Browsing by Subject "melanoma"
Now showing 1 - 10 of 10
Results Per Page
Sort Options
Item Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women(Nature Publishing Group, 2014-04-01) Wu, S; Han, J; Vleugels, R A; Puett, R; Laden, F; Hunter, D J; Qureshi, A A; Department of Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case–control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies. Methods: We conducted a cohort study among 108 578 women in the Nurses' Health Study (1976–2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood. Results: Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2–10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10−4 Robertson–Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC. Conclusions: Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers.Item An Epidemiological Review of Diet and Cutaneous Malignant Melanoma(AACR, 2018-10) Yang, Keming; Fung, Teresa T.; Nan, Hongmei; Epidemiology, School of Public HealthIncidence of cutaneous malignant melanoma has continued to rise despite public efforts to promote sun protection behaviors among populations at risk. However, dietary factors may also affect the development of melanoma. In the past few decades, findings from epidemiologic and experimental research have linked consumption of several foods and other nutrients to the risk of melanoma. Caffeine has been associated with a lower risk of melanoma, and citrus fruits and alcohol with increased risk. Associations between polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D with melanoma remain controversial. Diet likely influences melanoma development through several potential mechanisms, such as enhancing UV-induced apoptosis and increasing photosensitivity. We conducted a narrative review to summarize recent epidemiologic studies of diet and melanoma based on published literature. Given the high prevalence of the food items and nutrients covered in this review and the decades-long rising melanoma incidence worldwide, the associations we discuss may have important public health implications in terms of reducing melanoma incidence through dietary modification.Item Expression of the platelet-activating factor receptor enhances benzyl isothiocyanate-induced apoptosis in murine and human melanoma cells(Spandidos, 2015-02) Sahu, Ravi Prakash; Department of Pathology and Laboratory Medicine, IU School of MedicineMelanoma cells often express platelet‑activating factor receptor (PAF‑R), which has been demonstrated to increase metastatic behavior. However, the effect of PAF‑R on the responsiveness of melanoma to naturally occurring cytotoxic agents remains to be elucidated. The present study aimed to determine the relative cytotoxicity and mechanism of benzyl isothiocyanate (BITC), a component of cruciferous vegetables, in melanoma cells expressing PAF‑R. To evaluate the importance of PAF‑R signaling in melanoma cell growth, PAF‑R‑negative murine B16F10 cells were transduced with a retrovirus containing the cDNA for PAF‑R to generate cells stably expressing PAF‑R (B16‑PAF‑R) or an empty vector (MSCV) to generate PAF‑R‑deficient B16‑MSCV control cells. Activation of PAF‑R, using the PAF‑R agonist, 1‑hexadecyl‑2‑N‑methylcarbamoyl‑3‑glycerophosphocholine, induced an increase in the proliferation of B16‑PAF‑R cells compared with the B16‑MSCV cells. Reverse transcription quantitative polymerase chain reaction revealed the presence of functional PAF‑R in human melanoma SK23MEL cells, but not in SK5MEL cells. The present study investigated the effect of BITC treatments on the survival of murine and human melanoma cells, in the presence or absence of functional PAF‑R. The results revealed that treatment with BITC decreased the survival rate of the PAF‑R‑positive and negative murine and human melanoma cells. However, the expression of PAF‑R substantially augmented BITC‑mediated cytotoxicity in the PAF‑R‑positive cells at lower concentrations compared with the PAF‑R‑negative cells. In order to determine the underlying mechanism, flow cytometric analysis was used, which demonstrated a significant increase in the generation of reactive oxygen species (ROS) in the B16‑PAF‑R cells compared with the B16‑MSCV cells, which enhanced apoptosis by BITC, as measured by increased caspase‑3/7 luminescence. Notably, the BITC‑mediated decreased cell survival rate, increased ROS and increased apoptosis in the B16‑PAF‑R cells were significantly attenuated by the antioxidant, vitamin C, indicating ROS involvement. Additionally, the WEB2086 PAF‑R antagonist, inhibited the BITC‑mediated enhancement of apoptosis in the B16‑PAF‑R cells, indicating a role for PAF‑R‑signaling in the BITC‑mediated effects. These findings indicated that the selectivity of BITC towards PAF‑R in melanoma offers a promising chemopreventive agent for PAF‑R‑positive melanoma treatment.Item Glucose-independent Acetate Metabolism Promotes Melanoma Cell Survival and Tumor Growth(American Society for Biochemistry and Molecular Biology, 2016-10-14) Lakhter, Alexander J.; Hamilton, James; Konger, Raymond L.; Brustovetsky, Nickolay; Broxmeyer, Hal E.; Naidu, Samisubbu R.; Microbiology and Immunology, School of MedicineTumors rely on multiple nutrients to meet cellular bioenergetics and macromolecular synthesis demands of rapidly dividing cells. Although the role of glucose and glutamine in cancer metabolism is well understood, the relative contribution of acetate metabolism remains to be clarified. We show that glutamine supplementation is not sufficient to prevent loss of cell viability in a subset of glucose-deprived melanoma cells, but synergizes with acetate to support cell survival. Glucose-deprived melanoma cells depend on both oxidative phosphorylation and acetate metabolism for cell survival. Acetate supplementation significantly contributed to maintenance of ATP levels in glucose-starved cells. Unlike acetate, short chain fatty acids such as butyrate and propionate failed to prevent loss of cell viability from glucose deprivation. In vivo studies revealed that in addition to nucleo-cytoplasmic acetate assimilating enzyme ACSS2, mitochondrial ACSS1 was critical for melanoma tumor growth in mice. Our data indicate that acetate metabolism may be a potential therapeutic target for BRAF mutant melanoma.Item History of Severe Sunburn and Risk of Skin Cancer Among Women and Men in 2 Prospective Cohort Studies(Oxford University Press, 2016-05-01) Wu, Shaowei; Cho, Eunyoung; Li, Wen-Qing; Weinstock, Martin A.; Han, Jiali; Qureshi, Abrar A.; Epidemiology, School of Public HealthAbstract. Few studies have assessed the relationship between sunburn and risk of different skin cancers (melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC)) in prospective studies simultaneously, and little is known about the association of severe sunburns at different body sites with skin cancer risk. We used data on 87,166 women in the Nurses' Health Study (1982–2010) and 32,959 men in the Health Professionals Follow-up Study (1992–2010) to investigate skin cancer risk associated with history of severe sunburns at different body sites (face/arms, trunk, and lower limbs). After adjustment for other risk factors, overall baseline history of severe sunburn was more apparently associated with risk of melanoma than with risk of SCC and BCC in men (multivariable-adjusted hazard ratios were 2.41 (95% confidence interval (CI): 1.32, 4.41) for melanoma, 1.48 (95% CI: 1.08, 2.03) for SCC, and 1.18 (95% CI: 1.06, 1.32) for BCC) but not in women. Sunburn on the trunk appeared to be more closely associated with melanoma risk, but not risk of SCC and BCC, when compared with sunburns at other body sites (face/arms and lower limbs). These differences were more apparent in men than in women. Pending further investigation, our findings add novel insights to the existing literature on sunburn history and skin cancer riskItem Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women(Wiley, 2018) Chen, Steven T.; Li, Xin; Han, Jiali; Epidemiology, School of Public HealthMelanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC). We followed 77,288 female American nurses from the Nurses’ Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥0.8 mm or Clark's levels of IV and V according to history of NMSC. We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85–4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05–2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55–1.37)), Breslow thickness ≥0.8 mm (0.85 (0.59–1.21)) and Clark's levels IV and V (0.81(0.52–1.24)). Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from melanoma.Item Phosphodiesterase type 5 inhibitors and risk of melanoma: A meta-analysis(Elsevier, 2017-09) Tang, Huilin; Wu, Wenting; Fu, Shuangshuang; Zhai, Suodi; Song, Yiqing; Han, Jiali; Epidemiology, School of Public HealthBackground The association between phosphodiesterase type 5 (PDE5) inhibitors and melanoma risk is controversial. Objective We quantify the association between use of PDE5 inhibitors and melanoma. Methods We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for studies that were conducted up to July 13, 2016, and evaluated the association between PDE5 inhibitors and skin cancer. Random effects meta-analyses were used to calculate the adjusted odds ratio (OR) with the 95% confidence interval (CI). Results Five observational studies were included. Compared with PDE5 inhibitor nonuse, PDE5 inhibitor use was slightly but significantly associated with an increased risk for development of melanoma (OR, 1.12; 95% CI, 1.03-1.21) and basal cell carcinoma (OR, 1.14; 95% CI, 1.09-1.19) but not squamous cell carcinoma. For melanoma risk, none of the prespecified factors (dose of PDE5 inhibitor, study design, and study region) significantly affected the results (P > .05). Our sensitivity analysis confirmed the stability of the results. Limitations We included only observational studies, which had some heterogeneities and inconsistent controlling for potential confounders. Conclusions Use of PDE5 inhibitors may be associated with a slightly increased risk for development of melanoma and basal cell carcinoma but not squamous cell carcinoma. However, further large well-conducted prospective studies with adequate adjustment for potential confounders are required for confirmation.Item Platelet count correlates with stage and predicts survival in melanoma(Taylor & Francis, 2019) Rachidi, Saleh; Kaur, Maneet; Lautenschlaeger, Tim; Li, Zihai; Radiation Oncology, School of MedicineCancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35–5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma.Item Platelet-activating Factor-receptor agonists generated by chemotherapy thwart host anti-tumor immunity(Office of the Vice Chancellor for Research, 2014-04-11) Sahu, Ravi P; Ocana, Jesus A; Ferracini, Matheus; Touloukian, Christopher E; Konger, Raymond L; Travers, Jeffrey BPrevious studies have established that pro-oxidative stressors suppress host immunity due to their ability to generate oxidized glycerophosphocholine (Ox-GPC) lipids with Platelet-activating Factor-receptor (PAF-R) agonist activity. Because many chemotherapeutic agents also induce reactive oxygen species, the present studies were designed to define if chemotherapeutic agents could thwart host anti-tumor immunity against melanoma via PAF-R activation. We demonstrate that treatment of melanoma cell lines in vitro and tumors in vivo with chemotherapeutic agents generates PAF-R-agonists in a process blocked by antioxidants, indicating the involvement of non-enzymatic PAF-R-agonists in this event. In a model system consisting of implantation of two tumors, we show that intratumoral chemotherapy with melphalan or etoposide of one tumor significantly augments the growth of the other (untreated) tumor in wild-type but not PAF-R-deficient hosts. Chemotherapeutic agents-mediated PAF-R-dependent increased tumor growth is blocked by systemic administration of antioxidants and cyclooxygenase-2 inhibitors. In addition, depleting antibodies against regulatory T cells (Tregs) significantly attenuated chemotherapy-mediated growth of untreated tumors, suggesting the role of Tregs in this process. Moreover, using FoxP3EGFP transgenic mice, we show that COX-2 inhibitor blocked intratumoral Tregs, indicating that Tregs are downstream to COX-2. Furthermore, PAF-R agonists were identified in perfusates of patients undergoing isolated limb chemoperfusion for melanoma with melphalan chemotherapy. Finally, various novel Ox-GPCs are identified after chemotherapy by mass spectrometry. These findings provide evidence for a novel and previously unappreciated pathway by which Ox-GPC PAF-R agonists produced as a by-product of chemotherapy modulate tumor growth via the inhibition of anti-tumor immunity. These studies might explain some instances of chemotherapy treatment failure and offer insights into potential therapeutic strategies that could enhance the overall anti-tumor effectiveness of chemotherapy.Item Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases(Frontiers, 2022-12-07) Tan, Xiang-Lin; Le, Amy; Scherrer, Emilie; Tang, Huilin; Kiehl, Nick; Han, Jiali; Jiang, Ruixuan; Diede, Scott J.; Shui, Irene M.; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: More than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis. Objectives: To summarize clinical outcomes and prognostic factors in MBM patients. Methods: A systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied. Results: A total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM. Conclusion: This study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.