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1.
Updates in imaging in ocular oncology.
Davila, JR, Mruthyunjaya, P
F1000Research. 2019
Abstract
Innovations in ophthalmic imaging have made a profound impact on the diagnosis and treatment of ophthalmic disease. In ocular oncology, the development of optical coherence tomography with enhanced depth imaging and swept source technologies has made it possible to visualize the anatomical characteristics of retinoblastoma and uveal melanoma with a level of detail previously unobtainable on clinical exam alone. As a result, our understanding of the pathophysiology of vision loss in choroidal melanoma in particular has improved. These modalities have also helped identify fundoscopically "invisible" tumors and risk stratify pre-malignant choroidal lesions, making a strong case for their inclusion in all screening evaluations. Optical coherence tomography angiography, on the other hand, has allowed non-invasive imaging of the retinal and uveal vasculatures, providing insight into vascular changes associated with malignant transformation and vision loss following exposure to radiation. While the impact of new imaging technologies on clinical outcomes and overall survival in ocular oncology has yet to be determined, several reports cited herein offer promising results.
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2.
Potential use of melatonin in skin cancer treatment: A review of current biological evidence.
Pourhanifeh, MH, Mahdavinia, M, Reiter, RJ, Asemi, Z
Journal of cellular physiology. 2019;(8):12142-12148
Abstract
Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.
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3.
Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary.
von Schuckmann, LA, Wilson, LF, Hughes, MCB, Beesley, VL, Janda, M, van der Pols, JC, Smithers, BM, Khosrotehrani, K, Green, AC
Journal of the American Academy of Dermatology. 2019;(1):139-148.e4
Abstract
BACKGROUND Melanoma survivors are at high risk of further primary melanomas. OBJECTIVE To assess sun behavior after melanoma diagnosis and in relation to further primary melanomas. METHODS We applied repeated measures latent class analysis to reported primary prevention behavior at time of diagnosis and every 6 months for 2 years after diagnosis in patients with clinical stage IB or II melanoma. Correlates of behavior trajectories and risk of subsequent primaries were determined by using multivariable logistic and Cox regression analyses, respectively. RESULTS Among the 448 male and 341 female patients, sunscreen use fell into 3 trajectories: stable never-use (26% of males and 12% of females), stable sometimes-use (35% of males and 29% of females), and increased to often-use (39% of males and 59% of females). Most reduced their weekend sun exposure, but in 82% of males and 69% of females it remained increased. Males, smokers, the less educated, those who tanned, and those not self-checking their skin were more likely to have trajectories of inadequate protection. Patients with a history of melanoma before the study doubled their risk of another primary melanoma in the next 2 years if sunscreen use in that time was inadequate (hazard ratio, 2.45; 95% confidence interval, 1.00-6.06). LIMITATIONS Patient-reported data are susceptible to recall bias. CONCLUSION Our results may assist clinicians in identifying patients not using adequate sun protection and providing information for patient counseling.
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4.
Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies.
Naing, A, Infante, J, Goel, S, Burris, H, Black, C, Marshall, S, Achour, I, Barbee, S, May, R, Morehouse, C, et al
Journal for immunotherapy of cancer. 2019;(1):225
Abstract
BACKGROUND The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study in advanced solid malignancies. METHODS MEDI0680 was administered intravenously once every 2 weeks (Q2W) or once every 3 weeks at 0.1, 0.5, 2.5, 10 or 20 mg/kg. Two cohorts received 20 mg/kg once a week for 2 or 4 weeks, then 20 mg/kg Q2W. All were treated for 12 months or until progression. The primary endpoint was safety. Secondary endpoints were efficacy and pharmacokinetics. Exploratory endpoints included pharmacodynamics. RESULTS Fifty-eight patients were treated. Median age was 62.5 years and 81% were male. Most had kidney cancer (n = 36) or melanoma (n = 9). There were no dose-limiting toxicities. Treatment-related adverse events occurred in 83% and were grade ≥ 3 in 21%. Objective clinical responses occurred in 8/58 patients (14%): 5 with kidney cancer, including 1 with a complete response, and 3 with melanoma. The relationship between dose and serum levels was predictable and linear, with apparent receptor saturation at 10 mg/kg Q2W and all 20 mg/kg cohorts. CONCLUSIONS MEDI0680 induced peripheral T-cell proliferation and increased plasma IFNγ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression of IFNG, CD8A, CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration. TRIAL REGISTRATION NCT02013804 ; date of registration December 12, 2013.
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5.
Cutaneous Surgery in Patients Who Are Pregnant or Breastfeeding.
Li, JN, Nijhawan, RI, Srivastava, D
Dermatologic clinics. 2019;(3):307-317
Abstract
Dermatologic surgery in pregnant/postpartum patients requires deliberate consideration. Although surgery can be safely performed during any trimester, the second trimester and immediate postpartum period is optimal. Surgery should not be delayed for melanoma/high-risk skin cancers. Perioperative positioning, analgesic, antiseptic, and antibiotic selection should be deliberate to avoid risk to the patient/fetus/infant. The left lateral tilt position reduces aortocaval compression syndrome. Lidocaine and epinephrine can be used safely. Alcohol and chlorhexidine are considered safe. Antibiotics commonly used in skin surgery are safe in pregnancy and lactation. Acetaminophen is first line for pain management. Nonsteroidal antiinflammatory drugs should be avoided.
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6.
Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells.
Azzariti, A, Iacobazzi, RM, Di Fonte, R, Porcelli, L, Gristina, R, Favia, P, Fracassi, F, Trizio, I, Silvestris, N, Guida, G, et al
Scientific reports. 2019;(1):4099
Abstract
Over the past decade, cold atmospheric plasmas have shown promising application in cancer therapy. The therapeutic use of plasma-activated media is a topic addressed in an emerging field known as plasma pharmacy. In oncology, plasma-activated media are used to harness the therapeutic effects of oxidant species when they come in contact with cancer cells. Among several factors that contribute to the anticancer effect of plasma-activated liquid media (PALM), H2O2 and NO derivatives likely play a key role in the apoptotic pathway. Despite the significant amount of literature produced in recent years, a full understanding of the mechanisms by which PALM exert their activity against cancer cells is limited. In this paper, a sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species (RNS) from that of reactive oxygen species (ROS) on cancer cells. Two cancers characterized by poor prognosis have been investigated: metastatic melanoma and pancreatic cancer. Both tumour models exposed to PALM rich in H2O2 showed a reduction in proliferation and an increase in calreticulin exposure and ATP release, suggesting the potential use of activated media as an inducer of immunogenic cell death via activation of the innate immune system.
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7.
Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma.
Holderried, TAW, de Vos, L, Bawden, EG, Vogt, TJ, Dietrich, J, Zarbl, R, Bootz, F, Kristiansen, G, Brossart, P, Landsberg, J, et al
Clinical epigenetics. 2019;(1):161
Abstract
BACKGROUND The T cell immunoglobulin and mucin-domain containing-3 receptor TIM-3 (also known as hepatitis A virus cellular receptor 2, encoded by HAVCR2) and its ligand galectin 9 (LGALS9) are promising targets for immune checkpoint inhibition immunotherapies. However, little is known about epigenetic regulation of the encoding genes. This study aimed to investigate the association of TIM-3 and LGALS9 DNA methylation with gene expression, patients' survival, as well as molecular and immune correlates in malignant melanoma. RESULTS Methylation of all six TIM-3 CpGs correlated significantly with TIM-3 mRNA levels (P ≤ 0.05). A strong inverse correlation (Spearman's ρ = - 0.49) was found in promoter regions, while a strong positive correlation (ρ = 0.63) was present in the gene body of TIM-3. High TIM-3 mRNA expression (hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.81-0.97], P = 0.007) was significantly associated with better overall survival. Seven of the eight LGALS9 CpG sites correlated significantly with LGALS9 mRNA levels (P ≤ 0.003). Methylation at five CpG sites showed a strong inverse correlation (Spearman's ρ = - 0.67) and at two sites a weak positive correlation (Spearman's ρ = 0.15). High LGALS9 mRNA expression was significantly associated with increased overall survival (HR = 0.83, 95%CI [0.75-0.93], P = 0.001). In addition, we found significant correlations between TIM-3 and LGALS9 methylation and mRNA expression with immune cell infiltrates and significant differences among distinct immune cell subsets. CONCLUSIONS Our study points toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.
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8.
Immunotherapy and targeted therapies in older patients with advanced melanoma; Young International Society of Geriatric Oncology review paper.
Bastiaannet, E, Battisti, N, Loh, KP, de Glas, N, Soto-Perez-de-Celis, E, Baldini, C, Kapiteijn, E, Lichtman, S
Journal of geriatric oncology. 2019;(3):389-397
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Abstract
Malignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined with the longer life expectancy, this led to an increasing prevalence of melanoma in the older population. Recently, immune checkpoint inhibitors significantly improved the treatment of melanoma given their efficacy and tolerability profile. Two major classes of agents include the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors, such as ipilimumab, and the anti-programmed death-ligand 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab. Treatment of metastatic disease with immune checkpoint inhibitors demonstrated improved efficacy and better safety profiles compared to cytotoxic drugs and appears to be an attractive treatment option. Nevertheless, there is a need for tools designed to better predict which older patients will benefit from its use and who will experience toxicities related to the treatment. Current data do not show a major increase in toxicity rates in older patients. However, patients above 75 are often under-represented and those who are included are not representative of the general population of older patients, thereby also stressing the need for real-life data. Ongoing research is aiming at maximizing the potential treatment efficacy and developing novel immune-targeting modalities. Future studies should include older patients and assess geriatric domains in these older patients to better guide decision-making. This review discusses published clinical trials and where known, the efficacy and toxicity in older patients. Moreover, the clinical implications and future perspectives are discussed, with current recommendations for older patients, management of toxicities, and a proposal for an initial approach to the treatment of older patients with metastatic melanoma.
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8-Year Follow-up for Woman with Spinal Meningeal Melanocytoma in S1 Nerve Root: Case Report and Literature Review.
Yin, M, Ma, J, Ye, J, Xu, H, Mo, W
World neurosurgery. 2019;:143-147
Abstract
BACKGROUND Primary melanocytic neoplasms in the central nervous system are rare lesions arising from leptomeningeal melanocytes. These lesions produce neural deficits that resemble those of a meningioma or a schwannoma radiologically. CASE DESCRIPTION A tumor around the left S1 root with an extension into the left paraspinal compartment was identified in a 32-year-old female with persistent left leg pain for 6 months. The tumor was hyperintense on T1-weighted image and hypointense on T2-weighted image with a homogeneous enhancement. The clinical features, radiologic presentations, treatment choice, and pathologic characteristic were illustrated. The treatment outcome was compared with those reported in the previous literature. The tumor was en-bloc resected with the S1 nerve root reserved. Grossly, the tumor was a soft, capsulated, well-circumscribed, black pigmented lesion. Immunohistochemistry revealed that the tumor cells were positive for HMB-45, S-100 protein, and vimentin. The patient's symptoms were greatly relieved postoperatively. No signs of local recurrence were observed. CONCLUSIONS Spinal meningeal melanocytoma inside the nerve root is rare and benign. It is difficult to diagnose and often misdiagnosed as schwannoma or meningioma. HMB-45 has been suggested as a significant marker for the diagnosis of meningeal melanocytoma. Complete surgical resection is recommended as the primary treatment. Radiotherapy, chemotherapy, and other treatments can be selected as adjuvant therapies, but their effects are controversial. The recurrence and metastasis rates also remain unclear.
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10.
Vitamin D receptors (VDR), hydroxylases CYP27B1 and CYP24A1 and retinoid-related orphan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels.
Markiewicz, A, Brożyna, AA, Podgórska, E, Elas, M, Urbańska, K, Jetten, AM, Slominski, AT, Jóźwicki, W, Orłowska-Heitzman, J, Dyduch, G, et al
Scientific reports. 2019;(1):9142
Abstract
In recent years, a significant number of studies have investigated the preventive role of vitamin D in a number of different neoplasms. In this study, we analyze various components of the vitamin D signaling pathways in the human uveal tract and uveal melanoma, including analysis of the expression of vitamin D receptors (VDR), the activating and inactivating hydroxylases, respectively, CYP27B1 and CYP24A1, and the retinoic acid-related orphan receptors (ROR) α (RORα) and γ (RORγ) in these tissues. We further analyzed the expression of VDR, CYP27B1, CYP24A1, and ROR in relation to melanin levels, clinical stage and prognosis. Our study indicated that the uveal melanoma melanin level inversely correlated with VDR expression. We further showed that vitamin D is metabolized in uveal melanoma. This is significant because until now there has been no paper published, that would describe presence of VDR, hydroxylases CYP27B1 and CYP24A1, and RORα and RORγ in the human uveal tract and uveal melanomas. The outcomes of our research can contribute to the development of new diagnostic and therapeutic methods in uveal tract disorders, especially in uveal melanoma. The presented associations between vitamin D signaling elements and uveal melanoma in comparison to uveal tract encourage future clinical research with larger patients' population.