In vivo antitumor efficacy of 17-AAG loaded PMMA in a human multiple myeloma xenograft mouse model

Abstract To facilitate human multiple myeloma (MM) engraftment into NOD/SCID recipients, mice were depleted of CD122+ cells (NK and myeloid cells) by antibody-mediated ablation prior to transplantation with the MM cell lines (RPMI8226, RPMI8226-TGL or U226). The MM engraftment, skeletal MM distribution, osteolysis, lambda chain paraprotein and associating disease symptoms in CD122+ cell-depleted and CD122+ cellreplete mice were compared. The CD122+ cell-depleted mice engrafted at a significantly higher frequency with human CD38+, CD56+, PCA-1+ and CD138+ cells. In the CD122+ cell-depleted mice, bioluminescence MM signal involved the whole mouse compared to limited imaging signal in the CD122+ cell-replete mice. The majority 88%–100% of CD122+ cell-depleted mice developed MM engraftment throughout the appendicular and axial skeletons with osteolysis and rare subcutaneous plasmacytomas (11% of mice). Serum paraprotein appeared earlier at 4–5 weeks post-transplant in CD122+ cell-depleted mice and continued to increase during the 12–13 weeks of analysis. The majority, 92% of CD122+ cell-depleted mice developed hind-limb paralysis and had a significantly shortened 45 day survival. Thus, depletion of CD122+ cells reduced resistance to the human MM and produced a new MM xenograft-NOD/SCID model that recapitulates the clinical manifestations of MM and eliminates the major limitations associated with the published MM xenograft-mouse model.

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Force estimation from 4D OCT data in a human tumor xenograft mouse model

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-0022 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Maximilian Neidhardt ◽

Nils Gessert ◽

Tobias Gosau ◽

Julia Kemmling ◽

Susanne Feldhaus ◽

...

Keyword(s):

Deep Learning ◽

Mouse Model ◽

Haptic Feedback ◽

Human Tumor ◽

Tumor Xenograft ◽

Human Tumor Xenograft ◽

Force Estimation ◽

Xenograft Mouse Model ◽

Dead Tissue

AbstractMinimally invasive robotic surgery offer benefits such as reduced physical trauma, faster recovery and lesser pain for the patient. For these procedures, visual and haptic feedback to the surgeon is crucial when operating surgical tools without line-of-sight with a robot. External force sensors are biased by friction at the tool shaft and thereby cannot estimate forces between tool tip and tissue. As an alternative, vision-based force estimation was proposed. Here, interaction forces are directly learned from deformation observed by an external imaging system. Recently, an approach based on optical coherence tomography and deep learning has shown promising results. However, most experiments are performed on ex-vivo tissue. In this work, we demonstrate that models trained on dead tissue do not perform well in in vivo data. We performed multiple experiments on a human tumor xenograft mouse model, both on in vivo, perfused tissue and dead tissue. We compared two deep learning models in different training scenarios. Training on perfused, in vivo data improved model performance by 24% for in vivo force estimation.

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A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway

Cancer Cell International ◽

10.1186/s12935-021-01973-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xuejie Gao ◽

Bo Li ◽

Anqi Ye ◽

Houcai Wang ◽

Yongsheng Xie ◽

...

Keyword(s):

Mouse Model ◽

Tumor Burden ◽

High Rate ◽

Cell Counting ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Therapeutic Effects ◽

Xenograft Mouse Model

Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

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Anticancer effect of arsenic trioxide on cholangiocarcinoma: in vitro experiments and in vivo xenograft mouse model

Clinical and Experimental Medicine ◽

10.1007/s10238-013-0233-x ◽

2013 ◽

Vol 14 (2) ◽

pp. 215-224 ◽

Cited By ~ 4

Author(s):

Eun-Young Kim ◽

Sang Soo Lee ◽

Ji Hoon Shin ◽

Soo Hyun Kim ◽

Dong-Ho Shin ◽

...

Keyword(s):

Mouse Model ◽

Arsenic Trioxide ◽

In Vitro Experiments ◽

Anticancer Effect ◽

Xenograft Mouse Model

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Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms17111927 ◽

2016 ◽

Vol 17 (11) ◽

pp. 1927 ◽

Cited By ~ 21

Author(s):

Bingqian Xie ◽

Zhijian Xu ◽

Liangning Hu ◽

Gege Chen ◽

Rong Wei ◽

...

Keyword(s):

Multiple Myeloma ◽

Jnk Pathway ◽

Myeloma Cells ◽

Human Multiple Myeloma

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α-Hederin Inhibits the Growth of Lung Cancer A549 Cells in vitro and in vivo by Increasing SIRT6 Dependent Glycolysis

10.21203/rs.3.rs-36418/v1 ◽

2020 ◽

Author(s):

cong fang ◽

Yahui Liu ◽

Lanying Chen ◽

Yingying Luo ◽

Yaru Cui ◽

...

Keyword(s):

Lung Cancer ◽

Mouse Model ◽

Protein Expression ◽

Glucose Uptake ◽

A549 Cells ◽

Lactate Production ◽

Tumor Xenograft ◽

Xenograft Mouse Model ◽

Atp Generation

Abstract Background: α-hederin an effective component of Pulsatilla chinensis (Bunge) Regel, Studies showed that α-hederin exert many pharmacological activities, However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. Methods: CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin (5, 10 mg/kg). Glycolytic-related key enzymes hexokinase 2 (HK2), glucose transporters 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter (MCT4), c-Myc, Hypoxia inducible factor-1α (HIF-1α) and Sirtuin 6 (SIRT6) protein expression were detected by western blotting and immunohistochemical staining and SIRT6 inhibitors was verified in A549 cells. Results: Our results showed that cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited HK2, GLUT1, PKM2, LDHA, MCT4, c-Myc, HIF-1α and activated SIRT6 protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by activating SIRT6. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo. Conclusions: α-hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis. The mechanism of glycolysis inhibition includes α-hederin activating the expression of the glycolytic related protein SIRT6.

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A Novel Transgenic Mouse Model of the Human Multiple Myeloma Chromosomal Translocation t(14;16)(q32;q23)

Cancer Research ◽

10.1158/0008-5472.can-10-1057 ◽

2011 ◽

Vol 71 (2) ◽

pp. 339-348 ◽

Cited By ~ 25

Author(s):

Naoki Morito ◽

Keigyou Yoh ◽

Atsuko Maeda ◽

Takako Nakano ◽

Akiko Fujita ◽

...

Keyword(s):

Multiple Myeloma ◽

Mouse Model ◽

Transgenic Mouse ◽

Chromosomal Translocation ◽

Transgenic Mouse Model ◽

Human Multiple Myeloma

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Abstract 1569: Antitumor activity of SR16388 against human multiple myeloma in vitro and in vivo

10.1158/1538-7445.am10-1569 ◽

2010 ◽

Author(s):

Wan-Ru Chao ◽

Yihui Shi ◽

Dominic Dinh ◽

Carol Hou ◽

Lidia Sambucetti

Keyword(s):

Multiple Myeloma ◽

Antitumor Activity ◽

Human Multiple Myeloma

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A Clinically Relevant SCID-hu in Vivo Model of Human Multiple Myeloma.

Blood ◽

10.1182/blood.v104.11.2455.2455 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2455-2455

Author(s):

Pierfrancesco Tassone ◽

Paola Neri ◽

Daniel R. Carrasco ◽

Renate Burger ◽

Laurence Catley ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Fluorescence Imaging ◽

Scid Mice ◽

In Vivo Model ◽

Murine Models ◽

Fetal Bone ◽

Investigational Drugs ◽

Human Multiple Myeloma

Abstract Human multiple myeloma (MM) xenografts in immunodeficient mice have limitations as a model for the human disease since they lack the human bone marrow (huBM) microenvironment. In contrast, murine models harboring a huBM microenvironment with implantation of patient MM cells in the huBM recapitulate the in vivo pathophysiology of MM and have significant advantages over conventional murine models for pre-clinical evaluation of investigational drugs. However, there are significant limitations in using patient MM cells in such models since i) not all patient MM samples engraft in the huBM; ii) only a fraction of engrafted specimens produce measurable paraprotein and/or osteolytic lesions; and iii) a limited number of MM cells can be harvested from an individual patient, thus limiting the number of mice that can be injected with cells from the same patient. To overcome these limitations, we have developed a novel murine model of MM by engrafting INA-6, a cytokine-dependent human MM cell line into SCID mice previously implanted with a human fetal bone chip (SCID-hu mice). INA-6 cells require either exogenous IL-6 or interaction with the bone marrow stromal cells (BMSCs) to proliferate in vitro. In this model, we monitored the in vivo growth of INA-6 cells stably transfected with a green fluorescent protein (GFP) expression vector (INA-6GFP+). Serum soluble human IL-6 receptor (shuIL-6R) and fluorescence imaging of host animals were sensitive indicators of tumor burden with time dependent increase. Fluorescence imaging was able to detect the myeloma cell growth earlier than measurement of sIL-6R levels. INA-6 MM cells grew in SCID-hu mice, but not in SCID mice injected subcutaneously or intravenously without the human fetal bone. We have further confirmed the feasibility of this model in monitoring the response to therapeutic agents such as dexamethasone by detecting reduction in the intensity of the fluorescent lesions as well as shuIL-6R in SCID-hu mice following anti-MM treatment. This highly reproducible model therefore allows for evaluation of investigational drugs targeting MM cells in the huBM milieu.

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