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

NEW MATERIAL:A polysaccharide, KS-2-D, having the following physical and chemical properties. Elemental analysis, C 42.3+ or -1.5%, H 6.2+ or -0.3%, N 0.6+ or - 0.2%, ash 6.7+ or - 2.5%; molecular weight, 30,000-70,000, average molecular weight, 70,000; white amorphous powder; decomposition point, 185 deg.C (Capillary method); pH=7-8, nearly neutral; soluble in water, insoluble in ethanol, acetone, n-hexane, etc.; specific rotation, [alpha]D =+66.1-+97.5 deg. (average 82.9 deg.) (water, c=0.5%); positive to phenol-sulfuric acid reaction, anthron reaction, etc., negative to toluidine blue O staining; saccharide content, 65-80% (average 71%), protein content, 3.5-6% (average 4.8%), protein/saccharide ratio, 0.05-0.08 (average 0.07), etc. USE:Carcinostatic agent. Preventive and remedy for diseases caused by candida, Pseudomonas aeruginosa, Listeria, influenza virus, etc. PROCESS:The compound can be prepared by culturing strain of Lentinus edodes KSLE 28 (FERM-P No.4196), etc.

Polysaccharide kss22d and its preparation

PROBLEM TO BE SOLVED: To provide anticancer health food comprising brewed vinegar produced from distilled spirit residual liquid as a new use of the brewed vinegar. SOLUTION: The anticancer health food contains brewed vinegar produced by using distilled spirit residual liquid as raw material, and acetic bacteria. COPYRIGHT: (C)2005,JPO&NCIPI

Anticancer health food

PROBLEM TO BE SOLVED: To provide an electrostatic shielding structure for a stationary induction apparatus which is resistant to a mechanical force in the radial direction of a acting on a shielding plate and is capable of suppressing rise in the local field. SOLUTION: The electrostatic field structure of the stationary induction apparatus provided with the electrostatic shielding plate 4 between a coaxially wound primary coil and a coaxially wound secondary coil. The electrostatic shielding plate 4 is divided into a plurality of plates in a direction of the periphery. Side ends 10a, 10b, 11a, 11b, adjacent to the divided electrostatic shielding plate 4, are superimposed by having each sandwiching an insulating material 12 therebetween. COPYRIGHT: (C)2006,JPO&NCIPI

Electrostatic shielding structure for stationary induction apparatus

Aromatic compounds having unusual stability provide high-value chemicals and considerable promise for carbon storage. Terrestrial plants can convert atmospheric CO2 into diverse and abundant aromatic compounds. However, it is unclear how plants control the shikimate pathway that connects the photosynthetic carbon fixation with the biosynthesis of aromatic amino acids, the major precursors of plant aromatic natural products. This study identified suppressor of tyra2 (sota) mutations that deregulate the first step in the plant shikimate pathway by alleviating multiple effector-mediated feedback regulation in Arabidopsis thaliana. The sota mutant plants showed hyperaccumulation of aromatic amino acids accompanied by up to a 30% increase in net CO2 assimilation. The identified mutations can be used to enhance plant-based, sustainable conversion of atmospheric CO2 to high-energy and high-value aromatic compounds.

Point mutations that boost aromatic amino acid production and CO2 assimilation in plants

A composition for non-injection administration comprises a neocarzinostatin derivative and medium to long chain fatty acid glycerides and may orally, intrarectally, intrathoracically or intraperitoneally be administered to cancer patients.

Hiroshi Maeda

Papers

Polysaccharide kss22d and its preparation

Anticancer health food

Electrostatic shielding structure for stationary induction apparatus

Point mutations that boost aromatic amino acid production and CO2 assimilation in plants

Compositions of neocarzinostatin derivative for oral administration