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

Evaluation of Combustion Chamber Pressure of 1N-Class Green Monopropellant Thruster with Discharge Plasma System

Bacteriological and immunological assessment of periodontal infection during comprehensive periodontal therapy in a patient with generalized aggressive periodontitis：a case report

Preparation of Cyclic α‐Hydroxy Ketones from δ‐ and ε‐Keto Acids Induced by the Generation of a Novel Acyl Anion Equivalent from the Carboxyl Group.

前立腺癌に対する内分泌療法により動脈硬化がきたされ,その結果,高血圧や冠動脈疾患が発生する可能性があることが知られている.内分泌療法として,エストロゲン製剤を2年間投与されていた患者の腫瘍摘除術の麻酔中に,冠攣縮が発生した症例を経験した.麻酔維持は笑気-酸素-イソフルランで行なった.手術開始直後,心電図上著明なSTの上昇の後,心室性頻拍,ついで心室細動となった.心マッサージの施行およびニトログリセリンの投与により洞調律に回復した.長期にわたるエストロゲン製剤の投与により冠動脈に狭窄性病変が生じ,冠攣縮の誘因になったと考えられる.

https://www.jstage.jst.go.jp/article/jjsca1981/14/4/14_4_334/_pdf

Hiroshi Maeda

Papers

Evaluation of Combustion Chamber Pressure of 1N-Class Green Monopropellant Thruster with Discharge Plasma System

Bacteriological and immunological assessment of periodontal infection during comprehensive periodontal therapy in a patient with generalized aggressive periodontitis：a case report

Preparation of Cyclic α‐Hydroxy Ketones from δ‐ and ε‐Keto Acids Induced by the Generation of a Novel Acyl Anion Equivalent from the Carboxyl Group.

Intraoperative Coronary Spasm Possibly Associated with Estrogen Therapy

Cell-penetrating albumin enhances the sublingual delivery of antigens through macropinocytosis.