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Advances in Gold Nanoparticle-Based Combined Cancer Therapy.

According to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxicity. Among other inorganic NP systems, gold nanoparticle (GNP) based systems offer the means to fur

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… Paul Ehrlich’s magic bullet concept: 100 Years of progress. Nat. Rev. Cancer. 2008;8:473–480. doi: 10.1038/nrc2394. 15. Davis M.E., Chen Z., Shin D.M. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat. Rev. Drug Discov. 2008;7:771–782. doi: 10.1038/nrd2614. 16. …

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar).

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called "living drugs". Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017),

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… This scientific theory of “magic bullets” has later inspired the scientific community to explore numerous molecular cancer therapeutics. …

Journey of TRAIL from Bench to Bedside and its Potential Role in Immuno-Oncology.

Induction of apoptosis in cancer cells has increasingly been the focus of many therapeutic approaches in oncology field. Since its identification as a TNF family member, TRAIL (TNF-related apoptosis-inducing ligand) paved a new path in apoptosis inducing cancer therapies. Its selective ability to activate extrinsic and intrinsic cell death pathways in cancer cells only, independently from p53 mutations responsible for conventional therapeutics resistance, spotted TRAIL as a potent cancer apoptotic agent. Many recombinant preparations of TRAIL and death receptor targeting monoclonal antibodies

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… Thousands of researches have been dedicated to better understand the complex biology of that disease and to achieve a magic bullet treatment. Resection of the tumor mass, along with irradiation and chemotherapy aiming to killing mutant cells were and remain considerable treatment options. …

The concept of exceptionality: a legal farce?

How do we decide which treatments should be offered by the National Health Service (NHS) when we cannot afford to fund them all? In the absence of a positive appraisal by the National Institute for Health and Clinical Excellence (NICE), which mandates the provision of a treatment by the NHS, Primary Care Trusts (PCTs) are free to decide whether to provide a particular drug to some, or all, of their population. However, as public bodies, it is a well-established principle of Administrative Law that PCTs are not at liberty to fetter the exercise of their own discretion. They must recognise the p

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… This is not to refute that the cancer patients whom they are designed to treat do not have an ‘overriding clinical need’, but unfortunately in many cases it is a need for which no effective magic bullet exists. …

Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.

Chimeric antigen receptor (CAR) cell-based therapies have demonstrated limited success in solid tumors, including glioblastoma (GBM). GBMs exhibit high heterogeneity and create an immunosuppressive tumor microenvironment (TME). In addition, other challenges exist for CAR therapy, including trafficking and infiltration into the tumor site, proliferation, persistence of CARs once in the tumor, and reduced functionality, such as suboptimal cytokine production. Cytokine modification is of interest, as one can enhance therapy efficacy and minimize off-target toxicity by directly combining CAR thera

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… IL-15 Receptor Alpha as the Magic Wand to Boost the Success of IL-15 Antitumor Therapies: The Upswing of IL-15 Transpresentation Pharmacol. Ther. 2017 170 73 79 10.1016/j.pharmthera.2016.10.012 27777088 84. Li G. Zhang Z. Cai L. Tang X. Huang J. Yu L. Wang G. Zhong K. Cao Y. Liu C. …

Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects.

Angiogenesis and metastasis represent two challenging targets to combat cancer development in the later stages of its progression. Numerous studies have indicated the important role of natural products in blocking tumor angiogenesis signaling pathways in several advanced tumors. In recent years, the marine polysaccharides fucoidans emerged as promising anticancer compounds showing potent antitumor activity in both in vitro and in vivo models of different types of cancers. The objective of this review is to focus on the antiangiogenic and antimetastatic activities of fucoidans with special emph

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… Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet? Science. 2013;339:286–291. doi: 10.1126/science.1232227. 67. Crusz S.M., Balkwill F.R. Inflammation and Cancer: Advances and New Agents. Nat. Rev. Clin. Oncol. 2015;12:584–596. doi: 10.1038/nrclinonc.2015.105. 68. …

Review and Updates on Systemic Mastocytosis and Related Entities.

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosi

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… Midostaurin: A magic bullet that blocks mast cell expansion and activation. Ann. Oncol. 2017;28:2367–2376. doi: 10.1093/annonc/mdx290. 129. Gotlib J., Kluin-Nelemans H.C., George T.I., Akin C., Sotlar K., Hermine O., Awan F.T., Hexner E., Mauro M.J., Sternberg D.W., et al. …

Learn from antibody-drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy.

Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug

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… Antibody–drug conjugates (ADCs), which are developed based on the concept of “magic bullet” conceived by Paul Ehrlich 100 years ago, enable the targeting delivery of toxic drugs to cancer cells, providing an opportunity for delivering two distinctive therapeutic entities, the antibody and the small molecule …

History of hematopoietic cell transplantation: challenges and progress.

After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights fo

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… decision-making tool for choosing appropriate transplant regimens. 89 Serum biomarkers derived from the gastrointestinal tract, specifically ST2 and REG-3, have emerged as an additional method of predicting acute GvHD severity, as presented in a recent Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC …

Trial watch: Oncolytic viruses for cancer therapy.

Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several diffe

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… 34:6<1907::AID-CNCR2820340609>3.0.CO;2-4 4611607 132 Martuza RL Malick A Markert JM Ruffner KL Coen DM Experimental therapy of human glioma by means of a genetically engineered virus mutant Science 1991 252 854 6 10.1126/science.1851332 1851332 133 Bradbury J Oncolytic viral anti-cancer therapy: a magic …

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of

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… ADCs ADCs were designed to be the “magic bullets” that would achieve targeted delivery of a toxic payload to tumor cells only, thereby avoiding systemic toxicities associated with conventional chemotherapy regimens. …

Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances.

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug

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… Antibody Drug Conjugates An exciting approach to the targeted delivery of drugs in cancer therapy is the use of antibody-drug conjugates (ADC), which was named as the “magic bullet” by Paul Ehrlich [ 103 ]. …

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

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… Caffeine and human DNA metabolism: the magic and the mystery. Mutation Research. 2003;532(1-2):85–102. doi: 10.1016/j.mrfmmm.2003.08.012. 185. Roshankhah S., Rodsari B. A., Jalili C., Salahshoor M. R. …

Computational approaches in rheumatic diseases - Deciphering complex spatio-temporal cell interactions.

Inflammatory arthritis, including rheumatoid (RA), and psoriatic (PsA) arthritis, are clinically and immunologically heterogeneous diseases with no identified cure. Chronic inflammation of the synovial tissue ushers loss of function of the joint that severely impacts the patient's quality of life, eventually leading to disability and life-threatening comorbidities. The pathogenesis of synovial inflammation is the consequence of compounded immune and stromal cell interactions influenced by genetic and environmental factors. Deciphering the complexity of the synovial cellular landscape has accel

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… Magic-BLAST, an accurate RNA-seq aligner for long and short reads. BMC Bioinforma. 2019;20(1):405. doi: 10.1186/s12859-019-2996-x. 126. Xu J., Cai L., Liao B., Zhu W., Yang J. CMF-Impute: an accurate imputation tool for single-cell RNA-seq data. …

Bisphosphonate conjugation for bone specific drug targeting.

Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types. The bisphosphonate molecule class binds specifically to hydroxyapatite and inhibits

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… Fluorescently labeled risedronate and related analogues: "magic linker" synthesis Bioconjug. Chem. 19 12 2008 2308 2310 19032080 10.1021/bc800369c Kasugai S. Selective drug delivery system to bone: small peptide (Asp)6 conjugation J. Bone Miner. …

Emerging new therapeutic antibody derivatives for cancer treatment.

Monoclonal antibodies constitute a promising class of targeted anticancer agents that enhance natural immune system functions to suppress cancer cell activity and eliminate cancer cells. The successful application of IgG monoclonal antibodies has inspired the development of various types of therapeutic antibodies, such as antibody fragments, bispecific antibodies, and antibody derivatives (e.g., antibody-drug conjugates and immunocytokines). The miniaturization and multifunctionalization of antibodies are flexible and viable strategies for diagnosing or treating malignant tumors in a complex t

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… remarkedly improved by linking highly a cytotoxic small molecule to the mAb, generating a novel type of antibody derivative, an ADC. 6 ADCs can selectively deliver highly cytotoxic small-molecule drugs directly to targeted cancer cells and induce their apoptosis, 7 which fulfills the requirements of a “magic …

Mathematical modeling in cancer nanomedicine: a review.

Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine h

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… Conclusions Cancer nanomedicine has been inspired by Paul Ehrlich’s notion of the “magic bullet”, which visualizes the design of therapeutic agents that selectively attack diseased cells while sparing the healthy ones. …

Stem Cells and Organ Transplantation: Resetting Our Biological Clocks

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… Unless one invokes “magical” methods such as nanotechnology far in advance of current capabilities, a character will simply not be anywhere near fully recovered the day after a heart transplant. Our bodies also take a significant amount of time to heal and recuperate long after surgery. …

Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2018

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Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in is … in Ascona from 10 to 14 June 2012. In the unique scenario of the Maggiore lake and absorbed in the magic atmosphere of the Centro Stefano Franscini (CSF) at Monte Verità, we enjoyed three-and-a-half days of intense and inspiring activity, where not only many of the most prominent scientists working on macromolecular crowding, but also experts in closel …