Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin can...Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin cancer globally. Clothing provides a protective barrier that reduces the amount of ultraviolet radiation (UVR) reaching the skin. Australia pioneered the development of a relative ranking of the sun-protective capabilities of clothing based on the transmission of UVR through fabric. Standardized Ultraviolet Protection Factor (UPF) measurement procedures and associated labeling specifications are documented in the Australian and New Zealand Standard, AS/NZS 4399:1996. The standard was intended to enable consumers to make informed choices. Since its introduction, this standard has been adopted almost universally by the textile industry, and is still in use almost two decades on, with plans to revise it only commencing recently. However, AS/NZS 4399:1996 does not consider garment design, particularly in relation to body surface coverage. Although swim-shirts have grown in popularity in Australia since the late 1990s, particularly among children, clothing remains under-utilized as a form of sun-protection in contemporary society. Skin cancer prevention campaigns should emphasize the sun-protective benefits of clothing and collaboration with the fashion industry is urgently needed to improve the aesthetic appeal, comfort, durability and affordability of sun-protective clothing to increase its popularity in skin cancer prone populations. In light of recent evidence showing that high UPF clothing which covers more of the body surface reduces pigmented mole development in children (major risk factor for melanoma), the rating system for sun-protective clothing should incorporate body surface covered as well as the UPF of the fabric. We discuss progress towards developing a protocol for measuring the extent of coverage of sun-protective garments. Once fully evaluated and refined, the testing protocol developed from this research may influence future revisions of international standards for evaluating and classifying sun-protective clothing.展开更多
Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to s...Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this analysis.Patients were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort A.Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.展开更多
K-RAS is the most frequently mutated oncogene in solid tumors,such as pancreatic,colon or lung cancer.The GTPase K-RAS can either be in an active(GTP-loaded)or inactive(GDP-loaded)form.In its active form K-RAS forward...K-RAS is the most frequently mutated oncogene in solid tumors,such as pancreatic,colon or lung cancer.The GTPase K-RAS can either be in an active(GTP-loaded)or inactive(GDP-loaded)form.In its active form K-RAS forwards signals from growth factors,cytokines or hormones to the nucleus,regulating essential pathways,such as cell proliferation and differentiation.In turn,activating somatic mutations of this proto-oncogene deregulate the complex interplay between GAP(GTPase-activating)-and GEF(Guanine nucleotide exchange factor)-proteins,driving neoplastic transformation.Due to a rather shallow surface,K-RAS lacks proper binding pockets for small molecules,hindering drug development over the past thirty years.This review summarizes recent progress in the development of low molecular antagonists and further shows insights of a newly described interaction between mutant K-RAS signaling and PD-L1 induced immunosuppression,giving new hope for future treatments of K-RAS mutated cancer.展开更多
文摘Sunlight is a known skin carcinogen. Skin cancer is the most common form of cancer in humans, and typically affects sun-exposed parts of the body. Sunny Australia and New Zealand have the highest incidence of skin cancer globally. Clothing provides a protective barrier that reduces the amount of ultraviolet radiation (UVR) reaching the skin. Australia pioneered the development of a relative ranking of the sun-protective capabilities of clothing based on the transmission of UVR through fabric. Standardized Ultraviolet Protection Factor (UPF) measurement procedures and associated labeling specifications are documented in the Australian and New Zealand Standard, AS/NZS 4399:1996. The standard was intended to enable consumers to make informed choices. Since its introduction, this standard has been adopted almost universally by the textile industry, and is still in use almost two decades on, with plans to revise it only commencing recently. However, AS/NZS 4399:1996 does not consider garment design, particularly in relation to body surface coverage. Although swim-shirts have grown in popularity in Australia since the late 1990s, particularly among children, clothing remains under-utilized as a form of sun-protection in contemporary society. Skin cancer prevention campaigns should emphasize the sun-protective benefits of clothing and collaboration with the fashion industry is urgently needed to improve the aesthetic appeal, comfort, durability and affordability of sun-protective clothing to increase its popularity in skin cancer prone populations. In light of recent evidence showing that high UPF clothing which covers more of the body surface reduces pigmented mole development in children (major risk factor for melanoma), the rating system for sun-protective clothing should incorporate body surface covered as well as the UPF of the fabric. We discuss progress towards developing a protocol for measuring the extent of coverage of sun-protective garments. Once fully evaluated and refined, the testing protocol developed from this research may influence future revisions of international standards for evaluating and classifying sun-protective clothing.
文摘Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this analysis.Patients were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort A.Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.
基金This work was partially supported by the European Fond for Regional Development(EFRD)(EFRE-0800951)to Mörchen B and Helfrich I(EFRE-0800947)to Shkura O and Stoll R.
文摘K-RAS is the most frequently mutated oncogene in solid tumors,such as pancreatic,colon or lung cancer.The GTPase K-RAS can either be in an active(GTP-loaded)or inactive(GDP-loaded)form.In its active form K-RAS forwards signals from growth factors,cytokines or hormones to the nucleus,regulating essential pathways,such as cell proliferation and differentiation.In turn,activating somatic mutations of this proto-oncogene deregulate the complex interplay between GAP(GTPase-activating)-and GEF(Guanine nucleotide exchange factor)-proteins,driving neoplastic transformation.Due to a rather shallow surface,K-RAS lacks proper binding pockets for small molecules,hindering drug development over the past thirty years.This review summarizes recent progress in the development of low molecular antagonists and further shows insights of a newly described interaction between mutant K-RAS signaling and PD-L1 induced immunosuppression,giving new hope for future treatments of K-RAS mutated cancer.
