Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

Retinal Macroglial Responses in Health and Disease

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes andM¨uller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors.Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases.The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.

Effect of overnight orthokeratology on conjunctival goblet cells

Objective: To evaluate the differences between goblet cell density (GCD) and symptomatology after one month of orthokeratology lens wear. Methods: A pilot, short-term study was conducted. Twenty-two subjects (29.7. ±. 7.0 years old) participated voluntarily in the study. Subjects were divided into two groups: habitual silicone hydrogel contact lens wearers (SiHCLW) and new contact lens wearers (NCLW). Schirmer test, tear break up time (TBUT), Ocular Surface Disease Index (OSDI) questionnaire and conjunctival impression cytology. GCD, mucin cloud height (MCH) and cell layer thickness (CLT) were measured. All measurements were performed before orthokeratology fitting and one month after fitting to assess the evolution of the changes throughout this time. Results: No differences in tear volume and TBUT between groups were found (p>0.05). However, the OSDI score was statistically better after one month of orthokeratology lens wear than the baseline for the SiHCLW group (p=0.03). Regarding the goblet cell analysis, no differences were found in CLT and MCH from the baseline visit to the one month visit for the SiHCLW compared with NCLW groups (p>0.05). At baseline, the GCD in the SiHCLW group were statistically lower than NCLW group (p<0.001). There was a significant increase in GCD after orthokeratology fitting from 121±140cell/mm2 to 254±130cell/mm2 (p<0.001) in the SiHCLW group. Conclusion: Orthokeratology improves the dry eye subject symptoms and GCD after one month of wearing in SiHCLW. These results suggest that orthokeratology could be considered a good alternative for silicone hydrogel contact lens discomfort and dryness. © 2016 British Contact Lens Association.