The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

本文对国际科学计量学杂志《Ｓｃｉｅｎｔｏｍｅｔｒｉｃｓ》１９７９－１９９１年的研究论文内容、栏目、作者及国别和编委及国别作了计量分析，揭示出科学计量学研究的重点、活动的中心及发展趋势，说明了学科带头人在发展科学计量学这门新兴学科中的作用。

国际刊物《Scientometrics》文献计量研究

Danger signals: SOS to the immune system.

Computational and Mathematical Methods in Medicine

Many therapeutically active molecules are non-soluble in aqueous systems, chemically and biologically fragile or present severe side effects. Lipid-based nanoparticle (LBNP) systems represent one of the most promising colloidal carriers for bioactive organic molecules. Their current application in oncology has revolutionized cancer treatment by improving the antitumor activity of several chemotherapeutic agents. LBNPs advantages include high temporal and thermal stability, high loading capacity, ease of preparation, low production costs, and large-scale industrial production since they can be prepared from natural sources. Moreover, the association of chemotherapeutic agents with lipid nanoparticles reduces active therapeutic dose and toxicity, decreases drug resistance and increases drug levels in tumor tissue by decreasing them in healthy tissue. LBNPs have been extensively assayed in in vitro cancer therapy but also in vivo, with promising results in some clinical trials. This review summarizes the types of LBNPs that have been developed in recent years and the main results when applied in cancer treatment, including essential assays in patients.

https://www.mdpi.com/2079-4991/9/4/638/pdf

Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment.

Nanotechnology, along with related concepts such as nanomaterials, nanostructures and nanoparticles, has become a priority area for scientific research and technological development. Nanotechnology, i.e., the creation and utilization of materials and devices at nanometer scale, already has multiple applications in electronics and other fields. However, the greatest expectations are for its application in biotechnology and health, with the direct impact these could have on the quality of health in future societies. The emerging discipline of nanomedicine brings nanotechnology and medicine together in order to develop novel therapies and improve existing treatments. In nanomedicine, atoms and molecules are manipulated to produce nanostructures of the same size as biomolecules for interaction with human cells. This procedure offers a range of new solutions for diagnoses and “smart” treatments by stimulating the body’s own repair mechanisms. It will enhance the early diagnosis and treatment of diseases such as cancer, diabetes, Alzheimer’s, Parkinson’s and cardiovascular diseases. Preventive medicine may then become a reality.

https://www.mdpi.com/1422-0067/12/5/3303/pdf

Nanomedicine: Application Areas and Development Prospects

Background
The use of temozolomide (TMZ) has improved the prognosis for glioblastoma multiforme patients. However, TMZ resistance may be one of the main reasons why treatment fails. Although this resistance has frequently been linked to the expression of O6-methylguanine-DNA methyltransferase (MGMT) it seems that this enzyme is not the only molecular mechanism that may account for the appearance of drug resistance in glioblastoma multiforme patients as the mismatch repair (MMR) complex, P-glycoprotein, and/or the presence of cancer stem cells may also be implicated.

/pdf/temozolomide-resistance-in-glioblastoma-cell-lines-2cbmlkr85y.pdf

Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression.

Human gene therapy can be defined as the delivery of genetic material into a patient's cells with a therapeutic aim. The success or failure of gene therapy depends on the development and efficiency of the transfection of viral and non-viral vectors. Viral vectors typically offer higher transduction efficiency and long-term gene expression, but may be associated with toxicity, immunogenicity, restricted target cell specificity and high cost. Non-viral methods have become widespread because of their relative safety, capacity to transfer large genes, site-specificity and their non-inflammatory, non-toxic and non-infectious properties. However, the clinical usefulness of non-viral methods is limited by their low transfection efficiency and relatively poor transgene expression. In this review, we describe the progress made in the development of gene delivery technology and its possible application in clinical trials.

Non-viral and viral vectors for gene therapy.

Doxorubicin, one of the most effective anticancer drugs currently known, is commonly used against breast cancer. However, its clinical use is restricted by dose-dependent toxicity (myelosuppression and cardiotoxicity), the emergence of multidrug resistance and its low specificity against cancer cells. Nanotechnology is a promising alternative to overcome these limitations in cancer therapy as it has been shown to reduce the systemic side-effects and increase the therapeutic effectiveness of drugs. Indeed, the numerous nanoparticle-based therapeutic systems developed in recent years have shown low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. Furthermore, the wide range of nanoparticle systems available may provide a solution to the different problems encountered during doxorubicin-based breast cancer treatment. Thus, a suitable nanoparticle system may transport active drugs to cancer cells using the pathophysiology of tumours, especially their enhanced permeability and retention effects, and the tumour microenvironment. In addition, active targeting strategies may allow doxorubicin to reach cancer cells using ligands or antibodies against selected tumour targets. Similarly, doxorubicin resistance may be overcome, or at least reduced, using nanoparticles that are not recognized by P-glycoprotein, one of the main mediators of multidrug resistance, thereby resulting in an increased intracellular concentration of drugs. This paper provides an overview of doxorubicin nanoplatform-based delivery systems and the principal advances obtained in breast cancer chemotherapy.

Jose Prados

Papers

Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment.

Nanomedicine: Application Areas and Development Prospects

Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression.

Non-viral and viral vectors for gene therapy.

Doxorubicin-Loaded Nanoparticles: New Advances in Breast Cancer Therapy