Development of a Lung Cancer Model in Wistar Rat and In Silico Screening of its Biomarkers.

2020 ◽  
Vol 16 ◽  
Author(s):  
Nisat Alam ◽  
Hasina Najnin ◽  
Maidul Islam ◽  
Saleem Iqbal ◽  
Rana Zaidi
Keyword(s):  
Lung Cancer ◽  
In Silico ◽  
Wistar Rats ◽  
Molecular Targets ◽  
Total Binding Energy ◽  
Cancer Model ◽  
Lung Cancer Model ◽  
Male Wistar Rats ◽  
P38 Mapks

Background: Cancer is caused by three factors: Nutrition, inflammation and cigarette smoke. This study in rat experimental models would enable us to understand the mechanism of lung cancer caused by NNK to which humans are continuously exposed, help us understand possible molecular targets, design drugs for humans against lung cancer. Aim: A lung cancer model was developed by administering tobacco specific carcinogen: NNK [4-methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male wistar rats in 24 weeks. Further, In silico approach was followed to screen the molecular targets. Methods: A method was established in which subcutaneous and intraperitoneal injections of NNK were administered to male wistar rats simultaneously. For authentication of lung cancer in vivo we performed molecular docking simulations with protein biomarkers:Cox-2, p53, p38 MAPKs and EGFR using Hex-Discovery Studio, Schrödinger-maestro software. Results: Lung morphology and histopathology indicated the initiation of bronchiolar epithelial hyperplasia, squamous dysplasia beginning in cancer 1 group after 16 weeks NNK exposure. 66.66% incidence of squamous cell carcinoma (SCC), 33.3% incidence of adenocarcinoma in cancer 2 group after being exposed to NNK. Results indicated that the SCC and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and 33.33% to 42.58% in cancer 3 groups respectively. Docking results indicate the total binding energy and glide energy of Cox-2, p53, p38 MAPKs, EGFR : 38.14, -211.58, -181.58, - 213.05 Kcal/mol and -39.25, -32.16,-36.49, -40.19 Kcal/mol, respectively. Conclusion: Pulmonary adenocarcinoma developed in 24 weeks, in silico experiments confirm EGFR to be the most potential target for NNK induced lung Cancer.

scholarly journals Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model

2013 ◽  
Vol 8 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Anna T. Stratmann ◽  
David Fecher ◽  
Gaby Wangorsch ◽  
Claudia Göttlich ◽  
Thorsten Walles ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Biological Tissue ◽  
In Silico ◽  
Cancer Model ◽  
Model Based ◽  
In Silico Model ◽  
Lung Cancer Model ◽  
Tissue Matrix

Anti-lymphangiogenesis effects of a specific anti-interleukin 7 receptor antibody in lung cancer model in vivo

2013 ◽  
Vol 54 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Ming Jian ◽  
Zhang Qingfu ◽  
Jiang Yanduo ◽  
Jiang Guocheng ◽  
Qiu Xueshan
Keyword(s):  
Lung Cancer ◽  
Cancer Model ◽  
Receptor Antibody ◽  
Interleukin 7 ◽  
Lung Cancer Model

scholarly journals Antitumor immune activity by chemokine CX3CL1 in an orthotopic implantation of lung cancer model in vivo

2012 ◽  
Vol 1 (1) ◽  
pp. 35-40 ◽  
Author(s):  
JI-YE KEE ◽  
YOSHIHISA ARITA ◽  
KANNA SHINOHARA ◽  
YASUKATA OHASHI ◽  
HIROAKI SAKURAI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Model ◽  
Orthotopic Implantation ◽  
Immune Activity ◽  
Lung Cancer Model

In vivo cryochemotherapy of a human lung cancer model

Cryobiology ◽  
2005 ◽  
Vol 51 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Valérie Forest ◽  
Michel Peoc’h ◽  
Claude Ardiet ◽  
Lydia Campos ◽  
Denis Guyotat ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Cancer Model ◽  
Lung Cancer Model

Bevacizumab combined with apatinib enhances antitumor and anti-angiogenesis effects in a lung cancer model in vitro and in vivo

2020 ◽  
Vol 28 (9) ◽  
pp. 961-969 ◽  
Author(s):  
Mingting Wang ◽  
Qin Zeng ◽  
Yuan Li ◽  
Saber Imani ◽  
Danna Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Model ◽  
Lung Cancer Model

scholarly journals The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer

2019 ◽  
Vol 121 (8) ◽  
pp. 647-658
Author(s):  
Liesa-Marie Schreiber ◽  
Carles Urbiola ◽  
Krishna Das ◽  
Bart Spiesschaert ◽  
Janine Kimpel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adaptive Immune Response ◽  
Mouse Lung ◽  
Therapeutic Effects ◽  
Cancer Model ◽  
Adaptive Immune ◽  
Syngeneic Mouse ◽  
Tumour Spread ◽  
Lung Cancer Model

Abstract Background Oncolytic virotherapy is thought to result in direct virus-induced lytic tumour killing and simultaneous activation of innate and tumour-specific adaptive immune responses. Using a chimeric vesicular stomatitis virus variant VSV-GP, we addressed the direct oncolytic effects and the role of anti-tumour immune induction in the syngeneic mouse lung cancer model LLC1. Methods To study a tumour system with limited antiviral effects, we generated interferon receptor-deficient cells (LLC1-IFNAR1−/−). Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging (BLI), immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring® assays. Results Interferon insensitivity correlated with VSV-GP replication and therapeutic outcome. BLI revealed tumour-to-tumour spread of viral progeny in bilateral tumours. Histological and gene expression analysis confirmed widespread and rapid infection and cell killing within the tumour with activation of innate and adaptive immune-response markers. However, treatment outcome was increased in the absence of CD8+ T cells and surviving mice showed little protection from tumour re-challenge, indicating limited therapeutic contribution by the activated immune system. Conclusion These studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.

scholarly journals Effects of systemic glycine on accumbal glycine and dopamine levels and ethanol intake in male Wistar rats

2020 ◽  
Author(s):  
Yasmin Olsson ◽  
Helga Höifödt Lidö ◽  
Klara Danielsson ◽  
Mia Ericson ◽  
Bo Söderpalm
Keyword(s):  
Wistar Rats ◽  
In Vivo Microdialysis ◽  
Ethanol Intake ◽  
Water Model ◽  
Glycine Transporter 1 ◽  
Improved Outcomes ◽  
Male Wistar Rats ◽  
Treatment Principle ◽  
Reward Pathway

AbstractApproved medications for alcohol use disorder (AUD) display modest effect sizes. Pharmacotherapy aimed at the mechanism(s) by which ethanol activates the dopamine reward pathway may offer improved outcomes. Basal and ethanol-induced accumbal dopamine release in the rat involve glycine receptors (GlyR) in the nucleus accumbens (nAc). Glycine transporter 1 (GlyT-1) inhibitors, which raise extracellular glycine levels, have repeatedly been shown to decrease ethanol intake in the rat. To further explore the rational for elevating glycine levels in the treatment of AUD, this study examined accumbal extracellular glycine and dopamine levels and voluntary ethanol intake and preference in the rat, after systemic treatment with glycine. The effects of three different doses of glycine i.p. on accumbal glycine and dopamine levels were examined using in vivo microdialysis in Wistar rats. In addition, the effects of the intermediate dose of glycine on voluntary ethanol intake and preference were examined in a limited access two-bottle ethanol/water model in the rat. Systemic glycine treatment increased accumbal glycine levels in a dose-related manner, whereas accumbal dopamine levels were elevated in a subpopulation of animals, defined as dopamine responders. Ethanol intake and preference decreased after systemic glycine treatment. These results give further support to the concept of elevating central glycine levels to reduce ethanol intake and indicate that targeting the glycinergic system may represent a pharmacologic treatment principle for AUD.

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