A Novel Anti-EGFR mAb Ame55 with Lower Toxicity and Better Efficacy than Cetuximab When Combined with Irinotecan

To improve efficacy and minimize toxicity of EGFR inhibition treatment, we developed Ame55, a novel anti-EGFR IgG1 with lower affinity to EGFR than cetuximab (C225) from a human phage library. Ame55 had lower bioactivity than cetuximab in vitro but similar antitumor efficacy as cetuximab in vivo. Moreover, Ame55 was more efficacious than cetuximab in a Lovo cell xenograft tumor model when combined with irinotecan (CPT-11). Ame55 concentrates in the mouse xenograft tumor and has less toxicity than cetuximab in cynomolgus monkeys in an overdose study.

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mTORC2 promotes cell survival through c-Myc–dependent up-regulation of E2F1

The Journal of Cell Biology ◽

10.1083/jcb.201411128 ◽

2015 ◽

Vol 211 (1) ◽

pp. 105-122 ◽

Cited By ~ 17

Author(s):

Zhipeng Zou ◽

Juan Chen ◽

Anling Liu ◽

Xuan Zhou ◽

Qiancheng Song ◽

...

Keyword(s):

Cell Survival ◽

Tumor Model ◽

Xenograft Tumor ◽

In Vivo Experiments ◽

Xenograft Tumor Model ◽

Cancer Cell Survival ◽

Consequent Reduction ◽

Dependent Mechanism

Previous studies have reported that mTORC2 promotes cell survival through phosphorylating AKT and enhancing its activity. We reveal another mechanism by which mTORC2 controls apoptosis. Inactivation of mTORC2 promotes binding of CIP2A to PP2A, leading to reduced PP2A activity toward c-Myc serine 62 and, consequently, enhancement of c-Myc phosphorylation and expression. Increased c-Myc activity induces transcription of pri-miR-9-2/miR-9-3p, in turn inhibiting expression of E2F1, a transcriptional factor critical for cancer cell survival and tumor progression, resulting in enhanced apoptosis. In vivo experiments using B cell–specific mTORC2 (rapamycin-insensitive companion of mTOR) deletion mice and a xenograft tumor model confirmed that inactivation of mTORC2 causes up-regulation of c-Myc and miR-9-3p, down-regulation of E2F1, and consequent reduction in cell survival. Conversely, Antagomir-9-3p reversed mTORC1/2 inhibitor–potentiated E2F1 suppression and resultant apoptosis in xenograft tumors. Our in vitro and in vivo findings collectively demonstrate that mTORC2 promotes cell survival by stimulating E2F1 expression through a c-Myc– and miR-9-3p–dependent mechanism.

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LncRNA SNHG15 regulates osteosarcoma progression in vitro and in vivo via sponging miR-346 and regulating TRAF4 expression

Open Life Sciences ◽

10.1515/biol-2020-0039 ◽

2020 ◽

Vol 15 (1) ◽

pp. 423-436

Author(s):

Xuewu Chen ◽

Hongguang Xu

Keyword(s):

Binding Sites ◽

Biological Function ◽

Tumor Model ◽

Xenograft Tumor ◽

Positive Effects ◽

Xenograft Tumor Model ◽

Nucleolar Rna ◽

Common Primary Malignant Bone

AbstractOsteosarcoma (OS) is a common primary malignant bone tumor around the world. It has been reported that long noncoding RNAs (lncRNAs) take part in diverse pathological processes of OS; however, the mechanism remains unknown. This study aimed to uncover the profile of lncRNA small nucleolar RNA host gene 15 (SNHG15), its biological function, and its potential involvement in the mechanism of OS progression in vitro and in vivo. The expression of SNHG15 and TRAF4 was promoted in OS tissues opposite for that of miR-346. The silencing of SNHG15 limited the proliferation, invasion, and enhanced apoptosis of SaoS2 and HOS cells. Moreover, the putative binding sites between miR-346 and SNHG15 or TRAF4 were predicted by starBase and Targetscan software online, individually. Also, miR-346 deletion reversed the positive effects of SNHG15 elimination on proliferation, apoptosis, and invasion in cells. In addition, the upregulation of TRAF4 disrupted the biofunctional results from miR-346 promotion subsequently. Finally, SNHG15 knockdown repressed OS tumor growth in a xenograft tumor model. SNHG15 enhanced the progression of OS by regulating the miR-346/TRAF4 axis in vitro and in vivo.

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Combining Sodium Butyrate With Cisplatin Increases the Apoptosis of Gastric Cancer In Vivo and In Vitro via the Mitochondrial Apoptosis Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.708093 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yangbo Li ◽

Pengzhan He ◽

Yinghui Liu ◽

Mingming Qi ◽

Weiguo Dong

Keyword(s):

Sodium Butyrate ◽

Intestinal Flora ◽

Tumor Model ◽

Mitochondrial Apoptosis ◽

Xenograft Tumor ◽

Mouse Xenograft ◽

Xenograft Tumor Model ◽

Related Pathway

Introduction: The gastrointestinal malignancy, gastric cancer (GC), has a high incidence worldwide. Cisplatin is a traditional chemotherapeutic drug that is generally applied to treat cancer; however, drug tolerance affects its efficacy. Sodium butyrate is an intestinal flora derivative that has general anti-cancer effects in vitro and in vivo via pro-apoptosis effects and can improve prognosis in combination with traditional chemotherapy drugs. The present study aimed to assess the effect of sodium butyrate combined with cisplatin on GC.Methods: A Cell Counting Kit-8 assay was used to assess the viability of GC cells in vitro. Hoechst 33,258 staining and Annexin V-Phycoerythrin/7-Aminoactinomycin D were used to qualitatively and quantitatively detect apoptosis in GC cells. Intracellular reactive oxygen species (ROS) measurement and a mitochondrial membrane potential (MMP) assay kit were used to qualitatively and quantitatively reflect the function of mitochondria in GC cells. Western blotting was used to verify the above experimental results. A nude mouse xenograft tumor model was used to evaluate the anti-tumor efficacity of sodium and cisplatin butyrate in vivo.Results: Cisplatin combined with sodium butyrate increased the apoptosis of GC cells. In the nude mouse xenograft tumor model, sodium butyrate in combination with cisplatin markedly inhibited the growth of the tumor more effectively than either single agent. The combination of sodium butyrate and cisplatin increased the intracellular ROS, decreased the MMP, and suppressed the invasion and migration abilities of GC cells. Western blotting verified that the combination of sodium butyrate and cisplatin remarkably enhanced the levels of mitochondrial apoptosis-related pathway proteins.Conclusion: Sodium butyrate, a histone acetylation inhibitor produced by intestinal flora fermentation, combined with cisplatin enhanced the apoptosis of GC cells through the mitochondrial apoptosis-related pathway, which might be considered as a therapeutic option for GC.

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Circular RNA_CNST Promotes the Tumorigenesis of Osteosarcoma Cells by Sponging miR-421

Cell Transplantation ◽

10.1177/0963689720926147 ◽

2020 ◽

Vol 29 ◽

pp. 096368972092614

Author(s):

Ji-Hai Wang ◽

Xue-Jian Wu ◽

Yong-Zhuang Duan ◽

Feng Li

Keyword(s):

Colony Formation ◽

Specific Binding ◽

Tumor Model ◽

Gene Expression Omnibus ◽

Pcr Analysis ◽

Circular Rnas ◽

Xenograft Tumor ◽

Potential Biomarker

Circular RNAs (circRNAs) act crucial roles in the progression of multiple malignancies including osteosarcoma (OS). But, the underlying mechanisms by which hsa_circ_0017311 (circCNST) contributes to the tumorigenesis of OS remain poorly understood. Our present study aimed to explore the role and mechanisms of circCNST in OS tumorigenesis. The differentially expressed circRNAs were identified by the Gene Expression Omnibus database. The association of circCNST with clinicopathological features and prognosis in patients with OS was analyzed by RNA fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (PCR) analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assays, and a xenograft tumor model were conducted to assess the role of circCNST in OS cells in vitro and in vivo. CircCNST-specific binding with miR-421 was confirmed by FISH, luciferase gene report, and RNA immunoprecipitation assays. As a result, we found that the expression levels of circCNST were dramatically increased in OS tissues and cell lines as compared with the adjacent normal tissues, and it was associated with tumor size and poor survival in OS patients. Knockdown of circCNST repressed cell viability, colony formation, and xenograft tumor growth, while restored expression of circCNST reversed these effects. Furthermore, circCNST was colocalized with miR-421 in the cytoplasm and acted as a sponge of miR-421, which attenuated circCNST-induced proliferation-promoting effects in OS cells by targeting SLC25A3. In conclusion, our findings demonstrate that circCNST promotes the tumorigenesis of OS cells by sponging miR-421, and provides a potential biomarker for patients with OS.

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Circular RNA circ-CDYL sponges miR-1180 to elevate yes-associated protein in multiple myeloma

Experimental Biology and Medicine ◽

10.1177/1535370220918191 ◽

2020 ◽

Vol 245 (11) ◽

pp. 925-932 ◽

Cited By ~ 2

Author(s):

Fang Chen ◽

Xiaohui Wang ◽

Shuang Fu ◽

Shaokun Wang ◽

Yu Fu ◽

...

Keyword(s):

Multiple Myeloma ◽

Tumor Model ◽

Circular Rna ◽

Xenograft Tumor ◽

Functional Assays ◽

Xenograft Tumor Model ◽

Therapeutic Possibility ◽

Plasma Depletion ◽

Potential Therapeutic Intervention

The covalently closed circular RNA has recently been proposed as a pivotal player in tumorigenesis. In the current study, we found that circ-CDYL was notably elevated in multiple myeloma tissue and plasma samples and had good diagnostic and prognostic efficacy. Functional assays showed that circ-CDYL enhanced the viability and DNA synthesis of multiple myeloma cells and inhibited apoptosis. Mechanically, cytoplasmic circ-CDYL was co-localized with miR-1180, and circ-CDYL absorbed miR-1180 to upregulate yes-associated protein (YAP), thereby facilitating multiple myeloma progression. Importantly, we further confirmed the existence of this circ-CDYL/miR-1180/YAP regulatory axis in vivo by using the xenograft tumor model. Taken together, our data demonstrate that circ-CDYL is novel promoter of multiple myeloma, and targeting circ-CDYL and its associated network implicates the therapeutic possibility for multiple myeloma patients. Impact statement Multiple myeloma (MM) is an extremely complex and heterogeneous disease, and its pathogenesis is poorly understood. Here, we described an important MM-related circular RNA (circRNA), circ-CDYL. It was remarkably increased in both MM cells and plasma. Depletion of circ-CDYL evidently stunted MM growth. Circ-CDYL could absorb miR-1180 and alleviated the repression of miR-1180 on YAP, leading to increased YAP expression, ultimately triggering MM uncontrolled growth. Therefore, our findings advance the understanding of MM pathogenesis, and also raise the possibility of considering circ-CDYL as a potential therapeutic intervention for MM.

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Direct In Vivo Xenograft Tumor Model for Predicting Chemotherapeutic Drug Response in Cancer Patients

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.2008.200 ◽

2008 ◽

Vol 85 (2) ◽

pp. 217-221 ◽

Cited By ~ 89

Author(s):

B Rubio-Viqueira ◽

M Hidalgo

Keyword(s):

Cancer Patients ◽

Drug Response ◽

Tumor Model ◽

Chemotherapeutic Drug ◽

Xenograft Tumor ◽

Xenograft Tumor Model

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Control of optical contrast using gold nanoshells for optical coherence tomography imaging of mouse xenograft tumor model in vivo

Journal of Biomedical Optics ◽

10.1117/1.3233946 ◽

2009 ◽

Vol 14 (5) ◽

pp. 054015 ◽

Cited By ~ 38

Author(s):

James Chen Yong Kah ◽

Malini Olivo ◽

Tzu Hao Chow ◽

Kin San Song ◽

Karen Zhen Yu Koh ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Tumor Model ◽

Gold Nanoshells ◽

Xenograft Tumor ◽

Optical Contrast ◽

Mouse Xenograft ◽

Tomography Imaging ◽

Xenograft Tumor Model ◽

Optical Coherence Tomography Imaging

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Nano-Encapsulation of Plitidepsin: In Vivo Pharmacokinetics, Biodistribution, and Efficacy in a Renal Xenograft Tumor Model

Pharmaceutical Research ◽

10.1007/s11095-013-1220-3 ◽

2013 ◽

Vol 31 (4) ◽

pp. 983-991 ◽

Cited By ~ 12

Author(s):

Hugo Oliveira ◽

Julie Thevenot ◽

Elisabeth Garanger ◽

Emmanuel Ibarboure ◽

Pilar Calvo ◽

...

Keyword(s):

Tumor Model ◽

Xenograft Tumor ◽

Xenograft Tumor Model ◽

In Vivo Pharmacokinetics

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YAP Manipulates Proliferation Via PTEN/AKT/mTOR-mediated Autophagy in Lung Adenocarcinomas

10.21203/rs.3.rs-78208/v1 ◽

2020 ◽

Author(s):

Wei Xu ◽

Mingjiong Zhang ◽

Yue Li ◽

Yu Wang ◽

Kai Wang ◽

...

Keyword(s):

Hippo Pathway ◽

Tumor Model ◽

Gene Expression Omnibus ◽

Dependent Manner ◽

Autophagy Flux ◽

Xenograft Tumor Model ◽

Lung Adenocarcinomas ◽

Proliferation In Vitro

Abstract Background: Autophagy is a double-edged sword during the initiation or progression of multiple tumors. Hippo pathway core-factor YAP has been proved to be involved in autophagy processes. The present study aimed to identify the mechanism underlying modulation of YAP via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas (LUAD).Methods: Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were used to assess YAP expression in LUAD cell lines. CCK-8 assay, flow cytometry, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP manipulating autophagy in LUAD cells.Results: YAP significantly overexpressed in samples of LUAD patients and related to 5-year survival. YAP manipulates the proliferation and autophagy of A549 and H1299 LUAD cells. YAP induces activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.Conclusions: Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.

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