Patrick T Logan

The expression of cyclooxygenase-2 (COX-2) has been reported as an indicator of poor prognosis in a wide variety of human tumors, including colon, breast and uveal melanoma (UM). COX-2 inhibitors have shown promise in controlling the malignancy of several types of tumors. Previous studies have demonstrated the efficacy of a COX-2 inhibitor on the proliferation rates of human UM cells. The goal of this experiment was to investigate the efficiency of Nepafenac, a topically administered COX-2 inhibitor, in a rabbit model of UM. The animals were divided into two groups of 14 animals for the duration of the 12-week experiment. One animal per group was killed each week to evaluate disease progression and for histopathological studies. The experimental group received drops containing 0.3% Nepafenac solution. Intraocular tumor growth was evaluated weekly by fundoscopic examination and each animal was weighed prior to examination. Blood samples were taken weekly from all rabbits to detect circulating malignant cells (CMCs) throughout the experiment. After the second week of inoculation, the experimental group weighed significantly more than the control group. The control group developed more intraocular tumors and presented with metastases and higher detectable levels of CMCs before the treated group. These results indicate that the topical administration of a COX-2 inhibitor delayed the progression of this malignancy in our animal model. A clinical trail using an anti-COX-2 inhibitor for patients with UM should be considered.

PURPOSE:: To investigate the effect of nicotinamide on the secretion of pro-an giogenic and pro-inflammatory cytokines in uveal melanoma cell lines. METHODS:: Two human uveal melanoma cell lines (92.1 and OCM-1) were treated with nicotinamide (10 mmol/L) or control media for 48 hours in culture. The su perna tant from each culture was used in sandwich enzyme-linked immuno sorbent assay-based angiogenesis and inflammation arrays to evaluate the effects of exogenously administered nicotinamide on the secretion of a total of 20 pro-an gio genic and pro-inflammatory proteins. RESULTS:: Seven pro-angiogenic cytokines were detected under control conditions for both uveal melanoma cell lines. Treatment with nicotinamide resulted in a significant decrease in secretion of the following pro-angiogenic cytokines: angiogenin, angiopoietin-2, epidermal growth factor, and vascular epithelial growth factor-A in the 92.1 cells; basic fibroblast growth factor in the OCM-1 cells; and placenta growth factor in both cell lines. Among the pro-inflammatory proteins, monocyte chemotactic protein-1 and interleukin-8 were expressed in both untreated cell lines and both were significantly reduced when treated with nicotinamide. CONCLUSIONS:: Results from this in vitro model suggest that nicotinamide may have anti-inflammatory and anti-angiogenic properties, which may open the possibility of using it as a chemopreventive agent for uveal melanoma; however, further studies including animal models are warranted.

Superficial epithelioma with sebaceous differentiation is a rare benign epithelial neoplasm. It usually involves the head, neck or the back of a middle-age person. To the best of our knowledge, two ocular cases have been reported in the literature. A 46-year-old man of Italian descent, with a known history of testicular seminoma treated by orchiectomy with chemotherapy and radiotherapy, presented with a tan-colored lesion measuring 4mm in diameter in his right upper lid that had been growing over 10 months. It was clinically diagnosed as papilloma. An excisional biopsy was done. On histological examination, the lesion was a well-circumscribed and sharply demarcated epithelial tumor attached to the overlying epidermis and characterized by plate-like proliferation of basaloid to squamous cells with clusters of mature sebaceous cells and foci of ductal differentiation. After a follow-up period of 5 months, no recurrence of the lesion has been documented. Superficial epithelioma with sebaceous differentiation is part of the differential diagnoses of eyelid lesions. Arguments in the literature about the correct nomenclature of superficial epithelioma with sebaceous differentiation have resulted in under-diagnosed cases. The benign histological features and the lack of recurrence support its benign nature. Although no clear association has linked superficial epithelioma with sebaceous differentiation with Muir–Torre syndrome, further clinical correlation and close follow up for patients are recommended.

BACKGROUND: PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below -150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains. The cryogenic cold chain using liquid nitrogen (LN2) vapour phase (LNVP) cryoshippers, is simpler, more efficient than -80, -20 or 2-8 °C cold chains, and does not use electricity. This study was conducted to evaluate implementation and integration of a cryogenically distributed vaccine at travel and military immunization clinics. METHODS: We conducted sequential 28-day studies evaluating vaccine shipping, storage, maintenance and accession at two US military and two civilian travel health/immunization clinics. In each clinic, personnel were trained in equipment use, procurement and handling of LN2, temperature monitoring and inventory record keeping by in-person or video instruction. RESULTS: Sites required 2-4 h/person for two persons to assimilate and develop the expertise to manage vaccine storage and LNVP operations. LN2 for recharging cryoshippers was delivered every 1-2 weeks. Vaccine ordering, receipt, storage and inventory control was conducted effectively. Simulated single dose vaccine cryovial retrieval and thawing were performed successfully in different travel clinic settings. Continuous temperature monitoring at each site was maintained with only one short excursion above -150 °C (-145 °C) through shipping, use and reverse logistics. Staff, during and at study conclusion, provided feedback that has been incorporated into our models for cold chain logistics. CONCLUSIONS: These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel.