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

Chemical reactivity and state of tryptophan residues in neocarzinostatin under physiological condition.

A new high-field research center, the Tsukuba Magnet Laboratories (TML), belonging to the National Research Institute for Metals, is under construction in Tsukuba City located 60 km northeast of Tokyo. For the TML we are developing or preparing several high-field facilities, which include a 40 T class hybrid magnet, a 21 T superconducting magnet with large bore, a 80 T class long-pulsed magnet, and several kinds of small superconducting magnets. The high-field facilities will be installed in a new building, presently under construction.

Present status of the high-field research center at the National Research Institute for Metals, Japan

Das antitumoraktive Protein-Antibiotikum Neocarzinostatin wurde mit Dithiothreit in flussigem Ammoniak reduziert und mit Chloressigsaure alkyliert. Tryptische Spaltung des tetra-S-carboxymethylierten Proteins ergab 5 Fragmente. Die Sequenz von 25 Aminosaureresten im tyrosinhaltigen Fragment H3 wurde durchEdman-Abbau im automatisierten Sequenator ermittelt.

Partial sequence of the tyrosine region of neocarzinostatin

A modeling processing system is provided. The modeling processing system includes an acquisition unit, a memory, and a searching unit. The acquisition unit acquires information on a surface profile of a target three-dimensional object from a reading unit. The target three-dimensional object is a target for a modeling processing. The memory stores, for a plurality of modeled objects, a plurality of modeled object information, and each modeled object information includes surface profile information and internal structure information of the modeled object. The searching unit specifies, from among the plurality of modeled object information stored in the memory, at least one of the plurality of modeled object information based on the information on the surface profile of the target three-dimensional object acquired by the acquisition unit, as a candidate modeled object information for the modeling processing.

Modeling processing system, method of executing modeling processing, and non-transitory recording medium

RE-Ba-Cu-O (REBCO) high-temperature superconducting conductors have the advantage of high critical current density in a magnetic field above 10 T as well as tolerance to high tensile stress. REBCO high-temperature superconducting coils are expected to be applied to superconducting magnets using cryocoolers. While epoxy-resin-impregnated superconducting coils are considered to be appropriate for superconducting magnets using cryocoolers because the impregnation provides sufficient thermal conductivity, the degradation of epoxy-resin-impregnated REBCO coils due to extremely low nominal cleavage strength is a serious problem. This problem is negligible for wax (paraffin)-impregnated REBCO coils. A wax-impregnated GdBCO layer-wound coil using cryocoolers was successfully operated at a current between $-$ 300 and 300 A.

Hiroshi Maeda

Papers

Chemical reactivity and state of tryptophan residues in neocarzinostatin under physiological condition.

Present status of the high-field research center at the National Research Institute for Metals, Japan

Partial sequence of the tyrosine region of neocarzinostatin

Modeling processing system, method of executing modeling processing, and non-transitory recording medium

Operation of Wax-Impregnated GdBCO Layer-Wound Coil Using Cryocoolers