Monoclonal antibody (MoAb) for cancer treatment has been greatly progressed during this decade. Six kinds of MoAbs are now in clinical use in Japan. Here we review on the development of MoAbs such as rituximab, bevacizumab and cetuximab. The characterization and the nomenclature of MoAb are also described. Panitumumab, a new MoAb targeting epithelial growth factor receptor(EGFR), and the resistance of colorectal cancer with KRAS mutation for anti-EGFR MoAbs are on recent topics. The concept of bevacizumab beyond progression (BBP) and the unfavorable results of bevacizumab in elder nonsmall cell lung carcinoma patients are so suggestive considering the strategy of the individualized cancer therapy. Finally, "drug lag" for the development of anti-cancer agents between Eastern and Western has to be discussed.

Antibody therapy in cancer

The concept of invariance with respect to transformations of a group is one of the most important and successful ideas of nineteenth century mathematics. After the use of coordinates had dominated many branches of mathematics and physics for centuries, a critical review of these methods was initiated by a new look on its foundations.

The General Theory

Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia–reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO3·−, peroxyl radical, and less efficiently H2O2. By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular tra...

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Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Coumarins, a well-known class of naturally occurring compounds, display a remarkable array of biochemical and pharmacological actions, some of which suggest that certain members of this group of compounds may significantly affect the function of various mammalian cellular systems. The development of coumarins as antioxidant agents has attracted much attention in recent years. Coumarins afford an opportunity for the discovery of new antioxidants with truly novel mechanisms of action. This review updates and expands the 2006 review by the same author. The review considers and incorporates the most recently published literature on coumarins as related to their antioxidant properties. A lot of coumarins have been identified from natural sources, especially green plants. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. Beyond doubt, a deep understanding of the mechanisms of existing synthetic and natural coumarins will build the basis for the rational design.

Coumarins as antioxidants.

Most hypoxic tumors are insensitive to radiation, which is a major obstacle in the development of conventional radiotherapy for tumor treatment. Some drugs, such as cisplatin (CDDP), have been extensively used both as an anticancer drug and clinically as a radiosensitizer to enhance radiotherapy. Herein, we develop rattle-structured multifunctional up-conversion core/porous silica shell nanotheranostics (UCSNs) for delivering CDDP to tumors for synergetic chemo-/radiotherapy by CDDP radiosensitization and magnetic/luminescent dual-mode imaging. UCSNs had a dynamic light scattering diameter of 79.1 nm and excellent water dispersity and stability. In vitro studies showed that CDDP loaded in UCSNs (UCSNs-CDDP) was more effective than free CDDP as a radiosensitizer. After injection, UCSNs-CDDP also demonstrated unambiguously enhanced radiotherapy efficacy in vivo. Our report aims at presenting a novel strategy in biomedical nanotechnology that allows simultaneous dual-mode imaging and localized therapy via synergetic chemo-/radiotherapy, which may achieve optimized therapeutic efficacy in cancer treatment.

Rattle-structured multifunctional nanotheranostics for synergetic chemo-/radiotherapy and simultaneous magnetic/luminescent dual-mode imaging.

Peculiarities of the antioxidant and radioprotective effects of hydrated C60 fullerene nanostuctures in vitro and in vivo.

One of the promising ways to overcome microbial antibiotic resistance is the use of nanoparticles of metal oxides. As you know, a wide range of metals has antimicrobial action: Ag, Al, Cu, Fe, Mo, Mn, etc. The mechanisms of the antimicrobial action of metals are impaired functioning of microbial enzymes, generation of reactive oxygen species, damage to the cell membrane, and genotoxic action. ZnO nanoparticles have bacteriostatic and bactericidal action against gram-positive and gram-negative bacteria, as well as fungicidal activity. The mechanism of action is based on the release of Zn2+, generation of reactive oxygen species, damage to the cell membrane, binding to microbial proteins and nucleic acids. NPs based on ZnO have a number of advantages: high antibacterial efficiency at low concentrations (0.16-5.00 mM/l), action on a wide range of microbial strains, and relatively low production costs. Methods have now been found to improve the antimicrobial properties of nanoparticles. The use of several methods at the same time in some cases gives a synergistic effect. All of the above allows us to predict the use of ZnO nanoparticles as a new generation of antimicrobial agents in the near future.

/pdf/a-mini-review-of-antibacterial-properties-of-zno-1aty9exf12.pdf

A Mini Review of Antibacterial Properties of ZnO Nanoparticles

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

https://www.mdpi.com/1422-0067/17/1/33/pdf

Targeted Radionuclide Therapy of Human Tumors

Gudkov, S. V., Shtarkman, I. N., Smirnova, V. S., Chernikov, A. V. and Bruskov, V. I. Guanosine and Inosine Display Antioxidant Activity, Protect DNA In Vitro from Oxidative Damage Induced by Reactive Oxygen Species, and Serve as Radioprotectors in Mice. Radiat. Res. 165, 538–545 (2006). The effect of ribonucleosides on 8-oxoguanine formation in salmon sperm DNA dissolved in 1 mM phosphate buffer, pH 6.8, upon exposure to γ rays was examined by ELISA using monoclonal antibodies against 8-oxoguanine. Nucleosides (1 mM) decreased the radiation-induced yield of 8-oxoguanine in the order Guo > Ino > Ado > Thd > Urd > Cyd. Guanosine and inosine considerably reduced deamination of cytosine in the DNA solutions upon heating for 24 h at 80°C. The action of nucleosides on the heat-induced generation of reactive oxygen species in the phosphate buffer was studied. The concentration of hydrogen peroxide was measured by enhanced chemiluminescence in a peroxidase–luminol–p-iodophenol system; the hydroxyl radic...

Guanosine and Inosine Display Antioxidant Activity, Protect DNA In Vitro from Oxidative Damage Induced by Reactive Oxygen Species, and Serve as Radioprotectors in Mice

The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is one of the key microelements and plays an important role in the function of living systems of different hierarchies. Iron abundance and its physiological functions bring into question the ability of iron compounds at the same concentrations, on the one hand, to inhibit the microbial growth and, on the other hand, to positively affect mammalian cells. At present, multiple studies have been published that show the antimicrobial effect of IONPs against Gram-negative and Gram-positive bacteria and fungi. Several studies have established that IONPs have a low toxicity to eukaryotic cells. It gives hope that IONPs can be considered potential antimicrobial agents of the new generation that combine antimicrobial action and high biocompatibility with the human body. This review is intended to inform readers about the available data on the antimicrobial properties of IONPs, a range of susceptible bacteria, mechanisms of the antibacterial action, dependence of the antibacterial action of IONPs on the method for synthesis, and the biocompatibility of IONPs with eukaryotic cells and tissues.

https://www.mdpi.com/2079-6382/10/7/884/pdf

Sergey V. Gudkov

Papers

Peculiarities of the antioxidant and radioprotective effects of hydrated C60 fullerene nanostuctures in vitro and in vivo.

A Mini Review of Antibacterial Properties of ZnO Nanoparticles

Targeted Radionuclide Therapy of Human Tumors

Guanosine and Inosine Display Antioxidant Activity, Protect DNA In Vitro from Oxidative Damage Induced by Reactive Oxygen Species, and Serve as Radioprotectors in Mice

Do Iron Oxide Nanoparticles Have Significant Antibacterial Properties