Outcome of focal treatment to residual retinoblastoma after chemotherapy (Experience with Focal Treatment of Retinoblastoma).

We report a prospective case series on the anatomical, and functional outcomes, and complications of focal treatment of retinoblastoma to residual tumors in patients who had already received chemotherapy. We examined the patients of retinoblastoma under general anaesthesia with Ret Cam II. Patients with lesions from Group 1 to Group 5 of Reese Ellsworth classification at presentation. They were first given chemotherapy according to VEC (Vincristine, Etoposide and Carboplatin) protocol and then focal treatment. Solid State Green laser photocoagulation and/or cryotherapy were applied to the lesions with help of indirect ophthalmoscope. Thirty one eyes of 26 children were treated. The mean age at presentation was 35.5 ± 6.4 (median = 24, IQR = 36) months. Fourteen (57.7%) were male and 12 (42.3%) were female. Twenty three (88.5%) children had bilateral retinoblastoma and 3 (11.5%) had unilateral involvement. Complete regression was achieved in 25 (80.6%) eyes. Only 6 (19.4%) eyes had to be enucleated. Final mean LogMAR visual acuity after treatment was0.6 ± 0.64. Transient Corneal oedema was the most commonly observed adverse effect seen immediately after laser photocoagulation in 12 (38.7%) eyes. Focal treatment is a good and effective adjuvant to systemic treatment and ophthalmologists should be aware of this modality of treatment and competent enough to use these modalities appropriately to improve the outcome of RB patients in our population.

8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells.

Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer.

Lipoprotein(a) and SYNTAX Score Association with Severity of Coronary Artery Atherosclerosis in North India.

OBJECTIVES: This cross-sectional study investigated the association of lipoprotein(a) [Lp(a)] levels as an atherosclerosis predictor and their relationship to the severity of coronary artery disease (CAD). METHODS: 360 consecutive patients at Sanjay Gandhi Postgraduate Institute of Medical Sciences and King George's Medical University hospitals, Lucknow, North India, with chest pains, CAD symptoms and on lipid-lowering therapy were enrolled between June 2009 and October 2011. Before coronary artery angiography (CAG), a fasting blood sample was assessed for lipid and Lp(a) levels. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score was calculated according to the CAG results. Patients were divided into 3 groups based on CAD severity and SYNTAX scores. RESULTS: Angiography revealed CAD in 270 patients. Lp(a) levels were higher in CAD compared to non-CAD patients (48.7 ± 23.8 mg/dl versus 18.9 ± 11.1 mg/dl [P <0.0001]). The levels of Lp(a) were lower in single than in double and triple vessels (39.3 ± 18.4 mg/dl versus 58.0 ± 23.0 mg/dl, and 69.2 ± 24.1 mg/dl, [P <0.05]). Lp(a) levels were significantly higher in severe CAD with SYNTAX score >30 (88.0±24.0 mg/dl). Lp(a) levels correlated significantly with SYNTAX scores (r = 0.70, P <0.0001). CONCLUSION: In this study, Lp(a) levels were positively associated with a patient's SYNTAX score in diseased vessels. Furthermore, an elevated Lp(a) level was a causal, independent risk factor of CAD. Lowering Lp(a) levels would reduce CAD in primary and secondary prevention settings. There is an urgent need to define more precisely which patients to treat and which to target for earlier interventions.