scholarly journals Study on the absorption properties of sulphonated aluminum phthalocyanine in vivo and ex vivo in murine tumor models

1997 ◽  
Vol 2 (1) ◽  
pp. 131 ◽  
Author(s):  
Rinaldo Cubeddu
Keyword(s):  
Ex Vivo ◽  
Tumor Models ◽  
Absorption Properties ◽  
Murine Tumor ◽  
Aluminum Phthalocyanine

Combination of TLR9 agonist lefitolimod/MGN1703 with checkpoint inhibitors for cancer immunotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 634-634 ◽  
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Barbara Volz ◽  
Detlef Oswald ◽  
Burghardt Wittig
Keyword(s):  
Tumor Growth ◽  
Colon Carcinoma ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Phase Iii ◽  
Tumor Growth Inhibition ◽  
Tumor Models ◽  
Pilot Studies ◽  
Murine Tumor

634 Background: TLR9 agonists are potent activators of the immune system via induction of cellular and humoral responses. Preclinical and ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. Lefitolimod/MGN1703 is a covalently-closed dumbbell-like immune surveillance reactivator (ISR) with a broad immunomodulatory potential. After promising data from a phase II trial (IMPACT) as maintenance therapy after first-line induction chemotherapy in patients with metastatic colorectal cancer lefitolimod is recently evaluated in a phase III trial in mCRC patients (IMPALA). Methods: It was previously shown that lefitolimod can reduce tumor growth in several murine tumor models. Since the mode-of-action of lefitolimod starts upstream of the initiation points of checkpoint inhibitors aCTLA-4 or aPD-1/aPD-L1 a combinatory approach may result in an enhanced anti-tumor effect. Therefore, we employed two syngeneic murine tumor models: One with s.c. inoculation of CT26 cells and another with s.c. A20 cell challenge. Multiple doses of lefitolimod were injected s.c. or i.tu. Results: In the colon carcinoma CT26 model i.p. injection of aPD-L1 had no effect on the tumor growth, whereas peritumoral injection of lefitolimod led to a slowed tumor growth. The tumor growth was further inhibited by the combination (tumor growth inhibition, TGI - aPD-L1: no, lefitolimod: 28%, combination: 48%) resulting in prolonged survival of the mice. This combinatory effect was even more pronounced in the lymphoma A20 model: Injections of anti-PD-1 (i.p.) or lefitolimod (i.tu.) alone had a moderate anti-tumor effect which was vastly increased by the combination (TGI - aPD-1: 46%, lefitolimod: 50%, combination: 99%). Conclusions: In conclusion, we showed that lefitolimod, a member of dSLIM family of TLR9 agonists and an ISR, can enhance the limited anti-tumor effects of checkpoint inhibitors in pilot studies in murine colon carcinoma and lymphoma tumor models in vivo. These data show the promising potential for the combination with checkpoint inhibitors. In fact, a clinical trial in cooperation with MD Anderson evaluating the benefit of lefitolimod in combination with ipilimumab is currently ongoing.

New Antimitotic Agents with Activity in Multi-Drug-Resistant Cell Lines and in Vivo Efficacy in Murine Tumor Models

2001 ◽  
Vol 44 (25) ◽  
pp. 4416-4430 ◽  
Author(s):  
Bruce G. Szczepankiewicz ◽  
Gang Liu ◽  
Hwan-Soo Jae ◽  
Andrew S. Tasker ◽  
Indrani W. Gunawardana ◽  
...  
Keyword(s):  
Cell Lines ◽  
Resistant Cell ◽  
Drug Resistant ◽  
Tumor Models ◽  
In Vivo Efficacy ◽  
Murine Tumor ◽  
Drug Resistant Cell

scholarly journals CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Fokko J. Huizing ◽  
Javad Garousi ◽  
Jasper Lok ◽  
Gerben Franssen ◽  
Bianca A. W. Hoeben ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Ex Vivo ◽  
Blood Perfusion ◽  
Tracer Uptake ◽  
Tumor Models ◽  
Cancer Models ◽  
Caix Expression

AbstractHypoxia-induced carbonic anhydrase IX (CAIX) expression is a prognostic marker in solid tumors. In recent years many radiotracers have been developed, but a fair comparison of these compounds is not possible because of the diversity in tumor models and other experimental parameters. In this study we performed a direct in vivo comparison of three promising CAIX targeting radiotracers in xenografted head and neck cancer models. The biodistribution of [111In]In-DOTA-ZCAIX:2 was directly compared with [111In]In-DTPA-G250-F(ab′)2 and [111In] In-DTPA-G250 in female BALB/C nu/nu mice bearing two HNSCC xenografts with different levels of CAIX expression. In vivo biodistribution was quantified by means of microSPECT/CT scans and ex vivo biodistribution was determined with the use of a γ-counter. Tumors were snap frozen and sections were stained for CAIX expression, vessels, hypoxia (pimonidazole) and tumor blood perfusion. Tracer uptake was significantly higher in SSCNij153 tumors compared to SCCNij185 tumors for [111In]In-DOTA-HE3-ZCAIX:2: 0.32 ± 0.03 versus 0.18 ± 0.01%ID/g,(p = 0.003) 4 h p.i., for [111In]In-DTPA-girentuximab-F(ab′)2: 3.0 ± 0.5%ID/g and 1.2 ± 0.1%ID/g (p = 0.03), 24 h p.i. and for [111In]In-DTPA-girentuximab: 30 ± 2.1%ID/g and 7.0 ± 1.0%ID/g (p = 0.0002) 72 h p.i. SPECT imaging with both [111In]In-DTPA-girentuximab-F(ab′)2 and [111In]In-DTPA-girentuximab showed a clear difference in tracer distribution between the two tumor models. The whole IgG, i.e. [111In]In-DTPA-girentuximab, showed the highest tumor-to-muscle ratio. We showed that different CAIX-targeting radiotracers can discriminate a low CAIX-expressing tumor from a high CAIX-expressing head and neck cancer xenografts model. In these hypoxic head and neck xenograft models [111In]In-DTPA-girentuximab showed the most promising results.

The role of apolipoprotein- and vitronectin-enriched protein corona on lipid nanoparticles for in vivo targeted delivery and transfection of oligonucleotides in murine tumor models

Nanoscale ◽  
2019 ◽  
Vol 11 (40) ◽  
pp. 18806-18824 ◽  
Author(s):  
Dongyu Chen ◽  
Neha Parayath ◽  
Shanthi Ganesh ◽  
Weimin Wang ◽  
Mansoor Amiji
Keyword(s):  
Targeted Delivery ◽  
Protein Corona ◽  
Lipid Nanoparticles ◽  
Cell Transfection ◽  
Tumor Models ◽  
Profound Impact ◽  
Murine Tumor ◽  
Composition Changes

We demonstrated that protein corona can be altered by lipid nanoparticle composition changes. Protein corona composition differences had a profound impact on cell transfection, in vivo biodistribution and tumor-specific delivery.

In vivo antitumor activity of sparsomycin and its analogues in eight murine tumor models

1988 ◽  
Vol 6 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Zbigniew Zylicz ◽  
D. J. Theo Wagener ◽  
Helga van Rennes ◽  
Eppo van der Kleijn ◽  
Peter Lelieveld ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Models ◽  
Murine Tumor ◽  
In Vivo Antitumor Activity

An RNAi-based system for loss-of-function analysis identifies Raf1 as a crucial mediator of BCR-ABL–driven leukemogenesis

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2200-2210 ◽  
Author(s):  
Corinna Albers ◽  
Anna L. Illert ◽  
Cornelius Miething ◽  
Hannes Leischner ◽  
Melanie Thiede ◽  
...  
Keyword(s):  
Drug Targets ◽  
Function Analysis ◽  
Expression System ◽  
Hematopoietic Cells ◽  
Mouse Strains ◽  
Loss Of Function ◽  
Tumor Models ◽  
Murine Tumor

Abstract Genetic loss-of-function studies in murine tumor models have been essential in the analysis of downstream mediators of oncogenic transformation. Unfortunately, these studies are frequently limited by the availability of genetically modified mouse strains. Here we describe a versatile method allowing the efficient expression of an oncogene and simultaneous knockdown of targets of interest (TOI) from a single retroviral vector. Both oncogene and TOI-specific miR30-based shRNA are under the control of the strong viral long terminal repeat promoter, resulting in a single shared RNA transcript. Using this vector in a murine syngeneic BM transplantation model for BCR-ABL–induced chronic myeloid leukemia, we find that oncogene expression and target knockdown in primary hematopoietic cells with this vector is efficient both in vitro and in vivo, and demonstrate that Raf1, but not BRAF, modulates BCR-ABL–dependent ERK activation and transformation of hematopoietic cells. This expression system could facilitate genetic loss-of-function studies and allow the rapid validation of potential drug targets in a broad range of oncogene-driven murine tumor models.

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