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Ursolic Acid: A Pentacyclic Triterpene from Plants in Nanomedicine
Published in Mahfoozur Rahman, Sarwar Beg, Mazin A. Zamzami, Hani Choudhry, Aftab Ahmad, Khalid S. Alharbi, Biomarkers as Targeted Herbal Drug Discovery, 2022
Monalisha Sen Gupta, Md. Adil Shaharyar, Mahfoozur Rahman, Kumar Anand, Imran Kazmi, Muhammad Afzal, Sanmoy Karmakar
Trauma, infectious, tumor resection, and other diseases cause bone defects. These are the most challenging factors in orthopedics (Tansik et al., 2016; Xie et al., 2017; Nabiyouni et al., 2018). The bone defects make bring unhappiness and economic burden to the patient. Over the past several decades, a number of bone grafts have been used in the sector of bone tissue regeneration like autografts, allografts, and xenografts, which can significantly make a decent result for the patients. An autologous graft is believed as a gold standard (Kim et al., 2017), but it has some negative actions such as donor-site morbidity, lack of availability (Lin et al., 2017). Allografts and xenografts have also their disadvantages including disease transmission and immunogenicity (Duan et al., 2017; Chen et al., 2017). Therefore, it is crucial to originate novel bone
The Evolution of Anticancer Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the last decade, Patient-Derived Xenografts (PDX) models have been developed whereby tissue or cells from an individual patient’s tumor are implanted into an immunodeficient or humanized mouse (Figure 2.8A). This model has advantages over the use of established cancer cell lines (i.e., the Human Tumor Xenograft model) in that it is based on tumor cells directly removed from the patient rather than from cells growing in culture and derived from unknown patients. This is an important distinction, as the cell culturing process includes enzymatic processes and centrifugation, and cells that are better adapted to survive in culture are selected. In particular, tumor-resident cells and proteins that interact with and support cancer cells are eliminated, and the culture becomes phenotypically homogeneous. When implanted into immunodeficient mice, cell lines do not easily develop tumors and the result of any successfully grown tumor is a genetically divergent tumor unlike the one derived from a heterogeneous patient tumor. Researchers are beginning to attribute the reason as to why only 5% of anticancer agents are approved by the FDA after preclinical testing to the lack of tumor heterogeneity and the absence of the human stromal microenvironment. Furthermore, standard cell line-xenografts are often unproductive of drug response in primary tumors because cell lines do not follow the normal pathways of drug resistance or experience the effects of the microenvironment of in situ human primary tumors.
Tissue Grafting Techniques
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Skin grafts have been used to achieve successful repigmentation in vitiligo patients. Traditional types of autografts include full-thickness and split-thickness skin grafts. Some disadvantages of autografts include the need for a surgical procedure with anesthesia, creation of a second wound at the donor site, difficulty in obtaining uniform graft thickness, pain, and challenges with graft take and graft rejection. Allografts and xenografts address some of these disadvantages. However, chances of graft rejection are greater with allografts and xenografts than autografts. Some of these treatment modalities are painful procedures, require long recovery times for the donor site, and may increase operating room costs and potential donor site complications, such as infection. The rates of donor site complications vary, depending on donor site location, comorbidities of the patient, and other risk factors, and can be as high as 28% [1,2].
10th antibody industrial symposium: new developments in antibody and adoptive cell therapies
Published in mAbs, 2023
Ana Antunes, Luis Alvarez-Vallina, Federico Bertoglio, Nicolas Bouquin, Stéphanie Cornen, Francis Duffieux, Pierre Ferré, Raphaëlle Gillet, Christian Jorgensen, Mark B Leick, Bernard Maillère, Hélène Negre, Mireia Pelegrin, Nicolas Poirier, Dietmar Reusch, Bruno Robert, Guy Serre, Alain Vicari, Martin Villalba, Christoph Volpers, Gavin Vuddamalay, Hervé Watier, Thierry Wurch, Lennart Zabeau, Stefan Zielonka, Baolin Zhang, Alain Beck, Pierre Martineau
Diogo Rodrigues Ferreirinha and Ed McGowan (Charles River, UK) described an integrated pipeline to develop antibodies and other molecules (bispecific antibodies, ADC, CAR) and bring them into the clinic with the best chances of success. First, they can screen several highly diverse and already optimized antibody libraries against any target and reformat them into the therapeutic format for final testing. Then, the best candidates can be biophysically characterized to select the most stable and well-behaving molecules. This is followed by in vitro pharmacology studies to identify clones with the required functions and properties, such as affinity, epitope competition, species cross-reactivity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC). The next step is to analyze the specificity and off-target binding using a large collection of cells that express almost all possible antigens. Finally, in vivo experiments can be performed in animal models, including patient-derived xenografts. All the steps are independent and can be applied to any antibody.
Effects of I-125 seeds combined with anlotinib on tumor growth and bone metabolism in A549 tumor-bearing mice
Published in International Journal of Radiation Biology, 2021
Feilong He, Qi Bao, Jiangtao Bai, Jianping Wang, Jianglong Zhai, Qiquan Yu, Wentao Guo, Chunxiao Wu, Kun Zhang, Weizhen Shou, Guoying Zhu
Accumulating evidence demonstrated that monoclonal antibodies against VEGF or VEGFR have shown promising therapeutic anti-angiogenic and antitumor effects (Keating 2014; Wilke et al. 2014; Cooper et al. 2016). Anlotinib also has been shown to exhibit specific suppressive potential on angiogenesis and tumor development in clinical III phase trials and animal experiments (Sun et al. 2016; Lin et al. 2018; Wang et al. 2018; Xie et al. 2018; Zhou et al. 2019). With a daily administration dosage of 12 mg, anlotinib exhibits definite toxicity, a long half-life and a broad-spectrum of anti-cancer efficacy in clinical trials (Sun et al. 2016). In our study, following anlotinib treatment in single I-125 seed implantation-irradiation therapy, the volume and weight of the A549 lung tumor continually decreased and reached a minimum level, accompanied by increased necrosis, high apoptosis, reduced tumor cell proliferation and decreased angiogenesis, which suggested more specifical and effective therapy efficacy. Although such combined treatment with irradiation and anlotinib therapy may result in the side effect such as the decline of body weight combinatorial treatment strategies of I-125 seeds implantation brachytherapy and anti-angiogenic target drug may inform novel approaches to enrich the clinical potential of anlotinib in the future. Indeed, more research is needed to support the conclusions, especially in additional xenograft and immunocompetent allograft models.
Xenotransplantation
Published in Organogenesis, 2018
Srijan Tandukar, Sundaram Hariharan
The obvious advantage of xenotransplantation is the decrease in reliance on human organs. It also serves to counter the unmet need of organ deficit for transplantation worldwide. Besides, patients with high panel reactive antigen (PRA) have shown to be at no higher risk of rejecting a pig graft than patients with low or no PRA based on current limited evidence.13,14 In addition, certain diseases recur in a rapid fashion leading to kidney failure. Some of these patients may benefit from xenograft, as the possibility of recurrence may be low. In case of living donors, although very safe with modern surgical techniques, there is increasing evidence that living donors, especially certain racial and ethnic groups are at risk for developing chronic kidney disease few decades after donation.15–18 If xenotransplantation is feasible and successful, it will eliminate living donation for sure.