Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model

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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Berberine inhibits the proliferation of pancreatic cancer targeting pancreatic cancer stem cells

10.21203/rs.3.rs-282783/v1 ◽

2021 ◽

Author(s):

Mengmeng Liu ◽

Yue Pan ◽

Xufeng Tao ◽

Ning Li ◽

Kun Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Effectiveness ◽

The Novel ◽

Migration Assay ◽

Medicinal Value ◽

Anti Cancer ◽

Cancer Agent ◽

Pancreatic Cancer Stem Cells

Abstract BackgroundPDAC is universally acknowledged to be one of the highest mortality rate of cancer-related deaths. PCSCs, regulated by EMT, could promote the proliferation of PDAC. Berberine with high medicinal value has usually been used as an anti-cancer agent. Hence the purpose of this study is to investigate the anti-cancer effect of berberine in PDAC. MethodsMTT assay was used to verify berberine inhibiting the proliferation of PDAC. Immunofluorescence staining, stem cell sphere, wound healing and transwell migration assay were demonstrated the anti-proliferation and anti-stemness of PCSCs in vitro . PANC-02 cells were injected in C57BL/6 mice to establish the orthotopic pancreatic-cancer model in vivo . H&E and Ki67 immunohistogical staining assay were used to evaluated the effect of berberine in PDAC in vivo. q-PCR and Western blot methods were applied to detect the expression of EMT procedure.ResultsIn this study, berberine has selective anti-cancer effect in PDAC in vitro . Moreover, berberine suppressed the proliferation and stemness of PCSCs in PDAC. In vivo , berberine reduced the tumor size and decreased the expression of Ki67 in orthotopic pancreatic-cancer pancreases. In addition, berberine inhibit the EMT signaling pathway both in vitro and in vivo . ConclusionsOur study indicates that berberine inhibit the proliferation of PDAC in vivo and vitro . The mechanism of anti-cancer effect on berberine may suppress the PCSCs through inhibiting EMT procedure. Therefore, berberine may be the novel antineoplastic drug with clinical effectiveness in PDAC. Keywords: Berberine, PDAC, PCSCs, EMT, berberine

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Abstract 4811: Functional pathway analysis in pancreatic cancer cells treated with a novel anti-cancer agent, copper-tolfenamic acid

10.1158/1538-7445.am2019-4811 ◽

2019 ◽

Author(s):

Myrna Hurtado ◽

Laszlo Prokai ◽

Umesh T. Sankpal ◽

Blair Levesque ◽

Rajasekhar Maram ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Pathway Analysis ◽

Tolfenamic Acid ◽

Pancreatic Cancer Cells ◽

Anti Cancer ◽

Cancer Agent ◽

Functional Pathway

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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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PROBING CLINICAL RELEVANCE: ESTABLISHING THE EFFICACY OF C. NOVYI AGAINST A PANEL OF 2D CULTURED PANCREATIC CANCER CELLS

Biomedical Sciences Instrumentation ◽

10.34107/yhpn9422.0492 ◽

2021 ◽

Vol 57 (2) ◽

pp. 92-99

Author(s):

K.M. Dailey ◽

◽

R.I. Jacobson ◽

J. Kim ◽

S. Mallik ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Microenvironment ◽

Survival Rates ◽

Tumor Model ◽

Design Decision ◽

Unique Challenge ◽

Pancreatic Cancer Cells ◽

Anti Cancer ◽

Type C ◽

The Impact

Pancreatic cancer presents a unique challenge for the development of effective oncotherapies. The tumor microenvironment (TME) of this type of tumor typically contains a dense desmoplastic barrier composed of aberrant extracellular matrix proteins, as well as an acidic, hypoxic and necrotic core. Additionally, the immune system surrounding this type of tumor has often been suppressed by the TME. Hence, choosing the correct model of the tumor microenvironment within which to test a potential anti-cancer therapy is a critical experimental design decision. While the typical solid tumor contains a complex microenvironment including both phenotypic and genotypic heterogeneity, the methods used to model this disease state often do not reflect this complexity. This simplistic approach may have contributed to stagnant five-year survival rates experienced over the past four decades. Oncolytic bacteria, a class of bacteria with the innate ability to seek and destroy solid tumors has been revived from historical anecdotes in an attempt to overcome these challenges. Regardless of the promise of oncolytic bacteria, accurate assessment of their potential requires choosing the proper tumor model. This study explores the impact of cancer cell lines co-cultured with Wild-Type C. novyi to establish the efficacy of this oncolytic bacteria in a monolayer culture.

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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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