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Translational medicine in hepatocellular carcinoma

null

《医学前沿（英文）》 2012年第6卷第2期页码 122-133 doi: 10.1007/s11684-012-0193-7

摘要：

Hepatocellular carcinoma (HCC) is a highly complex disease that is generally resistant to commonly used chemotherapy and radiotherapy. Consequently, there is an urgent need for the development of new treatment strategies for this devastating disease. In the past decade, tremendous progress has been achieved in the molecular stratification of HCCs for diagnosis, prognosis, and therapeutic decision-making. To date, the molecular classification of HCCs has been carried out through transcriptomic, genetic and epigenetic profiling of tumors. Such research has led to identification of several potential molecular targets in HCC, and subsequently, development of novel systemic agents for the treatment of HCC has begun in earnest. In this article, we review the current knowledge of the molecular pathogenesis of HCC and outline potential areas for application of this knowledge in a clinical setting. As a typical virus and inflammation-associated cancer, both host immune response and tumor microenvironment have crucial roles in HCC pathogenesis. In addition, we examine the potential of immunotherapy and strategies targeting various components of the tumor microenvironment, as well as novel molecular and cellular targets in HCC such as cancer stem cells.

关键词： hepatocellular carcinoma molecular classification molecular targeted therapies tumor microenvironment immunotherapy

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Precision medicine in acute lymphoblastic leukemia

Ching-Hon Pui

《医学前沿（英文）》 2020年第14卷第6期页码 689-700 doi: 10.1007/s11684-020-0759-8

摘要： The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno- and cellular-therapy approaches together with precise risk stratification. Children with or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, -rearranged, Ph-positive and -positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.

关键词： acute lymphoblastic leukemia molecular therapeutics targeted therapy tyrosine kinase inhibitors immunotherapy CAR T-cell therapy

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Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

《医学前沿（英文）》 2013年第7卷第2期页码 157-171 doi: 10.1007/s11684-013-0272-4

摘要：

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

关键词： non-small-cell lung cancer molecular typing individualized medicine molecular-targeted therapy gene expression profiling

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Molecular authentication of the traditional Chinese medicine Tongren Dahuoluo Wan and its alternative

Jikun WANG, Jing DU, Meng CAO, Lu YAO, Suhua XIE, Jiafu CHEN, Xingbo ZHAO

《农业科学与工程前沿（英文）》 2017年第4卷第3期页码 353-357 doi: 10.15302/J-FASE-2017157

摘要： Tongren Dahuoluo Wan has been a popular traditional Chinese medicine in international pharmaceutical markets for hundreds of years. Leopard bone powder is the key element in its formulation. However, the leopard has been listed for wildlife conservation, which limits the use of the leopard bone supplies. Therefore, an alternative formulation which substitutes leopard bone with zokor bone in the formula of Tongren Dahuoluo Wan is now manufactured. To develop a simple and reliable molecular method for authenticating the two patent medicines, mitochondrial nucleotide polymorphic sites of , and genes were screened in leopard and zokor bones, and nine pairs of species-specific primers were verified for discriminating the two species. For the patent medicine authentication, we set up a molecular diagnostic assay to resolve the difficulties of low concentration of target DNAs and presence of PCR-inhibitory substances in this complex medicine, and successfully confirmed leopard or zokor content using the nine pairs of species-specific primers. We recommend a common technical strategy for authentication of species origins in traditional Chinese medicine, and discuss the experimental solutions for technical problems of molecular diagnostic assays.

关键词： Tongren Dahuoluo Wan molecular diagnostic assay Eospalax baileyi Panthera pardus species-specific primers

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Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿（英文）》 2018年第12卷第2期页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要：

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词： molecular classification precision medicine pembrolizumab PD-1/PD-L1 MSI-H

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精准烧伤医学：分子工程科学应用

Kristen Jakubowski, Michael Poellmann, Raphael C. Lee

《工程（英文）》 2015年第1卷第3期页码 280-281 doi: 10.15302/J-ENG-2015073

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Molecular targeted therapy of gynecological malignant tumors: the development and challenge, from laboratory

Pengming SUN PhD, MD , Jalid SEHOULI PhD, MD , Lihui WEI BM ,

《医学前沿（英文）》 2009年第3卷第3期页码 256-264 doi: 10.1007/s11684-009-0052-3

摘要： More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer, especially in ovarian cancer. In this article, we systematically review the current targeted therapeutic trials running in clinic. Large, randomized trials have been conducted in the treatment of ovarian cancer, endometrial cancer and cervical cancer by using small molecule, antisense, mutational gene as well as antibodies. Other planned or ongoing trials currentlytargeted at molecular markers which may play important roles in gynecological carcinogenesis andprogression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an importantoption.

关键词： target therapy gynecologic malignant tumors clinical trail molecular medicine

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Individualized medicine, health medicine, and constitutional theory in Chinese medicine

null

《医学前沿（英文）》 2012年第6卷第1期页码 1-7 doi: 10.1007/s11684-012-0173-y

摘要：

The patterns of modern science and changes in the medical model can result in the transformation of the current state of individualized and health medicines into being the primary trend in medical development. Chinese and Western medical systems are dissimilar in terms of value orientations, thinking style, and research directions because of their different historical and cultural backgrounds. Individualized treatment in modern medicine is mainly established based on individual genome information and the differences in mononucleotide polymorphi-sms. However, such treatment method is expensive, creates an uncertain genetic marker, and leads to different result interpretations, among other problems. The Chinese constitutional theory developed in the 1970s expresses the principle behind Chinese health medicine and individual treatment and provides the corresponding methods. The Chinese constitutional theory divides the constitution of the Chinese population into nine categories based on established classification criteria. It promotes the study of the relationship of each constitution to diseases and Chinese medicine preparation toward adjusting the constitution and preventing diseases. The theory also provides methods and tools for individualized treatment. Constitution identification shows the direction and provides the core technology for the evaluation of the health status. By combining the developments in modern biotechnology, new diagnostic techniques and treatment models of constitution-differentiation, disease-differentiation, and syndrome-differentiation can be established for the development of individualized Chinese medicine treatment and health medicine for the international medical community.

关键词： individualized medicine health medicine constitutional theory in Chinese medicine

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Thinking and practice of accelerating transformation of traditional Chinese medicine from experiencemedicine to evidence-based medicine

Baoyan Liu, Yanhong Zhang, Jingqing Hu, Liyun He, Xuezhong Zhou

《医学前沿（英文）》 2011年第5卷第2期页码 163-170 doi: 10.1007/s11684-011-0143-9

摘要： The gradual development of Chinese medicine is based on constant accumulation and summary of experience in clinical practice, but without the benefit of undergoing the experimental medicine stage. Although Chinese medicine has formed a systematic and unique theory system through thousands of years, with the development of evidence-based medicine, the bondage of the research methods of experience medicine to Chinese medicine is appearing. The rapid transition and transformation from experience medicine to evidence-based medicine have become important content in the development of Chinese medicine. According to the features of Chinese medicine, we propose the research idea of “taking two ways simultaneously,” which is the study both in the ideal condition and in the real world. Analyzing and constructing the theoretical basis and methodology of clinical research in the real world, and building the stage for research technique is key to the effective clinical research of Chinese medicine. Only by gradually maturing and completing the clinical research methods of the real world could we realize “taking two ways simultaneously” and complementing each other, continuously produce scientific and reliable evidence of Chinese medicine, as well as transform and develop Chinese medicine from experience medicine to evidence-based medicine.

关键词： Chinese medicine experience medicine evidence-based medicine real world

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Clinical research of traditional Chinese medicine in big data era

null

《医学前沿（英文）》 2014年第8卷第3期页码 321-327 doi: 10.1007/s11684-014-0370-y

摘要：

With the advent of big data era, our thinking, technology and methodology are being transformed. Data-intensive scientific discovery based on big data, named “The Fourth Paradigm,” has become a new paradigm of scientific research. Along with the development and application of the Internet information technology in the field of healthcare, individual health records, clinical data of diagnosis and treatment, and genomic data have been accumulated dramatically, which generates big data in medical field for clinical research and assessment. With the support of big data, the defects and weakness may be overcome in the methodology of the conventional clinical evaluation based on sampling. Our research target shifts from the “causality inference” to “correlativity analysis.” This not only facilitates the evaluation of individualized treatment, disease prediction, prevention and prognosis, but also is suitable for the practice of preventive healthcare and symptom pattern differentiation for treatment in terms of traditional Chinese medicine (TCM), and for the post-marketing evaluation of Chinese patent medicines. To conduct clinical studies involved in big data in TCM domain, top level design is needed and should be performed orderly. The fundamental construction and innovation studies should be strengthened in the sections of data platform creation, data analysis technology and big-data professionals fostering and training.

关键词： big data traditional Chinese medicine clinical evaluation evidence based medicine

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光照世界史坛的中医起源之谜

符友丰

《中国工程科学》 2006年第8卷第9期页码 1-12

摘要：

以疫病流行及其原型分析为线索，联系早期治法（如热熨、火灸、砭刺等）探讨了古代以腺鼠疫为代表的疫病流行与医学起源间的内在联系；以医源于疫的视野分析我国医史病史研究在出土文物、古文字和医学文献等方面丰富的信息资源与优势；分析解读疾病名实的古今变迁、比较中西医学及其在认识论与方法论上的差异，为审视我国传统医学在疫病防治方面的丰富经验与延至今日的独到成就与意义，疾病史研究成果与推广，实现古为今用，将为当今疫病防治的中西互补、中西医结合与比较提供宝贵的历史经验与借鉴。

关键词：世界医学史中医史医学起源鼠疫霍乱天花比较医学

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Practices, challenges, and opportunities: HIV/AIDS treatment with traditional Chinese medicine in China

Jian Wang, Wen Zou

《医学前沿（英文）》 2011年第5卷第2期页码 123-126 doi: 10.1007/s11684-011-0124-z

摘要： Traditional Chinese medicine (TCM) has become widely used in the treatment of acquired immune deficiency syndrome (AIDS) in China in recent years. In this article, we summarize the recent major developments in human immunodeficiency virus/AIDS (HIV/AIDS) treatment with TCM. The use of TCM is associated with preventing or alleviating HIV-related symptoms, reducing treatment side effects, and improving the quality of life. The potential beneficial effects of TCM should be confirmed through extensive and rigorous trials.

关键词： HIV/AIDS traditional Chinese medicine

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Traditional Chinese medicine in the new century

Jianxiang Liu, Zhu Chen

《医学前沿（英文）》 2011年第5卷第2期页码 111-114 doi: 10.1007/s11684-011-0125-y

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Special issue on “Molecular Sensors and Molecular Logic Gates”

Luling Wu , Tony D. James

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 1-3 doi: 10.1007/s11705-021-2134-y

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Design of bio-oil additives via molecular signature descriptors using a multi-stage computer-aided molecular

《化学科学与工程前沿（英文）》 2022年第16卷第2期页码 168-182 doi: 10.1007/s11705-021-2056-8

摘要： Direct application of bio-oil from fast pyrolysis as a fuel has remained a challenge due to its undesirable attributes such as low heating value, high viscosity, high corrosiveness and storage instability. Solvent addition is a simple method for circumventing these disadvantages to allow further processing and storage. In this work, computer-aided molecular design tools were developed to design optimal solvents to upgrade bio-oil whilst having low environmental impact. Firstly, target solvent requirements were translated into measurable physical properties. As different property prediction models consist different levels of structural information, molecular signature descriptor was used as a common platform to formulate the design problem. Because of the differences in the required structural information of different property prediction models, signatures of different heights were needed in formulating the design problem. Due to the combinatorial nature of higher-order signatures, the complexity of a computer-aided molecular design problem increases with the height of signatures. Thus, a multi-stage framework was developed by developing consistency rules that restrict the number of higher-order signatures. Finally, phase stability analysis was conducted to evaluate the stability of the solvent-oil blend. As a result, optimal solvents that improve the solvent-oil blend properties while displaying low environmental impact were identified.

关键词： computer-aided molecular design bio-oil additives molecular signature descriptor