scholarly journals Inhibition of c‐MET increases the antitumour activity of PARP inhibitors in gastric cancer models

2020 ◽  
Vol 24 (18) ◽  
pp. 10420-10431 ◽  
Author(s):  
Evangelos Koustas ◽  
Michalis V. Karamouzis ◽  
Panagiotis Sarantis ◽  
Dimitrios Schizas ◽  
Athanasios G. Papavassiliou
Keyword(s):  
Gastric Cancer ◽  
Antitumour Activity ◽  
Parp Inhibitors ◽  
Cancer Models

scholarly journals The antitumour activity of 2‐(4‐amino‐3‐methylphenyl)‐5‐fluorobenzothiazole in human gastric cancer models is mediated by AhR signalling

2019 ◽  
Vol 24 (2) ◽  
pp. 1750-1759
Author(s):  
Yuling Wang ◽  
Ying Liu ◽  
Tao Tang ◽  
Ying Luo ◽  
Malcolm F. G. Stevens ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumour Activity ◽  
Human Gastric Cancer ◽  
Cancer Models

scholarly journals Development of a Novel Orthotopic Gastric Cancer Mouse Model

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Wonyoung Kang ◽  
Leigh Maher ◽  
Michael Michaud ◽  
Seong-Woo Bae ◽  
Seongyeong Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Models ◽  
Cancer Metastasis ◽  
Soft Tissues ◽  
Tumor Formation ◽  
Cancer Model ◽  
Orthotopic Model ◽  
Cancer Models ◽  
Organotropic Metastasis ◽  
Nsg Mouse

Abstract Background Gastric cancer metastasis is a highly fatal disease with a five-year survival rate of less than 5%. One major obstacle in studying gastric cancer metastasis is the lack of faithful models available. The cancer xenograft mouse models are widely used to elucidate the mechanisms of cancer development and progression. Current procedures for creating cancer xenografts include both heterotopic (i.e., subcutaneous) and orthotopic transplantation methods. Compared to the heterotopic model, the orthotopic model has been shown to be the more clinically relevant design as it enables the development of cancer metastasis. Although there are several methods in use to develop the orthotopic gastric cancer model, there is not a model which uses various types of tumor materials, such as soft tissues, semi-liquid tissues, or culture derivatives, due to the technical challenges. Thus, developing the applicable orthotopic model which can utilize various tumor materials is essential. Results To overcome the known limitations of the current orthotopic gastric cancer models, such as exposure of tumor fragments to the neighboring organs or only using firm tissues for the orthotopic implantation, we have developed a new method allowing for the complete insertion of soft tissue fragments or homogeneously minced tissues into the stomach submucosa layer of the immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mouse. With this completely-closed transplantation method, tumors with various types of tissue may be used to establish orthotopic gastric cancer models without the risks of exposure to nearby organs or cell leakage. This surgical procedure was highly reproducible in generating forty-eight mouse models with a surgery success rate of 96% and tumor formation of 93%. Among four orthotopic patient-derived xenograft (PDX) models that we generated in this study, we verified that the occurrence of organotropic metastasis in either the liver or peritoneal cavity was the same as that of the donor patients. Conclusion Here we describe a new protocol, step by step, for the establishment of orthotopic xenograft of gastric cancer. This novel technique will be able to increase the use of orthotopic models in broader applications for not only gastric cancer research but also any research related to the stomach microenvironment.

scholarly journals The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin

2022 ◽  
Author(s):  
Dragomir B. Krastev ◽  
Shudong Li ◽  
Yilun Sun ◽  
Andrew J. Wicks ◽  
Gwendoline Hoslett ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Homologous Recombination ◽  
Ubiquitin Ligase ◽  
Antitumour Activity ◽  
Parp Inhibitor ◽  
Bound State ◽  
Parp Inhibitors ◽  
Tumour Cells ◽  
Wild Type ◽  
Endogenous Proteins

AbstractPoly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using wild-type and a trapping-deficient PARP1 mutant combined with rapid immunoprecipitation mass spectrometry of endogenous proteins and Apex2 proximity labelling, we delineated mass spectrometry-based interactomes of trapped and non-trapped PARP1. These analyses identified an interaction between trapped PARP1 and the ubiquitin-regulated p97 ATPase/segregase. We found that following trapping, PARP1 is SUMOylated by PIAS4 and subsequently ubiquitylated by the SUMO-targeted E3 ubiquitin ligase RNF4, events that promote recruitment of p97 and removal of trapped PARP1 from chromatin. Small-molecule p97-complex inhibitors, including a metabolite of the clinically used drug disulfiram (CuET), prolonged PARP1 trapping and enhanced PARP inhibitor-induced cytotoxicity in homologous recombination-defective tumour cells and patient-derived tumour organoids. Together, these results suggest that p97 ATPase plays a key role in the processing of trapped PARP1 and the response of tumour cells to PARP inhibitors.

Antitumour activity of coumarin in prostate and mammary cancer models

1994 ◽  
Vol 120 (S1) ◽  
pp. S14-S16 ◽  
Author(s):  
E. von Angerer ◽  
M. Kager ◽  
A. Maucher
Keyword(s):  
Mammary Cancer ◽  
Antitumour Activity ◽  
Cancer Models

scholarly journals Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Joo Young Jung ◽  
Min-Hee Ryu ◽  
Baek-Yeol Ryoo ◽  
Boram Han ◽  
Ji Woong Cho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Antitumour Activity ◽  
Metastatic Gastric Cancer ◽  
Second Line ◽  
First Line ◽  
Previously Treated ◽  
Grade 3 ◽  
Gastric Cancer Patients

Background.This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS).Patients and Methods.We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011.Results.A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%).Conclusion.FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.

Abstract 2208: Targeted inhibition of FGF/PDGF/VEGF signaling enhances nanoparticle taxane response in preclinical gastric cancer models

2019 ◽  
Author(s):  
Niranjan Awasthi ◽  
Kate Crawford ◽  
Erin Bontrager ◽  
Sazzad Hassan ◽  
Urs von Holzen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Vegf Signaling ◽  
Cancer Models ◽  
Targeted Inhibition

Abstract 2208: Targeted inhibition of FGF/PDGF/VEGF signaling enhances nanoparticle taxane response in preclinical gastric cancer models

2019 ◽  
Author(s):  
Niranjan Awasthi ◽  
Kate Crawford ◽  
Erin Bontrager ◽  
Sazzad Hassan ◽  
Urs von Holzen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Vegf Signaling ◽  
Cancer Models ◽  
Targeted Inhibition
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