Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.

https://zenodo.org/record/1230948/files/article.pdf

p53 mutations in human cancers

How useful is SBF in predicting in vivo bone bioactivity

Ceramics used for the repair and reconstruction of diseased or damaged parts of the musculo-skeletal system, termed bioceramics, may be bioinert (alumina, zirconia), resorbable (tricalcium phosphate), bioactive (hydroxyapatite, bioactive glasses, and glass-ceramics), or porous for tissue ingrowth (hydroxyapatite-coated metals, alumina). Applications include replacements for hips, knees, teeth, tendons, and ligaments and repair for periodontal disease, maxillofacial reconstruction, augmentation and stabilization of the jaw bone, spinal fusion, and bone fillers after tumor surgery. Carbon coatings are thromboresistant and are used for prosthetic heart valves. The mechanisms of tissue bonding to bioactive ceramics are beginning to be understood, which can result in the molecular design of bioceramics for interfacial bonding with hard and soft tissues. Composites are being developed with high toughness and elastic modulus match with bone. Therapeutic treatment of cancer has been achieved by localized delivery of radioactive isotopes via glass beads. Development of standard test methods for prediction of long-term (20-year) mechanical reliability under load is still needed.

/pdf/bioceramics-from-concept-to-clinic-2yhvynvuom.pdf

Bioceramics: From Concept to Clinic

Bioceramics : from concept to clinic

Pathology and genetics of tumors of soft tissue and bone

High-strength bioactive glass-ceramic A-W was soaked in various acellular aqueous solutions different in ion concentrations and pH. After soaking for 7 and 30 days, surface structural changes of the glass-ceramic were investigated by means of Fourier transform infrared reflection spectroscopy, thin-film x-ray diffraction, and scanning electronmicroscopic observations, in comparison with in vivo surface structural changes. So-called Tris buffer solution, pure water buffered with trishydroxymethyl-aminomethane, which had been used by various workers as a "simulated body fluid," did not reproduce the in vivo surface structural changes, i.e., apatite formation on the surface. A solution, ion concentrations and pH of which are almost equal to those of the human blood plasma--i.e., Na+ 142.0, K+ 5.0, Mg2+ 1.5, Ca2+ 2.5, Cl- 148.8, HCO3- 4.2 and PO4(2-) 1.0 mM and buffered at pH 7.25 with the trishydroxymethyl-aminomethane--most precisely reproduced in vivo surface structure change. This shows that careful selection of simulated body fluid is required for in vitro experiments. The results also support the concept that the apatite phase on the surface of glass-ceramic A-W is formed by a chemical reaction of the glass-ceramic with the Ca2+, HPO4(2-), and OH- ions in the body fluid.

Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W.

It has been shown for various types of glasses and glass-ceramics that the essential condition for them to bond to living bone is the formation of an apatite layer on their surfaces in the body. CaO,SiO 2 -based glasses formed the surface apatite layer in a simulated body fluid, whereas CaO,P 2 O 5 -based glasses did not form it. This means that the rate of the apatite nucleation on the surfaces of the former glasses is much higher than that of the latter glasses. The increase in the degree of the supersaturation of the surrounding fluid with respect to the apatite due to dissolution of the calcium ion from the CaO,SiO 2 -based glasses was almost equal to that due to dissolution of the phosphate ion from the CaO,P 2 O 5 -based glasses. The high rate of the apatite nucleation on the surface of the former glasses is therefore attributed to the lower interface energy between the apatite and the glass surfaces. The CaO,SiO 2 -based glasses form a silica hydrogel on their surfaces prior to formation of the apatite layer. This means that the hydrated silica provides specific favorable sites for the apatite nucleation.

Mechanism of apatite formation on CaOSiO2P2O5 glasses in a simulated body fluid

A new murine model of accelerated senescence

Glass-ceramic A-W, containing crystalline apatite and wollastonite in a MgO-CaO-SiO2 glassy matrix shows high bioactivity as well as high mechanical strength, but other ceramics containing the same kinds of crystalline phases in different glassy matrices do not show the same bioactivity. In order to investigate the bone-bonding mechanism of this type of glass-ceramic, surface structural changes of the glass-ceramics after exposure to simulated body fluid were analyzed with various techniques. A solution with ion concentrations which are almost equal to those of the human blood plasma was used as the simulated body fluid, instead of Tris-buffer solution hitherto used. For analyzing the surface structural changes, thin-film x-ray diffraction was used in addition to conventional techniques. It was found that a bioactive glass-ceramic forms a Ca, P-rich layer on its surface in the fluid but nonbioactive ones do not, and that the Ca, P-rich layer consists of carbonate-containing hydroxyapatite of small crystallites and/or defective structure. These findings were common to those of Bioglass-type glasses. So, we conclude that the essential condition for glass and glass-ceramic to bond to bone is the formation of the surface apatite layer in the body environment but it is not essential to contain apatite within the material. Bioactivity of glass and glass-ceramic can be evaluated in vitro by examining the formation of the surface apatite layer in the simulated body fluid described above.

Ca, P‐rich layer formed on high‐strength bioactive glass‐ceramic A‐W

Treatment of a chondral lesion in the knee, associated with anterior cruciate ligament disruption, is known to be difficult and controversial. This article presents an arthroscopic technique for transplantation of multiple osteochondral fragments, harvested from the same knee, to this chondral lesion. A 3-year follow-up shows excellent results with good cartilage repair confirmed by second-look arthroscopy.

Takao Yamamuro

Papers

Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W.

Mechanism of apatite formation on CaOSiO2P2O5 glasses in a simulated body fluid

A new murine model of accelerated senescence

Ca, P‐rich layer formed on high‐strength bioactive glass‐ceramic A‐W

Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption