3个不同版本《分子生药学》教材教学内容的变化研究

分别对3个不同版本《分子生药学》教材的整体结构内容和章节进行分析,通过总结其各自的优势,提出要结合各个版本教材的亮点,进一步增强将来新版本《分子生药学》教材的完整性、创新性和趣味性,以期为《分子生药学》教材内容的体系建设与发展提供依据。

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

Signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

Advances in molecular cell biology over the last de- cade have clarified the mechanisms involved in can- cer growth, invasion, and metastasis, and enabled the development of molecular-targeted agents. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase 111 randomized controlled trials, and has been approved worldwide. Phase 111 clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing. Those agents target the vascular endothelial growth factor, platelet-derived growth factor receptors, as well as target the epidermal growth factor receptor, insulin- like growth factor receptor and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. In addition, the combination of sorafenib with standard treatment, such as resection, ablation, transarterial em- bolization, and hepatic arterial infusion chemotherapy are ongoing. This review outlines the main pathways involved in the development and progression of hepato- cellular carcinoma and the new agents that target these pathways. Finally, the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.

Biliary tract tumors: past, present and future

Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction： obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU （response rate 20%） and gemcitabine （response rate of 13%-60%）, so they have been selected for further development in multiple phase II clinical trials to explore their efficacy and safety in combination with other agents. In a phase III clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.

Isolation and Characterization of Novel Chlorpyrifos Degrading Fungus Isaria Farinosa

Chlorpyrifos is a well known organophosphorus pesticide used worldwide. Microorganisms including bacteria, fungi and actinomycetes have been reported to be efficient degraders of chlorpyrifos. The present study was successful in isolating a novel fungus that could degrade chlorpyrifos effectively upto 800 ppm concentration. Morphological and molecular characterization studies revealed the identity of the fungus as Isariafarinosa.

Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants

Plants synthesize and accumulate large amount of specialized （or secondary） metabolites also known as natural products, which provide a rich source for modem pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. Th- ese natural products may share a common upstream path- way to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Under- standing of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation.

Application of Systems Biology Technology in Research of Traditional Chinese Medicine

Systems biology is an emerging science of the 21st century and its method and design of study resemble those of traditional Chinese medicine (TCM). Adopting systems biology technology will help to understand TCM Syndromes and modernize Chinese herbal medicine. The technology platforms of systems biology, especially proteomics can provide useful tools for exploring essence of TCM syndromes and understanding principle of herbal formulation. Moreover, compared with methods of molecular biology, such as genomics and proteomics, metabolomics provide more direct, rapid, concise and effective methods for study of kidney disease especially in the case of prevention and treatment with TCM.

Spectroscopic and electrochemical studies on molecular recognition of tetrathiafulvalene derivative with P-glycoprotein and drug-resistant leukemia cells

Cancer is still one of the important diseases that threatens the health of people. Multidrug resistance(MDR) is the main factor that leads to the failure of cancer chemotherapy. Thus, MDR diagnosis could facilitate the monitoring of the therapy process and realization of efficient treatment of tumors. In this study, we have tried to use a new tetrathiafulvalene(TTF) derivative(TTF-(COONBu4)2) to sensitively recognize the MDR through the multi-signal responsive strategy. The relevant electrochemical and spectroscopic studies demonstrate the specific binding behavior of TTF-(COONBu4)2 with P-glycoprotein(P-gp) as well as drug-resistant leukemia cells. Especially due to the over-expression of specific components of P-gp on the plasma membranes of drug resistant cells, the electrochemical and hydrophilic/hydrophobic features of drug resistant-leukemia cells are apparently different from those of other kinds of leukemia cells. Meanwhile, Fourier transform infrared spectroscopic study illustrates that the most intense vibration band of TTF moieties in the 1400–1600 cm-1 range is almost smeared out upon binding to P-gp, and the binding of TTF-(COONBu4)2 to P-gp may also lead to changes in protein secondary structure and backbone. This observation may advance the development of the new TTF agent for the promising clinical diagnosis and monitoring of MDR of tumors with the aim of successful chemotherapy for human cancer.