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

Leuprolide causes pure red cell aplasia

Aromatic aminotransferases (Aro ATs) are pyridoxal-5-phosphate (PLP)-dependent enzymes that catalyze the transamination reactions of an aromatic amino acid (AAA) or a keto acid. Aro ATs are involved in biosynthesis or degradation of AAAs and play important functions in controlling the production of plant hormones and secondary metabolites, such as auxin, tocopherols, flavonoids, and lignin. Most Aro ATs show substrate promiscuity and can accept multiple aromatic and non-aromatic amino and keto acid substrates, which complicates and limits our understanding of their in planta functions. Considering the critical roles Aro ATs play in plant primary and secondary metabolism, it is important to accurately determine substrate specificity and kinetic properties of Aro ATs. This chapter describes various methodologies of protein expression, purification and enzymatic assays, which can be used for biochemical characterization of Aro ATs. 

Biochemical characterization of plant aromatic aminotransferases.

Interferon inducing agent containing polysaccharide mainly

There is provision of an information processing device for processing three-dimensional information representing a three-dimensional shape of a solid object to be modeled by a solid object modeling device configured to model the solid object by depositing a plurality of layers each of which is formed by discharging the filamentary molding material on the flat surface. The information processing device is configured to acquire the three-dimensional information, generate a plurality of pieces of layer information corresponding to the respective layers of the filamentary molding materials, by slicing the three-dimensional information, generate deposition information used for depositing the filamentary molding material from the layer information, generate gap region information representing a gap region to be formed between the filamentary molding materials based on the deposition information, and generate discharging information for controlling discharge of the filamentary molding material, in accordance with the deposition information and the gap region information.

Information processing device, solid object modeling system, and information processing method

An unusual systemic arteriovenous malformation arising from the left 9th intercostal artery, taking a caudal course through the left paravertebral veins, eventually drained into the left ascending lumbar vein, as illustrated at computed tomography and angiography. An embryologic maldevelopment of the azygos venous system is not the only possible explanation for venous drainage in the caudal direction. We believe that predominant venous drainage can take place in either direction because of the potentially bidirectional flow in the vertebral venous systems.

Hiroshi Maeda

Papers

Leuprolide causes pure red cell aplasia

Biochemical characterization of plant aromatic aminotransferases.

Interferon inducing agent containing polysaccharide mainly

Information processing device, solid object modeling system, and information processing method

PARAVERTEBRAL ARTERIOVENOUS MALFORMATION WITH VENOUS CONNECTION TO LEFT ILIAC VEIN Report of a case