Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer

The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a limited (n=33) number of patients. Broad-spectrum matrix metalloproteinase activity and both the active and latent forms of the gelatinases matrix metalloproteinase-2 and -9 were higher in tumour than in normal mucosa. The ratio's between active and latent forms of matrix metalloproteinase-2 and -9 were highest in tumour tissue and normal mucosa, respectively. Matrix metalloproteinase-2 levels, both active and latent forms, correlated inversely with stage of disease, the tumours without synchronous distant metastases containing significantly (P=0.005) more active matrix metalloproteinase-2 than the others. At much lower levels of activity, the same trend was observed in distant normal mucosa. The level of latent form of matrix metalloproteinase-9 in tumour depended on tumour location. Neither the active form of matrix metalloproteinase-9 nor broad-spectrum matrix metalloproteinase activity in tumour tissue did correlate with any of the clinicopathological parameters investigated. The results demonstrate explicit differences between the activity of matrix metalloproteinase-2 and -9, indicating different roles for both gelatinases in tumour progression. Such data are necessary in order to develop rational anti-cancer therapies based on inhibition of specific matrix metalloproteinases

Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

Methods to Identify Linear Network Models: A Review

In many contexts we may be interested in understanding whether direct connections between agents, such as declared friendships in a classroom or family links in a rural village, affect their outcomes. In this paper we review the literature studying econometric methods for the analysis of linear models of social effects, a class that includes the ‘linear-in-means’ local average model, the local aggregate model, and models where network statistics affect outcomes. We provide an overview of the underlying theoretical models, before discussing conditions for identification using observational and experimental/quasi-experimental data

Biomechanical considerations in the pathogenesis of osteoarthritis of the knee

Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity

New biomedical polyurethane ureas with high tear strengths

Biodegradable polyurethanes ureas (PUU) were synthesized by a two step polymerization. First a poly (epsilon-caprolactone) prepolymer was terminated with three different diisocyanates: lysinediisocyanate (LDI), 1,6-hexanediisocyanate (HDI) and 1,4-butanediisocyanate (BDI). Second the prepolymers were chain extended with 1,4-butanediamine. The degradation products of these polymers are non-toxic. The mechanical properties of the PUU are compared with those of three PU's. Compared to these PU's, the HDI and BDI based PUU showed a very high resistance to tearing

Accuracy of a novel trace-registration method for dynamic navigation surgery.

A technology called Trace Registration (TR) has been introduced to allow dynamic navigation of implant placement without the need for a thermoplastic stent. This study was undertaken in order to validate the accuracy of the TR protocol for dynamically guided implant surgery. A retrospective, observational, in vivo study was performed using dynamic navigation via the TR protocol. The preoperative cone beam computed tomography (CBCT) plan was superimposed and registered (aligned) with the postoperative CBCT scan to assess accuracy parameters. A total of 136 implants were placed in 59 partially edentulous arches. Mean deviation between the planned and actual position for all implants was 0.67 mm at the coronal level (entry point), 0.9 mm at the apical level, and 0.55 mm in depth, with an angle discrepancy of 2.50 degrees. Tracing 5 to 6 teeth tended to improve accuracy results compared to tracing 3 to 4 teeth. TR is as accurate as traditional registration and statically guided methods for implant surgery