hematologic diseases. The vast majority (~90%) of patients with AML aberrantly express the transcription factor CDX2 in human bone marrow stem and progenitor cells (HSPC) (Scholl et al., J Clin Invest. 2007, 117(4):1037-48). The CDX2 protein binds to CDX2 consensus sequences within the KLF4 promoter, thereby suppressing KLF4 expression in HSPC (Faber et al., J Clin Invest. 2013, 123(1):299-314). Based on these observations, the anticancer activity of APTO-253 was examined in AML and other hematological cancers. APTO-253 showed potent antiproliferative activity in vitro against a panel of blood cancer cell lines, with ηM IC50values in AML (6.9 - 305 ηM), acute lymphoblastic leukemia and chronic myeloid leukemia (39 – 250 ηM), non-Hodgkin’s lymphoma (11 – 190 ηM) and multiple myeloma (72 – 180 ηM). To explore in vivo efficacy, dose scheduling studies were initially conducted in the H226 xenograft model in mice. In the H226 model, APTO-253 showed improved antitumor activity when administered for two consecutive days followed by a five day break from dosing (2T-5B) each week, i.e. on days 1,2, 8,9, 15,16, 22,23, compared to the 2T-12B-2T-12B schedule. The 2T-5B schedule was used to evaluate antitumor activity of APTO-253 in several AML xenograft models in mice. In Kasumi-1 AML and KG-1 AML xenograft models, APTO-253 showed significant antitumor activity (p = 0.028 and p=0.0004, respectively) as a single agent when administered using the 2T-5B schedule each week for four weeks compared to control animals. Mice treated with APTO-253 had no overt toxicity based on clinical observations and body weight measurements. Mice bearing HL-60 AML xenograft tumors were treated with APTO-253 for one day or two consecutive days per week for three weeks, either as a single agent or combined with azacitidine, or with azacitidine alone twice per week (on days 1,4, 8, 11, 15 and 18). APTO-253 as a single agent inhibited growth of HL-60 tumors to approximately the same extent as azacitidine. Furthermore, both once weekly and twice weekly dosing of APTO-253 in combination with azacitidine resulted in significantly enhanced antitumor activity relative to either single agent alone (p = 0.0002 and p = 0.0006 for 1X and 2X weekly APTO-253 treatment, respectively, compared to control). Likewise, using a THP-1 AML xenograft model, APTO-253 administered as a single agent using the 2T-5B per week schedule showed significant efficacy, similar to that of azacitidine, while the combination of APTO-253 and azacitidine demonstrated greatly improved antitumor effects relative to either drug alone. APTO-253 was effective and well tolerated as a single agent or in combination with azacitidine in multiple AML xenograft models, plus APTO-253 does not cause bone marrow suppression in animal models or humans. Taken together, our results indicate that APTO-253 may serve as a targeted agent for single agent use and may provide enhanced efficacy to standard of care chemotherapeutics for AML and other hematological malignancies. Disclosures Rice: Lorus Therapeutics Inc.: Employment. Vellanki:Lorus Therapeutics Inc.: Employment. Lee:Lorus Therapeutics Inc.: Employment. Lightfoot:Lorus Therapeutics Inc.: Employment. Peralta:Lorus Therapeutics Inc.: Employment. Jamerlan:Lorus Therapeutics Inc.: Employment. Jin:Lorus Therapeutics Inc.: Employment. Lum:Lorus Therapeutics Inc.: Employment. Cheng:Lorus Therapeutics Inc.: Employment.

scholarly journals Sabutoclax, a Mcl-1 Antagonist, Inhibits Tumorigenesis in Transgenic Mouse and Human Xenograft Models of Prostate Cancer

Neoplasia ◽  
2012 ◽  
Vol 14 (7) ◽  
pp. 656-IN24 ◽  
Author(s):  
Roger S. Jackson ◽  
William Placzek ◽  
Ana Fernandez ◽  
Shabnam Ziaee ◽  
Chia-Yi Chu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transgenic Mouse ◽  
Xenograft Models ◽  
Human Xenograft Models

scholarly journals Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer

Oncotarget ◽  
2013 ◽  
Vol 4 (12) ◽  
pp. 2451-2461 ◽  
Author(s):  
Luigi Fontana ◽  
Remi M. Adelaiye ◽  
Antonella L. Rastelli ◽  
Kiersten Marie Miles ◽  
Eric Ciamporcero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Dietary Protein ◽  
Protein Restriction ◽  
Dietary Protein Restriction ◽  
Xenograft Models ◽  
Human Xenograft Models

Workgroup 2: Human xenograft models of prostate cancer

The Prostate ◽  
1998 ◽  
Vol 36 (1) ◽  
pp. 56-58 ◽  
Author(s):  
Mark E. Stearns ◽  
Joy L. Ware ◽  
David B. Agus ◽  
Ching-Jer Chang ◽  
Isaiah J. Fidler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Xenograft Models ◽  
Human Xenograft Models
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