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Purpose: To determine whether postoperative oral 13-cis-retinoic acid (RA) treatment could improve the outcome of vitreoretinal surgery with silicone oil for the management of proliferative vitreoretinopathy (PVR). Design: Prospective controlled randomized interventional case series. Methods: This study included 35 eyes of 35 patients with primary rhegmatogenous retinal detachment and PVR. All patients underwent surgical repair by similar procedures. The RA group consisted of 16 patients who received 10 mg oral RA twice daily for eight weeks postoperatively. The control group included 19 patients without taking RA. The outcome measure included the rate of retinal attachment, macular pucker formation, ambulatory vision, and RA–related side effects. Results: At last follow-up (at least one year postoperatively), 15 of 16 eyes (93.8%) in the RA group and 12 of 19 eyes (63.2%) in the control group maintained retinal attachment (P = .047). The rate of macular pucker formation was significantly lower in the RA group (18.8% vs 78.9% in the control group; P = .001). A higher rate of ambulatory vision was achieved in the RA group as compared to the control group (56.3% vs 10.5%; P = .009). Conclusions: Postoperative administration with oral moderate dosage of RA for eight weeks appears to maintain retinal attachment, decrease the macular pucker, and improve vision after surgical repair for eyes with PVR. [Copyright &y& Elsevier]

Purpose: To investigate racial and ethnic differences in the incidence of conjunctival melanoma in a large population-based study. Design: Observational cross-sectional study. Methods: Using data from 1992 through 2003 provided by the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of conjunctival melanoma in various racial and ethnic groups (Black, American Indian, Asian and Pacific Islander, Hispanic, and non-Hispanic White). In addition, we calculated the standard incidence ratios (risk ratios) and 95% confidence intervals to describe the differences within these racial and ethnic groups. Results: From 1992 through 2003, there were a total of 168 conjunctival melanomas diagnosed in 13 SEER registries with known racial and ethnic groups. The annual age-adjusted incidence rates (per million population) of conjunctival melanoma was 0.18 (Blacks), 0.17 (American Indians), 0.15 (Asians), 0.33 (Hispanics), and 0.49 (non-Hispanic Whites). The difference in the incidence of conjunctival melanoma between Whites and Blacks or Asians was statistically significant, but was not significant between Blacks and Asians. Conclusions: The overall White-to-Black incidence ratio in conjunctival melanoma was 2.6:1, which is much less than that of uveal melanoma (18:1) and cutaneous melanoma (13:1 to 26:1), but is similar to that of mucosal melanoma (2.2:1 to 2.3:1). The cause and significance of this difference of racial and ethnic incidence in various melanomas are discussed. [Copyright &y& Elsevier]

Abstract: Involvement of activities of mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) remains unsolved in norcantharidin-associated breast cancer cell apoptosis. This study investigated the anti-cancer effect of norcantharidin and its underlying mechanism in two human breast cancer cell lines, estrogen receptor (ER)− HS-578T and ER+ MCF-7 cells. Norcantharidin induced potent cytotoxicity and arrested cell growth through increasing phosphorylation of Chk1, Chk2 and total p21Waf1/Cip1 and reducing cyclin B and cdc25c expression. It also induced apoptosis through extrinsic death receptor and intrinsic mitochondrial pathways by cytochrome c release, caspase activation, oligonucleosome appearance, PARP cleavage, and aberration of Bcl-2 family protein expression and phosphorylation. Although norcantharidin did not affect STAT1, STAT3, and STAT5 protein expression, it suppressed STAT3 and STAT5 phosphorylation in HS-578T cells, whereas it up-regulated STAT1 phosphorylation and down-regulated STAT5 phosphorylation in MCF-7 cells. Moreover, norcantharidin activated MAPK family member proteins, extracellular signal-regulated kinase (ERK), p38MAPK and c-Jun N-terminal kinase (JNK), were all phosphorylated by treatment. Pretreatment with selective kinase inhibitors significantly attenuated the norcantharidin-induced cytotoxicity in breast cancer cells. These findings suggest the potential involvement of MAPK and STAT pathways in norcantharidin-induced apoptogenesis. Norcantharidin may be an effective anti-cancer drug against breast cancer. [Copyright &y& Elsevier]

Abstract: Norcantharidin exhibits cytotoxicity in many cancer cell lines, including colorectal cancer (CRC) cells. Its cytotoxic potency on primary CRC cells and other normal constituent cells of the human body remains elusive. This study investigates whether norcantharidin differentially exhibits cytotoxicity on primarily isolated CRC cells and dermal fibroblasts. The in vitro chemosensitivity of norcantharidin was measured using a MTT tetrazolium assay and compared with 73 primary tumor cells from surgically excised colorectal tumors, six human CRC cell lines and dermal fibroblasts. Observations of cytotoxicity to primary tumor cells reveal significant differences among genders and histological types; however, drug-induced chemosensitivity was not correlated with age or clinical stages of CRC patients. Norcantharidin had a similar cytotoxic effect on primary tumor cells and CRC cell lines in a dose-dependent manner. In contrast, normal fibroblasts were more resistant to norcantharidin-induced cytotoxicity than CRC cells. DAPI staining results demonstrated that norcantharidin caused CRC cell apoptosis by nuclear fragmentation and chromatin condensation. The release of cytochrome c and the triggering of caspase-3, -8 and -9 activation mediated apoptotic induction. Conversely, pretreatment with caspases or mitogen-activated protein kinase (MAPK) inhibitors significantly suppressed norcantharidin-induced CRC cytotoxicity. These in vitro results suggest that norcantharidin may be a safe and effective anti-cancer drug for CRC. [Copyright &y& Elsevier]

Abstract: Oxidative damage from reactive oxygen species (ROS) has been implicated in many diseases, including age-related macular degeneration, in which the retinal pigment epithelium (RPE) is considered a primary target. The aim of this study was to determine whether erythropoietin (EPO) protects cultured human RPE cells against oxidative damage and to identify the pathways that may mediate protection. EPO (1 IU/ml) significantly increased the viability of oxidant-treated RPE cells, decreased the release of the inflammatory cytokines tumor necrosis factor-α and interleukin-1β, recovered the RPE cells'' barrier integrity disrupted by oxidative stress, prevented oxidant-induced cell DNA fragmentation and membrane phosphatidylserine exposure, and also reduced the levels of oxidant-induced intracellular ROS and restored cellular antioxidant potential, total antioxidant capacity, glutathione peroxidase, and superoxide dismutase and decreased malondialdehyde, the end product of lipid peroxidation. EPO inhibited caspase-3-like activity. Protection by EPO was partly dependent on the activation of Akt1 and the maintenance of the mitochondrial membrane potential. No enhanced or synergistic protection was observed during application of Z-DEVD-FMK (caspase-3 inhibitor) combined with EPO compared with cultures exposed to EPO and H2O2 alone. Together, these results suggest that EPO could protect against oxidative injury-induced cell death and mitochondrial dysfunction in RPE cells through modulation of Akt1 phosphorylation, mitochondrial membrane potential, and cysteine protease activity. [Copyright &y& Elsevier]

The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F2α receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible. [Copyright &y& Elsevier]