Sunglasses to hide behind may also prevent melanoma of the eyes.

In 1967, Sandy Posey pronounced that sunglasses are essential beachwear ( https://www.youtube.com/watch?v=4HVBEb-GA1Y ). Now, whole-genome sequencing reveals that ultraviolet radiation (UVR) can contribute to melanomas in the iris and conjunctiva, data that provide a molecular explanation for why it is important to protect our eyes from exposure to UVR.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Living with xeroderma pigmentosum: comprehensive photoprotection for highly photosensitive patients.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease of deoxyribonucleic acid (DNA) repair with ultraviolet (UV) radiation sensitivity and a 10 000-fold increased risk of skin cancer. Symptoms include: freckle-like pigmentation in sun-exposed skin before age 2 years, severe burns after minimal sun exposure (50% of patients) and damage to exposed surfaces of the eyes with loss of vision and ocular cancer. About 25% of patients develop a progressive neurodegeneration. The combination of an inherited inability to repair UV-induced DNA damage and environmental exposure to UV must occur for cutaneous and ocular symptoms to develop. There is no cure for XP, but many of its manifestations may be reduced or prevented through consistent UV protection; thus XP serves as a model for sun protection of patients with marked photosenstivity. Sun protective clothing including hats, sunglasses and face shields, sun screen lotions and avoidance of environmental sources of UV are cornerstones of prevention of skin and eye damage and cancer. Although XP is a serious disease with the potential for limitation of life expectancy, XP patients can live active lives while at the same time avoiding UV.

Outdoor workers' sun-related knowledge, attitudes and protective behaviours: a systematic review of cross-sectional and interventional studies.

Sun protection is a major concern for outdoor workers as they are particularly exposed to solar ultraviolet radiation and therefore at increased risk of developing some forms of skin cancer, cataract and ocular neoplasm. In order to provide an overview of outdoor workers' sun-related knowledge, attitudes and protective behaviours as reported in the literature and to evaluate the effectiveness of sun-safety education programmes in outdoor occupational settings, we conducted a systematic review of the literature by searching three electronic databases (PubMed, Embase, PsycINFO) from their inception up to 25 April 2012. An extensive hand search complemented the database searches. We identified 34 relevant articles on descriptive studies and 18 articles on interventional studies. Considerable numbers of outdoor workers were found to have sun-sensitive skin types; sunburn rates per season ranged from 50% to 80%. Data concerning outdoor workers' sun-related knowledge and attitudes were scarce and controversial. The reported sun-protective behaviours were largely inadequate, with many workers stating that they never or only rarely wore a long-sleeved shirt (50-80%), sun-protective headgear (30-80%) and sunscreen (30-100%) while working in the sun. However, there is growing evidence that occupational sun-safety education is effective in increasing outdoor workers' sun-protection habits and presumably in decreasing sunburn rates. Occupational sun-safety education programmes offer great potential for improving outdoor workers' largely insufficient sun-protective behaviours. It is hoped that, in the future, committed support from healthcare authorities, cancer foundations, employers and dermatologists will open the way for rapid and uncomplicated implementation of sun-safety education programmes.

CTL induction of tumoricidal nitric oxide production by intratumoral macrophages is critical for tumor elimination.

To characterize mechanisms of CTL inhibition within an ocular tumor microenvironment, tumor-specific CTLs were transferred into mice with tumors developing within the anterior chamber of the eye or skin. Ocular tumors were resistant to CTL transfer therapy whereas skin tumors were sensitive. CTLs infiltrated ocular tumors at higher CTL/tumor ratios than in skin tumors and demonstrated comparable ex vivo effector function to CTLs within skin tumors indicating that ocular tumor progression was not due to decreased CTL accumulation or inhibited CTL function within the eye. CD11b(+)Gr-1(+)F4/80(-) cells predominated within ocular tumors, whereas skin tumors were primarily infiltrated by CD11b(+)Gr-1(-)F4/80(+) macrophages (Ms), suggesting that myeloid derived suppressor cells may contribute to ocular tumor growth. However, CD11b(+) myeloid cells isolated from either tumor site suppressed CTL activity in vitro via NO production. Paradoxically, the regression of skin tumors by CTL transfer therapy required NO production by intratumoral Ms indicating that NO-producing intratumoral myeloid cells did not suppress the effector phase of CTL. Upon CTL transfer, tumoricidal concentrations of NO were only produced by skin tumor-associated Ms though ocular tumor-associated Ms demonstrated comparable expression of inducible NO synthase protein suggesting that NO synthase enzymatic activity was compromised within the eye. Correspondingly, in vitro-activated Ms limited tumor growth when co-injected with tumor cells in the skin but not in the eye. In conclusion, the decreased capacity of Ms to produce NO within the ocular microenvironment limits CTL tumoricidal activity allowing ocular tumors to progress.

Conjunctival sac fluid contains elevated levels of soluble TRAIL: implications for the anti-tumoral surveillance of the anterior surface of the eye.

Little is known on the ability of different epithelia to release soluble TNF-related apoptosis-inducing ligand (TRAIL) and the relevance of TRAIL secretion by epithelial cells is still incompletely understood. On these bases, we have measured the concentration of soluble TRAIL by ELISA in the conjunctival sac fluid. It was the highest ever detected in a biological fluid (mean value of 26,800 pg/ml), being approximately 20-fold greater than that found in human saliva and >200-fold greater than that detected in human serum. On the other hand, osteoprotegerin, the soluble decoy receptor of TRAIL, was almost undetectable in the conjunctival sac fluid. Of note, the levels of soluble TRAIL measured in conjunctival sac fluid were in the range able to induce in vitro apoptosis of lymphoma cells. By in situ immunohistochemistry, TRAIL protein expression was predominantly detected in the corneal epithelium and, to a less extent, in the conjunctival epithelium. By flow cytometry analysis, membrane-associated TRAIL was documented in isolated corneal epithelial cells obtained from patients undergoing photorefractive keratectomy (PRK). The key contribution provided by corneal epithelium to the production of soluble TRAIL was underscored in time-course experiments, in which a marked decrease of the levels of soluble TRAIL in the conjunctival sac fluid was demonstrated 1 day after PRK followed by a progressive recovery at days 5-30 after PRK. Taken together, our findings strongly support a major role of soluble TRAIL in protecting cornea and conjunctiva from tumor formation and/or invasion.

Germ-line gene modification and disease prevention: some medical and ethical perspectives.

There has been considerable debate about the ethics of human germ-line gene modification. As a result of recent advances in the micromanipulation of embryos and the laboratory development of transgenic mice, a lively discussion has begun concerning both the technical feasibility and the ethical acceptability of human germ-line modification for the prevention of serious disease. This article summarizes some of the recent research on germ-line gene modification in animal models. Certain monogenic deficiency diseases that ultimately might be candidates for correction by germ-line intervention are identified. Several of the most frequently considered ethical issues relative to human germ-line gene modification are considered in the context of professional ethics, parental responsibility, and public policy. Finally, it is suggested that there is merit in continuing the discussion about human germ-line intervention, so that this technique can be carefully compared with alternative strategies for preventing genetic disease.

CD4+ T-cell-dependent tumour rejection in an immune-privileged environment requires macrophages.

Although intraocular tumours reside in an immune-privileged site, they can circumvent immune privilege and undergo rejection. Ocular tumour rejection typically follows one of two pathways. One pathway involves CD4+ T cells, delayed-type hypersensitivity (DTH), and culmination in ischemic necrosis of the tumour and phthisis (atrophy) of the eye. The second pathway is DTH-independent and does not inflict collateral injury to ocular tissues, and the eye is preserved. In this study, we used a well-characterized tumour, Ad5E1, to investigate the role of CD4+ T cells in the non-phthisical form of intraocular tumour rejection. It has been previously documented that CD4+ T cells and interferon (IFN)-gamma are necessary for rejection of these tumours in the eye. In this study, we demonstrate that CD4+ T cells can circumvent immune privilege and infiltrate intraocular Ad5E1 tumours. Following tumour rejection, CD4+ T cells from tumour rejector mice could be adoptively transferred to severe combined immunodeficiency (SCID) mice and protect them from intraocular Ad5E1 tumour growth. Tumour-specific CD4+ T cells produced IFN-gamma in response to Ad5E1 tumour antigens. Macrophages also contributed to rejection, as they were present in intraocular Ad5E1 tumours, and local depletion of macrophages resulted in progressive tumour growth. Ocular macrophages contributed to Ad5E1 tumour rejection, as Ad5E1 tumour rejection did not occur in macrophage-depleted SCID mice reconstituted with rejector CD4+ T cells. This demonstrates that macrophage and CD4+ T-cell co-operation is needed for non-phthisical rejection of intraocular tumours.

Regulation of cell lineage specification by the retinoblastoma tumor suppressor.

Early studies of the retinoblastoma gene (RB) have uncovered its critical role as a regulator of the G(1)/S cell cycle phase progression. Surprisingly, genetic approaches in mammals and nematodes have also shown RB controls cell lineage specification and aspects of differentiation. The RB gene product accomplishes this by diverse mechanisms such as by interacting with tissue-specific transcription factors, enhancing RNA interference, and modifying chromatin structure. We review recent studies uncovering novel mechanisms by which RB works in several cell lineages and we provide perspectives on how these new findings might relate to RB tumor suppression.

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family.

Rb family proteins (pRb/p105, Rb2/p130 and p107) play a key role in cell cycle control and are worthily involved in transcription repression and tumor suppression. The mechanisms of transcriptional activation and repression by the Rb gene family has been extensively investigated: pRb, pRb2/p130 and p107 interact with different E2F family factors and can inhibit E2F responsive promoters, interfering with progression of cell cycle, gene transcription, initiation of apoptotic process and cell differentiation. Recent studies have indicated that Rb and Rb2/p130 may be involved in cellular response to DNA damage events, by influencing the transcription of factors involved in DNA repair pathways. In particular, evidences suggest that Rb loss and target gene deregulation impacts on the repair of UV-induced pyrimidine pyrimidone photoproducts (6-4 PP) by regulating the expression of several DNA damage factors involved in UV DNA damage repair processes, including proliferating cell nuclear antigen. Ongoing studies are focused on the mechanisms by which Rb family genes drive cell cycle exit following DNA damage induction, and how Rb gene family's interaction with chromatin remodeling factors can influence DNA repair dynamics.

Macrophages are vital in spontaneous intraocular tumor eradication.

PURPOSE: Injection of tumor cells transformed by the early region 1 of human adenovirus type 5 (Ad5E1) in the anterior chamber (AC) of C57BL/6 mice leads to intraocular tumor formation. This tumor disappears spontaneously 3 to 4 weeks after tumor inoculation without damaging the neighboring ocular tissues. Previous studies have shown that CD4+ T cells, IFNgamma, and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) play a role in the spontaneous eradication of this particular intraocular tumor. This study was conducted to determine whether macrophages are involved in the natural elimination of this intraocular tumor. METHODS: Ad5E1-expressing tumor cells were inoculated into the AC of syngeneic C57BL/6 mice. Macrophage depletion was obtained by subconjunctival (scj), subcutaneous (sc), or intravenous (iv) injection of clodronate liposomes 2, 8, and 14 days after tumor inoculation. Control C57BL/6 mice received PBS liposomes at similar time points after tumor injection or were left untreated. The presence of macrophages in the AC tumor was determined with the macrophage marker F4/80. RESULTS: Progressive tumor growth was observed in mice that were subconjunctivally depleted of macrophages, whereas spontaneous tumor eradication occurred in all other groups. F4/80 staining was negative in the AC tumors of mice treated scj with clodronate liposomes in contrast to the positive F4/80 staining in the tumors of the other groups. Ad5E1 tumor antigen still reached the tumor-draining lymph nodes (DLNs) of mice locally depleted for macrophages. CONCLUSIONS: Local macrophages in the eye are involved in the process of spontaneous AC tumor eradication in mice. However, it is not conclusive from these data exactly how tumor-specific CD4+ T cells and macrophages interact with each other to eliminate the Ad5E1-AC tumor without any collateral eye damage.

Termination of systemic immunity in the presence of intraocular tumors: influence of ocular immune privilege on tumor vaccines.

Ocular immune privilege preserves the visual axis by preventing the induction of sight-threatening nonspecific inflammation. Although privilege is essential for maintaining visual integrity, intraocular tumors exploit the privileged environment and grow progressively within the anterior chamber of the eye. Recently, a large number of laboratories have constructed genetically engineered tumor cell vaccines that express high levels of costimulatory signals. These vaccines are designed to bypass the normal pathways of T-cell activation and directly activate CD8+ tumor-specific T cells. In the following series of experiments, we determined whether a tumor cell vaccine that uses costimulatory signals (CD80 and IL-12) is capable of eliminating tumors within the immune-privileged anterior chamber. As expected, vaccine-immunized mice rejected subcutaneous flank tumors (a non-privileged site). However, the vaccine failed to protect mice from even a small number of tumor cells transplanted into the immune-privileged anterior chamber. Surprisingly, immunized mice that were simultaneously challenged with subcutaneous and anterior chamber tumors were unable to eliminate tumors at either site. The failure of systemic protective immunity coincided with the loss of tumor-specific delayed hypersensitivity and cytotoxic T cells. We conclude that tumor cell vaccines that induce complete protection against tumors in non-immune-privileged sites fail to protect against the same tumor within an ocular immune-privileged site. Moreover, a tumor that escapes elimination within the eye can terminate systemic protective immunity that is induced by the tumor cell vaccine.

A tribute to Dr. Robert C. Allen, an inspirational teacher, humanitarian, and friend (Nov. 18, 1950-Mar. 24, 2005).

Dr. Robert C. Allen was a gifted educator, as well as experienced ophthalmologist, who was a close personal friend of Dr. Edlich at the University of Virginia Health System. While serving on the faculty at the University of Virginia Health System, Dr. Allen proved to be a compassionate physician, who developed close personal relationships with the residents, faculty, and his patients. Dr. Allen was invited by Dr Edlich to be a member of the Editorial Board of the Journal of Long-Term Effects of Medical Implants. When Dr. Allen told Dr. Edlich that he had ocular melanoma in 2000, this news was a wake-up call to Dr. Edlich on the need to prevent skin cancer, as well as ocular melanoma. Empowered by this news, Dr. Edlich was honored to co-author four articles on skin cancer prevention, as well as the latest article focusing on prevention of ocular melanoma. The Ocular Melanoma Foundation (Richmond, VA (USA)) was founded in 2003 by Dr. Robert C. Allen to increase awareness, enhance education, and provide advocacy among both patients and health care professionals regarding this rare, but potentially lethal cancer. It has a website that provides patient information, up-to-date information and enables communication/ discourse between and among patients and practitioners (admin@ocularmelanoma.org). Dr. Allen died on March 24, 2005, at his home surrounded by family and loved ones. When surgeons are faced with challenging healthcare diseases, Dr. Edlich's mentor, Dr. Owen Wangensteen, advised Dr. Edlich that he should seek the advice and guidance of skilled basic scientists, who are familiar with the problem. Dr. Wangensteen is recognized as the greatest surgical teacher during the 20th century. Consequently, Dr. Edlich enlisted the advice and guidance from the two co-authors of the next article regarding the scientific basis for the selection of sunglasses to prevent the development of cataracts, pterygia, skin cancer, as well as ocular melanoma. Dr. Reichow is a Professor of Optometry at Pacific University College of Optometry (Forest Grove, OR (USA)). Dr. Citek is Associate Professor of Optometry at Pacific University College of Optometry (Forest Grove (USA)). In their comprehensive evaluation of sunglasses, they found some disturbing results. Despite being endorsed by The Skin Cancer Foundation, the Walgreens eyewear samples offer only partial protection to the potential hazards of sunlight exposure. Those individuals who spend considerable time outdoors should seek sun filter eyewear with impact resistant polycarbonate lenses that provide 100% ultraviolet filtration, high levels of blue light filtration, and full visual field lens/frame coverage as provided by high wrap eyewear. There are several brands that offer products with such protective characteristics. Performance sun eyewear by Nike Vision (Nike Inc., Portland OR [USA]), available in both corrective and plano (nonprescription) forms, is one such brand incorporating these protective features, as well as patented optical and tint designs. Numerous Nike styles offer interchangeable lens options to meet the changing environmental conditions encountered outdoors. These technologies are incorporated into performance-driven frame designs inspired by feedback from some of the world's best athletes. Nonprescription Nike eyewear are available on-line at http://www.nike.com/nikevision, as well as at various well-known retail outlets. Nonprescription and prescription Nike eyewear are also available at the offices of many eye care professionals. Even though our latest report did not include soft contact lens, it is important to emphasize that Dr. Reichow and Dr. Citek have played a leadership role in coordinating the development of the Nike MAXSIGHT, an innovative fully tinted soft contact lens. This contact lens provides distortion-free optics, whether or not you wear prescription contacts. They filter out more than 90% of harmful blue light and 95% of UVA and UVB. For the contact lens, you should go to the website for more information http://www.nike.com/nikevision/content.html. The website has a list of practitioners who can service the patients with the respective sunglasses. With their exciting technologic advances in sunglass products, as well as tinted soft contact lens, the authors would encourage Nike Vision to develop an expanded international marketing program that allows all individuals in the world to easily purchase its products.

Recombinant human mullerian inhibiting substance inhibits human ocular melanoma cell lines in vitro and in vivo.

Since Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian duct, the anlagen of the uterus, vagina, and fallopian tube, we expected and have previously observed that purified recombinant human MIS causes regression of gynecological tumors. However, recent experiments indicating that neural crest derivatives might be responsive to MIS prompted study of a group of human ocular melanoma cell lines in 4 in vitro inhibition assays, and a subrenal capsule assay in vivo. Ocular melanoma cell lines that grew well in a respective assay were studied with MIS to determine whether this biological modifier could inhibit growth. Three human ocular melanomas, OM431 (P less than 0.01), OM467 (P less than 0.02), and OM482 (P less than 0.03), were growth-inhibited by highly purified human recombinant MIS in soft agarose. A dose-dependent tumor inhibition was noted when OM431 cells were incubated with MIS in a liquid colony inhibition assay (P less than 0.05). In addition, OM467 was inhibited (P less than 0.05) by MIS in a multicellular tumor spheroid assay. Cell cycle analysis indicated that OM431 cells were inhibited in monolayer by MIS while in G1. At 100-fold lower serum concentrations than required in the media of in vitro assays, MIS delivered via i.p. osmotic pumps inhibited (P less than 0.05) in vivo the growth of OM431 implanted beneath the renal capsule of nude and CD-1 irradiated mice when compared to mice given implants of pumps containing no MIS. The responsiveness of ocular melanoma to MIS broadens the spectrum of tumors that might be treated with MIS and suggests further investigation of other neural crest tumors.

Angiogenesis inhibition by minocycline.

We describe a new inhibitor of angiogenesis, minocycline, a semisynthetic tetracycline antimicrobial with anticollagenase properties. Minocycline was incorporated into controlled release polymers and tested in the rabbit cornea against neovascularization in the presence of the VX2 carcinoma. Inhibition by minocycline was shown to be comparable to that of the combination of heparin and cortisone, a potent inhibitor of angiogenesis. Minocycline decreased tumor-induced angiogenesis by a factor of 4.5, 4.4, and 2.9 at 7, 14, and 21 days, respectively. At the end of the experiment, whereas the corneas with empty polymers had large, invasive, exophytic tumors, none of the corneas with minocycline had such vascular masses. Recently, studies of agents that disrupt collagen synthesis and deposition have yielded several new angiogenesis inhibitors. We suggest that investigation of agents that disrupt collagenolysis may similarly identify other angiogenesis inhibitors and further clarify the mechanisms of angiogenesis.

Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.

The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.

p53 protects against skin cancer induction by UV-B radiation.

To assess the role of the p53 tumor suppressor gene in skin carcinogenesis by UV radiation, mice constitutively lacking one or both copies of the functional p53 gene were compared to wild-type mice for their susceptibility to UV carcinogenesis. Heterozygous mice showed greatly increased susceptibility to skin cancer induction, and homozygous p53 knockout mice were even more susceptible. Accelerated tumor development in the heterozygotes was not associated with loss of the remaining wild-type allele of p53, as reported for tumors induced by other carcinogens, but in many cases was associated with UV-induced mutations in p53. Tumors arose on the ears and dorsal skin of mice of all three genotypes, and homozygous knockout mice also developed ocular tumors, mainly melanomas. Skin tumors in the p53 knockout mice were predominately squamous cell carcinomas and were associated with premalignant lesions resembling actinic keratoses, whereas those in the heterozygous and wild-type mice were mainly sarcomas. These results demonstrate the importance of p53 in protecting against UV-induced cancers, particularly in the eye and epidermis.

Rituximab in patients with mucosal-associated lymphoid tissue-type lymphoma of the ocular adnexa.

Eight patients with ocular adnexal mucosal-associated lymphpid tissue (MALT) lymphoma were treated with rituximab, at diagnosis (n=5) or relapse (n=3). All untreated patients achieved lymphoma regression, while relapsing patients had no benefit. Four responding patients experienced early relapse. The median time to progression was 5 months. The efficacy of rituximab in ocular adnexal lymphoma is lower than that reported for gastric MALT lymphomas.

Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas.

The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.

The antineoplastic effect of vitamin D in transgenic mice with retinoblastoma.

Vitamin D has been shown to inhibit growth of human retinoblastoma in tissue culture and nude mouse heterografts. We have described a heritable transgenic mouse model of retinoblastoma. The in vivo efficacy of 1,25-dihydroxycholecalciferol (vitamin D3) was examined by administering this agent to transgenic mice with retinoblastoma. Forty-six 8-10-week-old transgene-bearing mice were injected intraperitoneally for 5 wk. Experimental animals received 0.05 microgram (15 animals) or 0.025 microgram (15 animals) of vitamin D. Sixteen control animals received only a mineral oil vehicle. Eyes were enucleated at 5 mo and were examined histologically by two investigators in a masked fashion. All control animals demonstrated bilateral involvement of retinoblastoma. Four eyes in the low-dose group and six eyes in the high-dose group had no evidence of retinoblastoma. Eyes treated with vitamin D3 showed less extensive involvement of the retina by retinoblastoma. Vitamin D-treated animals demonstrated tumors confined to the retina, whereas control animals demonstrated larger tumors, more often invading the vitreous, anterior chamber, and choroid. Thus, Vitamin D inhibited the growth and local extension in a dose-dependent fashion.