Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway

The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depletion suppressed tumor growth but enhanced metastasis. Pericyte depletion was further associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation. Silencing of Twist or use of a Met inhibitor suppressed hypoxia and EMT/Met-driven metastasis. In addition, poor pericyte coverage coupled with high Met expression in cancer cells speculates the worst prognosis for patients with invasive breast cancer. Collectively, our study suggests that pericytes within the primary tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis.

The immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients initiating antiretroviral therapy (ART) results from restored immunity to specific infectious or non-infectious antigens. A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating therapy characterizes the syndrome. Potential mechanisms for the syndrome include a partial recovery of the immune system or exuberant host immunological responses to antigenic stimuli. The overall incidence of IRIS is unknown, but is dependent on the population studied and its underlying opportunistic infectious burden. The infectious pathogens most frequently implicated in the syndrome are mycobacteria, varicella zoster, herpesviruses, and cytomegalovirus (CMV). No single treatment option exists and depends on the underlying infectious agent and its clinical presentation. Prospective cohort studies addressing the optimal screening and treatment of opportunistic infections in patients eligible for ART are currently being conducted. These studies will provide evidence for the development of treatment guidelines in order to reduce the burden of IRIS. We review the available literature on the pathogenesis and epidemiology of IRIS, and present treatment options for the more common infectious manifestations of this diverse syndrome and for manifestations associated with a high morbidity.

https://cdr.lib.unc.edu/downloads/x920g009n

Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options

ヒト培養滑膜細胞における Matrix Metalloproteinase 産生

Diagnosis of macular pseudoholes and lamellar macular holes by optical coherence tomography

Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year-old male with posterior uveitis.

Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis

Prevalence, correlates, and natural history of epiretinal membranes surrounding idiopathic macular holes

In a search for a pharmacologic adjuvant in the management of posttraumatic proliferative vitreoretinopathy (PVR), we investigated the effect of intravitreal injection of prinomastat (AG3340) on an experimental model. Posterior penetrating eye trauma was created in one eye each of 24 New Zealand white rabbits. One week after the surgery, all rabbits were randomized (1:1) to receive 0.5 mg prinomastat or the vehicle of the drug intravitreally every week for 6 weeks. The degree of PVR for each hemiretina was scored, and the two scores were summed to obtain a total eye score. The mean total eye score was 3.58 in the treatment group and 5.75 in the control group (p = 0.0307). The numbers of eyes with tractional retinal detachment in the prinomastat-treated (n = 12) and control (n = 12) groups were 3 and 9, respectively (p = 0.0391). These results suggest that intravitreally administered prinomastat has an inhibitory effect on posttraumatic PVR.

The Effect of Prinomastat (AG3340), a Synthetic Inhibitor of Matrix Metalloproteinases, on Posttraumatic Proliferative Vitreoretinopathy

Purpose To determine the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase, in the treatment of experimental proliferative vitreoretinopathy (PVR) induced by intravitreal dispase injection Methods One eye each of 53 New Zealand white rabbits was injected in the vitreous cavity with 007 unit of dispase to induce PVR One week after PVR induction, 53 rabbits were randomized (27:26) to receive 05 mg prinomastat or the vehicle of the drug (acidified water) intravitreally every two weeks The scores of PVR severity (scale of 1–5) were graded to compare the prinomastat-treated animals with the control group Results The average PVR scores in the treatment and control groups were 262 and 357 respectively (p = 0038; Wilcoxon rank sum) Clinically significant PVR with retinal detachment (PVR = grade 3) developed in 76% of rabbits in the control group versus 51% of rabbits treated with prinomastat Conclusions Intravitreally administered prinomastat decreased development 

Ugur Ozerdem

Papers

Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year-old male with posterior uveitis.

Effect of anti-cytomegalovirus therapy on the incidence of immune recovery uveitis in AIDS patients with healed cytomegalovirus retinitis

Prevalence, correlates, and natural history of epiretinal membranes surrounding idiopathic macular holes

The Effect of Prinomastat (AG3340), a Synthetic Inhibitor of Matrix Metalloproteinases, on Posttraumatic Proliferative Vitreoretinopathy

The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinases, on a subacute model of proliferative vitreoretinopathy.