MicroRNA-138 Increases Chemo-Sensitivity of Glioblastoma through Downregulation of Survivin

Glioblastoma (GBM) is one of the most deadly cancers and poorly responses to chemotherapies, such as temozolomide (TMZ). Dysregulation of intrinsic signaling pathways in cancer cells are often resulted by dysregulated tumor suppressive microRNAs (miRNAs). Previously, we found miR-138 as one of tumor suppressive miRNAs that were significantly down-regulated in GBM. In this study, we demonstrated that ectopic over-expression of miR-138 sensitizes GBM cells to the treatment of TMZ and increased apoptotic cell death. Mechanistically, miR-138 directly repressed the expression of Survivin, an anti-apoptotic protein, to enhance caspase-induced apoptosis upon TMZ treatment. Using an intracranial GBM xenograft mice model, we also showed that combination of miR-138 with TMZ increases survival rates of the mice compared to the control mice treated with TMZ alone. This study provides strong preclinical evidence of the therapeutic benefit from restoration of miR-138 to sensitize the GBM tumor to conventional chemotherapy.

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4-Acetyl-12,13-Epoxyl-9-Trichothecene-3,15-Diol from Isaria japonica Mediates Apoptosis of Rat Bladder Carcinoma NBT-II Cells by Decreasing Anti-apoptotic Bcl-2 Expression and Increasing Pro-apoptotic Bax Expression

The American Journal of Chinese Medicine ◽

10.1142/s0192415x0400203x ◽

2004 ◽

Vol 32 (03) ◽

pp. 377-387 ◽

Cited By ~ 2

Author(s):

Hyung-Jin Kim ◽

Seon Il Jang ◽

Young-Jun Kim ◽

Hyun-Ock Pae ◽

Hae-Young Won ◽

...

Keyword(s):

Cell Death ◽

Bladder Carcinoma ◽

Cytotoxic Effect ◽

Caspase 3 ◽

Apoptotic Cell ◽

Morphological Changes ◽

Rat Bladder ◽

Apoptotic Protein ◽

Induction Of Apoptosis ◽

Induced Apoptosis

We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3,15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.

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Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

Cancers ◽

10.3390/cancers13184648 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4648

Author(s):

Eva Lhuissier ◽

Juliette Aury-Landas ◽

Marion Lenté ◽

Karim Boumediene ◽

Catherine Baugé

Keyword(s):

Tumor Volume ◽

Mice Model ◽

Antitumoral Effect ◽

Viable Cells ◽

Epigenetic Drug ◽

Xenograft Mice Model ◽

Xenograft Mice ◽

Tumoral Cells

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

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A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model

ACS Medicinal Chemistry Letters ◽

10.1021/acsmedchemlett.9b00161 ◽

2019 ◽

Vol 10 (10) ◽

pp. 1400-1406 ◽

Cited By ~ 1

Author(s):

Parichat Suebsakwong ◽

Jie Wang ◽

Phorntip Khetkam ◽

Natthida Weerapreeyakul ◽

Jing Wu ◽

...

Keyword(s):

Tumor Growth ◽

Mice Model ◽

Cucurbitacin B ◽

Xenograft Mice Model ◽

Xenograft Mice

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Establishment of an Orthotopic Xenograft Mice Model of Retinoblastoma Suitable for Preclinical Testing

Ocular Oncology and Pathology ◽

10.1159/000370156 ◽

2015 ◽

Vol 1 (3) ◽

pp. 200-206 ◽

Cited By ~ 6

Author(s):

Nathalie Cassoux ◽

Aur�lie Thuleau ◽

Franck Assayag ◽

Isabelle Aerts ◽

Didier Decaudin

Keyword(s):

Mice Model ◽

Preclinical Testing ◽

Orthotopic Xenograft ◽

Xenograft Mice Model ◽

Xenograft Mice

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Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

Journal of Cancer Biology and Therapeutics ◽

10.18314/gjct.v6i1.1995 ◽

2020 ◽

Vol 6 (1) ◽

pp. 301-307

Author(s):

Prashad N

Keyword(s):

Nervous System ◽

Tumor Growth ◽

Neuroblastoma Cells ◽

Xenograft Model ◽

Mice Model ◽

Xenograft Mice Model ◽

Mycn Expression ◽

Xenograft Mice ◽

Combination Of Sirnas

Neuroblastoma is a common tumor of the peripheral nervous system in children. Highly aggressive MYC-drivenneuroblastoma is defined by increased MYC and/or MYCN expression. HDAC8 overexpression is associated with advanced neuroblastoma. Previously, we have demonstrated that transient knockdown of both Myc and Hdac8 using siRNA significantly suppressed neuroblastoma cells proliferation compared to knockdown of either target in vitro. In this study, we further investigated whether combinational targeting Myc and Hdac8 in neuroblastoma xenograft mice model is consistent with our previous findings. Intratumoral treatment with siRNA-MYC and siRNA-HDAC8 reduced the levels of the target MYC protein by 64% and HDAC8 by 85%; in addition, we found that the average tumor growth was reduced by 80% compared to that of control tumors treated with NC-siRNA. Our results suggest the potential therapeutic effect of the combination of siRNA-MYC and siRNA-HDAC8 for neuroblastoma treatment.

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P08.10 Efficacy of Temozolomide and Aldoxorubicin combination in U87-luc glioblastoma xenograft mice model

Neuro-Oncology ◽

10.1093/neuonc/nox036.200 ◽

2017 ◽

Vol 19 (suppl_3) ◽

pp. iii55-iii56

Author(s):

M. Da Ros ◽

A. Iorio ◽

O. Fantappiè ◽

V. De Gregorio ◽

L. Bonaccorsi ◽

...

Keyword(s):

Mice Model ◽

Xenograft Mice Model ◽

Xenograft Mice

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LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000484116 ◽

2017 ◽

Vol 43 (5) ◽

pp. 1926-1938 ◽

Cited By ~ 42

Author(s):

Jia Xiao ◽

Yi Lv ◽

Fujun Jin ◽

Yingxia Liu ◽

Yi Ma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Therapeutic Target ◽

Mice Model ◽

Over Expression ◽

In Vivo Experiments ◽

Non Coding Rna ◽

Promising Therapeutic Target ◽

Induced Apoptosis ◽

Pathway Analyses

Background/Aims: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. Methods: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. Results: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3β in HCC. Conclusion: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.

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Systematic Analysis of a Xenograft Mice Model for KSHV+ Primary Effusion Lymphoma (PEL)

PLoS ONE ◽

10.1371/journal.pone.0090349 ◽

2014 ◽

Vol 9 (2) ◽

pp. e90349 ◽

Cited By ~ 10

Author(s):

Lu Dai ◽

Jimena Trillo-Tinoco ◽

Lihua Bai ◽

Baoli Kang ◽

Zengguang Xu ◽

...

Keyword(s):

Primary Effusion Lymphoma ◽

Mice Model ◽

Systematic Analysis ◽

Xenograft Mice Model ◽

Xenograft Mice

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Association of Bcl-2 with Misfolded Prion Protein Is Linked to the Toxic Potential of Cytosolic PrP

Molecular Biology of the Cell ◽

10.1091/mbc.e06-01-0083 ◽

2006 ◽

Vol 17 (8) ◽

pp. 3356-3368 ◽

Cited By ~ 67

Author(s):

Angelika S. Rambold ◽

Margit Miesbauer ◽

Doron Rapaport ◽

Till Bartke ◽

Michael Baier ◽

...

Keyword(s):

Prion Protein ◽

Protein Misfolding ◽

Apoptotic Cell ◽

Prion Diseases ◽

Protective Role ◽

Proteinase K ◽

Apoptotic Protein ◽

Induced Apoptosis ◽

Toxic Potential ◽

Cellular Compartments

Protein misfolding is linked to different neurodegenerative disorders like Alzheimer’s disease, polyglutamine, and prion diseases. We investigated the cytotoxic effects of aberrant conformers of the prion protein (PrP) and show that toxicity is specifically linked to misfolding of PrP in the cytosolic compartment and involves binding of PrP to the anti-apoptotic protein Bcl-2. PrP targeted to different cellular compartments, including the cytosol, nucleus, and mitochondria, adopted a misfolded and partially proteinase K–resistant conformation. However, only in the cytosol did the accumulation of misfolded PrP induce apoptosis. Apoptotic cell death was also induced by two pathogenic mutants of PrP, which are partially localized in the cytosol. A mechanistic analysis revealed that the toxic potential is linked to an internal domain of PrP (amino acids 115–156) and involves coaggregation of cytosolic PrP with Bcl-2. Increased expression of the chaperones Hsp70 and Hsp40 prevented the formation of PrP/Bcl-2 coaggregates and interfered with PrP-induced apoptosis. Our study reveals a compartment-specific toxicity of PrP misfolding that involves coaggregation of Bcl-2 and indicates a protective role of molecular chaperones.

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