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The high mortality of tumor is one of the most urgent problems to be solved. However, the current clinical trials provide limited quantitative descriptions on dynamic changes of drug efficacy, which restrict the selection of dosing regimens. Quantitative systems pharmacology (QSP) is a new approach for precise treatment of tumors. It quantifies the network relationship between drug action and diseases by integrating the tumor growth and molecules, cells in vivo, thereby predicting the efficacy, toxicity, and mechanism of antitumor drugs as well as identifying predictive biomarkers. In this review, we provide an overview of definition of QSP, current approaches and typical applications in research of antitumor drugs to enhance our understanding of QSP.
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With a deepening understanding of cancer treatment, immune checkpoint inhibitors are recognized widely as a novel fundamental remedy for various malignancies with effectiveness and safety. With the development of pharmacometrics, model-informed drug development (MIDD) has emerged to accelerate the process of clinical research for new drugs and improve the accuracy of decision-making in new drug research, especially for immune checkpoint inhibitors. As a typical illustration, the research development of pembrolizumab is presented in this review to highlight the application of MIDD, which may provide a reference for the development of other new antitumor drugs.
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Chest wall reconstruction is a key approach to restoring the structure and function of the defective chest wall after tumor excision. While autologous flaps have been ideal materials for soft tissue reconstruction,the optimal skeletal reconstructive material still remains controversial. Currently,besides autologous bones,non-biodegradable materials have been used widely,which offer sufficient strength and stability but with some inevitable complications. Many studies have explored the clinical applications of biodegradable materials and the improvements in their characteristics,and some of these materials may be clinically feasible. This article reviews the recent advances in the applications of reconstructive materials.
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BACKGROUND: With the development of chemical synthesis technology, the application of anti-osteoporosis drugs incorporated into scaffolds to promote bone regeneration in osteoporotic bone defects has become a hot issue nowadays. OBJECTIVE: To introduce bone tissue engineering scaffolds, and to discuss and summarize the application of the scaffolds carrying anti-osteoporosis drugs for osteogenesis in osteoporotic bone defects. METHODS: PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases were retrieved with "osteoporosis, bone defect, scaffold" as key words for relevant articles published from 2005 to 2017. Initially, 201 articles were retrieved, and finally 64 articles were selected for further analysis. RESULTS AND CONCLUSION: With the development of biochemical synthesis technology, various types of tissue-engineered bone scaffolds have been used for the treatment of osteoporotic bone defects. For example, the modified calcium phosphate cement, β-tricalcium phosphate, and hydroxyapatite all can promote bone regeneration. However, the ability of conventional scaffolds to promote bone regeneration is severely damaged under the state of osteoporosis. In this case, an anti-osteoporosis therapy becomes necessary. Considering severe adverse effects of systemic anti-osteoporosis drugs and limited local bone regeneration, the combination of scaffold implantation and local drug delivery can promote osteoporotic bone defect healing. Importantly, to incorporate bone regeneration inducers into scaffolds and steadily release with their biological activity is the key to success. Bisphosphonate, strontium, bone morphogenetic protein 2 and parathyroid hormone, traditional Chinese medicine and mesenchymal stem cells are the drugs commonly combined with tissue-engineered bone scaffolds. With the development of biotechnology, genetically modified stem cell-scaffold composites have gradually appealed to researchers.
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BACKGROUND:Stem cells combined with a three-dimensional scaffold have great potential for the treatment of osteoporotic bone defects. OBJECTIVE:To introduce the application of stem cells combined with the three-dimensional scaffold in repairing osteoporotic bone defects. METHODS:A computer-based search of PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases was performed for relevant articles published from 2007 to 2017 with "stem cells, scaffold, osteoporosis, bone defects" as key words in English and Chinese, repsectively. Initially, 142 articles were retrieved, and finally 45 articles were included in result analysis. RESULTS AND CONCLUSION:Due to the potential of self-renewal and multilineage differentiation, stem cells can be used to repair or regenerate damaged tissues, which are considered as an ideal cell source for the treatment of diseases in orthopedics. The suitable scaffold can provide a favorable microenvironment for repairing the attachment and growth of the cells related to the bone defect, which can promote the healing without additional side effects. Furthermore, stem cells combined with three-dimensional scaffolds provide a promising clinical application for the treatment of osteoporotic bone defects by regulation of bone metabolism. In addition, gene-modified stem cells with three-dimensional scaffolds bring a huge potential in the treatment of osteoporotic bone defects. In conclusion, the combination of stem cells and three-dimensional scaffolds provides a new approach for the treatment of osteoporotic bone defects, which may be one of the future therapeutic strategies.
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<p><b>OBJECTIVE</b>To evaluate the feasibility and efficacy of laparoscopy-assisted D2 radical gastrectomy for elderly patients with gastric cancer.</p><p><b>METHODS</b>From October 2007 to October 2012, 233 gastric cancer patients over 65 years underwent D2 lymph node dissection. Among them, 109 patients underwent laparoscopy-assisted radical gastrectomy(LAG group), while 124 patients underwent conventional open gastrectomy(OG group).</p><p><b>RESULTS</b>Compared to the OG group, LAG group was associated with less bleeding [(102.5±34.3) ml vs. (181.7±73.8) ml, P<0.05], quicker postoperative recovery of bowel function[(2.8±0.6) d vs. (4.0±1.2) d, P<0.05], shorter postoperative length of hospital stay[(10.7±7.5) d vs.(14.2±6.5) d, P<0.05], longer operative time [(231.2±51.4) min vs. (208.5±53.6) min, P<0.05]. The postoperative complication rate of LAG group and OG group was 10.1%(11/109) and 21.0%(26/124) respectively(P<0.05). Short-term quality of life of LAG group was better than that of OG group(P<0.05). The 5-year survival rates were 54.5% and 59.2% in LAG and OG groups respectively, and there was no significant difference(P>0.05).</p><p><b>CONCLUSIONS</b>Efficacy of laparoscopy-assisted D2 radical gastrectomy is similar to open gastrectomy in elderly gastric cancer patients with less invasiveness.</p>