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

An indigo dye plant, Polygonum tinctorium has been shown to have anti-inflammatory and antibacterial effects against pathogens causing periodontitis. In this study, the effect of Polygonum tinctorium extract on gingival inflammation was investigated in a double-blind fashion. Thirty patients with chronic periodontitis who had received supportive periodontal therapy (SPT) were enrolled. All subjects rubbed one gram of jell including Polygonum tinctorium extract on the gingiva three times per day after each meal and oral care for ten weeks. The clinical examinations of plaque index (PlI), probing pocket depth (PPD) and bleeding score (BOP) on four subjective teeth were performed before test and after five and ten weeks. We also measured the weight of gingival crevicular fluid (GCF) and TNF-αlevels in the GCF at same periods. 連絡先:畑中加珠 〒 700-8525 岡山県岡山市鹿田町 2-5-1 岡山大学大学院医歯薬学総合研究科歯周病態学分野 Kazu Hatanaka Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences 2-5-1 Shikata-cho, Okayama 700-8525, Japan E-mail : kazu_t@md.okayama-u.ac.jp 167

Effect of Polygonum tinctorium extract against gingival inflammation

PURPOSE:To provide an oil-based composition composed of aclarubicin (hydrochloride), a saturated medium fatty acid, unsaturated medium fatty acid or unsaturated higher fatty acid, and an iodized oil or vegetable oil, capable of transferring the antitumor substance to the tumor organ in high efficiency and improving the remedying effect of the substance. CONSTITUTION:The objective oil-based composition is composed of (A) aclarubicin or aclarubicin hydrochloride, (B) saturated or unsaturated medium fatty acid (e.g. capric acid, caprylic acid, etc.) and/or unsaturated higher fatty acid (e.g. linoleic acid and (C) an iodized oil (e.g. iodized poppy oil fatty acid ethyl ester) and/or a vegetable oil (e.g. sesame oil). Since the component A can be dissolved easily in the components B and C, a high-concentration solution of antitumor substance can be prepared. The concentration of the component A in the composition is 1-100mg(titer)/1ml, and the amount of the component B is 30-200pts.wt. per 1pt.wt. of aclarubicin hydrochloride.

Oil-based composition of aclarubicin or its hydrochloride

We report a case in which the completely obstructed ureter was successfully treated by endourological procedure. The patient was a 66-year-old male who had been admitted for panperitonitis caused by diverticulitis perforation of the sigmoid colon. About one month later, leakage of both stool and urine and left hydronephrosis were observed. Therefore, left percutaneous nephrostomy was performed and the artificial anus was created. Radiographic examination showed about 1 cm defect on the lower one-third of the left ureter. (1st Operation) A 9.5 Fr. rigid ureteroscope was inserted into the left ureter transurethrally and a 7.5 Fr. flexible ureteroscope was inserted percutaneously. Antegrade puncture using a stiff end of a 0.038-inch guidewire into the obstructed segment was failed. Then, we bit off the obliterated tissue with a biopsy forceps transurethrally towards the light from the flexible scope, and a 12 Fr. double-J stent was indwell. (2nd Operation) Eight weeks after the first operation, a 12 Fr. ureteroresectoscope was inserted transurethrally. Full-thickness cold-knife incision of the re-established ureter was failed, however. (3rd Operation) Two weeks after the second operation, a 12.5 Fr. ureteroscope was inserted transurethrally, and a full-thickness incision in the lateral position of the re-established ureter was successfully made by KTP-laser. Then, a 12 Fr. endopyelotomy stent was placed. (Result) Six weeks after the third operation, the stent was removed and DIP revealed the improvement in hydronephrosis. The patient presented no recurrence at 2-year follow up.

[Endoscopic ureteroureterostomy for a complete obstructed ureter: a case report].

[Angled view in cineangiocardiography (author's transl)].

An interesting observation reported that the critical micelle concentrations of an ionic amphiphilic block copolymer increased with the salt concentration. Numerical solutions of the Poisson–Boltzm...

Hiroshi Maeda

Papers

Effect of Polygonum tinctorium extract against gingival inflammation

Oil-based composition of aclarubicin or its hydrochloride

[Endoscopic ureteroureterostomy for a complete obstructed ureter: a case report].

[Angled view in cineangiocardiography (author's transl)].

An Electrostatic Model for the Unusual Salt Effect on the Stability of Ionic Copolymer Micelles