SU-FF-I-119: Novel MicroCT Imaging Techniques for In Vivo Quantification of Vascular Volume in Murine Tumor Models

2007 ◽  
Vol 34 (6Part4) ◽  
pp. 2365-2365 ◽  
Author(s):  
M Nyflot ◽  
J Grudzinski ◽  
R Jeraj
Keyword(s):  
Imaging Techniques ◽  
Tumor Models ◽  
Vascular Volume ◽  
Murine Tumor ◽  
Microct Imaging

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.

scholarly journals In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament

2019 ◽  
Vol 16 (154) ◽  
pp. 20190108 ◽  
Author(s):  
Jingxiao Zhong ◽  
Junning Chen ◽  
Richard Weinkamer ◽  
M. Ali Darendeliler ◽  
Michael V. Swain ◽  
...  
Keyword(s):  
Hydrostatic Pressure ◽  
Periodontal Ligament ◽  
Root Resorption ◽  
Imaging Techniques ◽  
Common Side Effect ◽  
Element Analysis ◽  
Clinical Observations ◽  
Microct Imaging ◽  
Orthodontic Forces

Orthodontic root resorption is a common side effect of orthodontic therapy. It has been shown that high hydrostatic pressure in the periodontal ligament (PDL) generated by orthodontic forces will trigger recruitment of odontoclasts, leaving resorption craters on root surfaces. The patterns of resorption craters are the traces of odontoclast activity. This study aimed to investigate resorptive patterns by: (i) quantifying spatial root resorption under two different levels of in vivo orthodontic loadings using microCT imaging techniques and (ii) correlating the spatial distribution pattern of resorption craters with the induced mechanobiological stimulus field in PDL through nonlinear finite-element analysis (FEA) in silico . Results indicated that the heavy force led to a larger total resorption volume than the light force, mainly by presenting greater individual crater volumes ( p < 0.001) than increasing crater numbers, suggesting that increased mechano-stimulus predominantly boosted cellular resorption activity rather than recruiting more odontoclasts. Furthermore, buccal–cervical and lingual–apical regions in both groups were found to have significantly larger resorption volumes than other regions ( p < 0.005). These clinical observations are complemented by the FEA results, suggesting that root resorption was more likely to occur when the volume average compressive hydrostatic pressure exceeded the capillary blood pressure (4.7 kPa).

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

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.

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

2019 ◽  
Author(s):  
Daniel Sun ◽  
Soumya Poddar ◽  
Roy D. Pan ◽  
Juno Van Valkenburgh ◽  
Ethan Rosser ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Small Cell Lung Carcinoma ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Tumor Models ◽  
Cell Lung Carcinoma ◽  
Adaptive Resistance ◽  
Cancer Models ◽  
Nanomolar Range

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone <b>HCT-13</b>, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC<sub>90</sub> values in the low-to-mid nanomolar range.<b> </b>We show that the cytotoxicity of <b>HCT-13</b> is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following <b>HCT-13 </b>treatment. Taken together, <b>HCT-13 </b>is potent against solid tumor models and warrants <i>in vivo</i> evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

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