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

To investigate stabilized materials in contact with oxide superconductors for current lead, the electrical resistivity and thermal conductivity of Ag-alloy samples were measured. Measured values obtained for the Ag-Au alloys showed a strong influence by Au content at low temperature, while those for Ag-Cu alloys showed a weakly depends on Cu content. Superconducting tapes of Bi-2212 and Bi-2223 stabilized with the alloys mentioned above were prepared. The critical current density Jc of the tapes were measured by the four-probe method. A strong dependence of Jc degradation on Cu content was recognized, but, no influences by Au could be observed. Values q(Heat input per critical current at low temperature end 4.2K) were calculated to evaluate the materials as for current lead use. The Ag-Au alloy sheathed superconducting tapes can impede heat flow with a q values smaller by 2 digits than the copper leads even though a magnetic field is present around 77K.

Bi-System Oxide Superconducting Tapes Based on Silver-Alloy for Power Current Leads

The value of the free-to-total serum prostate-specific antigen (f/t PSA) ratio was compared with that of the total prostate specific antigen (tPSA) value for the prediction of clinical stage in patients with prostate cancer. The f/t PSA ratio was obtained from the frozen sera of 56 untreated patients with histologically proven BPH and 78 patients with prostate cancer. The clinical stage was organ-confined in 36, locally advanced in 20 and metastatic in 22 patients. Serum levels of free PSA (fPSA) and tPSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the tPSA value and was compared with tPSA and fPSA in the correlation with clinical stage via the Spearman rank correlation test. Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The f/t PSA ratio did not differ between patients with clinically localized and metastatic cancer. tPSA and fPSA reflected the clinical stage and the extent of bone metastasis more accurately than the f/t PSA ratio. The extent of bone metastasis had no effect on the PSA ratio. The f/t PSA ratio had no additional value in clinical staging compared to tPSA. Our study suggests that the f/t PSA ratio does not reflect tumor load.

Free-to-total prostate specific antigen ratio in clinical staging of prostate cancer

[Purpose]

We recently reported frequent detection of antibiotic-resistant bacteria on the oral mucosa during the period of hematopoietic cell transplantation (HCT) and suggested an association between oral mucositis and antibiotic-resistant bacterial infection. Methicillin-resistant Staphylococcus spp. were frequently detected, and the oral cavity may be a reservoir of the gene mediating methicillin resistance, mecA. Here, we examined the frequency of mecA carriers in patients undergoing HCT.

[Methods]

Fifty-nine patients (male (M) = 37, female (F) = 22, 47.3 ± 11.0 years) receiving HCT were enrolled in this study. Buccal swab samples were obtained four times from day −7 to day +20 (once/week), and mecA was detected by PCR. Fifty-two subjects without systemic disease, who completed dental treatment, especially periodontal treatment (M = 21, F = 31, 55.4 ± 14.2 years), were also enrolled as controls and checked for mecA on the oral mucosa.

[Results]

Seventy-six percent (45/59) of the HCT patients carried mecA at least once in the study period (days −7 to +20), while no control subjects had mecA. The frequency of mecA carriers was 19.2 % from days −7 to −1, while it was significantly increased on days +7 to +13 and +14 to +20, with frequencies of 60.9 and 63.2 %, respectively (P < 0.01, ANOVA).

[Conclusions]

mecA was detected in oral mucosa of patients undergoing HCT. The high detection frequency of staphylococci resistant to penicillin and beta-lactams in our recent report was supported.

https://ousar.lib.okayama-u.ac.jp/files/public/5/53635/20160528121415148554/Supportive Care in Cancer_22_6_1679.pdf

Distribution of oral mucosal bacteria with mecA in patients undergoing hematopoietic cell transplantation

https://iopscience.iop.org/article/10.1143/JJAP.12.1959/pdf

Hiroshi Maeda

Papers

Bi-System Oxide Superconducting Tapes Based on Silver-Alloy for Power Current Leads

Free-to-total prostate specific antigen ratio in clinical staging of prostate cancer

Distribution of oral mucosal bacteria with mecA in patients undergoing hematopoietic cell transplantation

Strong Temperature Dependence of the Coercivity of Pr(Co 1-x Cu x ) 5 Compounds

Preparation of High-T_c Bi-Sr-Ca-Cu-O Superconductors : Electrical Properties of Condensed Matter