Cellular interaction with the extracellular matrix is thought to be a critical event in controlling angiogenesis and tumor growth. In our previous studies, genetically distinct noncollagenous (NC) domains of type-IV collagen were shown to interact with integrin receptors expressed on the surface of endothelial cells. Moreover, these NC1 domains were shown to inhibit angiogenesis in vivo. Here, we provide evidence that a recombinant form of the alpha2(IV)NC1 domain of type-IV collagen could bind integrins alpha1beta1 and alphavbeta3 expressed on melanoma cells and inhibit tumor cell adhesion in a ligand-specific manner. Systemic administration of recombinant alpha2(IV)NC1 domain potently inhibited M21 melanoma tumor growth within full thickness human skin and exhibited a dose-dependent inhibition of tumor growth in nude mice. Interestingly, alpha2(IV)NC1 domain enhanced cellular senescence in tumor cells in vitro and in vivo. Taken together, these results suggest that recombinant alpha2(IV)NC1 domain is not only a potent anti-angiogenic reagent, but it also directly impacts tumor cell behavior. Thus, alpha2(IV)NC1 domain represents a potent inhibitor of tumor growth by impacting both endothelial and tumor cell compartments.

Urinary retention is a common complication of post-surgery and anaesthesia and is commonly known as Post-operative Urinary Retention (POUR). The risk of retention is especially high following anorectal surgery, hernia repair, and orthopedic surgery and increases with advancing age of the patient. Many factors are thought to contribute to the development of POUR including traumatic catheterization, pre-existing urologic pathology, and increased fluid requirements of surgery combined with the use of analgesics, opiates and components of anaesthesia The regular capacity of the bladder ranges between 400-600 cc, with the first signal of micturition occurring when the bladder capacity is at 150 cc to the feeling of fullness when to capacity reaches 300 cc. The sensation of fullness occurs at a certain level of afferent activity. Once the voluntary signal to begin voiding has been issued, neurons in pontine micturition centre fire maximally causing the wall of the bladder to contract via the stretch receptors in the bladder. Consequently, the parasympathetic neurons are activated leading to the contraction of the detrusor muscle and relaxation of the bladder neck resulting in micturition. Hindrance to these pathways can accelerate the likelihood of developing POUR. Conservative measure are needed to assist the patient to pass urine, else the bladder will need to be drained using either an intermittent catheter or an indwelling urethral catheter. While there exists little information concerning the outcome of retrospective studies on POUR, this particular review sheds new light on the management strategies and risk factors for the development of POUR after orthopedic surgery to prevent the long-term consequences of this complication.

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