China
Africa
Explore chapters and articles related to this topic
Medicolegal aspects of death
Published in Jason Payne-James, Richard Jones, Simpson's Forensic Medicine, 2019
Jason Payne-James, Richard Jones
Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. Advances in xenotransplantation have the potential to resolve the issue of organ shortages. Organs or tissue such as heart valves, corneas, hearts and kidneys have been explored for potential as xenografts. However, such procedures may meet with a degree of concern from the public. Grafting of animal tissue into humans has always seemed tempting and clinical trials have been performed with some success. But there is, for example, considerable difficulty with cross-matching the tissues and considerable concern about the possibility of transfer of animal viruses to an immunocompromised human host. Strains of donor animals, usually pigs, are being bred in clinically clean conditions to prevent viral contamination, but there is still no guarantee of a close or ideal tissue match. There has also been an increasing interest in the development of patient-derived xenograft (PDX) models where human tumours are xenotransplanted into immunocompromised mice and such models act as translational tools in preclinical studies of cancer treatments. It is essential that clear protocols are in place for the study of the many aspects of xenotransplantation and for the introduction of such xenografts into the clinical setting. Such protocols must take into account the variable religious and cultural sensitivities which will influence individuals’ perception of such practices.
Precision medicine in oncology: An overview
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Fazilet Yılmaz, Sultan Ciftci Yılmaz, Esra Gunduz, Mehmet Gunduz
A xenograft is the transplant of one tissue to another species. Patient-derived xenograft (PDX) is transplanting cancer tissue of one individual to another species and aims to investigate the molecular characteristics, drug response, and the aggressiveness of the tumor formation. The most common application of PDX is transplanting the cancer tissue from a patient to a nude mouse with a suppressed immune system and obtaining information about histology, genomic structure, cellular heterogeneity, and drug responsiveness of the tumor. A treatment approach can be tested on this mouse model and the potential outcome of the treatment can be anticipated. It is an important development regarding personalized medicine for being an in vivo study at the single-patient level (Cho et al., 2016).
Mouse Models in Personalized Cancer Medicine
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
M.E. Beaulieu, T. Jauset, D. Massó-Vallés, L. Soucek, J.R. Whitfield
The obvious genetic and phenotypic gap between murine and human biological systems could limit the fidelity of GEMMs to recapitulate entirely the human disease. In an attempt to overcome this limitation and in the hope of informing better treatment decisions for individual patients, a different approach has been developed: patient-derived xenograft (PDX) mouse models (also termed patient-derived tumor xenografts or patient-derived tissue xenografts). In this approach, a small portion of a patient’s tumor is engrafted directly in an immunocompromised mouse. These PDX models, in addition to enabling the testing of therapies on primary human cancer cells in a more physiological, in vivo environment, hold the promise of facilitating the establishment of a personalized therapeutic regimen that would be designed according to the patient’s genomic and histologic profile and preclinically validated in the PDX (also called an “avatar” in this particular context). Using this strategy could unravel possible resistance mechanisms of the patient’s tumor and thus indicate novel targeted combinations to overcome them, and hopefully reduce the toxicity and cost associated with current non-targeted and potentially inefficient therapies.
Oncolytic adenovirus with MUC16-BiTE shows enhanced antitumor immune response by reversing the tumor microenvironment in PDX model of ovarian cancer
Published in OncoImmunology, 2022
Qiuman Wang, Xinyue Ma, Huan Wu, Chen Zhao, Jingying Chen, Rongrong Li, Shi Yan, Yingwei Li, Qing Zhang, Kun Song, Cunzhong Yuan, Beihua Kong
Four- to six-week-old female NCG (NOD-Prkdcem26Cd52IL2rgem26Cd22/Gpt) mice were purchased from the Nanjing Biomedical Research Institute of the Nanjing University (Nanjing, China). All the NCG mice were housed in specific-pathogen-free environments. 1 × 107 HEY-MUC16 cells were injected subcutaneously into the lower dorsal flank or axilla of NCG mice to establish the cell-derived xenograft (CDX) model. The establishment of the patient-derived xenograft (PDX) model was as previously described.27 Passage 2 (P2) were harvested, washed with PBS solution, homogenized, suspended in an isometric PBS solution, and mixed with Matrigel Matrix (Corning). The homogenate was injected subcutaneously into the lower dorsal flank or axilla of NCG mice. After 1 week, mice were randomized into six (CDX) or five (PDX) groups (n = 5 each) and were treated with a multi-center intratumoral injection of 5 × 109 PFU of the indicated viruses or PBS on days 0 and 3. One day after each round of virus injection, PBS or 1 × 107 preactivated T cells (activated by CD3/CD28-activating Dynabeads for 48 hours) were administered to mice by intravenous injection. In both models, tumor mass and volume were measured every 2–3 days. Tumor volume was calculated as V (mm3) = W2 × L/2, where W and L are the width and the length of the tumor, respectively. Finally, the tumors were collected, photographed, weighed, and sectioned.
Acute radiation syndrome drug discovery using organ-on-chip platforms
Published in Expert Opinion on Drug Discovery, 2022
Vijay K. Singh, Thomas M. Seed
Organoids are an emerging technology in drug discovery that serve to bridge monolayer cell culture and animal research, and are valuable in vitro cell systems for biomedical use for tissue homeostasis, injury, and disease modeling, drug testing, and regenerative medicine [31]. The 3D tissue constructs appear similar to natural tissue architecture in vivo and composite cellular subtypes, thus mimicking major features of native human tissues and organ systems of experimental animals [32,33]. In many respects, this is a more realistic and cost-effective in vitro model than patient-derived xenograft models in mice. Though organoids can be derived from cell lines, these are generated with embryonic stem cells, iPSC, or with ex vivo propagation of patient cells [34]. With time, organoids generated from iPSC cells are being utilized increasingly for both drug discovery and precision medicine [35]. However, there are also challenges associated with this new technology such as production-complexities, long growth times, and difficulty in producing enough reproducible organoids needed for drug discovery.
Characterization of sphere cells derived from a patient-derived xenograft model of lung adenocarcinoma treated with ionizing radiation
Published in International Journal of Radiation Biology, 2020
Jinhyang Choi, Eun Jung Ko, Eun Jin Ju, Seok Soon Park, Jin Park, Seol Hwa Shin, Se Jin Jang, Jung Shin Lee, Si Yeol Song, Seong-Yun Jeong, Eun Kyung Choi
Patient-derived xenograft (PDX) models are a popular and valuable tool for preclinical evaluation of novel therapeutic strategies against cancer (Moro et al. 2012; Siolas and Hannon 2013). PDXs faithfully recapitulate the patient’s original tumor with respect to immunohistochemical markers and genetic alterations as well as response to common therapeutics (Merk et al. 2009). They provide the original tumor heterogenicity, thereby allowing studies of specific cellular subpopulations and their modulation after drug or radiation treatment (Merk et al. 2009). PDXs have been also used for various cancers as a tool for studying CSCs. For example, pancreatic PDXs after chemotherapeutic treatment showed increased ALDH- and CD24-positive pancreatic cancer stem-like cells, and targeting these cells increased the efficacy of conventional treatment (Merk et al. 2009). Well-established lung cancer PDXs have been reported in many studies (Merk et al. 2009, Lee et al. 2015, Valtorta et al. 2017).