scholarly journals Assessment of the immune landscapes of advanced ovarian cancer in an optimized in vivo model

2021 ◽  
Vol 11 (10) ◽  
Author(s):  
Simone Pisano ◽  
Stefania Lenna ◽  
Gareth D. Healey ◽  
Fereshteh Izardi ◽  
Lucille Meeks ◽  
...  
2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Ying Zhang ◽  
Li Luo ◽  
Xueling Zheng ◽  
Tinghe Yu

A nude mouse received subcutaneous injection of human ovarian cancer cells HO-8910PM to form a tumor, and then the tumor fragment was surgically transplanted to the ovary of a recipient mouse to establish an orthotopic cancer model. Tumors occurred in 100% of animals. A mouse displayed an ovarian mass, ascites, intraperitoneal spread, and lung metastasis at natural death. The mean survival time was34.1±17.2days, with median survival time of 28.5 days. The findings indicated that the present mouse model can reflect the biological behavior of advanced human ovarian cancers. This in vivo model can be used to explore therapeutic means against chemoresistance and metastasis, and an effective treatment would prolong the survival time.


2012 ◽  
Vol 3 (3) ◽  
pp. 530-534 ◽  
Author(s):  
DANIEL T. REIN ◽  
ANNE KATHRIN VOLKMER ◽  
JENS VOLKMER ◽  
INES M. BEYER ◽  
WOLFGANG JANNI ◽  
...  

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Luiz Gustavo A Chuffa ◽  
Beatriz A Fioruci-Fontanelli ◽  
Leonardo O Mendes ◽  
Fábio R Ferreira Seiva ◽  
Marcelo Martinez ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 442 ◽  
Author(s):  
Concetta D’Ambrosio ◽  
Jessica Erriquez ◽  
Maddalena Arigoni ◽  
Sonia Capellero ◽  
Gloria Mittica ◽  
...  

Identifying cancer drivers and actionable mutations is critical for precision oncology. In epithelial ovarian cancer (EOC) the majority of mutations lack biological or clinical validation. We fully characterized 43 lines of Patient-Derived Xenografts (PDXs) and performed copy number analysis and whole exome sequencing of 12 lines derived from naïve, high grade EOCs. Pyrosequencing allowed quantifying mutations in the source tumours. Drug response was assayed on PDX Derived Tumour Cells (PDTCs) and in vivo on PDXs. We identified a PIK3R1W624R variant in PDXs from a high grade serous EOC. Allele frequencies of PIK3R1W624R in all the passaged PDXs and in samples of the source tumour suggested that it was truncal and thus possibly a driver mutation. After inconclusive results in silico analyses, PDTCs and PDXs allowed the showing actionability of PIK3R1W624R and addiction of PIK3R1W624R carrying cells to inhibitors of the PI3K/AKT/mTOR pathway. It is noteworthy that PIK3R1 encodes the p85α regulatory subunit of PI3K, that is very rarely mutated in EOC. The PIK3R1W624R mutation is located in the cSH2 domain of the p85α that has never been involved in oncogenesis. These data show that patient-derived models are irreplaceable in their role of unveiling unpredicted driver and actionable variants in advanced ovarian cancer.


2021 ◽  
Author(s):  
◽  
Simone Pisano

Treatment of ovarian cancer (OC) continues to present clinical challenges. It remains difficult to diagnose early stage disease, and because of this generally presents as advanced stage, with limited therapeutic options and often the development of resistance to chemotherapy. Furthermore, OC is considered as an immunologically “cold” tumour based on the poor response to immunotherapies. This lack of response to immunotherapy remains poorly understood, hence better models are needed in order to elucidate the fundamental mechanisms behind tumour immunosuppression, and for new and innovative therapeutic strategies to be tested. Exosomes have recently emerged as crucial players in the cell-cell communication and content exchange within the tumour microenvironment and have also been investigated for their capacity to act as cancer therapeutics or to be re-engineered to increase their performances and effects. In this work, two main research areas were explored. The first one focused on advanced ovarian cancer modelling. Indeed, the in vitro formation of multicellular spheroids that included a mixture of cancer cells and different macrophage phenotypes was optimised, and their characteristics explored. Additionally, an in vivo advanced OC model was created from immunocompetent mice and the tumours were characterised for their immune infiltrates presence. The ascitic fluid that arose from the tumour-bearing mice was also comprehensively analysed for its immune cells content by mass cytometry for the first time in an ovarian cancer setting. The second part of the work involved the exploration of two innovative OC therapeutics. Dendritic-cell (DC) derived exosomes were obtained from tumour antigen-pulsed DCs and tested for their efficacy both in vitro and in vivo. A semi-synthetic exosomes approach was also tested by forcing monocytic cells through pores of different sizes and obtaining Immune (Cell) Derived Exosome Mimetics (IDEM). IDEM were characterised and tested in vitro on both 2D and spheroid systems.


2021 ◽  
Author(s):  
Xiao Li ◽  
Caixia Wang ◽  
Shuang Wang ◽  
Yuexin Hu ◽  
Shan Jin ◽  
...  

Abstract Background: Malignant tumours of the female reproductive system threaten the lives and health of women worldwide, with ovarian cancer having the highest mortality rate among all malignant tumours. Based on previous work, this study analysed the expression and role of YWHAE in ovarian epithelial tumours. Methods: The interaction between YWHAE and HE4 was evaluated by immunoprecipitation, western blot analysis, and cellular immunofluorescence. Immunohistochemistry was used to address the relationship between YWHAE expression and clinicopathological parameters and patient prognosis. Changes in cell invasion, epithelial–mesenchymal transition, migration, proliferation, cell cycle, and apoptosis before and after differential expression of YWHAE were also explored in ovarian cancer cell lines and in vivo experiments. Results: YWHAE was found to directly interact with HE4, and its expression was positively correlated with HE4 expression. Moreover, YWHAE higher levels were associated with advanced ovarian cancer cases and with poorer patient outcome. YWHAE was found to enhance the invasion, migration, proliferation, and inhibition of apoptosis of ovarian cancer cells. These biological effects were found to be meditated by the activity of the PI3K/AKT and MAPK signalling pathways.Conclusions: Altogether, this study demonstrates that YWHAE is significantly increased in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream signals may represent new therapeutic targets to tackle ovarian cancer.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Binh Thanh Vu ◽  
Sophia Allaf Shahin ◽  
Jonas Croissant ◽  
Yevhen Fatieiev ◽  
Kotaro Matsumoto ◽  
...  

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