scholarly journals Penetration and Silencing Activity of VEGF Dicer Substrate siRNA Vectorized by Chitosan Nanoparticles in Monolayer Culture and a Solid Tumor ModelIn Vitrofor Potential Application in Tumor Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Maria Abdul Ghafoor Raja ◽  
Haliza Katas ◽  
Zariyantey Abd Hamid
Keyword(s):  
Solid Tumor ◽  
Monolayer Culture ◽  
Tumor Therapy ◽  
Chitosan Nanoparticles ◽  
Tumor Model ◽  
Tumor Growth Inhibition ◽  
Knock Down ◽  
Human Solid Tumors ◽  
Solid Tumor Model

Penetration and distribution of drug through the avascular regions of human solid tumors after extravasation are crucial concerns for antitumor efficacy. To address this issue, anin vitrosolid tumor model of multicellular layers (MCLs) of human colorectal cancer cells (DLD-1) was established. In an attempt to deliver Dicer substrate small interfering RNA (DsiRNA), chitosan (CS) nanoparticles have been developed for targeting vascular endothelial growth factor (VEGF) gene for tumor growth inhibition. The DsiRNA-CS nanoparticles prepared by ionic gelation method had provided maximal protection of DsiRNA in full human serum up to 48 h incubation. RT-PCR studies revealed significant concentration- and time-dependent knock-down ofVEGFmRNA and its product due to uniform penetration of DsiRNA-CS nanoparticles throughout MCLs. Taken together, this study also demonstrated that DsiRNA-CS nanoparticles could effectively knock downVEGFgene as therapeutic target in monolayer culture or in solid tumor model for potential treatment of human colorectal carcinoma.

Growth and Chemotherapeutic Response of Cells in a Hollow-Fiber In Vitro Solid Tumor Model

1994 ◽  
Vol 86 (24) ◽  
pp. 1846-1852 ◽  
Author(s):  
J. J. Casciari ◽  
M. G. Hollingshead ◽  
M. C. Alley ◽  
J. G. Mayo ◽  
L. Malspeis ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Hollow Fiber ◽  
Tumor Model ◽  
Chemotherapeutic Response ◽  
Solid Tumor Model

scholarly journals 1-(4-Methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one: A Diphenyl Chalcone Derivative with Potent Antitumor Activity Via Up-Regulation of p21 Gene

2021 ◽  
pp. 1-8
Author(s):  
Litty Joseph ◽  
Lakshmi PS ◽  
Litty Joseph
Keyword(s):  
Antitumor Activity ◽  
Cytotoxic Activity ◽  
Solid Tumor ◽  
Tumor Model ◽  
Pcr Analysis ◽  
Anticancer Activities ◽  
Abnormal Cells ◽  
Solid Tumor Model

Background and Aim: Cancer is a disease of complex aetiology and is characterised by uncontrolled growth of abnormal cells. It is a major worldwide health problem. Many natural and synthetic chalcone or their derivatives showed anticancer activities. The aim of the present study is to evaluate the anticancer activity of novel chalcone derivatives and also to establish possible mechanism of action. Materials and Methods: A series of chalcones 3-(3-phenoxyphenyl)-1-phenylprop-2-en-1-one (2a); 1-(4-chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2b); 1-(4-fluorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one (2c); 1-(4-Nitro-phenyl)-3-(3-phenoxy-phenyl)prop-2-en-1-one (2d); 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one(2e) were evaluated for the cytotoxic activity both in vitro and in vivo. The in vivo antitumor activity of these compounds was estimated on Daltons Ascites Lymphoma induced solid tumor model. The effect of promising compound was further analysed by flow cytometer and RT- PCR analysis. Results and Conclusion: 1-(4-methoxyphenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one and 1-(4- chlorophenyl)-3-(3-phenoxyphenyl) prop-2-en-1-one was showed in vitro cytotoxic activity, DNA damage and antiproliferative activity. DLA induced solid tumor model suggested that 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one significantly reduced the tumor volume, increase the percentage tumor inhibition and reverse the haematological parameters. Flow cytometry analysis concluded that the compound induces cell cycle arrest at G0/G1 phase due to the over expression of p21. 1-(4-methoxyphenyl)-3-(3- phenoxy phenyl) prop-2-en-1-one may be a potential agent for cancer treatment.

Baicalein exerts antitumor effect in cervical cancer

2021 ◽  
Vol 11 (8) ◽  
pp. 1347-1353
Author(s):  
Yuhui Luo ◽  
Mingyan Wang ◽  
Li Zhang ◽  
Weining Jia ◽  
Erzhe Wengu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Volume ◽  
Tumor Model ◽  
Ascites Tumor ◽  
Tumor Tissues ◽  
Solid Tumor Model

The work verified that baicalein (BCN) inhibited the appearance and progress of cervical cancer in vitro and in vivo. MTT and CCK-8 methods were used to detect the toxicity of BCN to C33A cells and the number of C33A cells, respectively. For in vivo assays, a solid tumor model of cervical cancer and ascites tumor model was successfully established. The body weight, tumor volume and weight, survival time, and ascites volume were recorded. The anti-tumor ratio and increasing rate of life span were computed. H&E staining was performed to examine the liver tissues, kidney tissues, and tumor tissues. BCN inhibits the proliferation of human cervical cancer cell line C33A and induces apoptosis. The results from in vivo assays showed that BCN suppressed tumor growth and progression with decreased tumor volume and weight in a solid tumor model. BCN significantly induced cell apoptosis in solid tumor tissues. BCN also reduced ascites volume, prolonged survival time, and increased life extension rate in the ascites tumor model. These findings indicated that BCN exerted an antitumor effect against cervical cancer both in vitro and in vivo. According to the results, BCN might act as an important antitumor agent against cervical cancer.

Penetration and efficacy of VEGF siRNA using polyelectrolyte complex micelles in a human solid tumor model in-vitro

2009 ◽  
Vol 137 (2) ◽  
pp. 130-135 ◽  
Author(s):  
Ahmed M. Al-Abd ◽  
Soo Hyeon Lee ◽  
Sun Hwa Kim ◽  
Jung-Ho Cha ◽  
Tae Gwan Park ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Polyelectrolyte Complex ◽  
Tumor Model ◽  
Human Solid Tumor ◽  
Complex Micelles ◽  
Solid Tumor Model

scholarly journals 589 Enhancement of the anti-tumor effects of CD47 blockade in solid tumors by combination with targeted radioimmunotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A619-A619
Author(s):  
Sagarika Pachhal ◽  
Emily Greer ◽  
Jesse Hwang ◽  
Qing Liang ◽  
Mary Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Cell ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Tumor Model ◽  
Blocking Antibody ◽  
First Time ◽  
Solid Tumor Model

BackgroundOne mechanism that tumors use to escape immunosurveillance is the overexpression of CD47, which inhibits the macrophage mediated phagocytosis pathway. Although blockade of the CD47-SIRPα axis is a promising approach to enhance tumor targeted phagocytosis, anti-CD47 monotherapies have not shown meaningful responses in clinical studies of solid tumors. Combination cancer therapies aim to increase the probability of response in settings of resistance by combining drugs with different mechanisms of action. Antibody radioconjugates (ARCs) specifically target and deliver therapeutic radiation directly to cancer cells. We rationalized that the immunogenic and cytotoxic properties of ARCs will upregulate calreticulin (CRT), a pro-phagocytic signal, thereby synergizing with CD47 blocking therapies to enhance phagocytosis and antitumor activity. Here for the first time, we demonstrate the combination benefit of a HER2 specific targeting ARC and a CD47 blocking antibody to enhance therapeutic efficacy in preclinical solid tumor models.MethodsThe anti-HER2 antibody trastuzumab was conjugated with p-SCN-DOTA and radiolabeled with Ac-225 or Lu-177. The biological activity of both radioconjugates was evaluated using human recombinant HER2 and receptor positive tumor cell lines. The cytotoxic effect of radioconjugates and the ability to upregulate CRT was evaluated using XTT assay and flow cytometry, respectively, in a panel of HER2 expressing cells. To evaluate the synergy of anti-HER2 ARC and CD47 antibody combination in vitro, a flow cytometry macrophage phagocytosis assay was developed. We further evaluated the antitumor synergy in vivo between anti-HER2 ARC and CD47 antibody in human HER2 positive tumor xenograft mouse model.ResultsThe anti-HER2 ARCs have similar binding properties to native antibody and demonstrate specific cytotoxicity. Importantly, we observe ARC-mediated CRT upregulation in HER2 expressing cells. Furthermore, the combination of HER2 targeting ARC and CD47 blocking antibody enhances in vitro macrophage mediated tumor cell phagocytosis compared to each agent alone. Remarkably, the in vivo anti-HER2 ARC and CD47 antibody combination shows enhanced therapeutic effect with reduced toxicity and improved survival benefit in a human preclinical solid tumor model.ConclusionsHere for the first time, we demonstrate enhanced therapeutic efficacy between an anti-HER2 ARC and CD47 blocking antibody combination in a preclinical solid tumor model. The finding suggests that ARC mediated upregulation of CRT potentiates the pro-phagocytic signal and synergizes with the anti-CD47 mode of action thereby enhancing antitumor immune response. This combination mechanism provides a very promising strategy to improve therapeutic responses in patients harboring solid tumors and warrants further preclinical evaluation.Ethics ApprovalAll animal experiments were approved by IACUC.

scholarly journals Tracing tumorigenesis in a solid tumor model at single-cell resolution

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Samantha D. Praktiknjo ◽  
Benedikt Obermayer ◽  
Qionghua Zhu ◽  
Liang Fang ◽  
Haiyue Liu ◽  
...  
Keyword(s):  
Single Cell ◽  
Solid Tumor ◽  
Tumor Model ◽  
Solid Tumor Model

31 Apoptosis and radiation clonogenic survival in a solid tumor model system expressing BCL-2

1995 ◽  
Vol 32 ◽  
pp. 156
Author(s):  
Marc S. Rudoltz ◽  
Eric J. Bernhard ◽  
Gary D. Kao ◽  
Vincent Baukanauskas ◽  
Ruth J. Muschel ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Tumor Model ◽  
Clonogenic Survival ◽  
Model System ◽  
Tumor Model System ◽  
Solid Tumor Model

scholarly journals Anticancer and Anti-Inflammatory Activities of a Standardized Dichloromethane Extract fromPiper umbellatumL. Leaves

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Leilane Hespporte Iwamoto ◽  
Débora Barbosa Vendramini-Costa ◽  
Paula Araújo Monteiro ◽  
Ana Lúcia Tasca Gois Ruiz ◽  
Ilza Maria de Oliveira Sousa ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Tumor Model ◽  
Oral Route ◽  
Paw Edema ◽  
Anti Inflammatory ◽  
Cancer And Inflammation

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research onPiper umbellatumspecies, here we describe the anticancer (in vitroantiproliferative activity andin vivoEhrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) fromP. umbellatumleaves, containing 23.9% of 4-nerolidylcatechol. SDE showedin vitroandin vivoantiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE fromPiper umbellatumleaves could involve antiproliferative and anti-inflammatory effects. These findings highlightP. umbellatumas a source of compounds against cancer and inflammation.

Anti-Tumor Activity of the Aurora a Inhibitor MLN8237 in Diffuse Large B-Cell Lymphoma Preclinical Models.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1592-1592 ◽  
Author(s):  
Jessica J Huck ◽  
Mengkun Zhang ◽  
Marc L Hyer ◽  
Mark G Manfredi
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Model ◽  
B Cell Lymphoma ◽  
Tumor Growth Inhibition ◽  
Aurora A ◽  
Hct 116 ◽  
Xenograft Models

Abstract Aurora A kinase is a serine/threonine protein kinase that is essential for normal transit of cells through mitosis. In many tumor types the Aurora A gene is amplified and/or the protein is over-expressed. The Aurora A small-molecule inhibitor MLN8237 demonstrated robust tumor growth inhibition in xenograft models of solid tumors grown subcutaneously (S.C.) in immunocompromised mice. Here we explored the antitumor activity of MLN8237 in models of diffuse large B-cell lymphoma (DLBCL) both in vitro and in vivo. In vivo three established DLBCL xenograft models (OCI-Ly7, OCI-Ly19, and WSU-DLCL2; all cells expressing luciferase) and a primary DLBCL tumor model PHTX-22-06 were tested using MLN8237 at different doses. Rituximab, an anti-CD20 monoclonal antibody that is active against CD20+ malignant B cells and is a standard of care agent was used for comparison. Using these model systems, tumor cells were injected either I.V. (to evaluate disseminated disease), or S.C. in severe combined immunodeficient mice (SCID). Animals were dosed orally for 21 days with MLN8237 (QD or BID) at various doses, or Rituximab dosed at 10mg/kg IV (once/week) and tumor growth inhibition was monitored using either bioluminescent imaging for the disseminated models or vernier calipers for the S.C. models. Tumor growth inhibition by MLN8237 was dose dependent with 20 mg/kg bid being the most efficacious dose (TGI>100% in both disseminated OCI-Ly19 and WSU models). All animals in the OCI-Ly19 disseminated model 20 mg/kg BID treatment group demonstrated regressions and remained disease free until the end of the study, day 65. In this study the Rituximab treated animals were euthanized on day 31 due to a high level of tumor burden. In the primary tumor model, PHTX-22-06, MLN8237 dosed at 20 mg/kg BID was also the most efficacious with a TGI of 95%. Moreover, tumor growth inhibition was durable as determined by prolonged tumor growth delay (>50 days). Significant efficacy was achieved in all models tested, whether grown as disseminated or subcutaneous models. A noted increase in durability of response was observed with MLN8237 treatment when compared with previous data from solid tumor models. In vitro, MLN8237 treatment increased levels of apoptosis in the OCI-Ly19 cells in comparison to the solid tumor cell line HCT-116 (colon). Greater Annexin V positive cells and greater cleaved PARP and Caspase-3 signals were detected in the MLN8237 treated OCI-Ly19 cells when compared to HCT-116 cells. The demonstration of robust and durable anti-tumor activity in preclinical models treated with MLN8237 provides the basis for its clinical evaluation as a treatment option for DLBCL. MLN8237 is currently in multiple Phase I clinical trials.

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