Correlation of 360-degree Surface Mapping In Vivo Bioluminescence with Multi-Spectral Optoacoustic Tomography in Human Xenograft Tumor Models

Abstract Background Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process. Methods Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting. Results Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy. Conclusions Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.

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311. In Vivo Anti-TumorActivity of Oncolytic Adenoviruses That Express GM-CSF in Xenograft Tumor Models

Molecular Therapy ◽

10.1016/s1525-0016(16)43141-2 ◽

2002 ◽

Vol 5 (5) ◽

pp. S103

Keyword(s):

Xenograft Tumor ◽

Tumor Models ◽

Gm Csf ◽

Oncolytic Adenoviruses

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The Impact of the Low Molecular Weight Heparin Tinzaparin on the Sensitization of Cisplatin-Resistant Ovarian Cancers—Preclinical In Vivo Evaluation in Xenograft Tumor Models

Molecules ◽

10.3390/molecules22050728 ◽

2017 ◽

Vol 22 (5) ◽

pp. 728 ◽

Cited By ~ 9

Author(s):

Thomas Mueller ◽

Daniel Pfankuchen ◽

Kathleen Wantoch von Rekowski ◽

Martin Schlesinger ◽

Franziska Reipsch ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Xenograft Tumor ◽

Tumor Models ◽

In Vivo Evaluation ◽

Ovarian Cancers ◽

The Impact

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TAK-573, an anti-CD38-targeted attenuated interferon alpha (IFNα) fusion protein, showed anti-myeloma tumor responses in combination with standard of care (SOC) agents in multiple myeloma (MM) xenograft tumor models in vivo

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2019.09.192 ◽

2019 ◽

Vol 19 (10) ◽

pp. e116 ◽

Cited By ~ 2

Author(s):

Marjan Fatholahi ◽

Miriam Valencia ◽

Armanini Mark ◽

Mingying Bi ◽

Sakeena Syed ◽

...

Keyword(s):

Multiple Myeloma ◽

Fusion Protein ◽

Interferon Alpha ◽

Standard Of Care ◽

Xenograft Tumor ◽

Tumor Models

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

10.26434/chemrxiv.7877987.v1 ◽

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 HCT-13, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC90 values in the low-to-mid nanomolar range. We show that the cytotoxicity of HCT-13 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 HCT-13 treatment. Taken together, HCT-13 is potent against solid tumor models and warrants in vivo evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

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Fluorophore Selection and Incorporation Contribute to Permeation and Distribution Behaviors of Hyperbranched Polymers in Multi-Cellular Tumor Spheroids and Xenograft Tumor Models

ACS Applied Bio Materials ◽

10.1021/acsabm.0c01616 ◽

2021 ◽

Author(s):

Joshua D. Simpson ◽

Patrícia F. Monteiro ◽

Gayathri R. Ediriweera ◽

Amber R. Prior ◽

Stefan E. Sonderegger ◽

...

Keyword(s):

Hyperbranched Polymers ◽

Xenograft Tumor ◽

Tumor Spheroids ◽

Tumor Models

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Enhanced anti-tumor efficacy of IL-7/CCL19-producing human CAR-T cells in orthotopic and patient-derived xenograft tumor models

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02853-3 ◽

2021 ◽

Author(s):

Shunsuke Goto ◽

Yukimi Sakoda ◽

Keishi Adachi ◽

Yoshitaka Sekido ◽

Seiji Yano ◽

...

Keyword(s):

T Cells ◽

Xenograft Tumor ◽

Tumor Models ◽

Car T Cells ◽

Patient Derived Xenograft ◽

Car T

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Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

Scientific Reports ◽

10.1038/s41598-021-91454-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shao-Yuan Chen ◽

Koichi Tsuneyama ◽

Mao-Hsiung Yen ◽

Jiunn-Tay Lee ◽

Jiun-Liang Chen ◽

...

Keyword(s):

Lung Cancer ◽

Solid Tumors ◽

Tumor Cells ◽

Hyperbaric Oxygen ◽

A549 Cell ◽

P53 Protein ◽

Tumor Hypoxia ◽

A549 Cells ◽

Xenograft Tumor ◽

Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

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Therapeutic Application of Brain-Specific Angiogenesis Inhibitor 1 for Cancer Therapy

Cancers ◽

10.3390/cancers13143562 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3562

Author(s):

Mitra Nair ◽

Chelsea Bolyard ◽

Tae Jin Lee ◽

Balveen Kaur ◽

Ji Young Yoo

Keyword(s):

Angiogenesis Inhibitor ◽

Suppressor Gene ◽

Chemotherapeutic Agents ◽

Tumor Models ◽

In Vivo Models ◽

Herpes Simplex Viruses ◽

Multiple Tumor ◽

And Function

Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1) is an adhesion G protein-coupled receptor that has been found to play key roles in phagocytosis, inflammation, synaptogenesis, the inhibition of angiogenesis, and myoblast fusion. As the name suggests, it is primarily expressed in the brain, with a high expression in the normal adult and developing brain. Additionally, its expression is reduced in brain cancers, such as glioblastoma (GBM) and peripheral cancers, suggesting that BAI1 is a tumor suppressor gene. Several investigators have demonstrated that the restoration of BAI1 expression in cancer cells results in reduced tumor growth and angiogenesis. Its expression has also been shown to be inversely correlated with tumor progression, neovascularization, and peri-tumoral brain edema. One method of restoring BAI1 expression is by using oncolytic virus (OV) therapy, a strategy which has been tested in various tumor models. Oncolytic herpes simplex viruses engineered to express the secreted fragment of BAI1, called Vasculostatin (Vstat120), have shown potent anti-tumor and anti-angiogenic effects in multiple tumor models. Combining Vstat120-expressing oHSVs with other chemotherapeutic agents has also shown to increase the overall anti-tumor efficacy in both in vitro and in vivo models. In the current review, we describe the structure and function of BAI1 and summarize its application in the context of cancer treatment.

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