scholarly journals Newcastle Disease Virus Expressing an Angiogenic Inhibitor Exerts an Enhanced Therapeutic Efficacy in Colon Cancer Model

2021 ◽  
Author(s):  
Fanrui Meng ◽  
Yukai Cao ◽  
Han Su ◽  
Limin Tian ◽  
Jiarui Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Vascular Endothelial Cells ◽  
Vital Role ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Growth Ratio ◽  
Ideal Agent ◽  
Angiogenic Inhibitor ◽  
Vegf Trap

Abstract Numerous studies demonstrate that the NDV-mediated gene therapy is a promising new approach for treatment of cancer. VEGF-Trap plays a vital role in anti-angiogenesis. Therefore, we hypothesize that a recombinant NDV (rNDV) expressing VEGF-Trap would be an ideal agent for the colon cancer therapy. In this study, VEGF-Trap gene was incorporated into the genome of rNDV (named rNDV-VEGF-Trap). rNDV-VEGF-Trap reduced cell growth ratio by 85.37% and migration ratio by 87.9% in EA.hy926 cells. In vivo studies, treatment with rNDV-VEGF-Trap reduced tumor volume of CT26-bearing mice by more than 3 folds and tumor weight by more than 4 folds. Immunohistochemistry analysis of CD34 showed rNDV-VEGF-Trap significantly decreased the number of vascular endothelial cells in the tumor tissues of the tumor-bearing mice. Moreover, Western blot analysis demonstrated that treatment with rNDV-VEGF-Trap significantly decreased the phosphorylation levels of AKT, ERK1/2 and STAT3 and increased the expression levels of P53, BAX and cleaved caspase-3 in the tumor tissue. In addition, to evaluate the toxicity of VEGF-Trap, serum chemistries were analyzed. The results showed that rNDV-VEGF-Trap caused insignificant changes of creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST). Futhermore, administration of rNDV-VEGF-Trap did not cause the diarrhoea，decreased appetite, weight decrease and haemorrhage of the experimental mice. These data suggest that rNDV-VEGF-Trap exhibits an enhanced inhibition of CT26-bearing mice by enhancing anti-angiogenesis and apoptosis. rNDV-VEGF-Trap is a potential candidate for carcinoma therapy especially for colon cancer.

scholarly journals In vitro and in vivo studies on stilbene analogs as potential treatment agents for colon cancer

2010 ◽  
Vol 45 (9) ◽  
pp. 3702-3708 ◽  
Author(s):  
Shiby Paul ◽  
Cassia S. Mizuno ◽  
Hong Jin Lee ◽  
Xi Zheng ◽  
Sarah Chajkowisk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
In Vivo Studies ◽  
Potential Treatment ◽  
Stilbene Analogs

scholarly journals Role of estrogen receptor coregulators in endocrine resistant breast cancer

2021 ◽  
pp. 385-400
Author(s):  
Kristin A. Altwegg ◽  
Ratna K. Vadlamudi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Therapy Resistance ◽  
Vital Role ◽  
In Vivo Studies ◽  
Scaffolding Proteins ◽  
Current State ◽  
Er Alpha

Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70-80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC.

scholarly journals Preparation nanoparticles of β-cyclodextrin loaded Scutellarein anti-tumor activity research by targeting integrin αvβ3

2021 ◽  
Author(s):  
JUNDONG WANG ◽  
TIANHAO LI ◽  
CHAOCHI YUE ◽  
SEN ZHONG ◽  
XIANGDONG YANG ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Water Solubility ◽  
Integrin Αvβ3 ◽  
Human Colon ◽  
In Vivo Studies ◽  
Human Colon Cancer ◽  
Proliferation And Apoptosis

Abstract BackgroundThe problems associated with poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of Scutellarein on human colon cancer cells in vitro by using a target αvβ-3 novel Scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD).Resultsβ-CD-CL-Scu-cRGD has a diameter of 140.2nm and a zeta potential of -11.3 mV with a constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of HT29, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis.ConclusionsAlthough further in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.

scholarly journals Amorphous Calcium Magnesium Phosphate Nanocomposites with Superior Osteogenic Activity for Bone Regeneration

2021 ◽  
Author(s):  
Yingying Jiang ◽  
Shuo Tan ◽  
Jianping Hu ◽  
Xin Chen ◽  
Feng Chen ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Repair ◽  
Magnesium Phosphate ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Collagen Scaffolds ◽  
Edge Structure ◽  
X Ray ◽  
Calcium Magnesium

Abstract The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules are considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple coprecipitation strategy. The physiochemical property of ACMP/SIM were explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO43-, when it is immersed in SBF at 37 °C, and a phase transformation occured during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

scholarly journals Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential

2021 ◽  
Vol 22 (21) ◽  
pp. 12018
Author(s):  
Julia K. Bar ◽  
Anna Lis-Nawara ◽  
Piotr Grzegorz Grelewski
Keyword(s):  
Dental Pulp ◽  
Therapeutic Potential ◽  
Nerve Tissue ◽  
In Vivo Studies ◽  
Deciduous Teeth ◽  
Cartilage Defects ◽  
Potential Candidate ◽  
Paracrine Effect

The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.

scholarly journals Identification on the potential mechanism of Radix pueraria on colon cancer based on network pharmacology

2021 ◽  
Author(s):  
Yi Li ◽  
Chunli Zhang ◽  
Xiaohan Ma ◽  
Liuqing Yang ◽  
Huijun Ren
Keyword(s):  
Colon Cancer ◽  
Chinese Medicine ◽  
Target Genes ◽  
Enrichment Analysis ◽  
In Vivo Studies ◽  
Network Pharmacology ◽  
Biological Mechanism ◽  
Active Components

Abstract Radix Puerariae (RP), a dry root of the Pueraria lobata (Willd.) Ohwi, is used to treat a variety of diseases, including cancer. Several in vitro and in vivo studies have demonstrated the efficacy of RP in the treatment of colon cancer (CC). However, the biological mechanism of RP in the treatment of colon cancer remains unclear. In this study, the active component of RP and its potential molecular mechanism against CC were studied by network pharmacology and enrichment analysis. The methods adopted included screening of active ingredients of Chinese medicine, prediction of target genes of Chinese medicine and disease, construction of protein interaction network, and GO and KEGG Enrichment Analysis. Finally, the results of network pharmacology were further validated by molecular docking experiments and cell experiments. 8 active constituents and 14 potential protein targets were screened from RP, including EGFR, JAK2 and SRC. The biological mechanism of RP against CC was analyzed by studying the relationship between active components, targets, and enrichment pathway. This provides a basis for understanding the clinical application of RP in CC.

scholarly journals In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads

2018 ◽  
Vol 9 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Geet P. Asnani ◽  
Chandrakant R. Kokare
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Colon Cancer Cell ◽  
In Vivo Studies ◽  
Ht 29

AbstractThe aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.

Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies

2010 ◽  
Vol 21 (6) ◽  
pp. 538-543 ◽  
Author(s):  
Chiu-Li Yeh ◽  
Man-Hui Pai ◽  
Cheng-Chung Li ◽  
Yu-Ling Tsai ◽  
Sung-Ling Yeh
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
In Vivo Studies ◽  
Human Colon Cancer

scholarly journals Synthesis of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging

2020 ◽  
Author(s):  
Yuping Xu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Junjie Yan ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Ex Vivo ◽  
Radiochemical Yield ◽  
Immunohistochemical Analysis ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Synthesis Time ◽  
Normal Tissues

Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [ 89 Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

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