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

A 20T large bore superconducting magnet has been developed at the National Research Institute for Metals. In this paper, design for its coils is mainly discussed. Design policy for this magnet system is to meet two contradicting requirements; large bore diameters and generation of high magnetic fields. The magnet consists of four coils, and should be operated at 1.8K in saturated superfluid helium to generate its highest field. Magnetic fields of 15T in a 314mmφ thermally insulated chamber, of 18T in a 160mmφ bore and of over 20T in a 44mmφ bore are designed to be generated with combinations of these four coils.

Development of 20T Large Bore Superconducting Magnet (III)

To improve the activity of a Koji mold protease in a solid or liquid culture medium in the production of foods (e.g., a seasoning), pharmaceuticals (e.g., a digestive agent), protease for use in a detergent and the like. Disclosed are a recombinant vector having capability of increasing the secretion of the Koji mold protease, a Koji mold which is transformed with the vector and has an increased expression of a gene for a protease or an increase secretion of the same, a method for the production of a protease by using the transformed Koji mold, and the like.

Recombinant vector capable of increasing secretion of koji mold protease

Mittel zur verbesserung der blutzirkulation

PROBLEM TO BE SOLVED: To provide a reactive power compensator by which when a power factor of a load changes, compensating capacity is easily adjusted and reactive power of an AC feeder circuit is appropriately compensated without large-scale changes in equipment. SOLUTION: The reactive power compensator includes a transformer 13 for compensation provided on a secondary side of a transformer for an AC feeder and a capacitor C provided in parallel on a secondary side of the transformer 13 for compensation. Taps 14, 15 to change a voltage are provided on a primary side and the secondary side of the transformer 13 for compensation. COPYRIGHT: (C)2004,JPO&NCIPI

Reactive power compensator

Glucosamine-bearing poly(styrene-co-maleic acid) (SMA-G) with the molecular weight of 1.8 × 104 is water soluble. We found that there is a weak hydrophobic interaction between water soluble serum p...

Hiroshi Maeda

Papers

Development of 20T Large Bore Superconducting Magnet (III)

Recombinant vector capable of increasing secretion of koji mold protease

Mittel zur verbesserung der blutzirkulation

Reactive power compensator

Weak Interplay between Hydrophobic Part of Water-soluble Polymers and Serum Protein