TLD1433 photosensitizer inhibits conjunctival melanoma cells in zebrafish ectopic and orthotopic tumour models

The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21mW/cm(2), 19 J.cm(-2), 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (RO) into the fish. Optimally, four consecutive PDT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW/cm(2), 114 J.cm(-2), 520 nm). This PDT protocol was not toxic to the fish. In the ectopic tumour model, both systemic administration by IV injection and RO injection of TLD1433 significantly inhibited growth of engrafted CRMM1 and CRMM2 cells. However, in the orthotopic model, tumour growth was only attenuated by localized RO injection of TLD1433. These data unequivocally prove that the zebrafish provides a fast vertebrate cancer model that can be used to test the administration regimen, host toxicity and anti-cancer efficacy of PDT drugs against CM. Based on our results, we suggest repurposing of TLD1433 for treatment of incurable CM and further testing in alternative pre-clinical models.Animal science

The intracrine renin-angiotensin system.

Item does not contain fulltextThe RAS (renin-angiotensin system) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, AngII (angiotensin II), is neither synthesized in nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate their function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is enhanced further by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The present review provides a synopsis of the literature on this system in different tissues.1 september 201

Differences of Clinical Characteristics and Drug Prescriptions between Men and Women with COPD in China

Background: Sex differences in symptoms exist in patients with COPD. Our aim is to measure the differences between men and women with COPD, focusing on risk factors, symptoms, quality of life and drug prescriptions. Methods: In this cross-sectional observational study, patients with COPD were collected in China; demographic characteristics, smoking history, occupational exposure, biomass exposure, lung function, dyspnea, quality of life, and prescriptions for inhaled medications were collected. The nearest neighbor algorithm was used to match female and male patients (ratio 2:1) on age, body mass index, and lung function. Results: Compared with 1462 men, the 731 women generally had lower educational levels and were married less (both p < 0.001). A total of 576 (90.0%) women did not smoke cigarettes. More men were exposed to occupational dust (539 (36.9%) vs. 84 (11.5%), p = 0.013), while more women were exposed to biomass smoke (330 (45.1%) vs. 392 (26.8%), p = 0.004). Except for phlegm and chest tightness, women had more complaints than men for cough, breathlessness, activities, confidence, sleep and energy (p < 0.05). In addition, more women were prescribed triple therapy than men (236 (36.3%) vs. 388 (31.0%), p = 0.020). Conclusions: There are obvious discrepancies in the quality of life and use of inhaled medications between male and female patients with COPD

Spatial and seasonal variations in chaetognath assemblages in the subtropical coastal waters of Hong Kong.

International audienc

Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning

10.1152/ajpheart.00244.2008American Journal of Physiology - Heart and Circulatory Physiology295