Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.

Nanocarriers as an emerging platform for cancer therapy

We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.

https://cancerres.aacrjournals.org/content/canres/46/12_Part_1/6387.full.pdf

A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs

Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

/pdf/nitric-oxide-and-peroxynitrite-in-health-and-disease-3uuuqgfdcz.pdf

Nitric Oxide and Peroxynitrite in Health and Disease

One apparent shortcoming of REBCO conductor coils is an extremely low fraction of conductor in the coil winding, as the REBCO conductor is as thin as 100–150 μm, comparable to the insulation thickness. If we wish to achieve high overall current densities for REBCO coils, the insulation thickness on REBCO conductor must be substantially reduced. Therefore, we have developed a 4 μm thick ultra-thin polyimide insulation coating by electro-deposition, which is 10-fold-thinner than conventional insulations on REBCO conductors. The fraction of REBCO conductor in the coil winding manufactured by this novel conductor becomes as high as 90%, which is comparable to that for a low temperature superconducting coil winding manufactured from Formvar-coated NbTi conductor. Thus, one important shortcoming of REBCO coils is satisfactorily overcome by using ultra-thin polyimide coated conductors, making possible a dramatic increase in the overall current density of such coils.

An ultra-thin polyimide insulation coating on REBCO conductors by electrodeposition produces a maximum overall current density for REBCO coils

Controlling oxidative stress: therapeutic and delivery strategies ☆

Single crystal growth of (Dy1−xGdx)3Al5O12 and (Dy1−x−yGdxYy)3Al5O12 garnets

Combined effects of both bacteria and gastric juice on pneumonia in mice.

A newly developed Cu-16 at % Ag alloy wire was evaluated by using it to wind multilayered coils for pulsed magnets with different bore diameters, with and without internal reinforcement by glass fiber composites. These magnets have a long pulse duration in the range 5–10ms. A peak field of 62.7 T was obtained in 15 mm bore of a coil without internal reinforcement but enclosed in an outer metal case. A magnet with optimized layer by layer reinforcement succeeded in generating 73.4 T in the 10 mm bore. It was thus established that this wire is highly promising for the construction of high performance pulsed magnets.

Hiroshi Maeda

Papers

An ultra-thin polyimide insulation coating on REBCO conductors by electrodeposition produces a maximum overall current density for REBCO coils

Controlling oxidative stress: therapeutic and delivery strategies ☆

Single crystal growth of (Dy1−xGdx)3Al5O12 and (Dy1−x−yGdxYy)3Al5O12 garnets

Combined effects of both bacteria and gastric juice on pneumonia in mice.

Coppersilver wire coils for pulsed magnet