scholarly journals The effect of PI3K inhibitor LY294002 and gemcitabine hydrochloride combined with ionizing radiation on the formation of vasculogenic mimicry of Panc-1 cells in vitro and in vivo

Neoplasma ◽  
2016 ◽  
Vol 63 (01) ◽  
pp. 80-92 ◽  
Author(s):  
R. BAI ◽  
T. DING ◽  
J. ZHAO ◽  
S. LIU ◽  
L. ZHANG ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Vasculogenic Mimicry ◽  
Pi3k Inhibitor ◽  
Pi3k Inhibitor Ly294002 ◽  
Gemcitabine Hydrochloride

Bi2 S3 -Tween 20 Nanodots Loading PI3K Inhibitor, LY294002, for Mild Photothermal Therapy of LoVo Cells In Vitro and In Vivo

2018 ◽  
Vol 7 (22) ◽  
pp. 1800830 ◽  
Author(s):  
Li Song ◽  
Xinghua Dong ◽  
Shuang Zhu ◽  
Chunfang Zhang ◽  
Wenyan Yin ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Pi3k Inhibitor ◽  
Tween 20 ◽  
Pi3k Inhibitor Ly294002 ◽  
Lovo Cells

scholarly journals Evaluation of Otlertuzumab (TRU-016), an Anti-CD37 ADAPTIRTM Therapeutic in Preclinical Combination Studies with Kinase Inhibitors and a Next Generation Anti-CD20 Mab in Vitro and in Animal Models of Non-Hodgkin’s Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3333-3333
Author(s):  
Jane Gross
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Kinase Inhibitors ◽  
Combination Index ◽  
Pi3k Inhibitor ◽  
Next Generation ◽  
Pi3k Inhibitor Ly294002 ◽  
Anti Cd20

Abstract Background: CD37 is a 50-55 kDa heavily glycosylated member of the tetraspanin superfamily of molecules. This cell surface protein is expressed on normal and transformed B-cells, and has been implicated in diverse processes including cellular activation and proliferation, cell motility, and cell-cell adhesion. Otlertuzumab is a novel humanized anti-CD37 therapeutic, built on the ADAPTIRTM (modular protein technology) platform that has been shown to mediate caspase-independent direct killing of normal and malignant B-cells, a mechanism of action that appears to be distinct from CD20 therapies. In addition, otlertuzumab results in killing through antibody directed cellular cytotoxicity (ADCC), mediated in part by NK cells. The therapeutic potential of otlertuzumab in the treatment of chronic lymphocytic leukemia (CLL) is currently being investigated in Phase 2 clinical studies in combination with bendamustine or rituximab. Preclinical vitro and in vivocombination studies for NHL to evaluate otlertuzumab in combination with other emerging drugs including kinase inhibitors (PI3K and BTK) and the next generation anti-CD20 mAb obinituzumab are reported here. Methods: The ability of otlertuzumab to interact and increase malignant B cell killing with kinase inhibitors was investigated, including a pan PI3K inhibitor (LY294002), a PI3K delta inhibitor (CAL101(GS-1101, idelalisib)), a PI3K delta/gamma inhibitor (IPI-145, (INK1197)) and an inhibitor of BTK (PCI-32765). Combination studies were assayed in vitro using the Minos (mantle cell lymphoma), DoHH-2 (follicular lymphoma) and Ramos (Burkitt’s B cell lymphoma) cell lines. In addition, studies were performed in vitro to test the combination of otlertuzumab and obinituzumab. Individual drugs were tested alone or in combination with otlertuzumab. Combination index analyses were performed for drug combinations over the 20-90% effect levels. To determine whether in vitro synergy could be repeated in vivo, the tumor line with the best in vitro combination characteristics was utilized in xenograft tumor models and treated with otlertuzumab ± LY294002 or otlertuzumab ± PCI-32765 or otlertuzumab ± obinituzumab. Results: Combination index analyses determined that the killing effects of otlertuzumab were synergistic with the pan PI3K inhibitor LY294002, demonstrating comparable results in all three cell lines tested in vitro. The combination of otlertuzumab and the BTK inhibitor PCI-32765 demonstrated synergy in vitro with the Ramos and Minos cell lines. The PI3K delta inhibitor (idelalisib) also demonstrated synergistic activity with all three cell lines when tested in combination with otlertuzumab in vitro. Finally, combination index analyses determined that the killing effects of otlertuzumab were synergistic with the obinituzumab, demonstrating comparable results in all three cell lines tested in vitro. In vivo, the combination of otlertuzumab plus the pan PI3K inhibitor (LY294002) or otlertuzumab plus obinituzumab resulted in greater efficacy relative to each agent alone in the DoHH-2 xenograft tumor models. The combination of otlertuzumab with PCI-32765 resulted in significant delay of tumor outgrowth compared to PCI-32765 alone in the MINO xenograft model of NHL. In vivo results indicated that the in vitro synergy results were applicable to a more complex in vivodisease model. Conclusions: Otlertuzumab tested in combination with multiple kinase inhibitors or next generation anti-CD20 had increased cell killing of NHL cell lines in vitro over that observed for each agent alone. Furthermore, the combinations of otlertuzumab with either obinituzumab, LY294002 or PCI-32765 displayed greater anti-tumor activity in vivo than each of the agents alone. These results provide preclinical rationale for the potential combinations of otlertuzumab with several emerging therapeutics for the treatment of NHL and related B-cell malignancies, including CLL. Disclosures Gross: Emergent BioSolutions Inc: Employment.

scholarly journals The Synthetic Compound Norcantharidin Induced Apoptosis in Mantle Cell Lymphoma In Vivo and In Vitro through the PI3K-Akt-NF-κB Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongyan Lv ◽  
Yan Li ◽  
Hengfei Du ◽  
Jie Fang ◽  
Xiaoning Song ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Signaling Pathway ◽  
Cell Lymphoma ◽  
Pi3k Inhibitor ◽  
Pi3k Inhibitor Ly294002 ◽  
Mantle Cell ◽  
Induced Apoptosis

This study aimed to elucidate the antitumor activity of norcantharidin (NCTD) against human mantle cell lymphoma (MCL). Cell proliferation and apoptosis were examined by MTS and flow cytometry. Caspase-3, -8, and -9 activities were detected with a colorimetric caspase protease assay. Apoptotic proteins—including PARP, cyclin D1, Bcl-2 family proteins, XIAP, and cIAP I—were studied by western blot. The phosphoinositide 3 kinase (PI3K) inhibitor LY294002 was used to investigate the involvement of the PI3K/Akt signaling pathway. In vivo studies were performed using Z138 cell xenografts in nude mice. NCTD inhibited proliferation and induced apoptosis of Z138 and Mino cells, both in vitro and in vivo. PI3Kp110αand p-Akt expressions were downregulated by NCTD treatment. NCTD downregulated NF-κB activity by preventing NF-κB phosphorylation and nuclear translocation. This effect was correlated with the suppression of NF-κB-regulated gene products, such as cyclin D1, BAX, survivin, Bcl-2, XIAP, and cIAP. This phenomenon was blocked by the PI3K inhibitor LY294002. Our results demonstrated that NCTD can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the PI3K/Akt/NF-κB signaling pathway. NCTD may have therapeutic and/or adjuvant therapeutic applications in the treatment of MCL.

scholarly journals Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Mu-Su Pan ◽  
Hui Wang ◽  
Kamar Hasan Ansari ◽  
Xin-Ping Li ◽  
Wei Sun ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Gallbladder Cancer ◽  
Molecular Mechanism ◽  
Poor Prognosis ◽  
Vasculogenic Mimicry ◽  
Tube Formation ◽  
Signal Pathway ◽  
Cancer Associated Fibroblasts

Abstract Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism. Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (−) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored. Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the upregulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway. Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is overexpressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

Combretastatin A4 phosphate treatment induces vasculogenic mimicry formation of W256 breast carcinoma tumor in vitro and in vivo

Tumor Biology ◽  
2015 ◽  
Vol 36 (11) ◽  
pp. 8499-8510 ◽  
Author(s):  
Nan Yao ◽  
Ke Ren ◽  
Cuihua Jiang ◽  
Meng Gao ◽  
Dejian Huang ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Vasculogenic Mimicry ◽  
Combretastatin A4 ◽  
Phosphate Treatment ◽  
Carcinoma Tumor

Therapeutic ionizing radiation induced bone loss: a review of in vivo and in vitro findings

2018 ◽  
Vol 59 (6) ◽  
pp. 509-522 ◽  
Author(s):  
Jian Zhang ◽  
Xinyu Qiu ◽  
Kedi Xi ◽  
Wentao Hu ◽  
Hailong Pei ◽  
...  
Keyword(s):  
Bone Loss ◽  
Ionizing Radiation ◽  
Radiation Induced

scholarly journals Baicalein suppresses vasculogenic mimicry through inhibiting RhoA/ROCK expression in lung cancer A549 cell line

2020 ◽  
Vol 52 (9) ◽  
pp. 1007-1015
Author(s):  
Zhe Zhang ◽  
Li Nong ◽  
Menglei Chen ◽  
Xiaoli Gu ◽  
Weiwei Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vasculogenic Mimicry ◽  
A549 Cells ◽  
A549 Cell Line ◽  
Traditional Herbal Medicine ◽  
Underlying Mechanisms ◽  
Filament Network ◽  
Lung Cancer A549 Cell

Abstract Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.

Sign in / Sign up

Export Citation Format

Share Document