Science.gov

Sample records for aggressive skin cancer

  1. Skin Cancer

    MedlinePlus

    ... States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ... If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ...

  2. Skin Cancer

    MedlinePlus

    ... early. If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ... and a type of laser light to kill cancer cells. Biologic therapy boosts your body's own ability to ...

  3. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  4. Learning about Skin Cancer

    MedlinePlus

    ... have red or blond hair and blue or light-colored eyes - although anyone can get skin cancer. Skin cancer is related to lifetime exposure to UV radiation, therefore most skin cancers appear after age ...

  5. Skin Cancer

    MedlinePlus

    ... are specialized skin cells that produce pigment called melanin. The melanin pigment produced by melanocytes gives skin its color. ... absorbing and scattering the energy. People with more melanin have darker skin and better protection from UV ...

  6. How to Check Your Skin for Skin Cancer

    MedlinePlus

    ... Home Cancer Types Skin Cancer Skin Cancer Patient Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer Prevention Skin Cancer Screening Health Professional Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer ...

  7. Skin Cancer Treatment

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  8. Stages of Skin Cancer

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  9. Skin Cancer

    MedlinePlus

    ... Review. 17 Wu S, Han J, Laden F, Qureshi AA. Long-term ultraviolet flux, other potential risk factors, ... MR, Shive ML, Chren MM, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin ...

  10. Skin Cancer

    MedlinePlus

    ... exposure to ultraviolet light, which is found in sunlight and in lights used in tanning salons. What ... the safe-sun guidelines. 1. Avoid the sun. Sunlight damages your skin. The sun is strongest during ...

  11. Basal cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. This type of skin ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  12. Squamous cell skin cancer

    MedlinePlus

    ... cell; NMSC - squamous cell; Squamous cell skin cancer; Squamous cell carcinoma of the skin ... squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type does not spread to ...

  13. Skin Cancer in Skin of Color

    PubMed Central

    Bradford, Porcia T.

    2009-01-01

    Skin cancers in skin of color often present atypically or with advanced stage in comparison to Caucasian patients. Health care providers must maintain a high index of suspicion when examining skin lesions in skin of color. PMID:19691228

  14. Anyone Can Get Skin Cancer

    Cancer.gov

    No matter if your skin is light, dark, or somewhere in between, everyone is at risk for skin cancer. Learn what skin cancer looks like, how to find it early, and how to lower the chance of skin cancer.

  15. Skin cancer and photoaging in ethnic skin.

    PubMed

    Halder, Rebat M; Ara, Collette J

    2003-10-01

    Skin cancer prevalence in ethnic skin is low. Squamous cell carcinoma, hypopigmented mycosis fungoides, and acral lentiginous melanoma are the most serious types of skin cancer noted in the darker-skinned population. Photoaging occurs less frequently and is less severe in ethnic skin. PMID:14717413

  16. Squamous cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. The earliest form of ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  17. Skin Cancer Foundation

    MedlinePlus

    ... Nevi Melanoma Merkel Cell Carcinoma Squamous Cell Carcinoma Skin Cancer Treatment Glossary Facts & Statistics Ask the Experts Early Detection ... About Us | Store The Skin Cancer ... prevention, early detection, and prompt treatment of the world’s most common cancer. Take your ...

  18. Facial reconstruction for radiation-induced skin cancer

    SciTech Connect

    Panje, W.R.; Dobleman, T.J. )

    1990-04-01

    Radiation-induced skin cancers can be difficult to diagnose and treat. Typically, a patient who has received orthovoltage radiotherapy for disorders such as acne, eczema, tinea capitis, skin tuberculosis, and skin cancer can expect that aggressive skin cancers and chronic radiodermatitis may develop subsequently. Cryptic facial cancers can lead to metastases and death. Prophylactic widefield excision of previously irradiated facial skin that has been subject to multiple recurrent skin cancers is suggested as a method of deterring future cutaneous malignancy and metastases. The use of tissue expanders and full-thickness skin grafts offers an expedient and successful method of subsequent reconstruction.

  19. Skin Cancer Prevention

    MedlinePlus

    ... Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at NCI (Intramural) ... is the body’s largest organ . It protects against heat, sunlight, injury, and infection . Skin also helps control ...

  20. Skin Cancer Screening

    MedlinePlus

    ... the body's largest organ . It protects against heat, sunlight, injury, and infection . Skin also helps control body ... cancer risk factors include: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  1. Drugs Approved for Skin Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Skin Cancer This page lists cancer ... in skin cancer that are not listed here. Drugs Approved for Basal Cell Carcinoma Aldara (Imiquimod) Efudex ( ...

  2. For Some Skin Cancers, Targeted Drug Hits the Mark

    MedlinePlus

    ... Cancer Types Skin Cancer Research Skin Cancer Patient Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer Prevention Skin Cancer Screening Health Professional Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer ...

  3. Skin cancer in skin of color.

    PubMed

    Bradford, Porcia T

    2009-01-01

    In general, skin cancer is uncommon in people of color when compared to Caucasians. When it does occur, it is often associated with increased morbidity and mortality. Differences in survival rates may be attributed to skin cancers being diagnosed at a more advanced stage, and socioeconomic factors such as lack of adequate insurance coverage and lack of transportation can function as barriers to timely diagnosis and early treatment. In addition to advanced stage at presentation, malignant skin lesions in skin of color often present in an atypical fashion. Because skin cancer prevention and screening practices historically have been lower among Hispanics, Blacks, and Asians, and given the changing demographics in the United States, interventions that are tailored to each of these groups will be needed. Public educational campaigns should be expanded to educate people of all skin types with emphasis on skin cancers occurring in areas not exposed to the sun (Byrd-Miles et al., 2007), since sunlight is not as important an etiologic factor in the pathogenesis of skin cancer in people of color. Dermatologists and primary care physicians should instruct their darker-skinned patients on how to perform routine skin self-examinations. Physicians should also encourage patients to ask their specialists such as their gynecologist, dentist, and ophthalmologist to look for abnormal pigmentation during routine exams. To reduce the burden of skin cancer, several prevention methods for all people have been strongly encouraged, including monthly self-examinations, daily use of SPF 30 or greater sunscreen, sunglasses with UV-absorbing lenses, and avoiding tanning booths (American Cancer Society, 2008) (see Table 7). In addition, recommendations for clinicians to promote the prevention of skin cancer in skin of color have also been made, including closely monitoring changing pigmented lesions on the palms and soles and hyperkeratotic or poorly healing ulcers in immunosuppressed patients

  4. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  5. Skin Cancers of the Feet

    MedlinePlus

    ... common cancers of the feet are: Basal Cell Carcinoma : Basal cell carcinoma frequently is seen on sun-exposed skin surfaces. ... damage but only rarely spreads beyond the skin. Basal cell cancers may appear as pearly white bumps or patches ...

  6. Ultraviolet radiation and skin cancer.

    PubMed

    Narayanan, Deevya L; Saladi, Rao N; Fox, Joshua L

    2010-09-01

    Skin cancer is the most common type of cancer in fair-skinned populations in many parts of the world. The incidence, morbidity and mortality rates of skin cancers are increasing and, therefore, pose a significant public health concern. Ultraviolet radiation (UVR) is the major etiologic agent in the development of skin cancers. UVR causes DNA damage and genetic mutations, which subsequently lead to skin cancer. A clearer understanding of UVR is crucial in the prevention of skin cancer. This article reviews UVR, its damaging effects on the skin and its relationship to UV immunosuppression and skin cancer. Several factors influence the amount of UVR reaching the earth's surface, including ozone depletion, UV light elevation, latitude, altitude, and weather conditions. The current treatment modalities utilizing UVR (i.e. phototherapy) can also predispose to skin cancers. Unnecessary exposure to the sun and artificial UVR (tanning lamps) are important personal attributable risks. This article aims to provide a comprehensive overview of skin cancer with an emphasis on carefully evaluated statistics, the epidemiology of UVR-induced skin cancers, incidence rates, risk factors, and preventative behaviors & strategies, including personal behavioral modifications and public educational initiatives. PMID:20883261

  7. Discovery – Preventing Skin Cancer

    Cancer.gov

    Cancer research includes stopping cancer before it spreads. NCI funded the development of the Melanoma Risk Assessment Tool and the ABC method. Both help to diagnose high-risk patients and prevent melanoma earlier in the fight against skin cancer.

  8. Drugs Approved for Skin Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  9. Epidemiology of skin cancer.

    PubMed

    Leiter, Ulrike; Eigentler, Thomas; Garbe, Claus

    2014-01-01

    Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of cancer in white populations. Both tumor entities show an increasing incidence rate worldwide but a stable or decreasing mortality rate. NMSC is the most common cancer in white-skinned individuals with a worldwide increasing incidence. NMSC is an increasing problem for health care services worldwide which causes significant morbidity. The rising incidence rates of NMSC are probably caused by a combination of increased exposure to ultraviolet (UV) or sun light, increased outdoor activities, changes in clothing style, increased longevity, ozone depletion, genetics and in some cases, immune suppression. An intensive UV exposure in childhood and adolescence was causative for the development of basal cell carcinoma (BCC) whereas for the etiology of SCC a chronic UV exposure in the earlier decades was accused. Cutaneous melanoma is the most rapidly increasing cancer in white populations, in the last 3 decades incidence rates have risen up to 5-fold. In 2008 melanoma was on place 5 in women and on place 8 in men of the most common solid tumor entities in Germany. The frequency of its occurrence is closely associated with the constitutive color of the skin, and the geographical zone. Changes in outdoor activities and exposure to sunlight during the past 50 years are an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show a stabilization in the USA, Australia and also in European countries. In contrast to SCC, melanoma risk seems to be associated with an intermittent exposure to sunlight. Prevention campaigns aim on reducing incidence and achieving earlier diagnosis, which resulted in an ongoing trend toward thin melanoma since the last two decades. However, the impact of primary prevention measures on incidence rates of melanoma is unlikely to be seen in the near future, rather increasing incidence rates to 40-50/100,000 inhabitants/year should be expected in

  10. Anyone Can Get Skin Cancer

    MedlinePlus

    ... doesn't matter whether you consider your skin light, dark, or somewhere in between. You are at risk for skin cancer. Being in the sun can damage your skin. Sunlight causes damage through ultraviolet, or UV rays, (they make up just one part of ...

  11. Quiz: Test Your Skin Cancer IQ

    MedlinePlus

    ... of skin is usually the first step in skin cancer treatment and may have already occurred in the process ... Skin Cancer" Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma Early / NIH Research ...

  12. [Radiotherapy of skin cancers].

    PubMed

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules. PMID:27522189

  13. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... html Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering ... fatty beef and cheese was linked with more aggressive prostate cancer, the researchers found. A diet high ...

  14. Low Vitamin D Levels May Signal More Aggressive Prostate Cancer

    MedlinePlus

    ... html Low Vitamin D Levels May Signal More Aggressive Prostate Cancer But men should not expect supplements ... 2016 (HealthDay News) -- Prostate cancer may be more aggressive in men who are deficient in vitamin D, ...

  15. Skin cancer prevention and screening.

    PubMed

    Holm, Richard P

    2015-01-01

    Skin cancer is the most common and recognizable of all cancers. The human dermis can turn malignant due to excessive solar exposure and chronic injury, with the influence of genetic risk and inherited pigmentation. Basal cell carcinoma, the most common skin cancer in lighter pigmented individuals, spreads locally, and usually appears pearly and often ulcerative. Squamous cell carcinoma, the most common skin cancer in darker pigmented people, metastasizes to lymph nodes 2-5 percent of the time, appears often scaly, smooth, nodular, ulcerative, or even pigmented. Malignant melanoma accounts for 2 percent of skin cancers, but for the vast majority of skin cancer deaths. All three can mimic each other. Solar or ultraviolet (UV) light exposure is the most common carcinogen; however, any chronic irritant can increase the risk, and efforts to avoid such exposure is apropos. Though not yet absolutely proven, skin cancer research strongly supports the following statements: sunscreen is protective, tanning devices are causative, and the routine screening of high-risk individuals is preventative. Authorities strongly recommend avoiding excess sun and UV light, using sunscreen, and keeping a watchful eye for unusual skin lesions. PMID:25985614

  16. Treatment Options for Nonmelanoma Skin Cancer

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  17. Risks of Skin Cancer Screening

    MedlinePlus

    ... the body's largest organ . It protects against heat, sunlight, injury, and infection . Skin also helps control body ... cancer risk factors include: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  18. Polyamines and nonmelanoma skin cancer

    SciTech Connect

    Gilmour, Susan K.

    2007-11-01

    Elevated levels of polyamines have long been associated with skin tumorigenesis. Tightly regulated metabolism of polyamines is critical for cell survival and normal skin homeostasis, and these controls are dysregulated in skin tumorigenesis. A key enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC) is upregulated in skin tumors compared to normal skin. Use of transgenic mouse models has demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. The formation of skin tumors in these transgenic mice is dependent upon polyamine biosynthesis, especially putrescine, since treatment with inhibitors of ODC activity blocks the formation of skin tumors and causes the rapid regression of existing tumors. Although the mechanism by which polyamines promote skin tumorigenesis are not well understood, elevated levels of polyamines have been shown to stimulate epidermal proliferation, alter keratinocyte differentiation status, increase neovascularization, and increase synthesis of extracellular matrix proteins in a manner similar to that seen in wound healing. It is becoming increasingly apparent that elevated polyamine levels activate not only epidermal cells but also underlying stromal cells in the skin to promote the development and progression of skin tumors. The inhibition of polyamine biosynthesis has potential to be an effective chemoprevention strategy for nonmelanoma skin cancer.

  19. Ultraviolet Light and Skin Cancer in Athletes

    PubMed Central

    Harrison, Shannon C.; Bergfeld, Wilma F.

    2009-01-01

    The incidence of melanoma and nonmelanoma skin cancers is increasing worldwide. Ultraviolet light exposure is the most important risk factor for cutaneous melanoma and nonmelanoma skin cancers. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Constitutive skin color and genetic factors, as well as immunological factors, play a role in the development of skin cancer. Ultraviolet light also causes sunburn and photoaging damage to the skin. PMID:23015891

  20. Folate in Skin Cancer Prevention

    PubMed Central

    Williams, J.D.; Jacobson, Elaine L.; Kim, H.; Kim, M.; Jacobson, M.K.

    2013-01-01

    Skin, the largest, most exposed organ of the body, provides a protective interface between humans and the environment. One of its primary roles is protection against exposure to sunlight, a major source of skin damage where the UV radiation (UVR) component functions as a complete carcinogen. Melanin pigmentation and the evolution of dark skin is an adaptive protective mechanism against high levels of UVR exposure. Recently, the hypothesis that skin pigmentation balances folate preservation and Vitamin D production has emerged. Both micronutrients are essential for reproductive success. Photodegradation of bioactive folates suggests a mechanism for the increased tendency of populations of low melanin pigmentation residing in areas of high UV exposure to develop skin cancers. Folate is proposed as a cancer prevention target for its role in providing precursors for DNA repair and replication, as well as its ability to promote genomic integrity through the generation of methyl groups needed for control of gene expression. The cancer prevention potential of folate has been demonstrated by large-scale epidemiological and nutritional studies indicating that decreased folate status increases the risk of developing certain cancers. While folate deficiency has been extensively documented by analysis of human plasma, folate status within skin has not been widely investigated. Nevertheless, inefficient delivery of micronutrients to skin and photolysis of folate argue that documented folate deficiencies will be present if not exacerbated in skin. Our studies indicate a critical role for folate in skin and the potential to protect sun exposed skin by effective topical delivery as a strategy for cancer prevention. PMID:22116700

  1. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... 159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead to better ... tissue samples from 170 people with a less aggressive type of brain tumor. This led to the ...

  2. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... 159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more risk, ... comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may be best to ...

  3. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  4. Skin Cancer in the Crosshairs

    PubMed Central

    Sinnya, Sudipta; Zwald, Fiona O.; Colegio, Oscar R.

    2015-01-01

    Abstract The International Transplant Skin Cancer Collaborative (ITSCC) is an organization comprising of physicians; transplant surgeons and basic science research scientists dedicated in providing optimal care and ongoing research advancements in solid organ transplant recipients to improve patient outcome and quality of life. As medical advances occur, it is anticipated that the sheer number of solid organ transplantations occurring worldwide will continue to increase. The long-term medication associated immunosuppression improves graft survival, but as a consequence, these individuals become increasingly susceptible to various cutaneous malignancies, lymphoproliferative disorders and infections. Squamous cell carcinoma is the most frequently encountered skin cancer and increases 65- to 250-fold [Jensen et al., Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177-186; Lindelöf et al., Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol. 2000; 143:513-519]. However, the rates of basal cell carcinoma, Merkel cell carcinoma and melanoma also increase in organ transplant recipients leading to significant morbidity as well as mortality [Berg and Otley. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002; 47:1-20]. In October 2014, the International Transplant Skin Cancer Collaborative and its equivalent European counterpart, Skin Care in Organ Transplant Recipients Europe held its 10th biennial meeting in Essex, MA to discuss the clinical conundrums and the evolving research pertinent to the field. This meeting report provides a synthesis of all the clinical and research data presented at the 4-day meeting.

  5. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  6. Skin cancer in the elderly

    SciTech Connect

    Pollack, S.V.

    1987-11-01

    Skin cancer is a major concern in geriatric populations. Cumulative exposure to carcinogens and age-related factors both contribute to the high prevalence of cutaneous malignancy in the elderly. Although mortality rates from skin cancer are relatively low, morbidity can be significant, particularly if lesions are neglected. Physicians can have a major impact on the course of basal cell carcinoma, squamous cell carcinoma, and malignant melanoma by nurturing a high index of suspicion for malignancy when unexplained cutaneous lesions are encountered. 56 references.

  7. Climate change and skin cancer.

    PubMed

    van der Leun, Jan C; de Gruijl, Frank R

    2002-05-01

    Depletion of the ozone layer and climate change by the increasing greenhouse effect are distinctly different processes. It is becoming quite clear, however, that the two global environmental problems are interlinked in several ways [D. L. Albritton, P. J Aucamp, G. Mégie, R. T. Watson, Scientific Assessment of Ozone Depletion, 1998, World Meteorological Organization, Global Ozone Research and Monitoring Project, Report No. 44 (WMO, Geneva, 1998)]. In the present analysis we deal with the possibility of such an interlinkage within one effect on human health, namely, skin cancer. The increase in the incidence of skin cancer is one of the most extensively studied effects of increasing ultraviolet radiation by ozone depletion (F. R. de Gruijl, Skin cancer and solar radiation, Eur. J Cancer, 1999, 35, 2003-2009). We wondered if this impact could also be influenced by increasing environmental temperatures. Here we show that it is likely that such an influence will occur. For the same reason, it is likely that the baseline incidence of skin cancer will be augmented by rising temperatures, which may become significant in magnitude. PMID:12653470

  8. [Skin cancers and environmental factors].

    PubMed

    Autier, P

    1998-09-01

    In the fair skinned populations of the industrialised nations, the number of cutaneous melanoma doubles every ten to twenty years. Currently, each year in Belgium, about 1,000 new cases of cutaneous melanoma and 15 to 20,000 basal cell or spinal cell epitheliomas are diagnosed. In Europe and in North America, the increase is essentially attributable to the considerable changes in sun exposure habits that took place after World War II. The type of ultraviolet radiation implicated in skin cancers is not known yet, but both the ultraviolet A and the ultraviolet B radiation could be involved in their occurrence. The impact of the stratospheric ozone depletion on skin cancer incidence remains uncertain. The impact of the stratospheric ozone depletion on skin cancer incidence remains uncertain. The sunbed tanning fashion represents another potential source of hazards for skin cancers. Their use must be discouraged. Some European countries have now adopted regulations about their commercialisation and utilisation. Current sun protection messages insist on the physical sun protection (wearing of clothes, staying in the shade), rather than on the use of a sunscreen. In fact, nearly all epidemiological studies done so far have found sunscreen use to be associated with a higher risk of melanoma or non-melanoma skin cancer. Because of their ability to delay sunburns, sunscreens could encourage excessive sun exposure. Sunscreen users should be told to voluntarily limit their sun exposure. New sun protection methods include the measurement of the individual exposure to ultraviolet radiation, with the emission of a signal when a critical level of exposure has been reached. PMID:9805971

  9. For Better Skin Cancer Checks, Partner Up

    MedlinePlus

    ... gov/medlineplus/news/fullstory_159632.html For Better Skin Cancer Checks, Partner Up Melanoma survivors benefited when ... out: Getting a partner trained to spot potential skin cancers can be a lifesaver for melanoma survivors, ...

  10. 'Sunscreen' Gene May Guard Against Skin Cancer

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158935.html 'Sunscreen' Gene May Guard Against Skin Cancer Researchers hope ... Scientists say they've identified a so-called "sunscreen" gene that may help protect against skin cancer. ...

  11. Protecting Our Children from Skin Cancer.

    ERIC Educational Resources Information Center

    Martin, Paul

    1993-01-01

    Skin cancer in the United States is epidemic. About 90% of skin cancers are caused by sun exposure. The age of patients developing melanoma is dropping dramatically. Parents must protect their children from the sun during all outdoor activities year round. The article presents recommendations for preventing skin cancer. (SM)

  12. Review - Skin cancer: Etiology and management.

    PubMed

    Qadir, Muhammad Imran

    2016-05-01

    Nowadays, occurrence of skin cancer is very common in humans. It is reported that the most common cause of the skin cancer is excessive exposure to sunlight as it contains harmful radiations; the ultra violet rays. Different management strategies are used for different types of skin cancers, which are chemotherapy, radiation therapy. PMID:27166545

  13. Hedgehog signaling in skin cancers

    PubMed Central

    Li, Chengxin; Chi, Sumin; Xie, Jingwu

    2011-01-01

    An increasing progress on the role of Hedgehog (Hh) signaling for carcinogenesis has been achieved since the link of Hh pathway to human cancer was firstly established. In particular, the critical role of Hh signaling in the development of Basal cell carcinoma (BCC) has been convincingly demonstrated by genetic mutation analyses, mouse models of BCCs, and successful clinical trials of BCCs using Hh signaling inhibitors. In addition, the Hh pathway activity is also reported to be involved in the pathogenesis of Squamous Cell Carcinoma (SCC), melanoma and Merkel Cell Carcinoma. These findings have significant new paradigm on Hh signaling transduction, its mechanisms in skin cancer and even therapeutic approaches for BCC. In this review, we will summarize the major advances in the understanding of Hh signaling transduction, the roles of Hh signaling in skin cancer development, and the current implications of “mechanism-based” therapeutic strategies. PMID:21397013

  14. Chemoprevention of Skin Cancer Program Project | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Skin cancer is the most common malignancy in the world. One out of three new cancers is a skin cancer. More than 1 million cases of non-melanoma skin cancer (NMSC) (basal cell carcinoma [BCC] and squamous cell cancers [SCC]) occur annually. While the incidence rates for non-melanoma skin cancers continue to rise, there continues to be a substantial impact on morbidity, health and health care costs. |

  15. CYLD regulates keratinocyte differentiation and skin cancer progression in humans

    PubMed Central

    Alameda, J P; Fernández-Aceñero, M J; Moreno-Maldonado, R; Navarro, M; Quintana, R; Page, A; Ramírez, A; Bravo, A; Casanova, M L

    2011-01-01

    CYLD is a gene mutated in familial cylindromatosis and related diseases, leading to the development of skin appendages tumors. Although the deubiquitinase CYLD is a skin tumor suppressor, its role in skin physiology is unknown. Using skin organotypic cultures as experimental model to mimic human skin, we have found that CYLD acts as a regulator of epidermal differentiation in humans through the JNK signaling pathway. We have determined the requirement of CYLD for the maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We show that CYLD overexpression increases keratinocyte differentiation while CYLD loss of function impairs epidermal differentiation. In addition, we describe the important role of CYLD in the control of human non-melanoma skin cancer progression. Our results show the reversion of the malignancy of human squamous cell carcinomas that express increased levels of CYLD, while its functional inhibition enhances the aggressiveness of these tumors which progress toward spindle cell carcinomas. We have found that the mechanisms through which CYLD regulates skin cancer progression include the control of tumor differentiation, angiogenesis and cell survival. These findings of the role of CYLD in human skin cancer prognosis make our results relevant from a therapeutic point of view, and open new avenues for exploring novel cancer therapies. PMID:21900959

  16. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering drugs may ... meats and cheese -- may affect how quickly their prostate cancer progresses, a new study suggests. "We show that ...

  17. Nonmelanoma skin cancer. Risks, treatment options, and tips on prevention.

    PubMed

    Kibarian, M A; Hruza, G J

    1995-12-01

    The incidence of nonmelanoma skin cancer is rapidly increasing. With early diagnosis and treatment, almost all basal cell and squamous cell carcinomas can be cured. Premalignant actinic keratoses are treated with cryosurgery; the CO2 laser is the treatment of choice for actinic cheilitis. Generally, nonmelanoma skin cancer can be effectively treated with excision, electrodesiccation and curettage, cryosurgery, or radiation therapy; 5-year cure rates are over 90%. Large, locally recurrent, and aggressive lesions, as well as lesions located in the central face, are best managed with Mohs' surgery; 5-year cure rates as high as 99% have been reported. Patient education about the dangers of sun exposure and tanning salons can potentially reduce the incidence of nonmelanoma skin cancer. The use of sunscreens starting early in life should be stressed. PMID:7501580

  18. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  19. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... news/fullstory_159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead ... 25, 2016 (HealthDay News) -- Researchers have identified immune genes that may affect how long people live after ...

  20. Prediction of reduction in aggressive behaviour of growing pigs using skin lesion traits as selection criteria.

    PubMed

    Desire, S; Turner, S P; D'Eath, R B; Doeschl-Wilson, A B; Lewis, C R G; Roehe, R

    2016-08-01

    Aggression at regrouping is a common issue in pig farming. Skin lesions are genetically and phenotypically correlated with aggression and have been shown to have a significant heritable component. This study predicts the magnitude of reduction in complex aggressive behavioural traits when using lesion numbers on different body regions at two different time points as selection criteria, to identify the optimum skin lesion trait for selection purposes. In total, 1146 pigs were mixed into new social groups, and skin lesions were counted 24 h (SL24h) and 3 weeks (SL3wk) post-mixing, on the anterior, centre and posterior regions of the body. An animal model was used to estimate genetic parameters for skin lesion traits and 14 aggressive behavioural traits. Estimated breeding values (EBVs) and phenotypic values were scaled and standardised to allow direct comparison across multiple traits. Individuals with SL24h and SL3wk EBVs in the least aggressive 10% of the population were compared with the population mean to predict the expected genetic and phenotypic response in aggressive behaviour to selection. At mixing, selection for low anterior lesions was predicted to affect substantially more behavioural traits of aggressiveness than lesions obtained on other body parts, with EBVs between -0.21 and -1.17 SD below the population mean. Individuals with low central SL24h EBVs also had low EBVs for aggressive traits (-0.33 to -0.55). Individuals with high SL3wk EBVs had low EBVs for aggression at mixing (between -0.24 and -0.53 SD below the population mean), although this was predicted to affect fewer traits than selection against SL24h. These results suggest that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Selection for increased SL3wk was predicted to reduce aggression at mixing; however, current understanding about aggressive behaviour under stable social conditions is insufficient

  1. What's New in Research and Treatment of Melanoma Skin Cancer?

    MedlinePlus

    ... Topic Additional resources for melanoma skin cancer What’s new in melanoma skin cancer research? Research into the ... Melanoma Talking With Your Doctor After Treatment What`s New in Skin Cancer - Melanoma Research? Other Resources and ...

  2. Non-melanoma skin cancer.

    PubMed

    Griffin, Liezel L; Ali, Faisal Rehman; Lear, John T

    2016-02-01

    Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC. PMID:26833519

  3. Skin cancer - an overview for dentists.

    PubMed

    Steel, B J

    2014-05-01

    Skin cancer is common and an increasing problem in the UK. It frequently occurs on the head and neck skin. A significant proportion of the adult population in the UK visits the dentist each year, thus making dental practitioners ideally placed to identify suspicious lesions, which could be skin cancer, as part of their routine extra-oral examination. These patients can then be referred on to hospital or their GP for further management. The dentist can also give advice on risk factors and self-monitoring to patients. This paper aims to describe the risk factors, pathology, presentation and treatments for the three most common forms of skin cancer - basal and squamous cell carcinomas, and malignant melanoma, to give the dental practitioner the knowledge and confidence to examine for and identify these skin cancers. PMID:24852988

  4. Skin cancer and solar UV radiation.

    PubMed

    de Gruijl, F R

    1999-12-01

    Ultraviolet (UV) radiation in sunlight is the most prominent and ubiquitous physical carcinogen in our natural environment. It is highly genotoxic but does not penetrate the body any deeper than the skin. Like all organisms regularly exposed to sunlight, the human skin is extremely well adapted to continuous UV stress. Well-pigmented skin is clearly better protected than white Caucasian skin. The sun-seeking habits of white Caucasians in developed countries are likely to have contributed strongly to the increase in skin cancer observed over the last century. Skin cancer is by far the most common type of cancer in the U.S.A. and Australia, which appears to be the result of an 'unnatural displacement' of people with sun-sensitive skin to sub-tropical regions. Although campaigns have been successful in informing people about the risks of sun exposure, general attitudes and behaviour do not yet appear to have changed to the extent that trends in skin cancer morbidity and the corresponding burden on public healthcare will be reversed. The relationship between skin cancer and regular sun exposure was suspected by physicians in the late 19th century, and subsequently substantiated in animal experiments in the early part of the 20th century. UV radiation was found to be highly genotoxic, and DNA repair proved to be crucial in fending off detrimental effects such as mutagenesis and cell death. In fact, around 1940 it was shown that the wavelength dependence of mutagenicity paralleled the UV absorption by DNA. In the 1970s research on UV carcinogenesis received a new impetus from the arising concern about a possible future depletion of the stratospheric ozone layer: the resulting increases in ambient UV loads were expected to raise skin cancer incidences. Epidemiological studies in the last decades of the 20th century have greatly refined our knowledge on the aetiology of skin cancers. Analyses of gene mutations in skin carcinomas have identified UV radiation as the cause

  5. What Is Melanoma Skin Cancer?

    MedlinePlus

    ... that can become melanoma. They make a brown pigment called melanin , which gives the skin its tan ... to the sun, melanocytes make more of the pigment, causing the skin to tan or darken. Melanoma ...

  6. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Cancer.gov

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  7. Anatomical and molecular imaging of skin cancer

    PubMed Central

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼ 5%) and nonmelanoma (∼ 95%), which can be further categorized into basal cell carcinoma, squamous cell carcinoma, and some rare skin cancer types. Biopsy is still the gold standard for skin cancer evaluation in the clinic. Various anatomical imaging techniques have been used to evaluate different types of skin cancer lesions, including laser scanning confocal microscopy, optical coherence tomography, high-frequency ultrasound, terahertz pulsed imaging, magnetic resonance imaging, and some other recently developed techniques such as photoacoustic microscopy. However, anatomical imaging alone may not be sufficient in guiding skin cancer diagnosis and therapy. Over the last decade, various molecular imaging techniques (in particular single photon emission computed tomography and positron emission tomography) have been investigated for skin cancer imaging. The pathways or molecular targets that have been studied include glucose metabolism, integrin αvβ3, melanocortin-1 receptor, high molecular weight melanoma-associated antigen, and several other molecular markers. Preclinical molecular imaging is thriving all over the world, while clinical molecular imaging has not lived up to the expectations because of slow bench-to-bedside translation. It is likely that this situation will change in the near future and molecular imaging will truly play an important role in personalized medicine of melanoma patients. PMID:21437135

  8. For Better Skin Cancer Checks, Partner Up

    MedlinePlus

    ... 159632.html For Better Skin Cancer Checks, Partner Up Melanoma survivors benefited when they and a loved ... the researchers explained. During two years of follow-up, 66 of the patients did go on to ...

  9. Global controversies and advances in skin cancer.

    PubMed

    Baldwin, Louise; Dunn, Jeff

    2013-01-01

    Advances and controversies of skin cancer prevention in the Asian-Pacific region are to be examined the world's first Global Controversies and Advances in Skin Cancer Conference to be held in Brisbane, Australia this November. APOCP Members are cordially invited to register early for the opportunity to contribute to the debate on a cancer which continues to be a prominent issue in the Asia Pacific and indeed worldwide. We need answers to the questions of why a cancer that is so preventable and easily detectable is still shrouded in controversy. Primary focuses will be on issues like viral involvement, vaccines and novel clinical approaches. PMID:23725105

  10. Climate change and human skin cancer.

    PubMed

    van der Leun, Jan C; Piacentini, Rubén D; de Gruijl, Frank R

    2008-06-01

    As part of an inventory of potential interactions between effects of ozone depletion and climate change, a possible effect of ambient temperature on sun-induced skin cancers was suggested. Mouse experiments had shown that increased room temperature enhanced ultraviolet (UV) radiation-induced carcinogenesis; the effective UV dose was increased by 3-7% per degrees C. The present investigation was aimed at studying a possible temperature effect on human skin cancer. Existing data on the incidence of human skin cancer were analyzed, as available from two special surveys of non-melanoma skin cancer in the United States. The incidence of non-melanoma skin cancer in the ten regions surveyed not only correlated significantly with the ambient UV dose but also with the average daily maximum temperature in summer. For squamous cell carcinoma the incidence was higher by 5.5% (SE 1.6%) per degrees C and for basal cell carcinoma by 2.9% (SE 1.4%) per degrees C. These values correspond to an increase of the effective UV dose by about 2% per degrees C. Although the precise nature of this correlation with temperature requires further studies, it can be concluded that the temperature rises coming with climate change can indeed amplify the induction of non-melanoma skin cancers by UV radiation in human populations. PMID:18528559

  11. Teaching Nursing Students about Skin Cancer Using a Skin Analyzer Machine.

    PubMed

    Siegel, Victoria; Stone, Alicia; George, Anna

    2016-01-01

    Nurses are in an excellent position to perform skin assessments and teach the public about skin cancer prevention. Knowledgeable nurses can help reduce the incidence of skin cancer. Determining the best method to teach nursing students about skin cancer is thus important. PMID:27323471

  12. Development of a Skin Cancer Prevention Program

    ERIC Educational Resources Information Center

    Hatmaker, Grace

    2003-01-01

    The Centers for Disease Control and Prevention (CDC) now categorizes skin cancer as epidemic. Nearly 90% of these deadly cancers start from sun exposure during the childhood years. This makes sun exposure in school-age children a serious public health risk, also one that school nurses can address. Solar radiation is now classified as a "known…

  13. Grenz ray-induced nonmelanoma skin cancer

    SciTech Connect

    Frentz, G.

    1989-09-01

    In 28 patients, nonmelanoma skin cancers developed in areas previously exposed to grenz rays. In 17 patients who did not have psoriasis, no other relevant carcinogenic exposure could be incriminated. Women were more often affected than men. Most of the tumors were basal cell cancers, and most of the patients had multiple tumors. No threshold dose could be established. The distribution of the latency time among patients without psoriasis was strictly normal (median 18 years). These observations suggest that usual therapeutic doses of grenz rays, as a single agent, are capable of causing skin cancer, but only in those persons who are abnormally sensitive to x-rays. 9 references.

  14. How Are Squamous and Basal Cell Skin Cancers Diagnosed?

    MedlinePlus

    ... often enough to cure basal and squamous cell skin cancers without further treatment. There are different types of skin biopsies. The ... and Prevention Early Detection, Diagnosis, and Staging Treating Skin Cancer - ... Your Doctor After Treatment What`s New in Skin Cancer - Basal and Squamous ...

  15. Radiation Therapy for Skin Cancer

    MedlinePlus

    ... Laser surgery Cancer cells are killed by laser beams.  Electrodessication The cancer is dried with an electric ... a chemical reaction that kills nearby cells. EXTERNAL BEAM RADIATION THERAPY External beam radiation therapy may be ...

  16. The many unanswered questions related to the German skin cancer screening programme.

    PubMed

    Stang, Andreas; Garbe, Claus; Autier, Philippe; Jöckel, Karl-Heinz

    2016-09-01

    In 2008, the first nationwide skin cancer screening (SCS) programme in the world was established in Germany. The main reason to implement the SCS programme in Germany was the expected reduction of costs of care due to earlier detection of skin cancer. The aim of this commentary is to raise and discuss several unanswered questions related to the German SCS programme. The evidence of a temporary mortality decline of skin melanoma after SCS in Schleswig-Holstein is lower than previously assumed and the temporary decline may have been caused by other factors than screening (e.g. awareness effects, selection bias, data artifact, and random fluctuation). The evaluation of the nationwide effect of SCS on skin cancer mortality is hampered by birth cohort effects and low quality of the routine cause-of-death statistics. The nationwide skin melanoma mortality did not decrease from 2007 through 2014. The time interval between screenings after a screening without pathological findings is unclear. Appropriate research designs are needed that monitor and evaluate the effect of SCS not only on skin cancer mortality but also on other factors that may help to judge the potential benefits and harms of SCS including aggressiveness of therapy, costs of care, quality of life, and stage-specific incidence rates of skin cancer. Furthermore, SCS may profit from a high-risk strategy instead of population-wide screening and from newer technologies for early detection of skin cancer (e.g. dermoscopy). PMID:27371911

  17. In vivo multiphoton tomography of skin cancer

    NASA Astrophysics Data System (ADS)

    König, Karsten; Riemann, Iris; Ehlers, Alexander; Buckle, Rainer; Dimitrow, Enrico; Kaatz, Martin; Fluhr, Joachim; Elsner, Peter

    2006-02-01

    The multiphoton tomograph DermaInspect was used to perform first clinical studies on the early non-invasive detection of skin cancer based on non-invasive optical sectioning of skin by two-photon autofluorescence and second harmonic generation. In particular, deep-tissue pigmented lesions -nevi- have been imaged with intracellular resolution using near infrared (NIR) femtosecond laser radiation. So far, more than 250 patients have been investigated. Cancerous tissues showed significant morphological differences compared to normal skin layers. In the case of malignant melanoma, the occurrence of luminescent melanocytes has been detected. Multiphoton tomography will become a novel non-invasive method to obtain high-resolution 3D optical biopsies for early cancer detection, treatment control, and in situ drug screening.

  18. Novel Medical Strategies Combating Nonmelanoma Skin Cancer

    PubMed Central

    Bhandari, Prasan R; Pai, Varadraj V

    2014-01-01

    The incidence of nonmelanoma skin cancer (NMSC) continues to rise, partly because of aging, the frequency of early childhood sunburns, and sporadic extreme recreational sun exposure. A nonsurgical approach to selected cutaneous malignancy could possibly reduce the cost as well as morbidity of surgical treatment for NMSC. There has been growing interest in isolating compounds that could suppress or reverse the biochemical changes necessary for cutaneous malignancies to progress by pharmacologic intervention. By targeting diverse pathways recognized as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. This preliminary information will expand to include more therapeutic options for NMSC in the future. PMID:25484380

  19. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  20. Topical therapies for skin cancer and actinic keratosis.

    PubMed

    Haque, Tasnuva; Rahman, Khondaker M; Thurston, David E; Hadgraft, Jonathan; Lane, Majella E

    2015-09-18

    The global incidence of skin cancer and actinic keratosis (AK) has increased dramatically in recent years. Although many tumours are treated with surgery or radiotherapy topical therapy has a place in the management of certain superficial skin neoplasms and AK. This review considers skin physiology, non-melanoma skin cancer (NMSC), the relationship between AK and skin cancer and drugs administered topically for these conditions. The dermal preparations for management of NMSC and AK are discussed in detail. Notably few studies have examined drug disposition in cancerous skin or in AK. Finally, recent novel approaches for targeting of drugs to skin neoplasms and AK are discussed. PMID:26091570

  1. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

  2. Overview on non-melanoma skin cancers in solid organ transplant recipients.

    PubMed

    Forchetti, G; Suppa, M; Del Marmol, V

    2014-08-01

    The risk of non-melanoma skin cancer (NMSC) is significantly increased in solid organ transplant recipients (SOTRs) due to the long-term immunosuppressive treatment. NMSCs can be more aggressive in SOTRs than in the general population, resulting in significantly higher morbidity and mortality. In contrast to the immunocompetent population, skin cancers in SOTRs are dominated by squamous cell carcinoma, followed by basal cell carcinoma. Life-long radiation exposure, male sex, fair skin, history of prior NMSC, genetic factors, age at transplant along with duration and extent of the immunosuppression therapy have been identified as risk factors for NMSC in SOTRs. Photo-protection, skin self-examination, early diagnosis and treatment of skin lesions, reduction of immunotherapy, switch to mammalian target-of-rapamycin inhibitors and chemoprevention with oral retinoids are effective measures for the reduction of the incidence of NMSC in such patients. PMID:25068224

  3. An Update on Nonmelanoma Skin Cancer

    PubMed Central

    Patel, Rita V.; Frankel, Amylynne

    2011-01-01

    Estimates from the American Cancer Society suggest that there are more than two million cases of nonmelanoma skin cancer in the United States per year. The following review highlights the topics of actinic keratoses, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, and Merkel cell carcinoma. This update on the cutting-edge clinical and dermpathologic research will assist the dermatologist in approaching, diagnosing, and managing nonmelanoma skin carcinoma. Immunologic and genetic research into nonmelanoma skin carcinoma has paved the way for novel therapeutic options for patients who were previously without any viable treatment alternatives. While still in preliminary stages, agents, such as ingenol mebutate, vismodegib, and sirolumus, may become integral drugs in the armamentarium of managing cutaneous carcinoma. PMID:21386954

  4. Noninvasive imaging for nonmelanoma skin cancer.

    PubMed

    Giavedoni, Priscila; Puig, Susana; Carrera, Cristina

    2016-03-01

    The development of noninvasive optical technologies is revolutionizing the diagnosis of skin tumors. Nonmelanoma skin cancer, the most frequent neoplasm, has become an important health and economic issue, and proper management can avoid unnecessary morbidity and mutilating treatment or relapses. Noninvasive treatment modalities and the recently approved systemic therapies for advanced basal cell carcinoma cases make noninvasive monitoring techniques necessary. Current knowledge, applications, and limitations of the tools most clinically implemented, such as dermoscopy, reflectance confocal microscopy, high frequency ultrasonography, and optical coherence tomography will be reviewed in this article. In addition to the improvement of diagnostic accuracy of skin cancer, using these tools individually or in combination facilitates better management of certain patients and tumors. PMID:26963115

  5. 'Sunscreen' Gene May Guard Against Skin Cancer

    MedlinePlus

    ... is an associate professor of molecular microbiology and immunology at the University of Southern California Keck School of Medicine. Cell damage from exposure to UV radiation causes more than 90 percent of melanoma skin cancers. Melanoma kills more than 10,000 people in ...

  6. Photocarcinogenesis and Skin Cancer Prevention Strategies.

    PubMed

    Seebode, Christina; Lehmann, Janin; Emmert, Steffen

    2016-03-01

    In this review the basic principles of UV-induced carcinogenesis are summarized and the state of the art diagnosis and therapeutic strategies are discussed. The prevalent keratinocyte-derived neoplasms of the skin are basal cell and squamous cell carcinomas. Cutaneous melanoma is less frequent but associated with high mortality. Common risk factors for all three tumor entities include sun exposure and DNA-repair deficiencies. Photocarcinogenesis follows a multistep model of cancer development in which ultraviolet-induced DNA damage leads to mutations resulting in activation of oncogenes or silencing of tumor-suppressor genes. This ends in a cellular mutator phenotype even more prone to mutation acquisition. DNA repair, especially the nucleotide excision repair (NER) pathway, counteracts mutation formation and skin cancer development. This is vividly demonstrated by the NER-defective disorder xeroderma pigmentosum. Primary skin cancer preventative strategies, therefore, include reduction of DNA photodamage by protection from the sun. Secondary preventative strategies include skin cancer screening. This implies standard examination techniques with the naked eye, an epiluminescence microscope, or digital epiluminescence microscopy. More advanced techniques include confocal laser scan microscopy. PMID:26977038

  7. Low spinophilin expression enhances aggressive biological behavior of breast cancer

    PubMed Central

    Ress, Anna Lena; Aigelsreiter, Ariane; Schauer, Silvia; Wagner, Karin; Langsenlehner, Tanja; Resel, Margit; Gerger, Armin; Ling, Hui; Ivan, Cristina; Calin, George Adrian; Hoefler, Gerald; Rinner, Beate; Pichler, Martin

    2015-01-01

    Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24-3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer. PMID:25857299

  8. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

    PubMed

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin). PMID:26112486

  9. Teledermatology protocol for screening of Skin Cancer*

    PubMed Central

    Piccoli, Maria Fernanda; Amorim, Bruna Dücker Bastos; Wagner, Harley Miguel; Nunes, Daniel Holthausen

    2015-01-01

    BACKGROUND Telemedicine refers to the use of technology as improvement of healthcare delivery to places where distance becomes an obstacle. Its use represents a great potential for dermatology, a specialty whose visual analysis phase is essential in diagnosis. OBJECTIVES To analyze the compatibility index of skin cancer diagnoses between primary care and teledermatology, and to validate a protocol for standardization of digital imaging to obtain the reports in teledermatology. METHODS An observational cross-sectional study developed through the census of 333 examination requests, received between January/2012 and July/2012, in the Center for Telemedicine and Telehealth of SES-SC. We used a protocol for photographic lesion standardization, consisting of three steps (panoramic photo, close-up with ruler and dermoscopy). After collection, the data were sent to a virtual site on the Internet, and recorded with the use of an electronic health record containing the images, the skin phototype and demographic characteristics. RESULTS The level of compatibility between the diagnosis of skin cancer in Santa Catarina's primary care and the diagnosis proposed by teledermatology was 19.02%. Proportionally, it was 21.21% for BCC, 44.44% for SCC and 6.98% for MM. The protocol was statistically significant (p <0.05), with an OR of 38.77. CONCLUSION The rate of diagnostic compatibility of skin cancer was low and the use of the protocol optimized the chance of validating requests for examination. PMID:25830990

  10. Hyperspectral imaging of skin and lung cancers

    NASA Astrophysics Data System (ADS)

    Zherdeva, Larisa A.; Bratchenko, Ivan A.; Alonova, Marina V.; Myakinin, Oleg O.; Artemyev, Dmitry N.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

    2016-04-01

    The problem of cancer control requires design of new approaches for instrumental diagnostics, as the accuracy of cancer detection on the first step of diagnostics in clinics is slightly more than 50%. In this study, we present a method of visualization and diagnostics of skin and lung tumours based on registration and processing of tissues hyperspectral images. In a series of experiments registration of hyperspectral images of skin and lung tissue samples is carried out. Melanoma, basal cell carcinoma, nevi and benign tumours are studied in skin ex vivo and in vivo experiments; adenocarcinomas and squamous cell carcinomas are studied in ex vivo lung experiments. In a series of experiments the typical features of diffuse reflection spectra for pathological and normal tissues were found. Changes in tissues morphology during the tumour growth lead to the changes of blood and pigments concentration, such as melanin in skin. That is why tumours and normal tissues maybe differentiated with information about spectral response in 500-600 nm and 600 - 670 nm areas. Thus, hyperspectral imaging in the visible region may be a useful tool for cancer detection as it helps to estimate spectral properties of tissues and determine malignant regions for precise resection of tumours.

  11. The causes of skin cancer: a comprehensive review.

    PubMed

    Saladi, Rao N; Persaud, Andrea N

    2005-01-01

    Skin cancer is the most common type of cancer in fair-skinned populations around the world. The incidence and mortality rates of skin cancers are dramatically increasing and thus pose a threat to public health. Understanding the etiology and pathogenesis of skin cancer remains a goal for healthcare systems. A clearer understanding of causative factors is an essential step in the prevention of skin cancer. This article comprehensively reviews the causative agents which play a role in the development of skin cancer. Ultraviolet radiation (UV) from sun exposure is the most important cause of skin cancer. Sunburns and excessive exposures cause cumulative damage which induces immunosuppression and skin cancers. Ozone depletion, the level of UV light, elevation, latitude, altitude and weather conditions influence the emission of UV radiation reaching the earth's surface. Organ transplant recipients and AIDS patients have an increased incidence of skin cancers. Some treatment modalities, including radiation therapy, phototherapy and psoralen and long-wave ultraviolet radiation (PUVA) can also predispose to skin cancers. Viral infections such as the human papilloma virus can cause squamous cell carcinomas. Individuals with familial genetic syndromes are susceptible to specific types of skin cancers. Ionizing radiation, environmental pollutants, chemical carcinogens and work-related exposures have been associated with skin cancers. Exposure to artificial UV radiation (tanning beds and lamps), aging, skin color, diet and smoking are attributable risks. Skin cancers have been found in dermatoses and various types of keratoses, chronically injured or nonhealing wounds, and scars. This article provides a comprehensive and thorough overview of skin cancer, with an emphasis on understanding its epidemiology, incidence, etiology and related risk factors. PMID:15753968

  12. Inflammatory Bowel Disease and Skin Cancer: An Assessment of Patient Risk Factors, Knowledge, and Skin Practices

    PubMed Central

    Kimmel, Jessica N.; Taft, Tiffany H.; Keefer, Laurie

    2016-01-01

    Objective. Patients with inflammatory bowel disease (IBD) are at increased risk from skin cancer. Aims include assessing IBD patients' risk factors and knowledge of skin cancer and current skin protection practices to identify gaps in patient education regarding skin cancer prevention in IBD. Methods. IBD patients ≥ 18 years were recruited to complete an online survey. Results. 164 patients (mean age 43.5 years, 63% female) with IBD (67% Crohn's disease, 31% ulcerative colitis, and 2% indeterminate colitis) were included. 12% (n = 19) of patients had a personal history and 34% (n = 55) had a family history of skin cancer. Females scored better on skin protection (16.94/32 versus 14.53/32, P ≤ 0.03) and awareness (35.16/40 versus 32.98/40, P ≤ 0.03). Patients over 40 years old scored better on prevention (17.45/28 versus 15.35/28, P = 0.03). Patients with skin cancer scored better on prevention (20.56/28 versus 15.75/28, P ≤ 0.001) and skin protection (21.47/32 versus 15.33/32, P ≤ 0.001). 61% of patients recognized the link between skin cancer and IBD. Conclusions. The majority of IBD patients are aware of the link between skin cancer and IBD; however, skin protection practices are suboptimal. This emphasizes the role of healthcare professionals in providing further education for skin cancer prevention in the IBD population. PMID:27034838

  13. Photodynamic therapy for skin cancer

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Julius, Clark E.; Hartman, Donald L.

    1996-04-01

    Photodynamic therapy was used to treat 111 lesions in 27 cases with squamous and basal cell carcinoma. There were 82 squamous cell carcinomas and 29 basal cell carcinomas. Photofrin was administered intravenously at either 1.0 mg/kg or 0.75 mg/kg. An argon/dye laser was used to deliver 630 nm light to the lesion superficially at either 215 J/cm2 or 240 J/cm2. In some cases the laser light was delivered both superficially and interstitially. The laser light was delivered two to four days after the Photofrin injection. There were 105 complete responses and 5 partial responses. One patient was lost to follow-up. Among partial responses were basal cell carcinoma on the tip of the nose and morphea basal cell carcinoma of the left cheek. Another partial response occurred in a basal cell carcinoma patient where insufficient margins were treated due to the proximity to the eye. When 0.75 mg/kg drug dose was used, the selectivity of tumor necrosis was improved. Decreased period of skin photosensitivity was documented in some cases.

  14. Characterization of aggressive prostate cancer using ultrasound RF time series

    NASA Astrophysics Data System (ADS)

    Khojaste, Amir; Imani, Farhad; Moradi, Mehdi; Berman, David; Siemens, D. Robert; Sauerberi, Eric E.; Boag, Alexander H.; Abolmaesumi, Purang; Mousavi, Parvin

    2015-03-01

    Prostate cancer is the most prevalently diagnosed and the second cause of cancer-related death in North American men. Several approaches have been proposed to augment detection of prostate cancer using different imaging modalities. Due to advantages of ultrasound imaging, these approaches have been the subject of several recent studies. This paper presents the results of a feasibility study on differentiating between lower and higher grade prostate cancer using ultrasound RF time series data. We also propose new spectral features of RF time series to highlight aggressive prostate cancer in small ROIs of size 1 mm × 1 mm in a cohort of 19 ex vivo specimens of human prostate tissue. In leave-one-patient-out cross-validation strategy, an area under accumulated ROC curve of 0.8 has been achieved with overall sensitivity and specificity of 81% and 80%, respectively. The current method shows promising results on differentiating between lower and higher grade of prostate cancer using ultrasound RF time series.

  15. Aggressive thyroid cancer in low-risk age population

    SciTech Connect

    Rosen, I.B.; Bowden, J.; Luk, S.C.; Simpson, J.A.

    1987-12-01

    Seventy-eight patients under the age of 40 (low-risk patients) who had undergone surgical treatment for well-differentiated thyroid carcinoma were referred from 1979 to 1986 to our hospital for adjuvant therapy. A subgroup of 37 patients, 14 with apparent aggressive cancer, was studied. This study group consisted of 27 female and 10 male patients with mixed papillary and follicular cancer, who ranged in age from 11 to 40 years. Nodal disease occurred in 27 (73%) patients and invasiveness in 30 (81%) patients and involved multiple areas in 9 (24%) patients. Recurrence occurred in 14 (38%) patients and visceral metastases occurred in eight (22%) patients. All patients underwent appropriate surgery, but microscopic residual disease was seen in 15 patients and gross residual disease in seven patients, so that 31 patients underwent iodine-131 therapy, and 17 of these patients also underwent external radiation therapy. Three patients died of their disease, whereas 24 (65%) patients are free of disease and 9 (24%) patients are alive with disease. An additional 7 (19%) patients were initially seen in the fifth to seventh decade after decades of neglected thyroid disease, which culminated in residual cancer and death. Although low-risk categorization for thyroid cancer appears valid, its rigid application in support of conservative treatment may lead to inadequate primary treatment and underdiagnosis of cancer in thyroid nodule disease in the low-risk age population.

  16. Evaluating a Skin Cancer Education Program for the Deaf Community

    PubMed Central

    Harry, Kadie M.; Malcarne, Vanessa L.; Branz, Patricia; Fager, Matthew; Garcia, Barbara D.; Sadler, Georgia Robins

    2014-01-01

    Skin cancer is the most common, preventable, and treatable cancer, so public education has been a priority. Unfortunately, for the Deaf community, most skin cancer information is difficult to access, so tailored approaches are needed. Participants (N = 136) were randomly assigned to view either a skin cancer education video in American Sign Language (ASL) (n = 75) or an alternate video (n = 61). All participants completed skin cancer knowledge questionnaires at baseline, immediately post-intervention, and two-months post-intervention. Control group participants could then transfer to the experimental condition, using their two-month follow-up data as their baseline. Participants who saw the skin cancer video gained significantly more knowledge than control participants, demonstrating the video’s effectiveness in increasing skin cancer control knowledge. There was no difference between the original experimental group and the delayed intervention group on knowledge gains. PMID:22544511

  17. Skin Conductance Level Reactivity Moderates the Association Between Parental Psychological Control and Relational Aggression in Emerging Adulthood.

    PubMed

    Wagner, Caitlin R; Abaied, Jamie L

    2016-04-01

    When studying factors that may heighten risk for relational aggression in youth, it is important to consider characteristics of both the individual and their environment. This research examined the associations between parental psychological control and reactive and proactive relational aggression in emerging adults in college. Given that sympathetic nervous system (SNS) activation may underlie differences between reactive and proactive aggression and has been shown to moderate the effects of parenting on youth development, the moderating role of SNS reactivity [indexed by skin conductance level reactivity (SCLR)] was also examined. Emerging adults (N = 180; 77.2 % female) self-reported on perceptions of parental psychological control and reactive and proactive relational aggression. SCLR was assessed in response to an interpersonal laboratory challenge task. Parental psychological control was positively associated with reactive relational aggression only for emerging adults who exhibited high SCLR. Parental psychological control was positively associated with proactive relational aggression only among emerging adults who showed low SCLR. This study extends previous research on parenting and aggression and suggests that parental psychological control is differentially associated with reactive versus proactive relational aggression, depending on emerging adults' SCLR to interpersonal stress. PMID:26762376

  18. Risk of Skin Cancer from Space Radiation. Chapter 11

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Kim, Myung-Hee Y.; George, Kerry A.; Wu, Hong-Lu

    2003-01-01

    We review the methods for estimating the probability of increased incidence of skin cancers from space radiation exposure, and describe some of the individual factors that may contribute to risk projection models, including skin pigment, and synergistic effects of combined ionizing and UV exposure. The steep dose gradients from trapped electrons, protons, and heavy ions radiation during EVA and limitations in EVA dosimetry are important factors for projecting skin cancer risk of astronauts. We estimate that the probability of increased skin cancer risk varies more than 10-fold for individual astronauts and that the risk of skin cancer could exceed 1 % for future lunar base operations for astronauts with light skin color and hair. Limitations in physical dosimetry in estimating the distribution of dose at the skin suggest that new biodosimetry methods be developed for responding to accidental overexposure of the skin during future space missions.

  19. HPV vaccination for prevention of skin cancer

    PubMed Central

    Vinzón, Sabrina E; Rösl, Frank

    2015-01-01

    Cutaneous papillomaviruses are associated with specific skin diseases, such as extensive wart formation and the development of non-melanoma skin cancer (NMSC), especially in immunosuppressed patients. Hence, clinical approaches are required that prevent such lesions. Licensed human papillomavirus (HPV) vaccines confer type-restricted protection against HPV types 6, 11, 16 and 18, responsible of 90% of genital warts and 70% of cervical cancers, respectively. However, they do not protect against less prevalent high-risk types or cutaneous HPVs. Over the past few years, several studies explored the potential of developing vaccines targeting cutaneous papillomaviruses. These vaccines showed to be immunogenic and prevent skin tumor formation in certain animal models. Furthermore, under conditions mimicking the ones found in the intended target population (i.e., immunosuppression and in the presence of an already established infection before vaccination), recent preclinical data shows that immunization can still be effective. Strategies are currently focused on finding vaccine formulations that can confer protection against a broad range of papillomavirus-associated diseases. The state-of-the-art of these approaches and the future directions in the field will be presented. PMID:25692212

  20. Glasses: Hiding or causing skin cancer?

    PubMed

    Zhang, Ze; Behshad, Soroosh; Sethi-Patel, Pooja; Valenzuela, Alejandra A

    2016-10-01

    This article evaluates malignant transformation of lesions presenting in the periocular skin under the eye spectacle nose pad. A non-comparative retrospective chart review of clinical features and pathological findings of patients presenting with periocular malignancies in the exact vicinity where the nose pads of their eye spectacles rested was completed. The study took place in one tertiary oculoplastic referral center between 2007-2013. Ten patients were included, six of whom were male. All subjects wore eye spectacles while awake for at least 15 years, and had an evident suspicious lesion in the exact area that coincided with the resting place of the nose pad. The mean age was 73.5 years (range 65-85 years) and all patients had the lesion present for at least one year. Most cases were squamous skin malignancies (five squamous cell carcinomas [SCC], 2 intra-epidermal carcinomas [IEC], while 3 basal cell carcinomas [BCC]). Treatment involved surgical excision of the lesion with frozen section for margin control and reconstruction with a myocutaneous flap. Periocular malignancies of the inferior medial canthal area, where the nose pad of eye spectacle places pressure, can be easily missed or misdiagnosed. Marjolin ulcers (MU) classically present as an aggressive SCC in area of chronic inflammation, which has been previously correlated to constant pressure, repetitive trauma, or non-healing wounds in other areas of the body. We propose that the traumatic chronic pressure in the infero-medial canthal region from long-term eye spectacle nose pad use, may induce poor lymphatic regeneration leading to an immune system deficiency that predisposes this skin to a malignant transformation. The presence of chronic eye spectacle nose pads also prevents proper and timely detection of such malignancies. Complete excision of these lesions with margin control, adequate follow-up for possible recurrence, and surveillance for new lesions on the patient's contralateral side, is

  1. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    PubMed Central

    IFERE, GODWIN O.; DESMOND, RENEE; DEMARK-WAHNEFRIED, WENDY; NAGY, TIM R.

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease. PMID:23934233

  2. MMSET is overexpressed in cancers: Link with tumor aggressiveness

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

    MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4; 14) (p16; q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

  3. Genetics of Skin Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of skin cancer — basal cell carcinoma, squamous cell carcinoma, and melanoma — including information about specific gene mutations and related cancer syndromes. The summary also contains information about interventions that may influence the risk of developing skin cancer in individuals who may be genetically susceptible to these syndromes.

  4. Skin cancer in skin of color: an update on current facts, trends, and misconceptions.

    PubMed

    Battie, Claire; Gohara, Mona; Verschoore, Michèle; Roberts, Wendy

    2013-02-01

    For many fair-skinned individuals around the world, skin cancer is the leading malignancy. Although skin cancer comprises only 1% to 2% of all malignancies in those with darker complexions, the mortality rates in this subgroup are substantially higher when compared with their Caucasian counterparts. This discrepancy is largely as a result of delayed detection/treatment, and a false perception among patient and physician that brown skin confers complete protection against skin cancer. Recent studies show that 65% of surveyed African Americans never wore sunscreen, despite living in sunny climates, and that more than 60% of minority respondents erroneously believed that they were not at risk for skin cancer. Dark skin offers some protection from ultraviolet (UV) light. However, there is considerable heterogeneity in skin of color, a phenomenon that is accentuated by mixed heritage. Ethnicity does not confer skin type anymore. People of color do experience sunburn, and from a biological point of view, all skin types appear to be sensitive to UV-induced DNA damage, with an inverse relationship between skin color and sensitivity to UV light. Our population is changing rapidly, and within the next few decades minority populations will become the majority. It is therefore imperative to educate both physicians and patients on the perceived immunity against cutaneous malignancies, the need for sun protection, and the clinical signs of skin cancer in non-Caucasian people, so that future unnecessary mortality can be avoided. PMID:23377393

  5. Skin manifestations associated with kidney cancer.

    PubMed

    Amin, Asim; Burgess, Earle F

    2016-06-01

    Kidney cancer is a heterogenous disease encompassing several distinct clinicopathologic entities with different underlying molecular aberrations and clinical outcomes. Renal cell carcinoma (RCC) has been shown to evoke immunologic responses that can impact the natural history of disease and clinical presentation. It is important to recognize atypical presentations of disease, including cutaneous manifestations. The incidence of skin metastases from RCC is low, yet needs to be appreciated in the appropriate setting; clinical presentation for these lesions is reviewed briefly. There are several hereditary syndromes that present with well characterized cutaneous lesions and are associated with an increased risk for RCC, including Von Hippel-Lindau and Birt-Hogg-Dubé syndromes. Given that these skin lesions may be the first presenting sign for RCC, timely recognition is of essence and both are discussed in some detail. Several therapeutic options based on immunomodulation are approved for the treatment of advanced RCC. Dermatologic toxicities observed with these agents are also briefly discussed. PMID:27178696

  6. PBX3 is a putative biomarker of aggressive prostate cancer.

    PubMed

    Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I; Bjartell, Anders; Eri, Lars Magne; Berge, Viktor; Svindland, Aud; Taskén, Kristin Austlid

    2016-10-15

    There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer. PMID:27273830

  7. Fluorescence lifetime imaging of skin cancer

    NASA Astrophysics Data System (ADS)

    Patalay, Rakesh; Talbot, Clifford; Munro, Ian; Breunig, Hans Georg; König, Karsten; Alexandrov, Yuri; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Chris

    2011-03-01

    Fluorescence intensity imaging and fluorescence lifetime imaging microscopy (FLIM) using two photon microscopy (TPM) have been used to study tissue autofluorescence in ex vivo skin cancer samples. A commercially available system (DermaInspect®) was modified to collect fluorescence intensity and lifetimes in two spectral channels using time correlated single photon counting and depth-resolved steady state measurements of the fluorescence emission spectrum. Uniquely, image segmentation has been used to allow fluorescence lifetimes to be calculated for each cell. An analysis of lifetime values obtained from a range of pigmented and non-pigmented lesions will be presented.

  8. Cognitive adaptation to nonmelanoma skin cancer.

    PubMed

    Czajkowska, Zofia; Radiotis, George; Roberts, Nicole; Körner, Annett

    2013-01-01

    Taylor's (1983) cognitive adaptation theory posits that when people go through life transitions, such as being diagnosed with a chronic disease, they adjust to their new reality. The adjustment process revolves around three themes: search for positive meaning in the experience or optimism, attempt to regain a sense of mastery in life, as well as an effort to enhance self-esteem. In the sample of 57 patients with nonmelanoma skin cancer the Cognitive Adaptation Index successfully predicted participants' distress (p < .001) accounting for 60% of the variance and lending support for the Taylor's theory of cognitive adaptation in this population. PMID:23844920

  9. CDC Grand Rounds: Prevention and Control of Skin Cancer.

    PubMed

    Watson, Meg; Thomas, Cheryll C; Massetti, Greta M; McKenna, Sharon; Gershenwald, Jeffrey E; Laird, Susan; Iskander, John; Lushniak, Boris

    2015-12-01

    Skin cancer is the most common cancer in the United States, and most cases are preventable. Persons with certain genetic risk factors, including having a lighter natural skin color; blue or green eyes; red or blonde hair; dysplastic nevi or a large number of common moles; and skin that burns, freckles, or reddens easily or becomes painful after time in the sun, have increased risk for skin cancer. Persons with a family or personal history of skin cancer, especially melanoma, are also at increased risk. Although these genetic factors contribute to individual risk, most skin cancers are also strongly associated with ultraviolet (UV) radiation exposure. Most UV exposure comes from the sun, although some persons use UV-emitting indoor tanning devices (e.g., beds, booths, and lamps). PMID:26633233

  10. Melanoma and other skin cancers in circumpolar areas.

    PubMed

    Oikarinen, A; Raitio, A

    2000-01-01

    During the recent decades, the thickness of the ozone layer over the northern hemisphere has declined by 10 to 40 percent during the winter and spring months. Since ozone is the major barrier protecting the earth from dangerous short wave UV-radiation (UVB), the depletion in the ozone layer consequently increases the amount of UV-radiation reaching the earth's surface. As a rule a 10 percent reduction in the ozone layer causes ca. 20% increase in UV-radiation and a 40% increase in skin cancers. Thus relatively minor changes in ozone layer thickness may a have marked impact on the health of humans. Skin cancer is the most common cancer in humans, i.e. in Finland about 4000 new basal cell carcinomas, 700 other skin cancers, mostly spinous cell carcinomas and 500 melanomas occur yearly. Up to recent years the incidence of skin cancers has steadily increased in northern countries. As an explanation, changes in sunbathing habits have been suggested to play a central role. Due to the high mortality rate in melanoma, and marked morbidity in other skin cancers, it is important to try to prevent skin cancers and inform the public about the risks of excessive sun exposure, and of the ways in which the skin can be protected. Proper clothing and use of sunscreens have been shown to reduce the incidence of both melanomas and other skin cancers. Furthermore, it is important to identify those at high risk for acquiring skin cancers, like individuals with type 1 skin character (fair skin which burns easily), or numerous dysplastic nevi, or a family history of skin cancers. PMID:10850007

  11. Skin cancer screening in Okinawa, Japan.

    PubMed

    Nagano, T; Ueda, M; Suzuki, T; Naruse, K; Nakamura, T; Taguchi, M; Araki, K; Nakagawa, K; Nagai, H; Hayashi, K; Watanabe, S; Ichihashi, M

    1999-04-01

    Depletion of the ozone layer has been observed on a global scale. Ozone depletion increases the amount of biologically harmful solar ultraviolet radiation (UV) that reaches the surface of the Earth, leading to an increased incidence of skin cancer. We previously reported the prevalence and incidence of actinic keratosis (AK) in Kasai City, which is located almost at the center of Japan. To evaluate the effects of different ambient annual UV doses on the prevalence and incidence of non-melanoma skin cancer and AK in Japan, we screened for skin cancer on Ie Island in Okinawa at the southern end of Japan, where the annual cumulative dose of UV is assumed to be the highest in Japan. The island had a population of 5562 in 1993. A prospective 4-year population-based study on the prevalence and incidence of cutaneous neoplasms was conducted by examining the sun-exposed skin of people over 40 years of age living on Ie Island. In 1993 1996, 86 cases of AK, nine of basal cell carcinoma (BCC), and two of squamous cell carcinoma were identified. The annual prevalence of AK on Ie Island was 1159.4 in 1993, 572.8 in 1994, 1014.3 in 1995 and 988.9 per 100000 Japanese in 1996. These values were significantly higher than those in Kasai City. The annual age-adjusted odds ratios for AK of Ie Island to Kasai City were 2.79, 1.38, 2.45 and 2.39, respectively. The incidences of AK on Ie Island per 100,000 were 637.0 in 1995 and 625.5 in 1996, which were also significantly higher than those in Kasai City (223.6 in 1993 and 171.2 in 1994). The prevalence of BCC was 123.6 and the incidence was 26.1. Together with our previous reports, the present results show a possible inverse relationship between the prevalence and incidence of AK and latitude among Japanese people. PMID:10215187

  12. Dynamic infrared imaging for skin cancer screening

    NASA Astrophysics Data System (ADS)

    Godoy, Sebastián E.; Ramirez, David A.; Myers, Stephen A.; von Winckel, Greg; Krishna, Sanchita; Berwick, Marianne; Padilla, R. Steven; Sen, Pradeep; Krishna, Sanjay

    2015-05-01

    Dynamic thermal imaging (DTI) with infrared cameras is a non-invasive technique with the ability to detect the most common types of skin cancer. We discuss and propose a standardized analysis method for DTI of actual patient data, which achieves high levels of sensitivity and specificity by judiciously selecting pixels with the same initial temperature. This process compensates the intrinsic limitations of the cooling unit and is the key enabling tool in the DTI data analysis. We have extensively tested the methodology on human subjects using thermal infrared image sequences from a pilot study conducted jointly with the University of New Mexico Dermatology Clinic in Albuquerque, New Mexico (ClinicalTrials ID number NCT02154451). All individuals were adult subjects who were scheduled for biopsy or adult volunteers with clinically diagnosed benign condition. The sample size was 102 subjects for the present study. Statistically significant results were obtained that allowed us to distinguish between benign and malignant skin conditions. The sensitivity and specificity was 95% (with a 95% confidence interval of [87.8% 100.0%]) and 83% (with a 95% confidence interval of [73.4% 92.5%]), respectively, and with an area under the curve of 95%. Our results lead us to conclude that the DTI approach in conjunction with the judicious selection of pixels has the potential to provide a fast, accurate, non-contact, and non-invasive way to screen for common types of skin cancer. As such, it has the potential to significantly reduce the number of biopsies performed on suspicious lesions.

  13. Dhoti cancer: a waistline skin cancer with review of literature.

    PubMed

    Akhtar, Murtaza A; Saxena, Divish K; Chikhlikar, Akanksha A; Bangde, Akshay P; Rangwala, Murtuza

    2015-01-01

    Skin cancers account for less than 1 % of all malignancies in India. Squamous cell carcinomas occurring over the waistline due to tying of cotton cloth called dhoti in males and sarees in females are predominantly seen in traditional Indian population. On wearing of these clothes for years, there is a constant irritation which produces depigmentation, glazing of the skin, acanthosis, scar formation, and later on malignant transformation. Presenting a case of a 65-year-old male with 7 × 5 cm ulceroproliferative growth over the right waistline with a history of prolonged use of dhoti. Wide local excision of the growth with 2-cm margin and primary closure of wound by mobilizing the skin was carried out. Histopathology showed well-differentiated squamous cell carcinoma. The patient is clinically disease free after postoperative follow-up of 1 year. PMID:26391587

  14. Glucose promotes breast cancer aggression and reduces metformin efficacy

    PubMed Central

    Wahdan-Alaswad, Reema; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Deng, Xin-Sheng; Arnadottir, Sigrid Salling; Richer, Jennifer K; Anderson, Steven M; Thor, Ann D

    2013-01-01

    Metformin treatment has been associated with a decrease in breast cancer risk and improved survival. Metformin induces complex cellular changes, resulting in decreased tumor cell proliferation, reduction of stem cells, and apoptosis. Using a carcinogen-induced rodent model of mammary tumorigenesis, we recently demonstrated that overfeeding in obese animals is associated with a 50% increase in tumor glucose uptake, increased proliferation, and tumor cell reprogramming to an “aggressive” metabolic state. Metformin significantly inhibited these pro-tumorigenic effects. We hypothesized that a dynamic relationship exists between chronic energy excess (glucose by dose) and metformin efficacy/action. Media glucose concentrations above 5 mmol/L was associated with significant increase in breast cancer cell proliferation, clonogenicity, motility, upregulation/activation of pro-oncogenic signaling, and reduction in apoptosis. These effects were most significant in triple-negative breast cancer (TNBC) cell lines. High-glucose conditions (10 mmol/L or above) significantly abrogated the effects of metformin. Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose. Significant changes in gene profiles related to apoptosis, cellular processes, metabolic processes, and cell proliferation occurred with metformin treatment in cells grown at 5 mmol/L glucose, whereas under high-glucose conditions, metformin did not significantly increase apoptotic/cellular death genes. These data indicate that failure to maintain glucose homeostasis may promote a more aggressive breast cancer phenotype and alter metformin efficacy and mechanisms of action. PMID:24107633

  15. minSKIN Does a multifaceted intervention improve the competence in the diagnosis of skin cancer by general practitioners? Study protocol for a randomised controlled trial

    PubMed Central

    2011-01-01

    Background In Switzerland, skin cancer is one of the most common neoplasms. Melanoma is the most aggressive one and can be lethal if not detected and removed on time. Nonmelanoma skin cancer is more frequent as melanoma; it is seldom lethal but can disfigure patients in advanced stages. General practitioners (GPs) are often faced with suspicious skin lesions of their patients. Methods/Design Design: Randomised controlled trial (RCT). Population: 60 GPs, randomised into intervention group and control group. Intervention: GPs get a Lumio loupe, a digital camera and continuous feedback based on pictures of skin lesions they send to the Dermatologist. Primary outcome: Competence in the diagnosis of skin cancer by GPs, measured as the percentage of correctly classified pictures of skin lesions. Measurements: At baseline, and prior to any intervention (T0), GPs will be asked to rate 36 pictures of skin lesions according to their likelihood of malignancy on a visual analogue scale (VAS). After a full day training course with both groups (T1) and after one year of continuous feedback (T2) with the intervention group, we will repeat the picture scoring session with both groups, using new pictures. Discussion We want to determine whether a multifaceted intervention (including technical equipment and a continuous feedback on skin lesions) leads to an improved competence in the diagnosis of skin cancer by GPs. This study addresses the hypothesis that an additional feedback loop, based on pictures performed in daily practice by GPs is superior to a simple educational intervention regarding diagnostic competence. We expect an improvement of the competence in skin cancer diagnosis by GPs in both groups after the full day training course. Beside this immediate effect, we also expect a long term effect in the intervention group because of the continuous problem based feedback. Trial registration ISRCTN: ISRCTN29854485 PMID:21718520

  16. Drug Shows Promise Against Rare, Aggressive Skin Cancer

    MedlinePlus

    ... New Orleans, and published online in the New England Journal of Medicine . An oncologist who was not ... annual meeting, New Orleans; April 19, 2016, New England Journal of Medicine online HealthDay Copyright (c) 2016 ...

  17. Combined inhibition of p38 and Akt signaling pathways abrogates cyclosporine A-mediated pathogenesis of aggressive skin SCCs

    SciTech Connect

    Arumugam, Aadithya; Walsh, Stephanie B.; Xu, Jianmin; Afaq, Farrukh; Elmets, Craig A.; Athar, Mohammad

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer p38 and Akt are the crucial molecular targets in the pathogenesis of SCCs in OTRs. Black-Right-Pointing-Pointer Combined inhibition of these targets diminished tumor growth by 90%. Black-Right-Pointing-Pointer Inhibition of these targets act through downregulating mTOR signaling pathway. -- Abstract: Non-melanoma skin cancers (NMSCs) are the most common neoplasm in organ transplant recipients (OTRs). These cancers are more invasive and metastatic as compared to those developed in normal cohorts. Previously, we have shown that immunosuppressive drug, cyclosporine A (CsA) directly alters tumor phenotype of cutaneous squamous cell carcinomas (SCCs) by activating TGF-{beta} and TAK1/TAB1 signaling pathways. Here, we identified novel molecular targets for the therapeutic intervention of these SCCs. We observed that combined blockade of Akt and p38 kinases-dependent signaling pathways in CsA-promoted human epidermoid carcinoma A431 xenograft tumors abrogated their growth by more than 90%. This diminution in tumor growth was accompanied by a significant decrease in proliferation and an increase in apoptosis. The residual tumors following the combined treatment with Akt inhibitor triciribine and p38 inhibitors SB-203580 showed significantly diminished expression of phosphorylated Akt and p38 and these tumors were less invasive and highly differentiated. Diminished tumor invasiveness was associated with the reduced epithelial-mesenchymal transition as ascertained by the enhanced E-cadherin and reduced vimentin and N-cadherin expression. Consistently, these tumors also manifested reduced MMP-2/9. The decreased p-Akt expression was accompanied by a significant reduction in p-mTOR. These data provide first important combinatorial pharmacological approach to block the pathogenesis of CsA-induced highly aggressive cutaneous neoplasm in OTRs.

  18. What's New in Research and Treatment of Basal and Squamous Cell Skin Cancers?

    MedlinePlus

    ... for basal and squamous cell skin cancers What’s new in basal and squamous cell skin cancer research? ... cancer cells. Researchers are working to apply this new information to strategies for preventing and treating skin ...

  19. Skin Cancer Can Strike Anyone | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Skin Cancer Skin Cancer Can Strike Anyone Past Issues / Summer 2013 ... removed. That is the most common form of skin cancer and not as dangerous as melanoma. Photo: ...

  20. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  1. Relationship Between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Zhou, Cindy Ke; Pfeiffer, Ruth M.; Cleary, Sean D.; Hoffman, Heather J.; Levine, Paul H.; Chu, Lisa W.; Hsing, Ann W.; Cook, Michael B.

    2015-01-01

    Purpose Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort—the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Methods We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric. Results During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer. Conclusion Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms. PMID:25225425

  2. Ultraviolet radiation and skin cancer of humans.

    PubMed

    Urbach, F

    1997-08-01

    Current scientific evidence indicates that stratospheric ozone has declined worldwide over the past 20 years. The trend estimates are markedly dependent on the geographical location and are highly seasonal. Winter trends are much more negative than those for summer and autumn. Projections based on current assumptions of chlorine release suggest that this decline will continue into the next century. On the basis of the decrease in ozone over the mid-latitudes, an increase in biologically effective ultraviolet radiation (UVR) of 4%-9% is expected, depending on the season and geographical location. However, the UVR penetration to the Earth's surface is greatly affected by clouds, aerosols and tropospheric ozone, and current increases, if any, have not been as large as this. Direct evidence for the induction of non-melanoma skin cancer (NMSC) due to UVR has been derived from animal experiments in mice and rats. Numerous epidemiological data confirm that this relationship also holds for human skin. The increase in NMSC incidence in the past two decades is not likely to be due to the decrease in ozone, given the long latency (two to three decades) associated with UVR effects on skin. A knowledge of the action spectrum for NMSC development suggests that a 1% depletion in stratospheric ozone may be expected to increase NMSC, at equilibrium, by about 2.0% The evidence on the role of UVR exposure in the development of malignant melanoma (MM) is less certain. It has been estimated that a 1% reduction in ozone may cause an increase in MM of 0.6%. PMID:9301039

  3. Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors.

    PubMed

    Jaju, Prajakta D; Ransohoff, Katherine J; Tang, Jean Y; Sarin, Kavita Y

    2016-03-01

    Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease. PMID:26892653

  4. Health system costs of skin cancer and cost-effectiveness of skin cancer prevention and screening: a systematic review.

    PubMed

    Gordon, Louisa G; Rowell, David

    2015-03-01

    The objective of this study was to review the literature for malignant melanoma, basal and squamous cell carcinomas to understand: (a) national estimates of the direct health system costs of skin cancer and (b) the cost-effectiveness of interventions for skin cancer prevention or early detection. A systematic review was performed using Medline, Cochrane Library and the National Health Service Economic Evaluation Databases as well as a manual search of reference lists to identify relevant studies up to 31 August 2013. A narrative synthesis approach was used to summarize the data. National cost estimates were adjusted for country-specific inflation and presented in 2013 euros. The CHEERS statement was used to assess the quality of the economic evaluation studies. Sixteen studies reporting national estimates of skin cancer costs and 11 cost-effectiveness studies on skin cancer prevention or early detection were identified. Relative to the size of their respective populations, the annual direct health system costs for skin cancer were highest for Australia, New Zealand, Sweden and Denmark (2013 euros). Skin cancer prevention initiatives are highly cost-effective and may also be cost-saving. Melanoma early detection programmes aimed at high-risk individuals may also be cost-effective; however, updated analyses are needed. There is a significant cost burden of skin cancer for many countries and health expenditure for this disease will grow as incidence increases. Public investment in skin cancer prevention and early detection programmes show strong potential for health and economic benefits. PMID:25089375

  5. Skin Cancer Surveillance Behaviors among U.S. Hispanic Adults

    PubMed Central

    Coups, Elliot J.; Stapleton, Jerod L.; Hudson, Shawna V.; Medina-Forrester, Amanda; Rosenberg, Stephen A.; Gordon, Marsha; Natale-Pereira, Ana; Goydos, James S.

    2012-01-01

    Background Little skin cancer prevention research has focused on the U.S. Hispanic population. Objective This study examined the prevalence and correlates of skin cancer surveillance behaviors among Hispanic adults. Methods A population-based sample of 788 Hispanic adults residing in five southern and western states completed an online survey in English or Spanish in September 2011. The outcomes were ever having conducted a skin self-examination (SSE) and having received a total cutaneous examination (TCE) from a health professional. The correlates included sociodemographic, skin cancer-related, and psychosocial factors. Results The rates of ever conducting a SSE or having a TCE were 17.6% and 9.2%, respectively. Based on the results of multivariable logistic regressions, factors associated with ever conducting a SSE included older age, English linguistic acculturation, a greater number of melanoma risk factors, more frequent sunscreen use, sunbathing, job-related sun exposure, higher perceived skin cancer risk, physician recommendation, more SSE benefits, and fewer SSE barriers. Factors associated with ever having a TCE were older age, English linguistic acculturation, a greater number of melanoma risk factors, ever having tanned indoors, greater skin cancer knowledge, higher perceived skin cancer severity, lower skin cancer worry, physician recommendation, more TCE benefits, and fewer SSE barriers. Limitations The cross-sectional design limits conclusions regarding the causal nature of observed associations. Conclusions Few Hispanic adults engage in skin cancer surveillance behaviors. The study highlights Hispanic subpopulations that are least likely to engage in skin cancer surveillance behaviors and informs the development of culturally appropriate interventions to promote these behaviors. PMID:23182066

  6. Behaviors, beliefs, and intentions in skin cancer prevention.

    PubMed

    Cody, R; Lee, C

    1990-08-01

    This study investigated knowledge, behaviors, and health beliefs of Australian university students (n = 312) regarding skin cancers and evaluated the effects of videotaped presentations. Students' knowledge and health beliefs were assessed, and they then viewed either an informational video, an emotionally involving video, or a control video. Knowledge and beliefs were assessed immediately and 10 weeks later. Postvideo skin protection intentions increased significantly from prevideo assessment among the two intervention groups compared to the controls. Maintenance of skin protection intentions was higher with the emotional video. Health belief variables, particularly perceived barriers, were significant predictors of knowledge, intention, and behavior. However, other variables such as skin type and previous experience with skin cancer were more important. Females had greater knowledge and stronger intentions to prevent skin cancer than males but reported fewer high-risk behaviors. PMID:2246784

  7. Guidelines for school programs to prevent skin cancer.

    PubMed

    Glanz, Karen; Saraiya, Mona; Wechsler, Howell

    2002-04-26

    Skin cancer is the most common type of cancer in the United States. Since 1973, new cases of the most serious form of skin cancer, melanoma, have increased approximately 150%. During the same period, deaths from melanoma have increased approximately 44%. Approximately 65%-90% of melanomas are caused by ultraviolet (UV) radiation. More than one half of a persons lifetime UV exposure occurs during childhood and adolescence because of more opportunities and time for exposure. Exposure to UV radiation during childhood plays a role in the future development of skin cancer. Persons with a history of > or = 1 blistering sunburns during childhood or adolescence are two times as likely to develop melanoma than those who did not have such exposures. Studies indicate that protection from UV exposure during childhood and adolescence reduces the risk for skin cancer. These studies support the need to protect young persons from the sun beginning at an early age. School staff can play a major role in protecting children and adolescents from UV exposure and the future development of skin cancer by instituting policies, environmental changes, and educational programs that can reduce skin cancer risks among young persons. This report reviews scientific literature regarding the rates, trends, causes, and prevention of skin cancer and presents guidelines for schools to implement a comprehensive approach to preventing skin cancer. Based on a review of research, theory, and current practice, these guidelines were developed by CDC in collaboration with specialists in dermatology, pediatrics, public health, and education; national, federal, state, and voluntary agencies; schools; and other organizations. Recommendations are included for schools to reduce skin cancer risks through policies; creation of physical, social, and organizational environments that facilitate protection from UV rays; education of young persons; professional development of staff involvement of families; health

  8. Aggressive chemosurgical debulking in patients with advanced ovarian cancer.

    PubMed

    Ng, L W; Rubin, S C; Hoskins, W J; Jones, W B; Hakes, T B; Markman, M; Reichman, B; Almadrones, L; Lewis, J L

    1990-09-01

    From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high-intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1-cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy. PMID:2227548

  9. A mobile system for skin cancer diagnosis and monitoring

    NASA Astrophysics Data System (ADS)

    Gu, Yanliang; Tang, Jinshan

    2014-05-01

    In this paper, we propose a mobile system for aiding doctors in skin cancer diagnosis and other persons in skin cancer monitoring. The basic idea is to use image retrieval techniques to help the users to find the similar skin cancer cases stored in a database by using smart phones. The query image can be taken by a smart phone from a patient or can be uploaded from other resources. The shapes of the skin lesions are used for matching two skin lesions, which are segmented from skin images using the skin lesion extraction method developed in 1. The features used in the proposed system are obtained by Fourier descriptor. A prototype application has been developed and can be installed in an iPhone. In this application, the iPhone users can use the iPhone as a diagnosis tool to find the potential skin lesions in a persons' skin and compare the skin lesions detected by the iPhone with the skin lesions stored in a database in a remote server.

  10. Sagging Skin

    MedlinePlus

    ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ...

  11. Intake of grains and dietary fiber and prostate cancer aggressiveness by race.

    PubMed

    Tabung, Fred; Steck, Susan E; Su, L Joseph; Mohler, James L; Fontham, Elizabeth T H; Bensen, Jeannette T; Hebert, James R; Zhang, Hongmei; Arab, Lenore

    2012-01-01

    Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50-0.97 and OR = 0.61; 95% CI, 0.40-0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23-0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35-0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men. PMID:23213538

  12. Intake of Grains and Dietary Fiber and Prostate Cancer Aggressiveness by Race

    PubMed Central

    Tabung, Fred; Steck, Susan E.; Su, L. Joseph; Mohler, James L.; Fontham, Elizabeth T. H.; Bensen, Jeannette T.; Hebert, James R.; Zhang, Hongmei; Arab, Lenore

    2012-01-01

    Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50–0.97 and OR = 0.61; 95% CI, 0.40–0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23–0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35–0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men. PMID:23213538

  13. Colorectal cancer implant in an external hemorrhoidal skin tag

    PubMed Central

    Liasis, Lampros

    2016-01-01

    External hemorrhoidal skin tags are generally benign. Colorectal cancer metastases to the squamous epithelium of perianal skin tags without other evidence of disseminated disease is a very rare finding. We present the case of a 61-year-old man with metastasis to an external hemorrhoidal skin tag from a midrectal primary adenocarcinoma. This case report highlights the importance of close examination of the anus during surgical planning for colorectal cancers. Abnormal findings of the perianal skin suggesting an implant or metastatic disease warrant biopsy, as distal spread and seeding can occur. In our patient, this finding appropriately changed surgical management. PMID:27034567

  14. Risk factors for skin cancer among Finnish airline cabin crew.

    PubMed

    Kojo, Katja; Helminen, Mika; Pukkala, Eero; Auvinen, Anssi

    2013-07-01

    Increased incidence of skin cancers among airline cabin crew has been reported in several studies. We evaluated whether the difference in risk factor prevalence between Finnish airline cabin crew and the general population could explain the increased incidence of skin cancers among cabin crew, and the possible contribution of estimated occupational cosmic radiation exposure. A self-administered questionnaire survey on occupational, host, and ultraviolet radiation exposure factors was conducted among female cabin crew members and females presenting the general population. The impact of occupational cosmic radiation dose was estimated in a separate nested case-control analysis among the participating cabin crew (with 9 melanoma and 35 basal cell carcinoma cases). No considerable difference in the prevalence of risk factors of skin cancer was found between the cabin crew (N = 702) and the general population subjects (N = 1007) participating the study. The mean risk score based on all the conventional skin cancer risk factors was 1.43 for cabin crew and 1.44 for general population (P = 0.24). Among the cabin crew, the estimated cumulative cosmic radiation dose was not related to the increased skin cancer risk [adjusted odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.57-1.00]. The highest plausible risk of skin cancer for estimated cosmic radiation dose was estimated as 9% per 10 mSv. The skin cancer cases had higher host characteristics scores than the non-cases among cabin crew (adjusted OR = 1.43, 95% CI: 1.01-2.04). Our results indicate no difference between the female cabin crew and the general female population in the prevalence of factors generally associated with incidence of skin cancer. Exposure to cosmic radiation did not explain the excess of skin cancer among the studied cabin crew in this study. PMID:23316078

  15. Epidemiology of skin cancer: role of some environmental factors.

    PubMed

    Fabbrocini, Gabriella; Triassi, Maria; Mauriello, Maria Chiara; Torre, Guglielma; Annunziata, Maria Carmela; De Vita, Valerio; Pastore, Francesco; D'Arco, Vincenza; Monfrecola, Giuseppe

    2010-01-01

    The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth's surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people's behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer. PMID:24281212

  16. Epidemiology of Skin Cancer: Role of Some Environmental Factors

    PubMed Central

    Fabbrocini, Gabriella; Triassi, Maria; Mauriello, Maria Chiara; Torre, Guglielma; Annunziata, Maria Carmela; Vita, Valerio De; Pastore, Francesco; D’Arco, Vincenza; Monfrecola, Giuseppe

    2010-01-01

    The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth’s surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people’s behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer. PMID:24281212

  17. Determinants for Aggressive End-of-Life Care for Oral Cancer Patients

    PubMed Central

    Chang, Ting-Shou; Su, Yu-Chieh; Lee, Ching-Chih

    2015-01-01

    Abstract Few studies have addressed the association between oral cancer and end-of-life (EOL) aggressive care using population data. We investigated the relationship between patient demographics, primary physician's specialty, and hospital characteristics of patients who died from oral cancer in Taiwan from 2009 to 2011 and the aggressiveness of their EOL care. This nationwide population-based, retrospective cohort study identified 5386 patients who died from oral cancer identified from Taiwan's National Register of Deaths Database and collected their claims data from Taiwan's National Health Insurance Research Database. Accepted indicators of aggressiveness of EOL care were examined using a composite measure adapted from Earle et al. Scores ranged from 0 to 6; the higher the score, the more aggressive the EOL care. The impact of each variable on the aggressiveness of EOL care was examined by multivariate analysis using a random-intercept model. The mean composite score for aggressiveness of EOL care was 2.68 ± 1.37. Oral cancer patients who were younger, had a higher level of comorbidity or metastasis, belonged to a lower-level individual socioeconomic status, were cared for by nononcologists, had longer postdiagnosis survival times, or resided in urban areas were more likely to receive aggressive care at EOL. Compared with previous studies, oral cancer patients near death in this nationwide study had a far higher utilization rate (>50%) of chemotherapy, emergency room services, and intensive care unit services. Our findings indicate that oral cancer patients receive extensive aggressive medical care at EOL. Future research may be needed to examine the effect of the means (indicators) of aggressive treatment on survival, quality of life, and medical costs, especially since current research suggests such care may adversely affect quality of life and important preparation of death in these patients. PMID:25634186

  18. The Kauai Skin Cancer Study--1983 to 1992

    SciTech Connect

    Reizner, G.T. )

    1993-05-01

    The Kauai Skin Cancer Study began as a modest effort in 1983 to look at this island's skin cancer incidence. David Elpern MD, Kauai's only dermatologist at the time, was interested in the large number of these tumors in his practice. He first enlisted his office staff to help keep track of the numbers and type of these skin cancers. Along with this information, the basic demographic data on each patient was collected. These records became the first entries into what has become a decade-long project.

  19. Evaluation of skin cancer risk for lunar and Mars missions

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Hee Y.; George, Kerry A.; Cucinotta, Francis A.

    Methods used to estimate the probability of excess incidence of skin cancer from space radiation exposure must take into consideration the variability of dose to different areas of the body and the individual factors that may contribute to increased risk, including skin pigment and synergistic effects from combined ionizing and UV exposure. We have estimated the skin cancer risk for future lunar and Mars missions using: (1) the multiplicative risk model for transferring the Japanese survivor data to the US population, (2) epidemiological data for the increased risk for skin locations exposed to combined UV and ionizing radiation, and (3) models of space radiation environments, transport, and anatomical shielding for 5260 skin loci. We have estimated that the probability for increased skin cancer risk from solar particle events varies more than 10-fold depending on the individual and area of skin exposed. We show that a skin cancer risk greater than 1% could occur for astronauts with light skin and hair color following exposure to medium or large class solar particle events during future lunar base operations, or from exposure to galactic cosmic rays during Mars missions.

  20. Inflammation and skin cancer: old pals telling new stories.

    PubMed

    Hensler, Sabine; Mueller, Margareta M

    2013-01-01

    Inflammation and the inflammatory infiltrate essentially contribute to tumor development and progression. For skin cancer, the observation that tumors arise in sites of chronic irritation and inflammation dates back to 1828 and has stimulated a whole field of research. Numerous animal models such as models of UV-induced or chemically induced skin carcinogenesis but also trangenic models support the role of a deregulated inflammation in the development of skin cancer. These models have greatly contributed to our understanding of the multistage process of carcinogenesis and have given important insights in the differences between physiological inflammation in a healing wound and the functional contribution of the deregulated tumor-associated inflammation to skin cancer growth and progression. Data from these models are supported by epidemiological studies that emphasize a connection of inflammatory conditions with the development of melanoma and epithelial skin cancer and give first indications for a beneficial effect of anti-inflammatory treatments in reducing the risk for skin cancer. Consequently, anti-inflammatory drugs might represent a highly interesting approach in the prevention and treatment of skin cancers. PMID:24270351

  1. Prediction of skin cancer occurrence by ultraviolet solar index

    PubMed Central

    Rivas, Miguel; Rojas, Elisa; Calaf, Gloria M.

    2012-01-01

    An increase in the amount of solar ultraviolet light that reaches the Earth is considered to be responsible for the worldwide increase in skin cancer. It has been reported that exposure to excessive levels of solar ultraviolet light has multiple effects, which can be harmful to humans. Experimental ultraviolet light measurements were obtained in several locations in Chile between 2006 and 2009 using wide-band solar light Biometer YES, calibrated according to World Meteorological Organization (WMO) criteria and integrated into the National Meteorological Center of Chile ultraviolet network (DMC). The aim of this study was to determine skin cancer rates in relation to experimental data accumulated during one year of studying the solar ultraviolet index in Chile, in order to explain the possible effect of radiation on skin cancer. The rate of skin cancer per 100,000 persons was considered in Arica, Santiago, Concepción and Valdivia and extrapolated to other cities. Results of the present study showed that the incidence of skin cancer was markedly correlated with accumulative ultraviolet radiation, and rates of skin cancer could be extrapolated to other locations in Chile. There is a steady increase in the rate of skin cancer in cities located nearest to the equator (low latitude) that receive greater accumulated solar ultraviolet radiation, due to the accumulative effects of this type of radiation on the skin. It can be concluded that Arica is a city at sea level that receives higher levels of ultraviolet solar radiation than other locations, which may explain the higher prevalence of skin cancer in the population of this location, compared with other cities in Chile. PMID:22741013

  2. Nuclear shape descriptors by automated morphometry may distinguish aggressive variants of squamous cell carcinoma from relatively benign skin proliferative lesions: a pilot study.

    PubMed

    Yang, Weixi; Tian, Rong; Xue, Tongqing

    2015-08-01

    We evaluated whether degrees of dysplasia may be consistently accessed in an automatic fashion, using different kinds of non-melanoma skin cancer (NMSC) as a validatory model. Namely, we compared Bowen disease, actinic keratosis, basal cell carcinoma, low-grade squamous cell carcinoma, and invasive squamous cell carcinoma. We hypothesized that characterizing the shape of nuclei may be important to consistently diagnose the aggressiveness of a skin tumor. While basal cell carcinoma is comparatively relatively benign, management of squamous cell carcinoma is controversial because of its potential to recur and intraoperative dilemma regarding choice of the margin or the depth for the excision. We provide evidence here that progressive nuclear dysplasia may be automatically estimated through the thresholded images of skin cancer and quantitative parameters estimated to provide a quasi-quantitative data, which can thenceforth guide the management of the particular cancer. For circularity, averaging more than 2500 nuclei in each group estimated the means ± SD as 0.8 ± 0.007 vs. 0.78 ± 0.0063 vs. 0.42 ± 0.014 vs. 0.63 ± 0.02 vs. 0.51 ± 0.02 (F = 318063.56, p < 0.0001, one-way analyses of variance). The mean aspect ratios were (means ± SD) 0.97 ± 0.0014 vs. 0.95 ± 0.002 vs. 0.38 ± 0.018 vs. 0.84 ± 0.0035 vs. 0.74 ± 0.019 (F = 1022631.931, p < 0.0001, one-way analyses of variance). The Feret diameters averaged over 2500 nuclei in each group were the following: 1 ± 0.0001 vs. 0.9 ± 0.002 vs. 5 ± 0.031 vs. 1.5 ± 0.01 vs. 1.9 ± 0.004 (F = 33105614.194, p < 0.0001, one-way analyses of variance). Multivariate analyses of composite parameters potentially detect aggressive variants of squamous cell carcinoma as the most dysplastic form, in comparison to locally occurring squamous cell carcinoma and basal cell carcinoma, or benign skin lesions. PMID:25753477

  3. Sunscreens, Skin Cancer, and Your Patient.

    ERIC Educational Resources Information Center

    Davidson, Terence M.; Wolfe, Dana P.

    1986-01-01

    The effects of sunlight on skin are described. The principal types of sunscreens and their properties are discussed. The three types of skin tumors, their cure rates, and treatment methods are examined. (Author/MT)

  4. The Epidemiology of Skin Cancer and its Trend in Iran

    PubMed Central

    Razi, Saeid; Enayatrad, Mostafa; Mohammadian-Hafshejani, Abdollah; Salehiniya, Hamid; Fathali-loy-dizaji, Mehri; Soltani, Shahin

    2015-01-01

    Background: One of the most common cancers is skin cancer worldwide. Since incidence and cost of treatment of the cancer are increasing, it is necessary to further investigate to prevent and control this disease. This study aimed to determine skin cancer trend and epidemiology in Iran. Methods: This study was done based on existing data. Data used in this study were obtained from a national registry of cancer cases and the Disease Management Center of Ministry of Health in Iran. All cases registered in the country were included during 2004–2008. Incidence rates were reported based on the direct method and standard population of World Health Organization. Results: Based on the results of this study, the incidence of skin cancer is rising in Iran and the sex ratio was more in men than women in all provinces. The age-standardized incidence rate (ASR) of skin cancer was highest in males in Semnan, Isfahan, and Hamedan provinces (34.9, 30.80, and 28.84, respectively). The highest ASRs were seen in females in Semnan, Yazd, and Isfahan provinces (26.7, 24.14, and 18.97, respectively). The lowest ASR in male was observed in Sistan and Baluchestan, and in female in Hormozgan provinces. Conclusions: The incidence of skin cancer is increasing in the country. Therefore, the plan for the control and prevention of this cancer must be a high priority for health policy makers. PMID:26288708

  5. Diet and Skin Cancer: The Potential Role of Dietary Antioxidants in Nonmelanoma Skin Cancer Prevention

    PubMed Central

    Katta, Rajani; Brown, Danielle Nicole

    2015-01-01

    Nonmelanoma skin cancer (NMSC) is the most common cancer among Americans. Ultraviolet (UV) radiation exposure is the major risk factor for the development of NMSC. Dietary AOs may prevent free radical-mediated DNA damage and tumorigenesis secondary to UV radiation. Numerous laboratory studies have found that certain dietary AOs show significant promise in skin cancer prevention. These results have been substantiated by animal studies. In human studies, researchers have evaluated both oral AO supplements and dietary intake of AOs via whole foods. In this review, we provide an overview of the role of AOs in preventing tumorigenesis and outline four targeted dietary AOs. We review the results of research evaluating oral AOs supplements as compared to dietary AOs intake via whole foods. While these specific supplements have not shown efficacy, intake of AOs via consumption of whole foods has shown some promise. Lessons learned from the field of hypertension research may provide important guidance in future study design. Further research on the role of dietary AOs in the prevention of NMSC is warranted and should focus on intake via whole food consumption. PMID:26583073

  6. AUTOMATED SKIN SEGMENTATION IN ULTRASONIC EVALUATION OF SKIN TOXICITY IN BREAST CANCER RADIOTHERAPY

    PubMed Central

    Gao, Yi; Tannenbaum, Allen; Chen, Hao; Torres, Mylin; Yoshida, Emi; Yang, Xiaofeng; Wang, Yuefeng; Curran, Walter; Liu, Tian

    2013-01-01

    Skin toxicity is the most common side effect of breast cancer radiotherapy and impairs the quality of life of many breast cancer survivors. We, along with other researchers, have recently found quantitative ultrasound to be effective as a skin toxicity assessment tool. Although more reliable than standard clinical evaluations (visual observation and palpation), the current procedure for ultrasound-based skin toxicity measurements requires manual delineation of the skin layers (i.e., epidermis-dermis and dermis-hypodermis interfaces) on each ultrasound B-mode image. Manual skin segmentation is time consuming and subjective. Moreover, radiation-induced skin injury may decrease image contrast between the dermis and hypodermis, which increases the difficulty of delineation. Therefore, we have developed an automatic skin segmentation tool (ASST) based on the active contour model with two significant modifications: (i) The proposed algorithm introduces a novel dual-curve scheme for the double skin layer extraction, as opposed to the original single active contour method. (ii) The proposed algorithm is based on a geometric contour framework as opposed to the previous parametric algorithm. This ASST algorithm was tested on a breast cancer image database of 730 ultrasound breast images (73 ultrasound studies of 23 patients). We compared skin segmentation results obtained with the ASST with manual contours performed by two physicians. The average percentage differences in skin thickness between the ASST measurement and that of each physician were less than 5% (4.8 ± 17.8% and −3.8 ± 21.1%, respectively). In summary, we have developed an automatic skin segmentation method that ensures objective assessment of radiation-induced changes in skin thickness. Our ultrasound technology offers a unique opportunity to quantify tissue injury in a more meaningful and reproducible manner than the subjective assessments currently employed in the clinic. PMID:23993172

  7. CEST-MRI detects metabolite levels altered by breast cancer cell aggressiveness and chemotherapy response.

    PubMed

    Chan, Kannie W Y; Jiang, Lu; Cheng, Menglin; Wijnen, Jannie P; Liu, Guanshu; Huang, Peng; van Zijl, Peter C M; McMahon, Michael T; Glunde, Kristine

    2016-06-01

    Chemical exchange saturation transfer (CEST) is an MRI contrast mechanism that detects the exchange of protons from distinct hydroxyl, amine, and amide groups to tissue water through the transfer of signal loss, with repeated exchange enhancing their effective signal. We applied CEST to detect systematically 15 common cellular metabolites in a panel of differentially aggressive human breast cancer cell lines. The highest CEST contrast was generated by creatine, myo-inositol, glutamate, and glycerophosphocholine, whose cellular concentrations decreased with increasing breast cancer aggressiveness. These decreased metabolite concentrations resulted in turn in a decreased CEST profile with increasing breast cancer aggressiveness in water-soluble extracts of breast cell lines. Treatment of both breast cancer cell lines with the chemotherapy drug doxorubicin resulted in increased metabolic CEST profiles, which correlated with significant increases in creatine, phosphocreatine, and glycerophosphocholine. CEST can detect breast cancer aggressiveness and response to chemotherapy in water-soluble extracts of breast cell lines. The presented results help shed light on possible contributions from CEST-active metabolites to the CEST contrast produced by breast cancers. The metabolic CEST profile may improve detection sensitivity over conventional MRS, and may have the potential to assess breast cancer aggressiveness and response to chemotherapy non-invasively using MRI if specialized metabolic CEST profile detection can be realized in vivo. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27100284

  8. Ozone, skin cancer, and the SST

    SciTech Connect

    Singer, S.F.

    1994-07-01

    In 1971, the U.S. Congress cut off funding for development of supersonic transport aircraft prototypes when it was argued that the pollution created by SSTs could reduce the stratospheric ozone content and increase the incidence of skin cancer. At present, the theory of ozone depletion is in a rather uncertain state. Two examples of this are cited. First, ozone depletion may depend more on the availability of surfaces of aerosols and particles than on the content of chlorine. Second, it has been discovered that NO(x) can tie up active chlorine and thus reduce depletion from that source. We are therefore left with the paradoxical result that under certain circumstances SSTs flying in the lower stratospheric can actually counteract, at least partially, any ozone-depleting effects of CFCs. A recent study by scientists at the Brookhaven National Laboratory showed that melanoma rates would not be affected by changes in the ozone layer. If these results are confirmed, then much of the fear associated with ozone depletion disappears. It is difficult to tell how all this will affect a future supersonic transport program, since it is not clear whether a fleet of SSTs will increase or offset ozone depletion.

  9. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed

    Ley, R D; Reeve, V E

    1997-06-01

    The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis. PMID:9255591

  10. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed Central

    Ley, R D; Reeve, V E

    1997-01-01

    The use of chemical and physical sunscreening agents has increased dramatically during the last two to three decades as an effective means of preventing sunbum. The use of high sunprotection factor sunscreens has also been widely promoted for the prevention of skin cancer, including melanoma. Whereas sunscreens are undoubtedly effective in preventing sunbum, their efficacy in preventing skin cancer, especially melanoma, is currently under considerable debate. Sunscreens have been shown to prevent the induction of DNA damage that presumably results from the direct effects of ultraviolet radiation (UVR) on DNA. DNA damage has been identified as an initiator of skin cancer formation. However, both laboratory and epidemiological studies indicate that sunscreens may not block the initiation or promotion of melanoma formation. These studies suggest that the action spectrum for erythema induction is different than the action spectrum for the induction of melanoma. Indeed, recent reports on the wavelength dependency for the induction of melanoma in a fish model indicate that the efficacy of ultraviolet A wavelengths (320-400 nm) to induce melanoma is orders of magnitude higher than would be predicted from the induction of erythema in man or nonmelanoma skin tumors in mice. Other strategies for the chemoprevention of skin cancer have also been reported. Low levels and degree of unsaturation of dietary fats protect against UVR-induced skin cancer in mice humens. Compounds with antioxidant activity, including green tea extracts (polyphenols), have been reported to inhibit UVR-induced skin carcinogenesis. PMID:9255591

  11. Before or after: is there a connection between the use of adjunctive nonmelanoma skin cancer treatments and subsequent invasive tumors?

    PubMed

    Ruiz, Emily Stamell; Cohen, Joel L; Friedman, Adam

    2015-05-01

    Although the therapeutic gold standard for basal cell carcinomas (BCCs) is surgical excision, imiquimod, fluorouracil cream, and photodynamic therapy are frequently used. All 3 modalities have been shown to be efficacious for the treatment of superficial BCCs as well as other nonmelanoma skin cancers; however, recent reports have emerged implicating these agents in causing more aggressive recurrent subtypes of BCCs. Here we review this literature as well as offer an alternative explanation for these tumors. PMID:25942661

  12. Vasectomy: potential links to an increased risk of aggressive prostate cancer?

    PubMed

    Gaines, Alexis R; Vidal, Adriana C; Freedland, Stephen J

    2015-01-01

    Several studies have found associations between aggressive prostate cancer (PC) and having a vasectomy. However, findings from two very recent meta-analyses have found that this is not the case. Therefore, the data are mixed. Herein, we detail the controversy between vasectomy and PC risk, particularly aggressive PC, by shedding some light on the molecular pathways, potential risk factors and suggested links for those considering vasectomy and medical professionals who perform it. We conclude by supporting the American Urological Association's position that there is no need to discuss potential prostate cancer risks with patients considering vasectomy given reasonably strong data finding no link between vasectomy and prostate cancer risk. PMID:26402245

  13. Skin cancer and new treatment perspectives: a review.

    PubMed

    Simões, M C F; Sousa, J J S; Pais, A A C C

    2015-02-01

    Skin cancers are by far the most common malignancy of humans, particularly in the white population. The growing incidence of cutaneous malignancies has heralded the need for multiple treatment options. Although surgical modalities remain the mainstay of treatment, new research and fresh innovation are still required to reduce morbidity and mortality. Approaches for skin cancer may pass through new technological methods instead of new molecules. The first part of this paper provides a review of the state of the art regarding skin cancer disease as well as epidemiology data. Then, it describes the gold standards of the current recommended therapies worldwide and the actual needs of these patients. This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy. PMID:25444899

  14. USP44+ Cancer Stem Cell Subclones Contribute to Breast Cancer Aggressiveness by Promoting Vasculogenic Mimicry.

    PubMed

    Liu, Tieju; Sun, Baocun; Zhao, Xiulan; Li, Yanlei; Zhao, Xueming; Liu, Ying; Yao, Zhi; Gu, Qiang; Dong, Xueyi; Shao, Bing; Lin, Xian; Liu, Fang; An, Jindan

    2015-09-01

    Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, describes the functional plasticity of aggressive cancer cells that form vascular networks. In our previous study, breast cancer stem cells (CSC) were shown to potentially participate in VM formation. In this study, breast CSCs presented centrosome amplification (CA) phenotype and ubiquitin-specific protease 44 (USP44) upregulation. USP44 expression contributed to the establishment of bipolar spindles in breast CSCs with supernumerary centrosomes by localizing at pole-associated centrosomes. The bipolar spindle patterns of breast CSCs with CA, including planar-like and apico-basal-like, functioned differently during the VM process of CSCs. Moreover, the ability of transendothelial migration in VM-forming cells was increased. In vivo experiment results showed that CSC xenografts presented linearly patterned programmed cell necrosis, which provided a spatial foundation for VM formation as well as angiogenesis. Breast CSCs further showed increased levels of IL6 and IL8. However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs. Finally, USP44(+) CSC subclones (ALDH1(+)/USP44(+)/IL6(+)/IL8(+)) were identified in breast cancer specimens through consecutive sections scanning. The subclones were related not only to CA, but also to VM. Statistical analysis suggested that USP44(+) CSC subclones could be used as an independent prognostic biomarker of poor clinical outcomes in patients with breast cancer. Collectively, the identification of USP44(+) CSC subclones may contribute to the prediction of VM formation and aggressive behavior. This study provides novel insights into the therapy for advanced breast cancer. PMID:26232424

  15. Botanical Agents for the Treatment of Nonmelanoma Skin Cancer

    PubMed Central

    2013-01-01

    Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers. PMID:23983679

  16. Botanical agents for the treatment of nonmelanoma skin cancer.

    PubMed

    Millsop, Jillian W; Sivamani, Raja K; Fazel, Nasim

    2013-01-01

    Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers. PMID:23983679

  17. Spermine and citrate as metabolic biomarkers for assessing prostate cancer aggressiveness.

    PubMed

    Giskeødegård, Guro F; Bertilsson, Helena; Selnæs, Kirsten M; Wright, Alan J; Bathen, Tone F; Viset, Trond; Halgunset, Jostein; Angelsen, Anders; Gribbestad, Ingrid S; Tessem, May-Britt

    2013-01-01

    Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.8%) were obtained using a new harvesting method, and metabolic profiles of samples representing different Gleason scores (GS) were acquired by high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine the ability to predict cancer aggressiveness by comparing low grade (GS = 6, n = 30) and high grade (GS≥7, n = 81) cancer with normal adjacent tissue (n = 47). High grade cancer tissue was distinguished from low grade cancer tissue by decreased concentrations of spermine (p = 0.0044) and citrate (p = 7.73·10(-4)), and an increase in the clinically applied (total choline+creatine+polyamines)/citrate (CCP/C) ratio (p = 2.17·10(-4)). The metabolic profiles were significantly correlated to the GS obtained from each tissue sample (r = 0.71), and cancer tissue could be distinguished from normal tissue with sensitivity 86.9% and specificity 85.2%. Overall, our findings show that metabolic profiling can separate aggressive from indolent prostate cancer. This holds promise for the benefit of applying in vivo magnetic resonance spectroscopy (MRS) within clinical MR imaging investigations, and HR-MAS analysis of transrectal ultrasound-guided biopsies has a potential as an additional diagnostic tool. PMID:23626811

  18. Biophysical basis for noninvasive skin cancer detection using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Feng, Xu; Moy, Austin J.; Markey, Mia K.; Fox, Matthew C.; Reichenberg, Jason S.; Tunnell, James W.

    2016-03-01

    Raman spectroscopy (RS) is proving to be a valuable tool for real time noninvasive skin cancer detection via optical fiber probe. However, current methods utilizing RS for skin cancer diagnosis rely on statistically based algorithms to provide tissue classification and do not elucidate the underlying biophysical changes of skin tissue. Therefore, we aim to use RS to explore skin biochemical and structural characteristics and then correlate the Raman spectrum of skin tissue with its disease state. We have built a custom confocal micro-Raman spectrometer system with an 830nm laser light. The high resolution capability of the system allows us to measure spectroscopic features from individual tissue components in situ. Raman images were collected from human skin samples from Mohs surgical biopsy, which were then compared with confocal laser scanning, two-photon fluorescence and hematoxylin and eosin-stained images to develop a linear model of skin tissue Raman spectra. In this model, macroscopic tissue spectra obtained from RS fiber probe were fit into a linear combination of individual basis spectra of primary skin constituents. The fit coefficient of the model explains the biophysical changes spanning a range of normal and various disease states. The model allows for determining parameters similar to that a pathologist is familiar reading and will be a significant guidance in developing RS diagnostic decision schemes.

  19. Behavioral Counseling to Prevent Skin Cancer

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of this counseling. This fact sheet explains the ... skin looking young and healthy. Potential Benefits and Harms of Behavioral Counseling The main potential benefit of ...

  20. Risk of Total and Aggressive Prostate Cancer and Pesticide Use in the Agricultural Health Study

    PubMed Central

    Koutros, Stella; Beane Freeman, Laura E.; Lubin, Jay H.; Heltshe, Sonya L.; Andreotti, Gabriella; Barry, Kathryn Hughes; DellaValle, Curt T.; Hoppin, Jane A.; Sandler, Dale P.; Lynch, Charles F.; Blair, Aaron; Alavanja, Michael C. R.

    2013-01-01

    Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993–2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; Ptrend < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; Ptrend = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; Ptrend = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; Ptrend = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer. PMID:23171882

  1. Estimating Skin Cancer Risk: Evaluating Mobile Computer-Adaptive Testing

    PubMed Central

    Djaja, Ngadiman; Janda, Monika; Olsen, Catherine M; Whiteman, David C

    2016-01-01

    Background Response burden is a major detriment to questionnaire completion rates. Computer adaptive testing may offer advantages over non-adaptive testing, including reduction of numbers of items required for precise measurement. Objective Our aim was to compare the efficiency of non-adaptive (NAT) and computer adaptive testing (CAT) facilitated by Partial Credit Model (PCM)-derived calibration to estimate skin cancer risk. Methods We used a random sample from a population-based Australian cohort study of skin cancer risk (N=43,794). All 30 items of the skin cancer risk scale were calibrated with the Rasch PCM. A total of 1000 cases generated following a normal distribution (mean [SD] 0 [1]) were simulated using three Rasch models with three fixed-item (dichotomous, rating scale, and partial credit) scenarios, respectively. We calculated the comparative efficiency and precision of CAT and NAT (shortening of questionnaire length and the count difference number ratio less than 5% using independent t tests). Results We found that use of CAT led to smaller person standard error of the estimated measure than NAT, with substantially higher efficiency but no loss of precision, reducing response burden by 48%, 66%, and 66% for dichotomous, Rating Scale Model, and PCM models, respectively. Conclusions CAT-based administrations of the skin cancer risk scale could substantially reduce participant burden without compromising measurement precision. A mobile computer adaptive test was developed to help people efficiently assess their skin cancer risk. PMID:26800642

  2. Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer

    PubMed Central

    Abe, Miyako; Xie, Wanling; Regan, Meredith M.; King, Irena B.; Stampfer, Meir J.; Kantoff, Philip W.; Oh, William K.; Chan, June M.

    2010-01-01

    Objective To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer. Patients and methods We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator-activated receptor γ coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and ‘X-ray repair complementing defective repair in Chinese hamster cell 1’ (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate-specific antigen (PSA) level (213 aggressive cases). Results Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70–0.99; and rs4816407, 1.27, 1.02–1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 μg/L, P = 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330). Conclusion While this study was cross-sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer. PMID:20477822

  3. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

  4. Continuous-wave terahertz imaging of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Joseph, Cecil Sudhir

    Continuous wave terahertz imaging has the potential to offer a safe, non-invasive medical imaging modality for detecting different types of human skin cancers. Terahertz pulse imaging (TPI) has already shown that there is contrast between basal cell carcinoma and normal skin. Continuous-wave imaging offers a simpler, lower cost alternative to terahertz pulse imaging. This project aims to isolate the optimal contrast frequency for a continuous wave terahertz imaging system and demonstrate transmission based, in-vitro , imaging of thin sections of non-melanoma skin cancers and correlate the images to sample histology. The aim of this project is to conduct a proof-of-principle experiment that establishes whether continuous-wave terahertz imaging can detect differences between cancerous and normal tissue while outlining the basic requirements for building a system capable of performing in vivo tests.

  5. Skin cancer in patients with chronic radiation dermatitis

    SciTech Connect

    Davis, M.M.; Hanke, C.W.; Zollinger, T.W.; Montebello, J.F.; Hornback, N.B.; Norins, A.L.

    1989-04-01

    The cases of 76 patients with chronic radiation dermatitis resulting from low-dose ionizing radiation for benign disease were reviewed retrospectively for risk factors leading to the development of neoplasia. The patients were studied with respect to original hair color, eye color, sun reactive skin type, benign disease treated, area treated, age at treatment, and age at development of first skin cancer. Analysis of data showed 37% of patients had sun-reactive skin type I, 27% had type II, and 36% had type III. Types IV through VI were not represented. There appeared to be an overrepresentation of types I and II. Increased melanin pigmentation may therefore be either directly or indirectly protective against the development of skin cancers in patients who have received low-dose superficial ionizing radiation for benign disease. The sun-reactive skin type of patients with chronic radiation dermatitis may be used as a predictor of skin cancer risk when the total dose of ionizing radiation is not known.

  6. Iron induces cancer stem cells and aggressive phenotypes in human lung cancer cells.

    PubMed

    Chanvorachote, Pithi; Luanpitpong, Sudjit

    2016-05-01

    Evidence has accumulated in support of the critical impact of cancer stem cells (CSCs) behind the chemotherapeutic failure, cancer metastasis, and subsequent disease recurrence and relapse, but knowledge of how CSCs are regulated is still limited. Redox status of the cells has been shown to dramatically influence cell signaling and CSC-like aggressive behaviors. Here, we investigated how subtoxic concentrations of iron, which have been found to specifically induce cellular hydroxyl radical, affected CSC-like subpopulations of human non-small cell lung carcinoma (NSCLC). We reveal for the first time that subchronic iron exposure and higher levels of hydroxyl radical correlated well with increased CSC-like phenotypes. The iron-exposed NSCLC H460 and H292 cells exhibited a remarkable increase in propensities to form CSC spheroids and to proliferate, migrate, and invade in parallel with an increase in level of a well-known CSC marker, ABCG2. We further observed that such phenotypic changes induced by iron were not related to an epithelial-to-mesenchymal transition (EMT). Instead, the sex-determining region Y (SRY)-box 9 protein (SOX9) was substantially linked to iron treatment and hydroxyl radical level. Using gene manipulations, including ectopic SOX9 overexpression and SOX9 short hairpin RNA knockdown, we have verified that SOX9 is responsible for CSC enrichment mediated by iron. These findings indicate a novel role of iron via hydroxyl radical in CSC regulation and its importance in aggressive cancer behaviors and likely metastasis through SOX9 upregulation. PMID:26911281

  7. Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration

    PubMed Central

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM

    2015-01-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  8. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

    PubMed

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, Y Y; Liphardt, J; Hwang, E S; Weaver, V M

    2015-10-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  9. Ozone depletion, related UVB changes and increased skin cancer incidence

    NASA Astrophysics Data System (ADS)

    Kane, R. P.

    1998-03-01

    Stratospheric ozone at middle latitudes shows a seasonal variation of about +/-20%, a quasi-biennial oscillation of 1-10% range and a long-term variation in which the level was almost steady up to about 1979 and declined thereafter to the present day by about 10%. These variations are expected to be reflected in solar UVB observed at the ground, but in an opposite direction. Thus UVB should have had a long-term increase of about 10-20%, which should cause an increase in skin cancer incidence of about 20-40%. Skin cancer incidence has increased all over the world, e.g. about 90% in USA during 1974-1990. It is popularly believed that this increase in skin cancer incidence is related to the recent ozone depletion. This seems to be incorrect, for two reasons. Firstly, the observed skin cancer increase is too large (90%) compared with the expected value (40%) from ozone depletion. Secondly, cancer does not develop immediately after exposure to solar UVB. The sunburns may occur within hours; but cancer development and detection may take years, even decades. Hence the observed skin cancer increase since 1974 (no data available for earlier periods) must have occurred due to exposure to solar UVB in the 1950s and 1960s, when there was no ozone depletion. Thus, the skin cancer increase must be attributed to harmful solar UVB levels existing even in the 1960s, accentuated later not by ozone depletion (which started only much later, by 1979) but by other causes, such as a longer human life span, better screening, increasing tendencies of sunbathing at beaches, etc., in affluent societies. On the other hand, the recent ozone depletion and the associated UVB increases will certainly take their toll; only that the effects will not be noticed now but years or decades from now. The concern for the future expressed in the Montreal Protocol for reducing ozone depletion by controlling CFC production is certainly justified, especially because increased UVB is harmful to animal and

  10. BCC skin cancer diagnosis based on texture analysis techniques

    NASA Astrophysics Data System (ADS)

    Chuang, Shao-Hui; Sun, Xiaoyan; Chang, Wen-Yu; Chen, Gwo-Shing; Huang, Adam; Li, Jiang; McKenzie, Frederic D.

    2011-03-01

    In this paper, we present a texture analysis based method for diagnosing the Basal Cell Carcinoma (BCC) skin cancer using optical images taken from the suspicious skin regions. We first extracted the Run Length Matrix and Haralick texture features from the images and used a feature selection algorithm to identify the most effective feature set for the diagnosis. We then utilized a Multi-Layer Perceptron (MLP) classifier to classify the images to BCC or normal cases. Experiments showed that detecting BCC cancer based on optical images is feasible. The best sensitivity and specificity we achieved on our data set were 94% and 95%, respectively.

  11. Study of photodynamic therapy in skin cancers and precancerous lesions

    NASA Astrophysics Data System (ADS)

    Wang, Jiabi; Gao, Menglin; Wen, Shijun; Wang, Mianjing

    1993-03-01

    Hematoporphyrin photodynamic therapy (HpD-PDT) was used to treat 50 patients (51 lesions) with skin cancers or precancerous lesions. The preliminary results were satisfactory, with 44 cases (45 lesions) obtaining excellent results, 4 cases good, 1 case fair, and 1 case poor. The effective rate was 98%, the significant remission rate 96%, and the complete remission rate 88.2%. Exposure to sunlight should be avoided after HpD injection, since it produces photosensitivity. A follow-up for 1 to 3 years confirmed that HpD-PDT is a good new adjuvant therapy for selected cases. It brings a hopeful future to the treatment of skin cancers.

  12. Increased Expression of Serglycin in Specific Carcinomas and Aggressive Cancer Cell Lines

    PubMed Central

    Korpetinou, Angeliki; Papachristou, Dionysios J.; Lampropoulou, Angeliki; Bouris, Panagiotis; Labropoulou, Vassiliki T.; Noulas, Argyrios; Karamanos, Nikos K.; Theocharis, Achilleas D.

    2015-01-01

    In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression. PMID:26581653

  13. Running behind a tourist: leisure-related skin cancer prophylaxis.

    PubMed

    Tan, S; Sinclair, C; Foley, P

    2012-08-01

    The most important risk factor in the development of skin cancer is exposure to ultraviolet (UV) radiation. Cumulative lifetime UV radiation exposure has been shown to be most important in the pathogenesis of squamous cell carcinoma, whereas intermittent high-dose UV radiation exposure in childhood and adolescence may be more important in the aetiology of basal cell carcinoma and cutaneous malignant melanoma. Using established methodology and best available estimates on UV-related mortality and morbidity, it has been estimated that annually around 1·5 million disability-adjusted life years are lost through excessive exposure to UV radiation. Skin cancer is a significant health problem and its burden is such that it causes the health system more to treat than any other forms of cancer. Prevention is the key action in managing skin cancer at a population level. Investment in prevention programmes such as SunSmart encourages protective behaviours that will reduce the human and financial costs of skin cancer. PMID:22881590

  14. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

    PubMed

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  15. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  16. Chronic psychological stress and its impact on the development of aggressive breast cancer

    PubMed Central

    Cormanique, Thayse Fachin; de Almeida, Lirane Elize Defante Ferreto; Rech, Cynthia Alba; Rech, Daniel; Herrera, Ana Cristina da Silva do Amaral; Panis, Carolina

    2015-01-01

    Objective To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire − SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors. PMID:26466057

  17. Breast cancer cells mechanosensing in engineered matrices: Correlation with aggressive phenotype.

    PubMed

    Li, Ji; Wu, Yang; Schimmel, Nicholas; Al-Ameen, Mohammad Ali; Ghosh, Gargi

    2016-08-01

    The pathogenesis of cancer is often driven by the modulation of the tumor microenvironment. Recent reports have highlighted that the progressive stiffening of tumor matrix is crucial for malignant transformation. Though extensive work has been done analyzing the mechanotransductive signals involved in tumor progression, it is still not clear whether the stiffness induced changes in cancer cell behavior is conserved across the invasive/aggressive phenotype of cells. Here, we used synthetic hydrogel based cell culture platform to correlate the aggressive potential of the breast cancer cells to the responses to matrix stiffness. The cellular functions such as proliferation, migration, and angiogenic capability were characterized. We report that the proliferation and motility of the highly aggressive cell line MDA-MB-231 increased with increase in matrix rigidity. We also demonstrated for the first time that the change in matrix stiffness stimulated the angiogenic activity of these cells as manifested from enhanced expression of vascular endothelial growth factor (VEGF). Inhibition of actomyosin contractility attenuated proliferation of MDA-MB-231 cells on stiff matrices while promoted the growth on soft gels. In addition, the release of VEGF was reduced upon inhibition of contractility. The less and non-aggressive breast cancer cells, SKBr3 and MCF-7 respectively displayed less dependency on matrix stiffness. PMID:26874251

  18. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Cancer.gov

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  19. Molecular profiles of cancer stem-like cell populations in aggressive thyroid cancers.

    PubMed

    Dima, Mariavittoria; Pecce, Valeria; Biffoni, Mauro; Di Gioia, Cira Rosaria Tiziana; Tallini, Giovanni; Biffoni, Marco; Rosignolo, Francesca; Verrienti, Antonella; Sponziello, Marialuisa; Damante, Giuseppe; Russo, Diego; Durante, Cosimo

    2016-07-01

    A substantial proportion of patients with advanced thyroid carcinoma fail to respond to or at some point become refractory to conventional therapies. This resistance and the phenomena of thyroid cancer progression and metastasis themselves are thought to be related to tumor-cell sub-populations with stem-like properties. We isolated thyrospheres from four advanced thyroid carcinomas that were resistant to radioiodine therapy and analyzed their molecular profiles. ALDH activity and proteomic profile of main stem cell markers were used to assess stem cell properties. The TaqMan Low Density Array approach was used to evaluate the expression of several genes involved in the EMT process. The phosphorylation status of tyrosine kinase receptors (RTKs) was analyzed to identify potential markers for targeted therapies. We then investigated the effects of the EMT-inhibitor crizotinib on both cell proliferation and phosphorylation status of RTK targets. The cancer stem-like properties of a subset of cells from primary cultures of each tumor were demonstrated. A wide variability among thyrospheres arising from the four thyroid cancers in terms of ALDH activity, stem cell marker expression, and phosphoproteome profiling was present. Dysregulated expression of genes involved in the EMT was observed in all four thyrosphere lines. Treatment with crizotinib was ineffective in cancer stem-like cells, suggesting the presence of a mechanism of resistance in thyrospheres. Collectively, our data indicate that thyroid cancer stem-like populations vary markedly from tumor to tumor and require detailed molecular and biological characterization if they are to be used as the basis of "personalized" treatment of aggressive disease. PMID:26370117

  20. Risk of skin cancer in patients with diabetes mellitus

    PubMed Central

    Tseng, Hui-Wen; Shiue, Yow-Ling; Tsai, Kuo-Wang; Huang, Wei-Chun; Tang, Pei-Ling; Lam, Hing-Chung

    2016-01-01

    Abstract Increasing evidence suggests that certain types of cancers are more common in people with diabetes mellitus (DM). This study aimed to investigate the risk of skin cancer in patients with DM in Taiwan. In this retrospective cohort study using data from the Taiwan Longitudinal Health Insurance Research Database, the risk of developing overall skin cancer, including nonmelanoma skin cancer (NMSC) and melanoma, was compared by Poisson regression analysis and Cox regression analysis between the DM and non-DM cohorts. The DM cohort with newly diagnosed DM (n = 41,898) and a non-DM cohort were one-to-one matched by age, sex, index date, and comorbidities (coronary artery disease, hyperlipidemia, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and obesity). Compared with non-DM cohort statistically, for the people with DM aged ≥60 years, the incidence rates of overall skin cancer and NMSC were significantly higher (overall: DM/non-DM: number [n] = 99/76, incidence rate ratio [IRR] = 1.44, P = 0.02; NMSC: DM/non-DM: n = 94/66, IRR = 1.57, P = 0.005). By Cox regression analysis, the risk of developing overall skin cancer or NMSC was significantly higher after adjusting for sex, comorbidities, and overall diseases with immunosuppression status (overall: adjusted hazard ratio [AHR] = 1.46, P = 0.01; NMSC: AHR = 1.6, P = 0.003). Other significant risk factors were older males for skin cancer (overall: AHR = 1.68, P = 0.001; NMSC: AHR = 1.59, P = 0.004; melanoma: AHR = 3.25, P = 0.04), chronic obstructive pulmonary disease for NMSC (AHR = 1.44, P = 0.04), and coronary artery disease for melanoma (AHR = 4.22, P = 0.01). The risk of developing melanoma was lower in the DM cohort than in the non-DM cohort, but without significance (AHR = 0.56, P = 0.28; DM/non-DM: n = 5/10). The incidence rate and risk of developing overall skin cancer, including NMSC, was significantly higher in older adults with DM. Other significant risk factors for older

  1. Frequent DPH3 promoter mutations in skin cancers

    PubMed Central

    Denisova, Evgeniya; Heidenreich, Barbara; Nagore, Eduardo; Rachakonda, P. Sivaramakrishna; Hosen, Ismail; Akrap, Ivana; Traves, Víctor; García-Casado, Zaida; López-Guerrero, José Antonio; Requena, Celia; Sanmartin, Onofre; Serra-Guillén, Carlos; Llombart, Beatriz; Guillén, Carlos; Ferrando, Jose; Gimeno, Enrique; Nordheim, Alfred; Hemminki, Kari; Kumar, Rajiv

    2015-01-01

    Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at −8 and −9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to −8/−9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined. PMID:26416425

  2. Frequent DPH3 promoter mutations in skin cancers.

    PubMed

    Denisova, Evgeniya; Heidenreich, Barbara; Nagore, Eduardo; Rachakonda, P Sivaramakrishna; Hosen, Ismail; Akrap, Ivana; Traves, Víctor; García-Casado, Zaida; López-Guerrero, José Antonio; Requena, Celia; Sanmartin, Onofre; Serra-Guillén, Carlos; Llombart, Beatriz; Guillén, Carlos; Ferrando, Jose; Gimeno, Enrique; Nordheim, Alfred; Hemminki, Kari; Kumar, Rajiv

    2015-11-01

    Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined. PMID:26416425

  3. Quiz: Test Your Skin Cancer IQ | NIH MedlinePlus the Magazine

    MedlinePlus

    ... most dangerous form of skin cancer is melanoma squamous cell carcinoma basal cell carcinoma 4. The most common type of skin cancer is melanoma squamous cell carcinoma basal cell carcinoma 5. Men tend to develop ...

  4. Skin Cancer: Biology, Risk Factors & Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... risk factor for skin cancer is exposure to sunlight (UV radiation), but there are also other risk ... the three most common types of skin cancer: Sunlight: Sunlight is a source of UV radiation. It's ...

  5. Home Remedy for Skin Cancer May Cause Damage, Mask New Growth

    MedlinePlus

    ... medlineplus/news/fullstory_158984.html Home Remedy For Skin Cancer May Cause Damage, Mask New Growth 'Black ... promise of an "easy and natural" treatment for skin cancer, home remedies such as black salve can ...

  6. Skin Cancer: Biology, Risk Factors & Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table of ... May spread to other parts of the body Risk Factors When you're told that you have ...

  7. Some Smart Yet Easy Ways to Shield Yourself from Skin Cancer

    MedlinePlus

    ... Smart Yet Easy Ways to Shield Yourself From Skin Cancer Dermatologist offers advice on how to prevent, ... HealthDay News) -- One in five Americans will develop skin cancer at some point in their life, but ...

  8. Skin Cancer in the Crosshairs: Highlights from the Biennial Scientific Retreat of International Transplant Skin Cancer Collaborative and Skin Care in Organ Transplant Recipients Europe.

    PubMed

    Sinnya, Sudipta; Zwald, Fiona O; Colegio, Oscar R

    2015-08-01

    The International Transplant Skin Cancer Collaborative (ITSCC) is an organization comprising of physicians; transplant surgeons and basic science research scientists dedicated in providing optimal care and ongoing research advancements in solid organ transplant recipients to improve patient outcome and quality of life. As medical advances occur, it is anticipated that the sheer number of solid organ transplantations occurring worldwide will continue to increase. The long-term medication associated immunosuppression improves graft survival, but as a consequence, these individuals become increasingly susceptible to various cutaneous malignancies, lymphoproliferative disorders and infections. Squamous cell carcinoma is the most frequently encountered skin cancer and increases 65- to 250-fold [Jensen et al., Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177-186; Lindelöf et al., Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol. 2000; 143:513-519]. However, the rates of basal cell carcinoma, Merkel cell carcinoma and melanoma also increase in organ transplant recipients leading to significant morbidity as well as mortality [Berg and Otley. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002; 47:1-20]. In October 2014, the International Transplant Skin Cancer Collaborative and its equivalent European counterpart, Skin Care in Organ Transplant Recipients Europe held its 10th biennial meeting in Essex, MA to discuss the clinical conundrums and the evolving research pertinent to the field. This meeting report provides a synthesis of all the clinical and research data presented at the 4-day meeting. PMID:27500228

  9. Beta Genus Papillomaviruses and Skin Cancer

    PubMed Central

    Howley, Peter M.; Pfister, Herbert J.

    2015-01-01

    A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. PMID:25724416

  10. p53 and the pathogenesis of skin cancer

    SciTech Connect

    Benjamin, Cara L.; Ananthaswamy, Honnavara N.

    2007-11-01

    The p53 tumor suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific 'signature' mutations that can result in oncogenic transformation. There are certain 'hot-spots' in the p53 gene where mutations are commonly found that result in a mutated dipyrimidine site. This review discusses the role of p53 from normal function and its dysfunction in pre-cancerous lesions and non-melanoma skin cancers. Additionally, special situations are explored, such as Li-Fraumeni syndrome in which there is an inherited p53 mutation, and the consequences of immune suppression on p53 mutations and the resulting increase in non-melanoma skin cancer in these patients.

  11. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers

    PubMed Central

    Pannu, Vaishali; Mittal, Karuna; Cantuaria, Guilherme; Reid, Michelle D.; Li, Xiaoxian; Donthamsetty, Shashikiran; McBride, Michelle; Klimov, Sergey; Osan, Remus; Gupta, Meenakshi V.; Rida, Padmashree C.G.; Aneja, Ritu

    2015-01-01

    Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients. PMID:25868856

  12. NIH researchers complete whole-exome sequencing of skin cancer

    Cancer.gov

    A team led by researchers at NIH is the first to systematically survey the landscape of the melanoma genome, the DNA code of the deadliest form of skin cancer. The researchers have made surprising new discoveries using whole-exome sequencing, an approach that decodes the 1-2 percent of the genome that contains protein-coding genes.

  13. An overview of skin cancers. Incidence and causation.

    PubMed

    Marks, R

    1995-01-15

    The incidence and mortality rates of skin cancer are rising in the United States and in many other countries. Concerns about stratospheric ozone depletion adding to the problem have made many organizations look at public and professional health programs as a possible solution. Early detection can reduce the problem in the short term, because mortality due to melanoma is clearly related to the depth of invasion of the tumor when it is removed. This is the factor which is amenable to change in an education program on early detection. Exposure to sunlight is clearly related to risk of development of skin cancer, including both melanoma and nonmelanoma skin cancers. This is the component of the equation of constitutional predisposition plus exposure to environmental risk factors leading to skin cancer that is amenable to change as a result of educational programs. On the basis of available data, there is a case for further development, provision, and evaluation of public and professional education programs designed to control what is becoming a major public health problem in the community. PMID:7804986

  14. Communicating to Farmers about Skin Cancer: The Behavior Adaptation Model.

    ERIC Educational Resources Information Center

    Parrott, Roxanne; Monahan, Jennifer; Ainsworth, Stuart; Steiner, Carol

    1998-01-01

    States health campaign messages designed to encourage behavior adaptation have greater likelihood of success than campaigns promoting avoidance of at-risk behaviors that cannot be avoided. Tests a model of health risk behavior using four different behaviors in a communication campaign aimed at reducing farmers' risk for skin cancer--questions…

  15. Sun Protection Motivational Stages and Behavior: Skin Cancer Risk Profiles

    ERIC Educational Resources Information Center

    Pagoto, Sherry L.; McChargue, Dennis E.; Schneider, Kristin; Cook, Jessica Werth

    2004-01-01

    Objective: To create skin cancer risk profiles that could be used to predict sun protection among Midwest beachgoers. Method: Cluster analysis was used with study participants (N=239), who provided information about sun protection motivation and behavior, perceived risk, burn potential, and tan importance. Participants were clustered according to…

  16. Skin Cancer, Irradiation, and Sunspots: The Solar Cycle Effect

    PubMed Central

    Zurbenko, Igor

    2014-01-01

    Skin cancer is diagnosed in more than 2 million individuals annually in the United States. It is strongly associated with ultraviolet exposure, with melanoma risk doubling after five or more sunburns. Solar activity, characterized by features such as irradiance and sunspots, undergoes an 11-year solar cycle. This fingerprint frequency accounts for relatively small variation on Earth when compared to other uncorrelated time scales such as daily and seasonal cycles. Kolmogorov-Zurbenko filters, applied to the solar cycle and skin cancer data, separate the components of different time scales to detect weaker long term signals and investigate the relationships between long term trends. Analyses of crosscorrelations reveal epidemiologically consistent latencies between variables which can then be used for regression analysis to calculate a coefficient of influence. This method reveals that strong numerical associations, with correlations >0.5, exist between these small but distinct long term trends in the solar cycle and skin cancer. This improves modeling skin cancer trends on long time scales despite the stronger variation in other time scales and the destructive presence of noise. PMID:25126567

  17. Nonmelanoma skin cancer of the head and neck: prevention.

    PubMed

    Oghan, Fatih; Eskiizmir, Görkem; Unlu, Halis; Cingi, Cemal

    2012-11-01

    The importance and effectiveness of prevention efforts and strategies for skin cancers are reviewed. Topical sunscreens and their proper use are presented. Topical and ingested forms of natural, synthetic, or biologic chemical agents that are potentially efficacious for chemoprevention are listtdldted and discussed. PMID:23084302

  18. Preventing Skin Cancer Through Reduction of Indoor Tanning

    PubMed Central

    Watson, Meg; Holman, Dawn M.; Fox, Kathleen A.; Guy, Gery P.; Seidenberg, Andrew B.; Sampson, Blake P.; Sinclair, Craig; Lazovich, DeAnn

    2015-01-01

    Exposure to ultraviolet radiation from indoor tanning devices (tanning beds, booths, and sun lamps) or from the sun contributes to the risk of skin cancer, including melanoma, which is the type of skin cancer responsible for most deaths. Indoor tanning is common among certain groups, especially among older adolescents and young adults, adolescent girls and young women, and non-Hispanic whites. Increased understanding of the health risks associated with indoor tanning has led to many efforts to reduce use. Most environmental and systems efforts in the U.S. (e.g., age limits or requiring parental consent/accompaniment) have occurred at the state level. At the national level, the U.S. Food and Drug Administration and the Federal Trade Commission regulate indoor tanning devices and advertising, respectively. The current paper provides a brief review of (1) the evidence on indoor tanning as a risk factor for skin cancer; (2) factors that may influence use of indoor tanning devices at the population level; and (3) various environmental and systems options available for consideration when developing strategies to reduce indoor tanning. This information provides the context and background for the companion paper in this issue of the American Journal of Preventive Medicine, which summarizes highlights from an informal expert meeting convened by the CDC in August 2012 to identify opportunities to prevent skin cancer by reducing use of indoor tanning devices. PMID:23683987

  19. The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

    PubMed Central

    Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margaret R.; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A.; Kida, Masatoshi; Monawar Hosain, GM; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L.; Grubb, Robert L.; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H. Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.; Cortessis, Victoria K.; Conti, David V.; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H. Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J.; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

    2014-01-01

    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell cycle protein. We performed genetic fine mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2≥0.7) associated with increased bladder cancer risk. From this group we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWAS, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele odds ratio (OR) =1.18 (95%CI=1.09-1.27, p=4.67×10−5 vs. OR =1.01 (95%CI=0.93-1.10, p=0.79) for non-aggressive disease, with p=0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (p=0.013) and, independently, with each rs7257330-A risk allele (ptrend=0.024). Over-expression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E over-expression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. PMID:25320178

  20. Ultraviolet light exposure, skin cancer risk and vitamin D production

    PubMed Central

    RIVAS, MIGUEL; ROJAS, ELISA; ARAYA, MARÍA C.; CALAF, GLORIA M.

    2015-01-01

    The danger of overexposure to solar ultraviolet radiation has been widely reviewed since the 1980s due to the depletion of the ozone layer. However, the benefits of mild exposure of the skin to ultraviolet (UV) light have not been widely investigated. Numerous reports have demonstrated that an association exists between low light exposure to the sun, non-melanoma skin cancer and a lack of vitamin D synthesis. As vitamin D synthesis in the body depends on skin exposure to UVB radiation from the sun (wavelength, 290–320 nm), experimental measurements for this type of solar radiation are important. The present study analyzed data obtained from a laboratory investigating UV radiation from the sun at the University of Tarapacá (Arica, Chile), where systematic experimental UVB measurements had been performed using a calibrated biometer instrument since 2006. These data were compared with skin cancer data from the local population. The results demonstrated that the incidence of skin cancer systematically increased from 7.4 to 18.7 in men and from 10.0 to 21.7 in women between 2000 and 2006 in Arica, respectively; this increase may be due to multiple factors, including the lack of adequate levels of vitamin D in risk groups such as post-menopausal women and senior age. This marked increase may also be due to the high levels of UV radiation measured in this region throughout the year. However, it is not certain that the local population has adequate vitamin D levels, nor that their skin has been predominantly exposed to artificial light that does not allow adequate vitamin D synthesis. Thus, the current study presents the association between skin type IV, the time to induce solar erythema and the time required to produce 1,000 international units of vitamin D. PMID:26622830

  1. Noninvasive skin cancer diagnosis using multimodal optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Moy, Austin J.; Feng, Xu; Markey, Mia K.; Reichenberg, Jason S.; Tunnell, James W.

    2016-02-01

    Skin cancer is the most common form of cancer in the United States and is a recognized public health issue. Diagnosis of skin cancer involves biopsy of the suspicious lesion followed by histopathology. Biopsies, which involve excision of the lesion, are invasive, at times unnecessary, and are costly procedures ( $2.8B/year in the US). An unmet critical need exists to develop a non-invasive and inexpensive screening method that can eliminate the need for unnecessary biopsies. To address this need, our group has reported on the continued development of a multimodal spectroscopy (MMS) system towards the goal of a spectral biopsy of skin. Our approach combines Raman spectroscopy, fluorescence spectroscopy, and diffuse reflectance spectroscopy to collect comprehensive optical property information from suspicious skin lesions. We describe our present efforts to develop an updated MMS system composed of OEM components that will be smaller, less expensive, and more clinic-friendly than the previous system. Key system design choices include the selection of miniature spectrometers, a fiber-coupled broadband light source, a fiber coupled diode laser, and a revised optical probe. Selection of these components results in a 50% reduction in system footprint, resulting in a more clinic-friendly system. We also present preliminary characterization data from the updated MMS system, showing similar performance with our revised optical probe design. Finally, we present in vivo skin measurements taken with the updated MMS system. Future work includes the initiation of a clinical study (n = 250) of the MMS system to characterize its performance in identifying skin cancers.

  2. Combined Treatments with Photodynamic Therapy for Non-Melanoma Skin Cancer

    PubMed Central

    Lucena, Silvia Rocío; Salazar, Nerea; Gracia-Cazaña, Tamara; Zamarrón, Alicia; González, Salvador; Juarranz, Ángeles; Gilaberte, Yolanda

    2015-01-01

    Non-melanoma skin cancer (NMSC) is the most common form of cancer in the Caucasian population. Among NMSC types, basal cell carcinoma (BCC) has the highest incidence and squamous cell carcinoma (SCC) is less common although it can metastasize, accounting for the majority of NMSC-related deaths. Treatment options for NMSC include both surgical and non-surgical modalities. Even though surgical approaches are most commonly used to treat these lesions, Photodynamic Therapy (PDT) has the advantage of being a non-invasive option, and capable of field treatment, providing optimum cosmetic outcomes. Numerous clinical research studies have shown the efficacy of PDT for treating pre-malignant and malignant NMSC. However, resistant or recurrent tumors appear and sometimes become more aggressive. In this sense, the enhancement of PDT effectiveness by combining it with other therapeutic modalities has become an interesting field in NMSC research. Depending on the characteristics and the type of tumor, PDT can be applied in combination with immunomodulatory (Imiquimod) and chemotherapeutic (5-fluorouracil, methotrexate, diclofenac, or ingenol mebutate) agents, inhibitors of some molecules implicated in the carcinogenic process (COX2 or MAPK), surgical techniques, or even radiotherapy. These new strategies open the way to a wider improvement of the prevention and eradication of skin cancer. PMID:26516853

  3. 78 FR 47320 - Preventing Skin Cancer Through Reduction of UV Exposure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ... HUMAN SERVICES Centers for Disease Control and Prevention Preventing Skin Cancer Through Reduction of UV... information from the public on preventing skin cancer through the reduction of UV exposure. The information... problem of skin cancer. DATES: Written comments must be received on or before September 4, 2013....

  4. The relationship between skin cancers, solar radiation and ozone depletion.

    PubMed Central

    Moan, J.; Dahlback, A.

    1992-01-01

    During the period 1957-1984 the annual age-adjusted incidence rate of cutaneous malignant melanoma (CMM) increased by 350% for men and 440% for women in Norway. The annual exposure to carcinogenic sunlight in Norway, calculated by use of measured ozone levels, showed no increasing trend during the same period. Thus, ozone depletion is not a cause of the increasing trend of the incidence rates of skin cancers. The incidence rates of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) increase with decreasing latitude in Norway. The same is true for CMM in Norway, Sweden, and Finland. Our data were used to estimate the implications of a future ozone depletion for the incidence rates of skin cancer: a 10% ozone depletion was found to give rise to a 16-18% increase in the incidence rate of SCC (men and women), a 19% increase in the incidence rate of CMM for men and a 32% increase in the incidence rate of CMM for women. The difference between the numbers for men and women is almost significant and may be related to a different intermittent exposure pattern to sunlight of the two sexes. The increasing trend in the incidence rates of CMM is strongest for the trunk and lower extremities of women, followed by that for the trunk of men. The increasing incidence rates of skin cancers as well as the changing pattern of incidence on different parts of the body is most likely due to changing habits of sun exposure. Comparisons of relative densities of CMM, SCC, LMM and SCC falling per unit area of skin at different parts of the body indicate that sun exposure is the main cause of these cancer forms although other unknown factors may play significant roles as well. For the population as a whole sun exposure during vacations to sunny countries has so far been of minor importance in skin cancer induction. PMID:1616864

  5. Implications of climate change for skin cancer prevention in Australia.

    PubMed

    Makin, Jen

    2011-12-01

    It is estimated that nearly 450,000 Australians get skin cancer every year. Ultraviolet (UV) radiation from sunlight has been identified as the cause of more than 95% of skin cancers in Australia. Accordingly, the focus of skin cancer prevention programs is reducing exposure to UV radiation. In Victoria, improvements in sun protection behaviours and reductions in sunburn and melanoma incidence rates among younger people have been observed since the SunSmart program was established in 1988. However, climate change has the potential to undermine these successes. First, surface UVB radiation is dependent on stratospheric total ozone amounts. While signs of impact of international restrictions on the production of ozone-depleting substances have been observed, improvements have not yet returned ozone to pre-1970s levels. Interactions between ozone depletion and climate change may slow the recovery of the ozone layer and compound increases in UV radiation at some latitudes. Before recovery, it is expected that higher levels of UV radiation will continue in most Australian regions, with an associated higher risk of skin cancer. Indeed, recent data show increases in surface UV radiation throughout Australia since the 1970s. Second, mean temperatures in Australia have increased over the past 30 years and are projected to rise further by 2030. Australian data shows that with higher temperatures, adults spend more time outdoors, are less likely to wear covering clothing and more likely to be sunburnt. Hence, rising temperatures can be expected to result in increases in sun exposure, sunburn and correspondingly, skin cancer risk. PMID:22518918

  6. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs. PMID:22149431

  7. Skin Cancer Education Materials: Selected Annotations.

    ERIC Educational Resources Information Center

    National Cancer Inst. (NIH), Bethesda, MD.

    This annotated bibliography presents 85 entries on a variety of approaches to cancer education. The entries are grouped under three broad headings, two of which contain smaller sub-divisions. The first heading, Public Education, contains prevention and general information, and non-print materials. The second heading, Professional Education,…

  8. Whole exome sequencing of rare aggressive breast cancer histologies.

    PubMed

    Dieci, Maria Vittoria; Smutná, Veronika; Scott, Véronique; Yin, Guangliang; Xu, Ran; Vielh, Philippe; Mathieu, Marie-Christine; Vicier, Cécile; Laporte, Melanie; Drusch, Francoise; Guarneri, Valentina; Conte, Pierfranco; Delaloge, Suzette; Lacroix, Ludovic; Fromigué, Olivia; André, Fabrice; Lefebvre, Celine

    2016-02-01

    Little is known about mutational landscape of rare breast cancer (BC) subtypes. The aim of the study was to apply next generation sequencing to three different subtypes of rare BCs in order to identify new genes related to cancer progression. We performed whole exome and targeted sequencing of 29 micropapillary, 23 metaplastic, and 27 pleomorphic lobular BCs. Micropapillary BCs exhibit a profile comparable to common BCs: PIK3CA, TP53, GATA3, and MAP2K4 were the most frequently mutated genes. Metaplastic BCs presented a high frequency of TP53 (78 %) and PIK3CA (48 %) mutations and were recurrently mutated on KDM6A (13 %), a gene involved in histone demethylation. Pleomorphic lobular carcinoma exhibited high mutation rate of PIK3CA (30 %), TP53 (22 %), and CDH1 (41 %) and also presented mutations in PYGM, a gene involved in glycogen metabolism, in 8 out of 27 samples (30 %). Further analyses of publicly available datasets showed that PYGM is dramatically underexpressed in common cancers as compared to normal tissues and that low expression in tumors is correlated with poor relapse-free survival. Immunohistochemical staining on formalin-fixed paraffin-embedded tissues available in our cohort of patients confirmed higher PYGM expression in normal breast tissue compared to equivalent tumoral zone. Next generation sequencing methods applied on rare cancer subtypes can serve as a useful tool in order to uncover new potential therapeutic targets. Sequencing of pleomorphic lobular carcinoma identified a high rate of alterations in PYGM. These findings emphasize the role of glycogen metabolism in cancer progression. PMID:26907767

  9. Evaluation of selenium in biological sample of arsenic exposed female skin lesions and skin cancer patients with related to non-exposed skin cancer patients.

    PubMed

    Kolachi, Nida F; Kazi, Tasneem G; Wadhwa, Sham K; Afridi, Hassan I; Baig, Jameel A; Khan, Sumaira; Shah, Faheem

    2011-08-01

    The antagonistic effects between selenium (Se) and arsenic (As) suggest that low Se status plays an important role in arsenism development. The objective of present study was to assess Se contents in biological samples of As exposed females have skin lesions and cancer with related to non-exposed skin cancer patients. The biological samples (blood and scalp hair) of As exposed group comprises, female skin cancer (ESC) patients admitted in cancer hospitals have skin lesions (ESL) and exposed referents have not both diseases (ER), belongs to As exposed area of Pakistan. For comparative purposes, age matched female skin cancerous patient (RP) and non-cancerous females (NER) belong to non-exposed areas were also selected. The As and Se in acid digests of biological samples were pre-concentrated by complexing with chelating agent (ammonium pyrrolidinedithiocarbamate), and resulted complexes were extracted into non-ionic extractant (Triton X-114), prior to analysis by electrothermal atomic absorption spectrometry. The enhancement factor of about 25 was obtained by pre-concentrating 10 mL of sample solutions. The accuracy of the optimized procedure was evaluated by using certified reference material (BCR 397) with certified values for Se and As and standard addition method at three concentration levels in real samples. No significant differences was observed (p>0.05) when comparing the values obtained by the proposed method, added and certified values of both elements. The biological samples of ESC patients had 2-3 folds higher As and lower Se levels as compared to RP (p<0.001). Understudied exposed referents have high level of As and lower Se contents as compared to referents subjects of non-exposed area (p<0.01). The higher concentration of As and lower levels of Se in biological samples of cancerous patients are consisted with reported studies. PMID:21624640

  10. Chronic ethanol exposure enhances the aggressiveness of breast cancer: the role of p38γ.

    PubMed

    Xu, Mei; Wang, Siying; Ren, Zhenhua; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Ke, Zun-Ji; Shi, Xianglin; Luo, Jia

    2016-01-19

    Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12-48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the scattering of MCF7, BT20 and T47D cell colonies in a 3-dimension culture system. Chronic ethanol exposure also increased colony formation in an anchorage-independent condition and stimulated cell invasion/migration. Chronic ethanol exposure increased cancer stem-like cell (CSC) population by more than 20 folds. Breast cancer cells exposed to ethanol in vitro displayed a much higher growth rate and metastasis in mice. Ethanol selectively activated p38γ MAPK and RhoC but not p38α/β in a concentration-dependent manner. SP-MCF7 cells, a derivative of MCF7 cells which compose mainly CSC expressed high levels of phosphorylated p38γ MAPK. Knocking-down p38γ MAPK blocked ethanol-induced RhoC activation, cell scattering, invasion/migration and ethanol-increased CSC population. Furthermore, knocking-down p38γ MAPK mitigated ethanol-induced tumor growth and metastasis in mice. These results suggest that chronic ethanol exposure can enhance the aggressiveness of breast cancer by activating p38γ MAPK/RhoC pathway. PMID:26655092

  11. Recontouring, resurfacing, and scar revision in skin cancer reconstruction.

    PubMed

    Brenner, Michael J; Perro, Christopher A

    2009-08-01

    Residual disfigurement is a common problem for patients who have undergone skin cancer reconstruction. Restoring form and function in these patients is an artistic and technical endeavor. The efficacy of surgical scar revision, dermabrasion, chemical peels, and laser resurfacing is predicated upon the skin's innate ability to regenerate over time in response to mechanical, chemical, and thermal or ablative stresses. The patient and surgeon should be accepting of a process that is often gradual and may proceed in stages. Achieving proficiency with the secondary procedures for improving scars and local flaps may allow the motivated surgeon to mold an initially passable surgical result into an excellent one. PMID:19698924

  12. [The educational website Dermaguard to prevent the incidence of skin cancer after transplantation].

    PubMed

    Bühler, Meret N; Feldmeyer, Laurence; Wüthrich, Rudolf P; French, Lars E; Djamei, Vahid; Serra, Andreas L; Hofbauer, Günther F L

    2013-11-13

    Solid organ transplant recipients are highly susceptible to skin cancer. The major driving factors are immunosuppressive medication and ultraviolet light. Appropriate sun protection markedly reduces the development of skin cancer. Skin cancer recognized at an early stage can reliably be cured, and fatal outcomes can be prevented. The aim of this work is to educate organ transplant recipients and health care professionals involved in their care, to increase awareness of skin cancer in this high-risk population and thus to optimize the long-term outcome of patients with skin cancer. Our newly developed website provides free access to various educational materials, including leaflets, presentations and interactive elements using edutainment. PMID:24220062

  13. The Role of Optical Radiations in Skin Cancer

    PubMed Central

    Palla, Marco; Di Trolio, Rossella; Mozzillo, Nicola; Ascierto, Paolo A.

    2013-01-01

    Purpose. Electromagnetic radiation with wavelength in the range 100 nm to 1 mm is known as optical radiation and includes ultraviolet radiation, the visible spectrum, and infrared radiation. The deleterious short- and long-term biological effects of ultraviolet radiation, including melanoma and other skin cancers, are well recognized. Infrared radiation may also have damaging biological effects. Methods. The objective of this review was to assess the literature over the last 15 years and to summarize correlations between exposure to optical radiation and the risk of melanoma and other cancers. Results. There is a clear correlation between exposure to UV radiation and the development of skin cancer. Most importantly, a strong association between artificial UV radiation exposure, for example, tanning devices, and the risk of melanoma and squamous cell carcinoma has been clearly demonstrated. There is no clear evidence that exposure to IR and laser radiation may increase the risk of skin cancer, although negative health effects have been observed. Conclusions. Preventative strategies that involve provision of public information highlighting the risks associated with exposure to sunlight remain important. In addition, precautionary measures that discourage exposure to tanning appliances are required, as is legislation to prevent their use during childhood. PMID:23710365

  14. Circadian Dysrhythmias, Physiological Aberrations, and the Link to Skin Cancer

    PubMed Central

    Gutierrez, Daniel; Arbesman, Joshua

    2016-01-01

    Circadian rhythms are core regulators of a variety of mammalian physiologic processes and oscillate in a 24-h pattern. Many peripheral organs possess endogenous rhythmicity that is then modulated by a master clock; the skin is one of these peripheral organs. The dysregulation of rhythms is associated with decreased ability to ameliorate cellular stressors at a local and global level, which then increases the propensity for the development of neoplastic growths. In this article, we review the implications of altered circadian rhythms on DNA repair as well as modified gene expression of core clock proteins with particular focus on skin models. These findings are then correlated with epidemiologic data regarding skin cancer to showcase the effects of circadian disruption on this phenomenon. PMID:27128901

  15. A hyperspectral fluorescence lifetime probe for skin cancer diagnosis.

    PubMed

    De Beule, P A A; Dunsby, C; Galletly, N P; Stamp, G W; Chu, A C; Anand, U; Anand, P; Benham, C D; Naylor, A; French, P M W

    2007-12-01

    The autofluorescence of biological tissue can be exploited for the detection and diagnosis of disease but, to date, its complex nature and relatively weak signal levels have impeded its widespread application in biology and medicine. We present here a portable instrument designed for the in situ simultaneous measurement of autofluorescence emission spectra and temporal decay profiles, permitting the analysis of complex fluorescence signals. This hyperspectral fluorescence lifetime probe utilizes two ultrafast lasers operating at 355 and 440 nm that can excite autofluorescence from many different biomolecules present in skin tissue including keratin, collagen, nicotinamide adenine dinucleotide (phosphate), and flavins. The instrument incorporates an optical fiber probe to provide sample illumination and fluorescence collection over a millimeter-sized area. We present a description of the system, including spectral and temporal characterizations, and report the preliminary application of this instrument to a study of recently resected (<2 h) ex vivo skin lesions, illustrating its potential for skin cancer detection and diagnosis. PMID:18163714

  16. Brachytherapy in the treatment of skin cancer: an overview.

    PubMed

    Skowronek, Janusz

    2015-10-01

    The incidence of skin cancer worldwide is constantly growing and it is the most frequently diagnosed tumor. Brachytherapy (BT) in particular localizations is a valuable tool of the exact radiation depot inside the tumor mass. In localizations such as the face, skull skin and inoperable tumors, relapses after surgery, radiotherapy are usually not suitable for primary or secondary invasive treatment. Brachytherapy is a safe procedure for organs at risk according to rapid fall of a dose outside the axis of the applicator with satisfactory dose localization inside the target. The complications rate is acceptable and treatment costs are low. In some tumors (great skin lesions in the scalp, near eyes or on the nose) BT allows for a great dose reduction in surrounding healthy tissues. Brachytherapy provides minimal dose delivery to surrounding healthy tissue, thus enabling good functional and cosmetic results. Treatment is possible almost in all cases on an outpatient basis. PMID:26759545

  17. A hyperspectral fluorescence lifetime probe for skin cancer diagnosis

    NASA Astrophysics Data System (ADS)

    De Beule, P. A. A.; Dunsby, C.; Galletly, N. P.; Stamp, G. W.; Chu, A. C.; Anand, U.; Anand, P.; Benham, C. D.; Naylor, A.; French, P. M. W.

    2007-12-01

    The autofluorescence of biological tissue can be exploited for the detection and diagnosis of disease but, to date, its complex nature and relatively weak signal levels have impeded its widespread application in biology and medicine. We present here a portable instrument designed for the in situ simultaneous measurement of autofluorescence emission spectra and temporal decay profiles, permitting the analysis of complex fluorescence signals. This hyperspectral fluorescence lifetime probe utilizes two ultrafast lasers operating at 355 and 440nm that can excite autofluorescence from many different biomolecules present in skin tissue including keratin, collagen, nicotinamide adenine dinucleotide (phosphate), and flavins. The instrument incorporates an optical fiber probe to provide sample illumination and fluorescence collection over a millimeter-sized area. We present a description of the system, including spectral and temporal characterizations, and report the preliminary application of this instrument to a study of recently resected (<2h) ex vivo skin lesions, illustrating its potential for skin cancer detection and diagnosis.

  18. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

    PubMed Central

    Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub

    2016-01-01

    Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases. PMID:27621747

  19. [The relationship between the ozone layer and skin cancer].

    PubMed

    Sánchez C, Francisca

    2006-09-01

    In the recent decades, a sustained increase in the worldwide incidence of skin cancer has been observed and Chile is not the exception. The most important risk factor is the exaggerated and repeated exposure to ultraviolet radiation coming from the sun. The ozone layer restricts the transmission of type B and C ultraviolet light. Since 1980, a sustained depletion of stratospheric ozone levels is occurring, specially in middle latitudes (-30 to -60). Along with this depletion, the amount of ultraviolet light that reaches the earth surface is increasing. This article reviews some basic concepts about the ozone layer and the association between its depletion and skin cancer. The general population should be informed about the risks of inadequate and exaggerated exposure to sunlight. PMID:17171222

  20. Do lasers or topicals really work for nonmelanoma skin cancers?

    PubMed

    Brightman, Lori; Warycha, Melanie; Anolik, Robert; Geronemus, Roy

    2011-03-01

    Novel strategies are urgently needed to address the millions of nonmelanoma skin cancers treated in the United States annually. The need is greatest for those patients who are poor surgical candidates or those prone to numerous nonmelanoma skin cancers and therefore at risk for marked disfigurement. Traditional treatment strategies include electrosurgery with curettage, radiation therapy, cryotherapy, excision, and Mohs micrographic surgery. Alternatives to traditional treatment, including topical medications and light or laser therapies, are becoming popular; however, there are various degrees of efficacy among these alternative tactics. These alternatives include topical retinoids, peels, 5-fluorouracil, imiquimod, photodynamic therapy, and lasers. The purpose of this paper is to review the available data regarding these alternative strategies and permit the reader to have a sense of which therapies are reasonable options for care. PMID:21540017

  1. Human papillomavirus status in extragenital nonmelanoma skin cancers.

    PubMed

    Drvar, Daniela Ledic; Lipozenčić, Jasna; Sabol, Ivan; Mokos, Zrinka Bukvic; Ilic, Ivana; Grce, Magdalena

    2014-01-01

    About 5% of all cancers worldwide can be attributed to human papillomaviruses (HPVs); namely, six sites are strongly associated with HPV infections: cervix, penis, vulva, vagina, anus, and oropharynx. Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) are the most common malignancies in Caucasians. In fact, there is an intense connection between sunlight exposure, fair skin, HPV, and development of NMSC. We have conducted a pilot study that included tissue samples from 26 carcinoma patients, of which there were 13 BCC and 13 SCC. HPV detection and typing was done with DNA amplification and sequencing, respectively. In total, 23.1% of SCC samples (3/13) and 7.7% of BCC samples (1/13) were positive for HPV DNA. The importance of understanding all aspects of NMSC carcinogenesis may be to reveal novel therapeutic options or preventive measures for HPV containing NMSC patients. PMID:24559560

  2. Policy and practice for preventing skin cancer in children.

    PubMed

    Masso, Malcolm

    2006-01-01

    This paper identifies what is known and what is not known about the link between sun exposure and skin cancer and what can be done to reduce sun exposure in children. There is evidence for the use of sun protective clothing and of the effectiveness of sunscreens for some, but not all, forms of skin cancer. While there is some evidence to support interventions in schools, there is insufficient evidence to support other interventions aimed at children or their caregivers. There is no clear means of assessing the "trade-off" between the benefits and harms of sunlight exposure, and the impact of sun protection strategies on other health promotion messages aimed at children is unknown. Reliance on educational interventions in schools may benefit from a broader approach that includes more emphasis on protective clothing and structural changes in the school day. Sun protection messages should be linked with other health promotion messages targeting children. PMID:16817808

  3. Study in mice shows that an aggressive type of breast cancer is linked to an inflammatory protein

    Cancer.gov

    Aberrant expression of an inflammatory protein, nitric oxide synthase 2 (NOS2), may enhance the progression and metastasis of an aggressive and less common form of breast cancer, known as the estrogen receptor-negative type of disease.

  4. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer

    PubMed Central

    Ragnum, H B; Vlatkovic, L; Lie, A K; Axcrona, K; Julin, C H; Frikstad, K M; Hole, K H; Seierstad, T; Lyng, H

    2015-01-01

    Background: The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer. Methods: Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation. Results: Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively. Conclusions: Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes. PMID:25461803

  5. Skin artifact removal technique for breast cancer radar detection

    NASA Astrophysics Data System (ADS)

    Caorsi, S.; Lenzi, C.

    2016-06-01

    In this paper we propose a new model-based skin artifact cleaning technique with the aim to remove skin reflections with good effectiveness, without introducing significant signal distortions, and without assuming a priori information on the real structure of the breast. The reference cleaning model, constituted by a two-layer geometry skin-adipose tissue, is oriented to all the ultrawideband radar methods able to detect the tumor starting by the knowledge of each trace recorded around the breast. All the radar signal measurements were simulated by using realistic breast models derived from the University of Wisconsin computational electromagnetic laboratory database and the finite difference time domain (FDTD)-based open source software GprMax. First, we have searched for the best configuration for the reference cleaning model with the aim to minimize the distortions introduced on the radar signal. Second, the performance of the proposed cleaning technique has been assessed by using a breast cancer radar detection technique based on the use of artificial neural network (ANN). In order to minimize the signal distortions, we found that it was necessary to use the real skin thickness and the static Debye parameters of both skin and adipose tissue. In such a case the ANN-based radar approach was able to detect the tumor with an accuracy of 87%. By extending the performance assessment also to the case when only average standard values are used to characterize the reference cleaning model, the detection accuracy was of 84%.

  6. Confocal microscopy patterns in nonmelanoma skin cancer and clinical applications.

    PubMed

    González, S; Sánchez, V; González-Rodríguez, A; Parrado, C; Ullrich, M

    2014-06-01

    Reflectance confocal microscopy is currently the most promising noninvasive diagnostic tool for studying cutaneous structures between the stratum corneum and the superficial reticular dermis. This tool gives real-time images parallel to the skin surface; the microscopic resolution is similar to that of conventional histology. Numerous studies have identified the main confocal features of various inflammatory skin diseases and tumors, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. Confocal patterns and diagnostic algorithms have been shown to have high sensitivity and specificity in melanoma and nonmelanoma skin cancer. Possible present and future applications of this noninvasive technology are wide ranging and reach beyond its use in noninvasive diagnosis. This tool can also be used, for example, to evaluate dynamic skin processes that occur after UV exposure or to assess tumor response to noninvasive treatments such as photodynamic therapy. We explain the characteristic confocal features found in the main nonmelanoma skin tumors and discuss possible applications for this novel diagnostic technique in routine dermatology practice. PMID:24002008

  7. Environmental factors in nonmelanoma and melanoma skin cancer.

    PubMed

    Woodhead, A D; Setlow, R B; Tanaka, M

    1999-12-01

    We discuss the role of sunlight, mostly ultraviolet light (UV), in the induction of nonmelanoma and melanoma skin cancer. Whilst the former seems to be correlated with accumulated exposure, the causation of melanoma is more complex, and may also involve the pattern of, and age at, exposure. The efficacy of sunscreens is debatable; while they protect against UVB wavelengths (290-320 nm), and so extend the time that may be spent in the sun before becoming sunburnt, their use may subject wearers to excessive exposure to UVA (320-400 nm) and visible light. Both epidemiological surveys and experiments with animal models suggest that UVA, and perhaps the visible, may induce melanomas. Although Japanese have a much lower incidence of skin cancer than Caucasians, the dramatic rise in skin cancer in Japanese-Americans in Hawaii exposed to high-intensity irradiation raises concerns. If the Japanese people adopt sun-seeking behavior, or should the levels of UV irradiation rise significantly through depletion of the ozone layer, then this could become an important health problem in future. PMID:10709358

  8. Neuromodulators for Aging Skin

    MedlinePlus

    ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ...

  9. In vitro photodynamic effect of aluminum tetrasulfophthalocyanines on melanoma skin cancer and healthy normal skin cells.

    PubMed

    Maduray, K; Odhav, B; Nyokong, T

    2012-03-01

    Photodynamic therapy is a medical treatment that uses an inactive dye/drug and lasers as a light source to activate the dye/drug to produce a toxic form of oxygen that destroys the cancer cells. This study aimed at investigating the cytotoxic effects of different concentrations of aluminum tetrasulfophthalocyanines in its inactive and active state (laser induced) on melanoma skin cancer cells, healthy normal skin fibroblast and keratinocyte cells. Experimentally, 3 × 10⁴ cells/ml were seeded in 24-well plates before treatment with different concentrations of aluminum tetrasulfophthalocyanines. After 2h, cells were irradiated with a light dose of 4.5 J/cm². Post-irradiated cells were incubated for 24h before cell viability was measured using the CellTiter-Blue Viability Assay. Results showed that aluminum tetrasulfophthalocyanines at high concentrations were cytotoxic to melanoma cells in the absence of laser activation. In the presence of laser activation of aluminum tetrasulfophthalocyanines at a concentration of 40 μg/ml decreased cell viability of melanoma cells to 45%, fibroblasts to 78% and keratinocytes to 73%. At this photosensitizing concentration of aluminum tetrasulfophthalocyanines the efficacy of the treatment light dose 4.5 J/cm² and the cell death mechanism induced by photoactivated aluminum tetrasulfophthalocyanines was evaluated. A light dose of 4.5 J/cm² was more efficient in killing a higher number of melanoma cells and a lower number of fibroblast and keratinocyte cells than the other light doses of 2.5 J/cm², 7.5 J/cm² and 10.5 J/cm². Apoptosis features such as blebbing, nucleus condensation, nucleus fragmentation and the formation of apoptotic bodies were seen in the photodynamic therapy treated melanoma skin cancer cells. This in vitro photodynamic therapy study concludes that using aluminum tetrasulfophthalocyanines at a photosensitizing concentration of 40 μg/ml in combination with a laser dose of 4.5 J/cm² was potentially lethal

  10. Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

    PubMed

    Jang, S; Yu, X-M; Odorico, S; Clark, M; Jaskula-Sztul, R; Schienebeck, C M; Kupcho, K R; Harrison, A D; Winston-McPherson, G N; Tang, W; Chen, H

    2015-08-01

    To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy. PMID:26251030

  11. A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes

    PubMed Central

    Andreas, Jonathan; Patel, Shashank J.; Zhang, Suiyuan; Chines, Peter; Elkahloun, Abdel; Chandrasekharappa, Settara; Gutkind, J. Silvio; Molinolo, Alfredo A.; Crawford, Nigel P. S.

    2014-01-01

    Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL) mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ) F2 intercross males (n = 228), which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ) F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322) were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A) were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2) harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such approaches will

  12. Melanoma skin cancer screenings. A how-to approach.

    PubMed

    Dobes, W L

    1995-01-15

    Development of a workshop on skin cancer screening should begin with physicians who are able to best diagnose and treat skin cancer, that is, dermatologists who are board certified or board eligible. Local societies should then be involved as well as organizations that can offer ancillary help such as screening, clinics' location and assisting with personnel financial aid, and exposure to the public, such as advertising. Support groups then become essential to a good screening. The help of the American Cancer Society, local churches, clubs, and others is beneficial. The organization should have a central organizing body that sets the dates and locations for the clinics and that helps get supplies, such as tables, screens for privacy, and literature. Volunteers can help with sign-in and sign-out sheets for the screening and can act as traffic directors and assist the physicians. Media exposure then becomes important. A TV or radio show can get the public's attention, for example, by releasing the latest data on skin cancer or by presenting a solar meter project showing the local risk of ultraviolet radiation. The workshop itself should begin on time. Additionally, a cutoff time is also needed. In the final stage, the forms should be processed and a follow-up evaluation should be done on the number of patients seen, precancerous and cancerous lesions found, and the potential for future functions. Popular ancillary aids are good literature on the subjects discussed, and samples of sunscreens (SPF 15 or better) that are donated by pharmaceutical companies. PMID:7804998

  13. Applications of slow positrons to cancer research: Search for selectivity of positron annihilation to skin cancer

    NASA Astrophysics Data System (ADS)

    Jean, Y. C.; Li, Ying; Liu, Gaung; Chen, Hongmin; Zhang, Junjie; Gadzia, Joseph E.

    2006-02-01

    Slow positrons and positron annihilation spectroscopy (PAS) have been applied to medical research in searching for positron annihilation selectivity to cancer cells. We report the results of positron lifetime and Doppler broadening energy spectroscopies in human skin samples with and without cancer as a function of positron incident energy (up to 8 μm depth) and found that the positronium annihilates at a significantly lower rate and forms at a lower probability in the samples having either basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) than in the normal skin. The significant selectivity of positron annihilation to skin cancer may open a new research area of developing positron annihilation spectroscopy as a novel medical tool to detect cancer formation externally and non-invasively at the early stages.

  14. Genetic validation of postmixing skin injuries in pigs as an indicator of aggressiveness and the relationship with injuries under more stable social conditions.

    PubMed

    Turner, S P; Roehe, R; D'Eath, R B; Ison, S H; Farish, M; Jack, M C; Lundeheim, N; Rydhmer, L; Lawrence, A B

    2009-10-01

    The objective of the study was to estimate genetic correlations between skin lesions and aggressive behavior postmixing and under more stable social conditions as a potential means of selecting against pig aggressiveness. Postmixing aggression in commercial pig production is common, compromises welfare and profitability, and cannot be significantly reduced by low-cost changes to the environment. A genetic component to individual aggressiveness has been described in pigs and other species. Selective breeding against aggressiveness ought to be possible if an easily measured indicator trait can be shown to be genetically associated with aggressive behavior. Aggressive behavior was recorded continuously for 24 h after mixing, and a count of skin lesions (lesion count, LC) was recorded at 24 h and 3 wk postmixing on 1,663 pigs. Two behavioral traits were found to have a moderate to high heritability similar to that of growth traits; duration of involvement in reciprocal fighting (0.43 +/- 0.04) and delivery of nonreciprocal aggression (NRA; 0.31 +/- 0.04), whereas receipt of NRA had a lower heritability (0.08 +/- 0.03). Genetic correlations (r(g)) suggested that lesions to the anterior region of the body 24 h after mixing were associated with reciprocal fighting (r(g) = 0.67 +/- 0.04), receipt of NRA (r(g) = 0.70 +/- 0.11), and to a lesser extent, delivery of NRA (r(g) = 0.31 +/- 0.06). Lesions to the center and rear were primarily genetically associated with receipt of NRA (r(g) = 0.80 +/- 0.05, 0.79 +/- 0.05). Genetic correlations indicated that pigs that engaged in reciprocal fighting delivered NRA to other animals (r(g) = 0.84 +/- 0.04) but were less likely to receive NRA themselves (r(g) = -0.41 +/- 0.14). A genetic merit index using lesions to the anterior region as one trait and those to the center or rear or both as a second trait should allow selection against animals involved in reciprocal fighting and the delivery of NRA. Positive correlations between LC 24 h

  15. Baseline Comorbidities in a Skin Cancer Prevention Trial in Bangladesh

    PubMed Central

    Argos, Maria; Rahman, Mahfuzar; Parvez, Faruque; Dignam, James; Islam, Tariqul; Quasem, Iftekhar; Hore, Samar Kumar; Haider, Ahmed Talat; Hossain, Zahid; Patwary, Tazul Islam; Rakibuz-Zaman, Muhammad; Sarwar, Golam; La Porte, Paul; Harjes, Judith; Anton, Kristen; Kibriya, Muhammad G.; Jasmine, Farzana; Khan, Rashed; Kamal, Mohammed; Shea, Christopher R.; Yunus, Muhammad; Baron, John A.; Ahsan, Habibul

    2014-01-01

    Background Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods, and baseline analyses from the Bangladesh Vitamin E and Selenium Trial (BEST), a population based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. Materials and methods BEST is a 2×2 full factorial double-blind randomized controlled trial of 7,000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 μg daily) for the prevention of non-melanoma skin cancer. Results In cross-sectional analyses, we observed significant associations of skin lesion severity with male sex (female prevalence odds ratio (POR)=0.87; 95% CI=0.79–0.96), older age (aged 36–45 POR=1.27; 95% CI=1.13–1.42; aged 46–55 POR=1.44; 95% CI=1.27–1.64; and aged 56–65 POR=1.50; 95% CI=1.26–1.78 compared to aged 25–35), hypertension (POR=1.29; 95% CI=1.08–1.55), diabetes (POR=2.13; 95% CI=1.32–3.46), asthma (POR=1.55; 95% CI=1.03–2.32), and peptic ulcer disease (POR=1.20; 95% CI=1.07–1.35). Conclusions We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond. PMID:23590571

  16. Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia.

    PubMed

    Iannacone, Michelle R; Sinnya, Sudipta; Pandeya, Nirmala; Isbel, Nikky; Campbell, Scott; Fawcett, Jonathan; Soyer, Peter H; Ferguson, Lisa; Davis, Marcia; Whiteman, David C; Green, Adèle C

    2016-07-01

    The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services. PMID:26968258

  17. [Skin cancer and sun radiation: peruvian experience in the prevention and early detection of skin cancer and melanoma].

    PubMed

    Sordo, Carlos; Gutiérrez, César

    2013-03-01

    The excessive exposure to sun radiation, especially to ultraviolet radiation (UV), has led to various diseases, in particular to skin cancer. In 1995, the Peruvian Dermatological Association conducted the first "Campaign for Education, Prevention and Early Detection of Skin Cancer and Melanoma" called "Mole's Day". The Ministry of Health has turned it into an official event, and the Health Social Security (EsSalud) also participates. This is a free campaign that takes place every year nationwide. 118,092 people attended from 1995 to 2011 in 76 sites distributed in 18 cities throughout the country. A cutaneous lesion were malignancy was suspected was identified in 2.8% of people attending, out of which 64.9% corresponded to basal cell carcinoma, 26.7% to cutaneous melanoma, and 8.4% to squamous cell carcinoma. These campaigns are highly important not only because of the assistance given, but also because of the educational activities aimed at promoting a prevention culture in favor of the most vulnerable populations. Finally, we believe it is important to continue educating the population on skin cancer prevention, to build awareness among the authorities so that they actively participate in the performance of these activities, and to ask all physicians to coordinately join this initiative, in order to continue growing, and to improve all that has been attained for the benefit of our country. PMID:23612823

  18. A lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers

    PubMed Central

    Drake, Penelope M.; Schilling, Birgit; Niles, Richard K.; Prakobphol, Akraporn; Li, Bensheng; Jung, Kwanyoung; Cho, Wonryeon; Braten, Miles; Inerowicz, Halina D.; Williams, Katherine; Albertolle, Matthew; Held, Jason M.; Iacovides, Demetris; Sorensen, Dylan J.; Griffith, Obi L.; Johansen, Eric; Zawadzka, Anna M.; Cusack, Michael P.; Allen, Simon; Gormley, Matthew; Hall, Steven C.; Witkowska, H. Ewa; Gray, Joe W.; Regnier, Fred; Gibson, Bradford W.; Fisher, Susan J.

    2012-01-01

    We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n = 5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ~90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNAseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were upregulated in triple negative vs. luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype. PMID:22309216

  19. Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients

    PubMed Central

    Subbiah, Vivek; Bupathi, Manojkumar; Kato, Shumei; Livingston, Andrew; Slopis, John; Anderson, Pete M.; Hong, David S.

    2015-01-01

    Background The aggressive biology of cancers arising in adolescent and young adult (AYA; ages 15–39 years) patients is thought to contribute to poor survival outcomes. Methods We used clinical next-generation sequencing (NGS) results to examine the molecular alterations and diverse biology of cancer in AYA patients referred to the Phase 1 program at UT MD Anderson Cancer Center. Results Among the 28 patients analyzed (14 female and 14 male), 12 had pediatric-type cancers, six had adult-type cancers, and ten had orphan cancers. Unique, hitherto unreported aberrations were identified in all types of cancers. Aberrations in TP53, NKX2-1, KRAS, CDKN2A, MDM4, MCL1, MYC, BCL2L2, and RB1 were demonstrated across all tumor types. Five patients harbored TP53 aberrations; three patients harbored MYC, MCL1, and CDKN2A aberrations; and two patients harbored NKX2-1, KRAS, MDM4, BCL2L2, and RB1 alterations. Several patients had multiple aberrations; a patient with wild-type gastrointestinal stromal tumor harbored five alterations (MDM4, MCL1, KIT, AKT3, and PDGRFA). Conclusions This preliminary report of NGS of cancer in AYA patients reveals diverse and unique aberrations. Further molecular profiling and a deeper understanding of the biology of these unique aberrations are warranted and may lead to targeted therapeutic interventions. PMID:26328274

  20. Impact of consumption of vegetable, fruit, grain, and high glycemic index foods on aggressive prostate cancer risk

    PubMed Central

    Hardin, Jill; Cheng, Iona; Witte, John S.

    2011-01-01

    Prostate cancer is a common but complex disease, and distinguishing modifiable risk factors such as diet for more aggressive disease is extremely important. Previous work has detected intriguing associations between vegetable, fruit, and grains and more aggressive prostate cancer, although these remain somewhat unclear. Here we further investigate such potential relationships with a case-control study of 982 men (470 more aggressive prostate cancer cases and 512 control subjects). Comparing the highest to lowest quartiles of intake, we found that increasing intakes of leafy vegetables were inversely associated with risk of aggressive prostate cancer (adjusted odds ratio (OR) =0.66, 95% CI: 0.46, 0.96, P-trend=0.02), as was higher consumption of high carotenoid vegetables (OR=0.71, 95% CI: 0.48, 1.04; P-trend=0.04). Conversely, increased consumption of high glycemic index foods were positively associated with risk of aggressive disease (OR=1.64, 95% CI: 1.05, 2.57; P-trend=0.02). These results were driven by a number of specific foods within the food groups. Our findings support the hypothesis that diets high in vegetables and low in high glycemic index foods decrease risk of aggressive prostate cancer. PMID:21774611

  1. Patient Satisfaction after Treatment of Nonmelanoma Skin Cancer

    PubMed Central

    Asgari, Maryam M.; Bertenthal, Daniel; Sen, Saunak; Sahay, Anju; Chren, Mary-Margaret

    2009-01-01

    Background Patient satisfaction is an important aspect of patient-centered care, but has not been systematically studied after treatment of nonmelanoma skin cancer (NMSC), the most prevalent cancer. Objective To compare patient satisfaction after treatment for NMSC and to determine factors associated with better satisfaction. Methods We prospectively measured patient, tumor and care characteristics in 834 consecutive patients at two centers before and after destruction, excision and Mohs surgery. We evaluated factors associated with short-term and long-term satisfaction. Results In all treatment groups, patients were more satisfied with the interpersonal manners of the staff, communication, and financial aspects of their care, than with the technical quality, time with the clinician, and accessibility of their care (p<0.05). Short-term satisfaction did not differ across treatment groups. In multivariable regression models adjusting for patient, tumor, and care characteristics, higher long-term satisfaction was independently associated with younger age, better pre-treatment mental health and skin-related quality of life, and treatment with Mohs surgery (p<0.05). Conclusions Long-term patient satisfaction after treatment of NMSC is related to pre-treatment patient characteristics (mental health, skin-related quality of life) as well as treatment type (Mohs) but not related to tumor characteristics. These results can guide informed decision-making for treatment of NMSC. PMID:19438672

  2. Dose Distribution Calculation in Skin Cancer Treatment Using Leipzig Applicator

    NASA Astrophysics Data System (ADS)

    Mowlawi, Ali Asghar; Yazdani, Majed

    The combination of 192Ir seed with the Leipzig applicators is used in a considerable number of clinical trials for skin cancer treatment. As is known, the beneficial effects of ionizing radiation for tumor treatment depends on the dosimetry accuracy. Nowadays, dosimetry calculations are supported by the characteristics provided by the manufacturer, which have been obtained from measurements with an ionization chamber in a phantom. Despite their benefit, the experimental data involves errors related to the positioning, energy, and angular dependence of the detectors. Thus, in order to get a detailed and more accurate dosimetry, the Monte Carlo code MCNP4C2 — Monte Carlo Neutron Particle, 4C2 version — has been employed to analyze the dose distribution in depth and at the surface in the skin cancer treatment using Leipzig applicators. On the other hand, some different measurements have been taken to validate the method and compare results. The results for this material of phantom (the skin with 0.5 cm thick over infinite soft tissue) can be used in treatment planning systems and also for computation of model dependent parameters like anisotropy dose function.

  3. Skin cancer comic book: evaluation of a public educational vehicle.

    PubMed

    Putnam, G L; Yanagisako, K L

    1982-01-01

    A 16-page 4-color comic book was developed as part of a multimedia public education campaign designed to improve skin cancer knowledge and prevention/detection behavior. A concentrated comic book distribution to each of 8,000 households in a predominantly Caucasian area was preceded and followed by personal interviews with 300 residents randomly selected from this area. In households reading the comic book (N-122), respondents reported the following changes as a direct result of readership--avoidance of sun exposure between 10 am and 2 pm (44.3%), use of sunscreens with SPF 8 and over (38.5%), skin self-examination (34.4%), and use of protective clothing (29.5%). To a lesser extent nonreaders also showed positive increases, suggesting exposure to other educational efforts of the skin cancer campaign. Over 90% of the readers felt that the comic book was easy to read, easy to understand, and interesting. The comic book appealed less to males and to those above the age of 50 years. PMID:7151069

  4. Skin cancer risk perceptions: A comparison across ethnicity, age, education, gender, and income

    PubMed Central

    Buster, Kesha J.; You, Zhiying; Fouad, Mona; Elmets, Craig

    2013-01-01

    Background Studies of non-cutaneous and cutaneous malignancies support the hypothesis that poor risk-perception status contributes to health disparity. Objective We evaluated skin cancer risk perceptions across race and other demographic markers using the Health Information National Trends Survey (HINTS) and compared them to discover differences in perception that may contribute to the disparities in skin cancer diagnosis and treatment. Methods Respondents with no prior history of skin cancer were randomly selected to answer questions assessing perceived risk and knowledge of preventive strategies of skin cancer. Logistic regression was performed to identify associations between perceptions of skin cancer and demographic variables including self-described race, age, sex, education, income, and health insurance status. Results Blacks, the elderly, and people with less education perceived themselves as at lower risk of developing skin cancer. They, along with Hispanics, were also more likely to believe that one cannot lower their skin cancer risk and that there are so many different recommendations on how to prevent skin cancer that it makes it difficult to know which ones to follow. Lower education also correlated with greater reluctance to have a skin exam. Limitations HINTS is a cross-sectional instrument, thus it only provides a snapshot of skin cancer perceptions. Conclusion Uncertainty and altered perceptions are more common in the skin cancer risk perceptions of ethnic minorities, the elderly, and those with less education. These are the same groups that are subject to disparities in skin cancer outcomes. Educational programs directed at these demographic groups may help to reduce the skin cancer-related health disparities. PMID:21875760

  5. Skin cancer control practices among physicians in a university general medicine practice.

    PubMed

    Dolan, N C; Martin, G J; Robinson, J K; Rademaker, A W

    1995-09-01

    Physician counseling about sun protection and routine screening for skin cancer in high-risk individuals have been widely recommended. The purpose of this study was to assess the skin cancer control practices and knowledge among physicians in a university-based general medicine practice. Fifty-two physicians completed a survey on attitudes toward, behaviors in, and knowledge of skin cancer control. In addition, the ability of general medicine residents and attending physicians to correctly identify and make biopsy recommendations for ten photographed skin lesions was compared with that of third-year medical students and dermatology residents and attendings. The results of the survey illustrate a need for improving primary care physicians' knowledge and identification of skin cancer risk factors, and increasing the frequency and consistency with which they perform skin cancer prevention counseling and complete skin examination in high-risk patient groups. PMID:8523156

  6. A cancer-causing gene is positively correlated with male aggression in Xiphophorus cortezi

    PubMed Central

    Fernandez, André A.

    2010-01-01

    The persistence of seemingly maladaptive genes in organisms challenges evolutionary biological thought. In Xiphophorus fishes, certain melanin patterns form malignant melanomas due to a cancer-causing gene (Xiphophorus melanoma receptor kinase; Xmrk), which arose several millions years ago from unequal meiotic recombination. Xiphophorus melanomas are male biased and induced by androgens however male behavior and Xmrk genotype has not been investigated. This study found that male X. cortezi with the spotted caudal (Sc) pattern, from which melanomas originate, displayed increased aggression in mirror image trials. Furthermore, Xmrk males (regardless of Sc phenotype) bit and performed more agonistic displays than Xmrk deficient males. Male aggressive response decreased when males viewed their Sc image as compared to their non-Sc image. Collectively, these results indicate that Xmrk males experience a competitive advantage over wild-type males and that intrasexual selection could be an important component in the evolutionary maintenance of this oncogene within Xiphophorus. PMID:20021547

  7. Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

    PubMed

    Wu, Dapeng; Yu, Hongjie; Sun, Jielin; Qi, Jun; Liu, Qiang; Li, Ruipeng; Zheng, Siqun Lily; Xu, Jianfeng; Kang, Jian

    2015-07-01

    Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population. PMID:25738283

  8. Voriconazole-associated phototoxic dermatoses and skin cancer.

    PubMed

    Goyal, Rakesh K

    2015-01-01

    Voriconazole's antifungal spectrum, oral bioavailability, and proven efficacy in treatment of invasive mycoses have led to its widespread off-label use for antifungal prophylaxis. There is an increasing recognition that long-term voriconazole use is associated with accelerated sun-induced skin changes that include acute phototoxicity reactions, photoaging, actinic keratosis and esp. among immunocompromised patients, skin cancers. The mechanisms underlying these dermatologic adverse events are not clearly understood. Population-risks of long-term voriconazole use need to be prospectively investigated. This review aims to provide an in-depth assessment of published literature and highlight salient findings from retrospective studies and case series. A broad practical guideline for assessment and management of these patients is provided. PMID:26488688

  9. SA-SVM based automated diagnostic system for skin cancer

    NASA Astrophysics Data System (ADS)

    Masood, Ammara; Al-Jumaily, Adel

    2015-03-01

    Early diagnosis of skin cancer is one of the greatest challenges due to lack of experience of general practitioners (GPs). This paper presents a clinical decision support system aimed to save time and resources in the diagnostic process. Segmentation, feature extraction, pattern recognition, and lesion classification are the important steps in the proposed decision support system. The system analyses the images to extract the affected area using a novel proposed segmentation method H-FCM-LS. The underlying features which indicate the difference between melanoma and benign lesions are obtained through intensity, spatial/frequency and texture based methods. For classification purpose, self-advising SVM is adapted which showed improved classification rate as compared to standard SVM. The presented work also considers analyzed performance of linear and kernel based SVM on the specific skin lesion diagnostic problem and discussed corresponding findings. The best diagnostic rates obtained through the proposed method are around 90.5 %.

  10. Use of Tanning Beds and Incidence of Skin Cancer

    PubMed Central

    Zhang, Mingfeng; Qureshi, Abrar A.; Geller, Alan C.; Frazier, Lindsay; Hunter, David J.; Han, Jiali

    2012-01-01

    Purpose We sought to evaluate the risk effect of tanning bed use on skin cancers among teenage and young adults. We also expected to determine whether a dose-response relationship was evident. Patients and Methods We observed 73,494 female nurses for 20 years (from 1989 to 2009) in a large and well-characterized cohort in the United States and investigated whether frequency of tanning bed use during high school/college and at ages 25 to 35 years were associated with a risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We used Cox proportional hazards models and carefully adjusted for host risk factors, ultraviolet index of residence, and sun exposure behaviors at a young age. Results During follow-up, 5,506 nurses were diagnosed with BCC, 403 with SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin cancer for an incremental increase in use of tanning beds of four times per year during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95% CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a significantly higher risk of BCC for use during high school/college (multivariable-adjusted HR for use more than six times per year compared with no use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for heterogeneity < .001). Conclusion Our data provide evidence for a dose-response relationship between tanning bed use and the risk of skin cancers, especially BCC, and the association is stronger for patients with a younger age at exposure. PMID:22370316

  11. Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study.

    PubMed

    Vance, Terrence M; Wang, Ying; Su, L Joseph; Fontham, Elizabeth T H; Steck, Susan E; Arab, Lenore; Bensen, Jeannette T; Mohler, James L; Chen, Ming-Hui; Chun, Ock K

    2016-01-01

    The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms. PMID:26847416

  12. Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer.

    PubMed

    Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

    2015-04-01

    The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med 1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways-wnt/β-catenin and sonic hedgehog (SHH). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas, VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of SHH expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. PMID:25445917

  13. Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers

    PubMed Central

    Rousseaux, Sophie; Debernardi, Alexandra; Jacquiau, Baptiste; Vitte, Anne-Laure; Vesin, Aurélien; Nagy-Mignotte, Hélène; Moro-Sibilot, Denis; Brichon, Pierre-Yves; Lantuejoul, Sylvie; Hainaut, Pierre; Laffaire, Julien; de Reyniès, Aurélien; Beer, David G.; Timsit, Jean-François; Brambilla, Christian; Brambilla, Elisabeth; Khochbin, Saadi

    2016-01-01

    Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale “off-context” gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature–guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors. PMID:23698379

  14. Readability of skin cancer prevention brochures targeting parents of young children.

    PubMed

    Slaten, D; Parrott, R; Steiner, C

    1999-06-01

    Long-term exposure to UV radiation and severe sunburns increase one's risk of experiencing malignant melanoma later in life, so parents need to be informed about how to protect children from overexposure to the sun. We attempted to determine readability of skin cancer brochures targeted toward parents of young children. SMOG and FOG readability formulas were applied to 8 brochures published by the American Cancer Society, Skin Cancer Foundation, American Academy of Dermatology, and the Anti-Cancer Council. Readability levels of the brochures ranged between the 8th and 12th grade levels. To reduce the incidence of skin cancer, sun-safe knowledge and behavior should start in childhood. Pediatricians need access to brochures written at readability levels for the average parent. Skin cancer brochures written at the eighth or ninth grade comprehension levels may allow pediatricians to educate more parents about the importance of skin cancer prevention in childhood. PMID:10365934

  15. Breast cancer after radiotherapy for skin hemangioma in infancy

    SciTech Connect

    Lundell, M.; Mattsson, A.; Hakulinen, T.; Holm, L.E.

    1996-02-01

    Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range < 0.01-35.8 Gy). The breast cancer incidence was analyzed by record linkage with the Swedish Cancer Register for the period 1958-1986. Seventy-five breast cancers were found after a mean absorbed dose of 1.5 Gy in the breasts with cancer. The analyses showed a significant dose-response relationship with a linear model estimate for the excess relative risk (ERR) of 0.38 at 1 Gy (95% CI 0.09-0.85). This relationship was not modified significantly by age at exposure or by dose to the ovaries. The ERR increased significantly with time after exposure and for > 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10{sup 4} breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation. 17 refs., 6 figs.

  16. PVT1 Exon 9: A Potential Biomarker of Aggressive Prostate Cancer?

    PubMed Central

    Ilboudo, Adeodat; Chouhan, Jyoti; McNeil, Brian K.; Osborne, Joseph R.; Ogunwobi, Olorunseun O.

    2015-01-01

    Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were performed to evaluate expression of all 12 PVT1 exons. Each qPCR was performed in quadruplicates. At least four separate qPCR experiments were performed. Expression of PVT1 exons was inconsistent except for exon 9. There was no significant difference in exon 9 expression between cell lines derived from Caucasian males (CM), and an indolent cell line derived from MoAA. However, exon 9 expression in the aggressive MDA PCa 2b and E006AA-hT cell lines derived from MoAA was significantly higher than in other cell lines. Consequently, we observed differential expression of exon 9 of PVT1 in a manner that suggests that PVT1 exon 9 may be associated with aggressive PCa in MoAA. PMID:26703666

  17. KeraStat Skin Therapy in Treating Radiation Dermatitis in Patients With Newly Diagnosed Stage 0-IIIA Breast Cancer

    ClinicalTrials.gov

    2014-11-28

    Ductal Breast Carcinoma in Situ; Skin Reactions Secondary to Radiation Therapy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  18. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  19. An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin

    PubMed Central

    Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

    2015-01-01

    Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis. PMID:26097804

  20. Polarization speckle imaging as a potential technique for in vivo skin cancer detection

    NASA Astrophysics Data System (ADS)

    Tchvialeva, Lioudmila; Dhadwal, Gurbir; Lui, Harvey; Kalia, Sunil; Zeng, Haishan; McLean, David I.; Lee, Tim K.

    2013-06-01

    Skin cancer is the most common cancer in the Western world. In order to accurately detect the disease, especially malignant melanoma-the most fatal form of skin cancer-at an early stage when the prognosis is excellent, there is an urgent need to develop noninvasive early detection methods. We believe that polarization speckle patterns, defined as a spatial distribution of depolarization ratio of traditional speckle patterns, can be an important tool for skin cancer detection. To demonstrate our technique, we conduct a large in vivo clinical study of 214 skin lesions, and show that statistical moments of the polarization speckle pattern could differentiate different types of skin lesions, including three common types of skin cancers, malignant melanoma, squamous cell carcinoma, basal cell carcinoma, and two benign lesions, melanocytic nevus and seborrheic keratoses. In particular, the fourth order moment achieves better or similar sensitivity and specificity than many well-known and accepted optical techniques used to differentiate melanoma and seborrheic keratosis.

  1. Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.

    PubMed

    Rodrigues, Lindsey Ulkus; Rider, Leah; Nieto, Cera; Romero, Lina; Karimpour-Fard, Anis; Loda, Massimo; Lucia, M Scott; Wu, Min; Shi, Lihong; Cimic, Adela; Sirintrapun, S Joseph; Nolley, Rosalie; Pac, Colton; Chen, Haitao; Peehl, Donna M; Xu, Jianfeng; Liu, Wennuan; Costello, James C; Cramer, Scott D

    2015-03-15

    Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS(-) subtype of aggressive prostate cancer (ERG(-)MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7-shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with dual MAP3K7-CHD1 loss also displayed neuroendocrine and neural characteristics. In addition, dual Map3k7-Chd1 suppression promoted E-cadherin loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also correlated with Gleason grade and E-cadherin loss in clinical samples. To further validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7-shCHD1 LNCaP xenografts displayed increased tumor growth and decreased survival compared with shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development. PMID:25770290

  2. LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

    PubMed Central

    Michelotti, Gregory; Jiang, Xiaoyin; Sosa, Julie Ann; Diehl, Anna Mae; Henderson, Brittany Bohinc

    2015-01-01

    PURPOSE Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness. PATIENTS AND METHODS Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3–1), we report LGR5 and R-spondin (RSPO1–3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients). RESULTS Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%–72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%–97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005). CONCLUSION We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC. PMID:26416247

  3. Quality of life in non-melanoma skin cancer.

    PubMed

    Gaulin, Charles; Sebaratnam, Deshan F; Fernández-Peñas, Pablo

    2015-02-01

    Basal cell carcinoma and squamous cell carcinoma are the most common malignancies and are classified under the umbrella of non-melanoma skin cancer (NMSC). NMSC exerts a small but appreciable decrement in quality of life (QOL). The impact posed may arise from the tumour itself or as a result of treatment, and through symptoms, functional limitations, cosmetic burden and auxiliary considerations such as cost and disturbance to the activities of daily living. Researchers have evaluated this burden using a variety of outcome measures including generic, dermatology-specific and disease-specific instruments. The skin cancer index represents a promising disease-specific patient-reported outcome measure in this setting. To overcome some of the constraints inherent to disease-specific instruments, and to allow comparisons with other diseases, utility weightings have been developed. Utility weightings represent a cardinal measure for a specific health status and are established through methods such as the standard gamble, willingness-to-pay and time trade-off, and have also been employed to generate utility weightings for NMSC. Utilities are becoming increasingly important as a means of comparing health states across medicine and are of particular importance from a health-care policy perspective as they are used for resource allocation. The small but definite impact on the individual's QOL posed by NMSC should be a clinical consideration for physicians and it should be recognised by researchers as a potential outcome measure. PMID:25196191

  4. UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement.

    PubMed Central

    Nakazawa, H; English, D; Randell, P L; Nakazawa, K; Martel, N; Armstrong, B K; Yamasaki, H

    1994-01-01

    Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer. Images Fig. 2 Fig. 3 Fig. 4 PMID:8278394

  5. Circular polarization terahertz iolarization of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Martin, Jillian P.

    The use of terahertz (THz) radiation for imaging human tissue and delineating tumor margins has become an appealing topic in the biomedical field because THz radiation is non-ionizing and has the demonstrated ability to differentiate between cancerous and normal tissue without the need for exogenous contrast agents. Previously, a reflective continuous-wave (CW) THz imaging system utilizing a linear polarization-sensitive detection technique was demonstrated and used to delineate tumor margins for nonmelanoma skin cancers [1, 2] and determine reflectivity differences between normal and cancerous colon tissue [3 - 5]. This detection technique involves illuminating ex vivo tissue samples with linearly polarized light and collecting the signal remitted by the sample after passing through an analyzing wire grid polarizer oriented with its transmission axis perpendicular to the linear polarization incident on the sample. By collecting the cross-polarization signal, the strong Fresnel surface reflections from the sample holder interfaces are eliminated and predominantly signal from within the tissue volume is obtained. The aim of the proposed research is to enhance this polarization-sensitive detection technique by incorporating circular polarization illumination and detection channels. This technique has been demonstrated at optical wavelengths [6], where the scattering of light within the tissue volume has been extensively studied; however, it has yet to be implemented using THz radiation. In addition, this detection technique has the potential to demonstrate increased contrast between cancerous and normal tissue, and experimental results may shed light on the mechanism behind the observed contrast.

  6. Clinical study of imaging skin cancer margins using polarized light imaging

    NASA Astrophysics Data System (ADS)

    Samatham, Ravikant; Lee, Ken; Jacques, Steven L.

    2012-02-01

    Skin cancer is most commons type of cancer in United States that occur on sun-exposed cosmetically sensitive areas like face, neck, and forearms. Surgical excision of skin cancer is challenging as more than one-third the actual margins extend beyond the clinically determined margins. Polarized light camera (polCAM) provides images of the superficial layers of the tissue with enhanced contrast which was used to image skin cancer margins. In a NIH-funded pilot study polCAM was used to image skin cancer in patients undergoing Mohs micrographic surgery for skin cancer. Polarized light imaging utilizes the polarization properties of light to create an image of a lesion comprised only of light scattering from the superficial layers of the skin which yields a characteristic "fabric pattern" of the putative lesion and the surrounding normal tissue. In several case studies conducted with a system developed for the clinic, we have found that skin cancer disrupts this fabric pattern, allowing the doctor a new means of identifying the margins of the lesion. Data is acquired before the patient underwent surgery. The clinically determined skin cancer margins were compared with margins determined by examination of the polCAM images. The true margins were provided by the dermatophathologist on examination of the frozen sections. Our initial data suggests that the contrast due to polarization changes associated with cancerous lesions can elucidate margins that were not recognized by the surgeon under normal conditions but were later confirmed by the pathologist.

  7. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  8. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  9. Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

    PubMed

    Agresti, Roberto; Meneghini, Elisabetta; Baili, Paolo; Minicozzi, Pamela; Turco, Alberto; Cavallo, Ilaria; Funaro, Francesco; Amash, Hade; Berrino, Franco; Tagliabue, Elda; Sant, Milena

    2016-05-01

    Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53-4.24) and insulin resistance (OR 1.90, 95 % CI 1.05-3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03-4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43-6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16-3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16-5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis. PMID:27117160

  10. MUC5B Leads to Aggressive Behavior of Breast Cancer MCF7 Cells

    PubMed Central

    Valque, Hélène; Gouyer, Valérie; Gottrand, Frédéric; Desseyn, Jean-Luc

    2012-01-01

    The mucin MUC5B has a critical protective function in the normal lung, salivary glands, esophagus, and gallbladder, and has been reported to be aberrantly expressed in breast cancer, the second leading cause of cancer-related deaths among women worldwide. To understand better the implication of MUC5B in cancer pathogenesis, the luminal human breast cancer cell line MCF7 was transfected with a vector encoding a recombinant mini-mucin MUC5B and was then infected with a virus to deliver a short hairpin RNA to knock down the mini-mucin. The proliferative and invasive properties in Matrigel of MCF7 subclones and subpopulations were evaluated in vitro. A xenograft model was established by subcutaneous inoculation of MCF7 clones and subpopulations in SCID mice. Tumor growth was measured, and the tumors and metastases were assessed by histological and immunological analysis. The mini-mucin MUC5B promoted MCF7 cell proliferation and invasion in vitro. The xenograft experiments demonstrated that the mini-mucin promoted tumor growth and MCF7 cell dissemination. In conclusion, MUC5B expression is associated with aggressive behavior of MCF7 breast cancer cells. This study suggests that MUC5B may represent a good target for slowing tumor growth and metastasis. PMID:23056409

  11. Claudin-20 promotes an aggressive phenotype in human breast cancer cells

    PubMed Central

    Martin, Tracey A; Lane, Jane; Ozupek, Hulya; Jiang, Wen G

    2013-01-01

    Claudin-20 is a member of the Claudin family of transmembrane proteins located in the tight junction (TJ) of cells of epithelial origin. Due to the increasing evidence supporting the role of TJ proteins in preventing tumor cell metastatic behavior, this study sought to evaluate the distribution of Claudin-20 in human breast cancer and the effect of Claudin-20 overexpression in human breast cancer cells. Q-PCR data from breast cancer primary tumors (n = 114) and matched background tissue (n = 30) showed that high claudin-20 expression was correlated with poor survival of patients with breast cancer (p = 0.022). Following transformation of the breast cancer cell lines MDA-MB-231 and MCF7 with a Claudin-20 expression construct functional assays were performed to ascertain changes in cell behavior. Claudin-20 transformed cells showed significantly increased invasion (p < 0.005) and were significantly less adhesive than wild type cells (p < 0.05). There was no effect on growth (either in vitro or in vivo) for either cell line. Overexpression of Claudin-20 resulted in reduced transepithelial resistance (induced by the motogen HGF at 25 ng/ml, p = 0.0007). Interestingly, this was not mirrored by paracellular permeability, as overexpression of Claudin-20 caused a decrease in permeability. The introduction of Claudin-20 into human breast cancer cells resulted in breast cancer cells with an aggressive phenotype and reduced trans-epithelial resistance. There was no corresponding decrease in paracellular permeability, indicating that this Claudin has a differential function in epithelial TJ. This provides further insight into the importance of correctly functioning TJ in preventing the progression of human breast cancer. PMID:24665404

  12. Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells.

    PubMed

    Sponziello, Marialuisa; Rosignolo, Francesca; Celano, Marilena; Maggisano, Valentina; Pecce, Valeria; De Rose, Roberta Francesca; Lombardo, Giovanni Enrico; Durante, Cosimo; Filetti, Sebastiano; Damante, Giuseppe; Russo, Diego; Bulotta, Stefania

    2016-08-15

    In this study we analyzed the expression levels of markers of epithelial-to-mesenchymal transition (EMT) in several papillary thyroid carcinomas (PTCs) and the relation with tumor genotypes and clinicopathological characteristics. The role of fibronectin-1 (FN1) was investigated by analyzing the effects of FN1 silencing in two human thyroid cancer cell lines. Most of EMT markers were significantly over-expressed in a group of 36 PTCs. In particular, FN1 mRNA levels were higher in tumor vs non-tumor tissue (117.3, p < 0.001) and also in aggressive and BRAF(V600E) samples. Similar results were observed (and confirmed at the protein level) when FN1 expression was analyzed in a validation group of 50 PTCs and six lymph node (LN) metastases. Silencing of FN1 in TPC-1 and BCPAP thyroid cancer cells significantly reduced proliferation, adhesion, migration, and invasion in both cell lines. Collectively, our data indicate that FN1 overexpression is an important determinant of thyroid cancer aggressiveness. PMID:27173027

  13. ERK1/2 regulation of CD44 modulates oral cancer aggressiveness

    PubMed Central

    Judd, Nancy P.; Winkler, Ashley E.; Murillo-Sauca, Oihana; Brotman, Joshua J.; Law, Jonathan H.; Lewis, James S.; Dunn, Gavin P.; Bui, Jack D.; Sunwoo, John B.; Uppaluri, Ravindra

    2011-01-01

    Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from DMBA-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. While several lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with EMT and putative cancer stem cells. MEK inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof of concept to target this pathway as a strategy to treat head and neck cancer. PMID:22086849

  14. Mitochondrial oncobioenergetic index: A potential biomarker to predict progression from indolent to aggressive prostate cancer

    PubMed Central

    Vayalil, Praveen K.; Landar, Aimee

    2015-01-01

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease. PMID:26515588

  15. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-02-01

    Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  16. Neglected skin cancer in the elderly: a case of basosquamous cell carcinoma of the right shoulder.

    PubMed

    Bisgaard, Erika; Tarakji, Michael; Lau, Frank; Riker, Adam

    2016-01-01

    Skin cancer remains the most common cancer worldwide, and basal cell carcinoma represents the largest portion of non-melanomatous skin cancers with over 3 million cases diagnosed annually. Locally advanced disease is frequently seen in the elderly posing clinical challenges regarding proper treatment.We report on an 86-year-old female presenting with fatigue, anemia and a large ulcerated skin lesion along the right upper back. A biopsy of the lesion revealed a basosquamous cell carcinoma. She underwent a wide local excision with complex wound reconstruction.Neglected skin cancers in the elderly can present difficult clinical scenarios. There are associated adjuvant therapies that should be considered following resection, such as local radiation therapy and other novel therapies. Newer therapies, such as with vismodegib, may also be considered. A comprehensive, multimodal approach to treatment should be considered in most cases of locally advanced, non-melanoma skin cancers. PMID:27534889

  17. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

    PubMed Central

    Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C.; Marcucci, Guido; Byrd, John C.; Volinia, Stefano; Shapiro, Charles L.; Freitas, Michael A.

    2013-01-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  18. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model

    PubMed Central

    Zhou, Kejin; Nguyen, Liem H.; Miller, Jason B.; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T.; Siegwart, Daniel J.

    2016-01-01

    RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 < 0.02 mg/kg siRNA against FVII (siFVII)] in dose–response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors (>75 mg/kg dendrimer repeated dosing). Delivery of let-7g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer’s own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs. PMID:26729861

  19. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.

    PubMed

    Pichiorri, Flavia; Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C; Marcucci, Guido; Byrd, John C; Volinia, Stefano; Shapiro, Charles L; Freitas, Michael A; Croce, Carlo M

    2013-05-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  20. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model.

    PubMed

    Zhou, Kejin; Nguyen, Liem H; Miller, Jason B; Yan, Yunfeng; Kos, Petra; Xiong, Hu; Li, Lin; Hao, Jing; Minnig, Jonathan T; Zhu, Hao; Siegwart, Daniel J

    2016-01-19

    RNA-based cancer therapies are hindered by the lack of delivery vehicles that avoid cancer-induced organ dysfunction, which exacerbates carrier toxicity. We address this issue by reporting modular degradable dendrimers that achieve the required combination of high potency to tumors and low hepatotoxicity to provide a pronounced survival benefit in an aggressive genetic cancer model. More than 1,500 dendrimers were synthesized using sequential, orthogonal reactions where ester degradability was systematically integrated with chemically diversified cores, peripheries, and generations. A lead dendrimer, 5A2-SC8, provided a broad therapeutic window: identified as potent [EC50 < 0.02 mg/kg siRNA against FVII (siFVII)] in dose-response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors (>75 mg/kg dendrimer repeated dosing). Delivery of let-7 g microRNA (miRNA) mimic inhibited tumor growth and dramatically extended survival. Efficacy stemmed from a combination of a small RNA with the dendrimer's own negligible toxicity, therefore illuminating an underappreciated complication in treating cancer with RNA-based drugs. PMID:26729861

  1. Involvement of activation-induced cytidine deaminase in skin cancer development

    PubMed Central

    Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro

    2016-01-01

    Most skin cancers develop as the result of UV light–induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus–dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics. PMID:26974156

  2. Non-melanoma skin cancer in Portuguese kidney transplant recipients - incidence and risk factors*

    PubMed Central

    Pinho, André; Gouveia, Miguel; Cardoso, José Carlos; Xavier, Maria Manuel; Vieira, Ricardo; Alves, Rui

    2016-01-01

    Background Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. Objectives To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Methods Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. Results We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Conclusion Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies. PMID:27579740

  3. ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer.

    PubMed

    Zhang, Feng; Zhang, Xutao; Meng, Jin; Zhao, Yong; Liu, Xinli; Liu, Yanxia; Wang, Yukun; Li, Yuhua; Sun, Yang; Wang, Zhipeng; Mei, Qibing; Zhang, Tao

    2015-06-30

    The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis. PMID:25938545

  4. ING5 inhibits cancer aggressiveness via preventing EMT and is a potential prognostic biomarker for lung cancer

    PubMed Central

    Zhao, Yong; Liu, Xinli; Liu, Yanxia; Wang, Yukun; Li, Yuhua; Sun, Yang; Wang, Zhipeng; Mei, Qibing; Zhang, Tao

    2015-01-01

    The proteins of the Inhibitor of Growth (ING) candidate tumor suppressor family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is the new member of the family whose actual role in tumor suppression is not known. Here we show that ING5 overexpression in lung cancer A549 cells inhibited cell proliferation and invasiveness, while ING5 knockdown in lung cancer H1299 cells promoted cell aggressiveness. ING5 overexpression also abrogated tumor growth and invasive abilities of lung cancer cells in mouse xenograft models. Further study showed that ING5 overexpression inhibited EMT indicated by increase of E-cadherin and decrease of N-cadherin, Snail and slug at mRNA and protein levels, which was accompanied with morphological changes. cDNA microarray and subsequent qRT-PCR validation revealed that ING5 significantly downregulated expression of EMT (epithelial to mesenchymal transition)-inducing genes including CEACAM6, BMP2 and CDH11. Clinical study by tissue microarray showed that nuclear ING5 negatively correlated with clinical stages and lymph node metastasis of lung cancer. Furthermore, high level of nuclear ING5 was associated with a better prognosis. Taken together, these findings uncover an important role for ING5 as a potent tumor suppressor in lung cancer growth and metastasis. PMID:25938545

  5. UV-induced skin cancer in a hairless mouse model.

    PubMed

    de Gruijl, F R; Forbes, P D

    1995-07-01

    Ultraviolet (UV) radiation is a very common carcinogen in our environment, but epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very restricted. In hairless mice the process of UV carcinogenesis can be studied in depth. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In combination with epidemiological data, these experimental results can be transposed to humans. Comparative studies on molecular, cellular and physiological changes in mouse and man can further our fundamental understanding of UV carcinogenesis in man. This is likely to improve risk assessments such as those related to stratospheric ozone depletion, and to yield well-targeted intervention schemes, e.g. prescribing a specific drug or diet, for high-risk individuals. PMID:7646487

  6. Mohs micrographic surgery for the management of nonmelanoma skin cancers.

    PubMed

    Cumberland, Lara; Dana, Ali; Liegeois, Nanette

    2009-08-01

    Many treatment modalities have been described to address the growing epidemic of nonmelanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is a surgical technique that allows complete and precise microscopic margin analysis by using horizontal frozen sections. The purpose of MMS is twofold: to ensure definitive excision and to minimize loss of normal surrounding tissue. MMS offers the advantages of superior cure rates and, because tissue removal is minimized, excellent cosmetic outcomes. Therefore, MMS has become the treatment of choice for many high-risk tumors. Because this technique is labor intensive, MMS is not indicated in certain situations. Understanding the indications, advantages, and disadvantages of MMS remains paramount for facial plastic surgeons managing NMSC. PMID:19698914

  7. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  8. Behavioral community intervention to reduce the risk of skin cancer.

    PubMed

    Lombard, D; Neubauer, T E; Canfield, D; Winett, R A

    1991-01-01

    Peer leader modeling, posted feedback, posted goals, and a commitment raffle were used at two swimming pools to increase behaviors associated with skin cancer prevention. During the intervention condition, pool lifeguards modeled the protective behaviors by wearing sunglasses, t-shirts, and hats, using zinc oxide and sunscreen, and staying in the shade. Children and adolescents (1 to 16 years old) increased their use of two or more protective behaviors from a baseline mean of 6.5% to 26.9% during the intervention. Adults (older than 16 years) increased their protective behaviors from a baseline mean of 22% to 37.95% during the intervention. The lifeguards increased their use of all the protective behaviors from a baseline mean of 16.7% to 63.5% during intervention. Ways to improve and expand this intervention are discussed. PMID:1797771

  9. Development magnet for portable MRI device: Investigate skin cancer

    NASA Astrophysics Data System (ADS)

    Dogan, Nurcan

    2013-03-01

    Nuclear magnetic resonance (NMR) is well known from diagnostic medical imaging and analytical chemical spectroscopy. The sample is brought into the laboratory to be investigated with radio-waves inside stationary magnets. This paper describes a new approach useful to reduce the gradient strength of the magnetic field. Despite of the recent progress in magnet design, homogeneity of permenant magnet is still very limited. Fortunately for medical applications usually there is need in high-field homogeneity to obtain the high-resolution spectra that provide the detailed chemical shift and coupling-constant. In this work we discuss various permanent magnet design-without cooling system- for magnetic imaging. The magnet used for the present application consists of two units. The main unit is built from static magnet blocks and generates the main magnetic field. The second one is the shim unit. It consists of smaller movable magnets used to correct in a controlled manner the magnetic field generated by the main unit. By combining the two units, magnetic fields with defined spatial dependence can be generated with high accuracy. The performance of the magnet in terms of resolution and sensitivity is first evaluated and compared with conventional other magnets of higher gradient strength using phantoms of known geometry and relaxation times. After integration of magnet with spectrometer, Our new system is used to profile the structures of healty and unhealthy (cancer) human skins in vivo. To understand the contrast between the different skin type, the distribution of relaxation times T1 is spatially investigated.

  10. Aspirin for the primary prevention of skin cancer: A meta-analysis

    PubMed Central

    ZHU, YUN; CHENG, YANG; LUO, RONG-CHENG; LI, AI-MIN

    2015-01-01

    Skin cancer is one of the most common cancers worldwide. There are three major skin cancer types: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. General risk factors for skin cancer include fair skin, a history of tanning and sunburn, family history of skin cancer, exposure to ultraviolet rays and a large number of moles. The incidence of skin cancer has increased in the USA in recent years. Aspirin intake is associated with chemoprotection against the development of a number of types of cancer. However, whether aspirin intake can reduce the risk of development of skin cancer is unclear. The present meta-analysis of available human studies is aimed at evaluating the association between aspirin exposure and the risk of skin cancer. All available human observational studies on aspirin intake for the primary prevention of skin cancer were identified by searching MEDLINE (Pubmed), BIOSIS, EMBASE, Cochrane Library and China National Knowledge Infrastructure prior to March 2013. The heterogeneity and publication bias of all studies were evaluated using Cochran’s Q and I2 statistics, followed by a random-effect model where applicable. The pooled data were analyzed by odds ratios (ORs) and 95% confidence intervals (CIs). A total of eight case-control and five prospective cohort studies from 11 publications were selected for this analysis. There was no evidence of publication bias in these studies. Statistical analyses of the pooled data demonstrated that that a daily dose of 50–400 mg aspirin was significantly associated with a reduced risk of skin cancers (OR, 0.94; 95% CI, 0.90–0.99; P=0.02). Stratification analysis indicated that the continual intake of low dose aspirin (≤150 mg) reduced the risk of developing skin cancer (OR, 0.95; CI, 0.90–0.99; P=0.15) and that aspirin intake was significantly associated with a reduced risk of non-melanoma skin cancers (OR, 0.97; CI, 0.95–0.99; P=0.22). Overall, these findings indicated that aspirin

  11. Optical imaging modalities: From design to diagnosis of skin cancer

    NASA Astrophysics Data System (ADS)

    Korde, Vrushali Raj

    This study investigates three high resolution optical imaging modalities to better detect and diagnose skin cancer. The ideal high resolution optical imaging system can visualize pre-malignant tissue growth non-invasively with resolution comparable to histology. I examined 3 modalities which approached this goal. The first method examined was high magnification microscopy of thin stained tissue sections, together with a statistical analysis of nuclear chromatin patterns termed Karyometry. This method has subcellular resolution, but it necessitates taking a biopsy at the desired tissue site and imaging the tissue ex-vivo. My part of this study was to develop an automated nuclear segmentation algorithm to segment cell nuclei in skin histology images for karyometric analysis. The results of this algorithm were compared to hand segmented cell nuclei in the same images, and it was concluded that the automated segmentations can be used for karyometric analysis. The second optical imaging modality I investigated was Optical Coherence Tomography (OCT). OCT is analogous to ultrasound, in which sound waves are delivered into the body and the echo time and reflected signal magnitude are measured. Due to the fast speed of light and detector temporal integration times, low coherence interferometry is needed to gate the backscattered light. OCT acquires cross sectional images, and has an axial resolution of 1-15 mum (depending on the source bandwidth) and a lateral resolution of 10-20 mum (depending on the sample arm optics). While it is not capable of achieving subcellular resolution, it is a non-invasive imaging modality. OCT was used in this study to evaluate skin along a continuum from normal to sun damaged to precancer. I developed algorithms to detect statistically significant differences between images of sun protected and sun damaged skin, as well as between undiseased and precancerous skin. An Optical Coherence Microscopy (OCM) endoscope was developed in the third

  12. The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview.

    PubMed

    Treglia, Giorgio; Annunziata, Salvatore; Muoio, Barbara; Salvatori, Massimo; Ceriani, Luca; Giovanella, Luca

    2013-01-01

    Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis. PMID:23653645

  13. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    PubMed Central

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R.; Wiklund, Fredrik; Berndt, Sonja I.; Benlloch, Sara; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Hunter, David J.; Henderson, Brian E.; Thun, Michael J.; Gaziano, Michael; Giovannucci, Edward L.; Siddiq, Afshan; Travis, Ruth C.; Cox, David G.; Canzian, Federico; Riboli, Elio; Key, Timothy J.; Andriole, Gerald; Albanes, Demetrius; Hayes, Richard B.; Schleutker, Johanna; Auvinen, Anssi; Tammela, Teuvo L.J.; Weischer, Maren; Stanford, Janet L.; Ostrander, Elaine A.; Cybulski, Cezary; Lubinski, Jan; Thibodeau, Stephen N.; Schaid, Daniel J.; Sorensen, Karina D.; Batra, Jyotsna; Clements, Judith A.; Chambers, Suzanne; Aitken, Joanne; Gardiner, Robert A.; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Brenner, Hermann; Habuchi, Tomonori; Ingles, Sue; John, Esther M.; Dickinson, Joanne L.; Cannon-Albright, Lisa; Teixeira, Manuel R.; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Park, Jong Y.; Cooney, Kathleen A.; Muir, Kenneth R.; Leongamornlert, Daniel A.; Saunders, Edward; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; Govindasami, Koveela; O'Brien, Lynne T.; Wilkinson, Rosemary A.; Hall, Amanda L.; Sawyer, Emma J.; Dadaev, Tokhir; Morrison, Jonathan; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin S.; Lophatonanon, Artitaya; Southey, Melissa C.; Hopper, John L.; English, Dallas; Virtamo, Jarmo; Le Marchand, Loic; Campa, Daniele; Kaaks, Rudolf; Lindstrom, Sara; Diver, W. Ryan; Gapstur, Susan; Yeager, Meredith; Cox, Angela; Stern, Mariana C.; Corral, Roman; Aly, Markus; Isaacs, William; Adolfsson, Jan; Xu, Jianfeng; Zheng, S. Lilly; Wahlfors, Tiina; Taari, Kimmo; Kujala, Paula; Klarskov, Peter; Nordestgaard, Børge G.; Røder, M. Andreas; Frikke-Schmidt, Ruth; Bojesen, Stig E.; FitzGerald, Liesel M.; Kolb, Suzanne; Kwon, Erika M.; Karyadi, Danielle M.; Orntoft, Torben Falck; Borre, Michael; Rinckleb, Antje; Luedeke, Manuel; Herkommer, Kathleen; Meyer, Andreas; Serth, Jürgen; Marthick, James R.; Patterson, Briony; Wokolorczyk, Dominika; Spurdle, Amanda; Lose, Felicity; McDonnell, Shannon K.; Joshi, Amit D.; Shahabi, Ahva; Pinto, Pedro; Santos, Joana; Ray, Ana; Sellers, Thomas A.; Lin, Hui-Yi; Stephenson, Robert A.; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Tsuchiya, Norihiko; Narita, Shintaro; Cao, Guang-Wen; Slavov, Chavdar; Mitev, Vanio; Chanock, Stephen; Gronberg, Henrik; Haiman, Christopher A.; Kraft, Peter; Easton, Douglas F.; Eeles, Rosalind A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03–1.21), P = 1.4 × 10−8]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis. PMID:23065704

  14. Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea.

    PubMed

    Linden, Kenneth G; Carpenter, Philip M; McLaren, Christine E; Barr, Ronald J; Hite, Pamela; Sun, Joannie D; Li, Kou-Tung; Viner, Jaye L; Meyskens, Frank L

    2003-01-01

    Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed. PMID:12903852

  15. Diagnosis of skin cancer by correlation and complexity analyses of damaged DNA.

    PubMed

    Namazi, Hamidreza; Kulish, Vladimir V; Delaviz, Fatemeh; Delaviz, Ali

    2015-12-15

    Skin cancer is a common, low-grade cancerous (malignant) growth of the skin. It starts from cells that begin as normal skin cells and transform into those with the potential to reproduce in an out-of-control manner. Cancer develops when DNA, the molecule found in cells that encodes genetic information, becomes damaged and the body cannot repair the damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to diagnose the skin cancer, first DNA walk plots of genomes of patients with skin cancer were generated. Then, the data so obtained was checked for complexity by computing the fractal dimension. Furthermore, the Hurst exponent has been employed in order to study the correlation of damaged DNA. By analysing different samples it has been found that the damaged DNA sequences are exhibiting higher degree of complexity and less correlation compared to normal DNA sequences. This investigation confirms that this method can be used for diagnosis of skin cancer. The method discussed in this research is useful not only for diagnosis of skin cancer but can be applied for diagnosis and growth analysis of different types of cancers. PMID:26497203

  16. Diagnosis of skin cancer by correlation and complexity analyses of damaged DNA

    PubMed Central

    Namazi, Hamidreza; Kulish, Vladimir V.; Delaviz, Fatemeh; Delaviz, Ali

    2015-01-01

    Skin cancer is a common, low-grade cancerous (malignant) growth of the skin. It starts from cells that begin as normal skin cells and transform into those with the potential to reproduce in an out-of-control manner. Cancer develops when DNA, the molecule found in cells that encodes genetic information, becomes damaged and the body cannot repair the damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to diagnose the skin cancer, first DNA walk plots of genomes of patients with skin cancer were generated. Then, the data so obtained was checked for complexity by computing the fractal dimension. Furthermore, the Hurst exponent has been employed in order to study the correlation of damaged DNA. By analysing different samples it has been found that the damaged DNA sequences are exhibiting higher degree of complexity and less correlation compared to normal DNA sequences. This investigation confirms that this method can be used for diagnosis of skin cancer. The method discussed in this research is useful not only for diagnosis of skin cancer but can be applied for diagnosis and growth analysis of different types of cancers. PMID:26497203

  17. Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers

    PubMed Central

    Veeraraghavan, Jamunarani; Tan, Ying; Cao, Xi-Xi; Kim, Jin-Ah; Wang, Xian; Chamness, Gary C.; Maiti, Sourindra N.; Cooper, Laurence J. N.; Edwards, Dean P.; Contreras, Alejandro; Hilsenbeck, Susan G.; Chang, Eric C.; Schiff, Rachel; Wang, Xiao-Song

    2014-01-01

    Characterizing the genetic alterations leading to the more aggressive forms of estrogen receptor positive (ER+) breast cancers are of critical significance in breast cancer management. Here we identify recurrent rearrangements between estrogen receptor gene ESR1 and its neighbor CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal-B tumors, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170 positive tumors. These fusions encode N-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity, and enhanced xenograft tumor formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signaling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer. PMID:25099679

  18. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    PubMed

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology. PMID:22294438

  19. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    PubMed

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  20. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer

    PubMed Central

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385–0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  1. Genomic analysis to define molecular basis of aggressiveness in a mouse model of oral cancer

    PubMed Central

    Chalivendra, Varun; Kanchi, Krishna Latha; Onken, Michael D.; Winkler, Ashley E.; Mardis, Elaine; Uppaluri, Ravindra

    2014-01-01

    To investigate the molecular basis underlying aggressive behavior in oral squamous cell carcinoma (OSCC), our laboratory developed a carcinogen-induced mouse oral cancer (MOC) cell line model that encompasses the growth and metastasis spectrum of its human counterpart. We performed next-generation sequencing (NGS) and gene expression microarray profiles to explore the genomic and transcriptional backgrounds of the differential MOC line phenotypes, as well as, the cross-species relevance of the model. Here we describe the comparative analysis of NGS (www.ncbi.nlm.nih.gov/biosample?LinkName=bioproject_biosample_all&from_uid=247825) and expression microarray (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50041) data from the MOC lines and corresponding human data, as described in our recent publication [1]. PMID:25729643

  2. Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate Induces Canine Mammary Cancer Cell Aggressiveness

    PubMed Central

    de Oliveira, Joana T.; Santos, Ana L.; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J.; Vasconcelos, M. Helena; Oliveira, Maria José; Reis, Celso A.; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  3. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    PubMed

    de Oliveira, Joana T; Santos, Ana L; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J; Vasconcelos, M Helena; Oliveira, Maria José; Reis, Celso A; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  4. Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.

    PubMed

    Marsh, Timothy; Wong, Irene; Sceneay, Jaclyn; Barakat, Amey; Qin, Yuanbo; Sjödin, Andreas; Alspach, Elise; Nilsson, Björn; Stewart, Sheila A; McAllister, Sandra S

    2016-05-15

    Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow-derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932-43. ©2016 AACR. PMID:27197230

  5. Regorafenib inhibits growth, angiogenesis, and metastasis in a highly aggressive, orthotopic colon cancer model.

    PubMed

    Abou-Elkacem, Lotfi; Arns, Susanne; Brix, Gunnar; Gremse, Felix; Zopf, Dieter; Kiessling, Fabian; Lederle, Wiltrud

    2013-07-01

    The combination of target-specific drugs like bevacizumab with chemotherapeutics has improved treatment efficacy in advanced colorectal cancer (CRC). However, the clinical prognosis of metastatic CRCs is still poor, and novel drugs are currently assessed with respect to their efficacies in patients with CRCs. In a phase III study, the multikinase inhibitor regorafenib (BAY 73-4506) has recently been shown to prolong survival of patients with CRCs after standard therapies failed. In the present study, the activity of regorafenib was investigated in comparison with the angiogenesis inhibitor DC101 in the highly aggressive, murine CT26 metastatic colon cancer model. While a treatment for 10 days with DC101 given at a dose of 34 mg/kg every third day significantly delayed tumor growth compared with vehicle-treated animals, regorafenib completely suppressed tumor growth at a daily oral dose of 30 mg/kg. Regorafenib also induced a stronger reduction in tumor vascularization, as longitudinally assessed in vivo by dynamic contrast-enhanced MRI (DCE-MRI) and confirmed by immunohistochemistry. In addition, regorafenib inhibited the angiogenic activity more strongly and induced a three times higher apoptosis rate than DC101. Even more important, regorafenib completely prevented the formation of liver metastases, whereas in DC101-treated animals, the metastatic rate was only reduced by 33% compared with the vehicle group. In addition, regorafenib significantly reduced the amount of infiltrating macrophages. These data show that the multikinase inhibitor regorafenib exerts strong antiangiogenic, antitumorigenic, and even antimetastatic effects on highly aggressive colon carcinomas indicative for its high potential in the treatment of advanced CRCs. PMID:23619301

  6. Adolescent cancer survivors’ smoking intentions are associated with aggression, attention, and smoking history

    PubMed Central

    Tyc, Vida L.; Wilson, Stephanie J.; Nelms, Jenna; Hudson, Melissa M.; Wu, Shengjie; Xiong, Xiaoping; Hinds, Pamela S.

    2011-01-01

    Introduction The present study examines behavioral and psychosocial factors associated with smoking intentions and experimentation among adolescent survivors of pediatric cancer. Methods Adolescent survivors of brain tumor and acute lymphoblastic leukemia (n=99) provided information about their smoking histories and their intentions to smoke in the future. Behavior rating scales were completed by survivors, parents, and teachers. Results Past experimentation with smoking and higher levels of self-reported aggression were associated with intentions to smoke in the future (OR=4.18, 95%CI 1.02–17.04, and OR=1.08, 95% CI 1.01–1.15, respectively), while teacher-ratings of inattention in the classroom were negatively associated with intentions to smoke (OR=0.94, 95% CI.88–.99), all p<.05. Experimentation with smoking was more likely among older survivors (OR=1.76, 95% CI 1.16–2.66, p<.01) and those whose parents had divorced (OR=4.40, 95% CI 1.21–16.06, p<.05). Discussion A concerning minority of adolescent survivors have clear intentions to smoke, a behavior that adds to their overall health risk. Smoking intentions and experimentation are important precursors to regular smoking. Prevention efforts are needed to interrupt the progression from intentions and experimentation to established smoking and nicotine dependence in this medically vulnerable population. Implications for cancer survivors Assessment of an adolescent’s history of parental divorce, past experimentation with smoking, and aggressive behavior will identify those survivors who are likely to consider smoking in the future. Screening for these characteristics will allow clinicians to be more vigilant in health promotion. PMID:20922493

  7. Development of the Facial Skin Care Index: A Health-Related Outcomes Index for Skin Cancer Patients

    PubMed Central

    Matthews, B. Alex; Rhee, John S.; Neuburg, Marcy; Burzynski, Mary L.; Nattinger, Ann B.

    2006-01-01

    BACKGROUND Existing health-related quality-of-life (HRQOL) tools do not appear to capture patients' specific skin cancer concerns. OBJECTIVE To describe the conceptual foundation, item generation, reduction process, and reliability testing for the Facial Skin Cancer Index (FSCI), a HRQOL outcomes tool for skin cancer researchers and clinicians. METHODS Participants in Phases I to III consisted of adult patients (N = 134) diagnosed with biopsy-proven nonmelanoma cervicofacial skin cancer. Data were collected via self-report surveys and clinical records. RESULTS Seventy-one distinct items were generated in Phase I and rated for their importance by an independent sample during Phase II; 36 items representing six theoretical HRQOL domains were retained. Test–retest I results indicated that four subscales showed adequate reliability coefficients (α = 0.60 to 0.91). Twenty-six items remained for test–retest II. Results indicated excellent internal consistency for emotional, social, appearance, and modified financial/work subscales (range 0.79 to 0.95); test–retest correlation coefficients were consistent across time (range 0.81 to 0.97; lifestyle omitted). CONCLUSION Pretesting afforded the opportunity to select items that optimally met our a priori conceptual and psychometric criteria for high data quality. Phase IV testing (validity and sensitivity before surgery and 4 months after Mohs micrographic surgery) for the 20-item FSCI is under way. PMID:16875475

  8. Glycoprotein Biomarkers for the Early Detection of Aggressive Prostate Cancer — EDRN Public Portal

    Cancer.gov

    The Early Detection Research Network of the NCI is charged with the discovery, development and validation of biomarkers for early detection and prognosis related to neoplastic disease. Our laboratory is an NCI EDRN (U01CA152813) working on "Glycoprotein biomarkers for the early detection of aggressive prostate cancer". This EDRN administratiVE! supplement is a collaboration with Robert Veltri on his project to identify men with very low risk (indolent) prostate cancer (CaP) at the diagnostic biopsy at selection for active surveillance (AS). We will assess biopsy tissue using quantitative nuclear histomorphometric measurements and molecular biomarkers to predict an unexpected catastrophic CaP in such men with indolent CaP. At Johns Hopkins Hospital w1e use the Epstein criteria that includes; PSA density (PSAD) <0.15 ng/mVcm3, Gleason score SS, S2 cons involved with cancer, and ::;;SO% of any core involved with cancer to select AS. Our approach will study 140 AS men (70 with a expected outcome and 70 with a disastrous outcome) using nuclear histomorphometry and pre-qualified biomarkers quantified by digital microscopy. Previously, our laboratory combined measurements of DNA content and (-2)pPSA in the serum and (-5,-?)pPSA in biopsy tissue to identify 7/10 men that would fail surveillance based on the primary diagnostic biopsy. We now will devHiop a clinical, morphological and biomarker 'signature' for identifying severe aggressive disease from a AS diagnostic biopsy. Our approach will combine nuclear morphometry measured by digital microscopy with a unique biopsy tissue biomarker profile (DNA content, Ki67, Her2neu, CACND1 and periostin). Fc•r the molecular targets we will us•e a multiplex tissue blot (MTB) immunohistochemistry method. The Aims o'f our work include 1) to utilize retrospective archival biopsy material from 70 AS cases where the outcome was unexpected and disastrous and collect an equal number of AS cases (n=140) and perform assays for morphology

  9. DNMT3B7 Expression Promotes Tumor Progression to a More Aggressive Phenotype in Breast Cancer Cells

    PubMed Central

    Brambert, Patrick R.; Kelpsch, Daniel J.; Hameed, Rabia; Desai, Charmi V.; Calafiore, Gianfranco; Godley, Lucy A.; Raimondi, Stacey L.

    2015-01-01

    Epigenetic changes, such as DNA methylation, have been shown to promote breast cancer progression. However, the mechanism by which cancer cells acquire and maintain abnormal DNA methylation is not well understood. We have previously identified an aberrant splice form of a DNA methyltransferase, DNMT3B7, expressed in virtually all cancer cell lines but at very low levels in normal cells. Furthermore, aggressive MDA-MB-231 breast cancer cells have been shown to express increased levels of DNMT3B7 compared to poorly invasive MCF-7 cells, indicating that DNMT3B7 may have a role in promoting a more invasive phenotype. Using data gathered from The Cancer Genome Atlas, we show that DNMT3B7 expression is increased in breast cancer patient tissues compared to normal tissue. To determine the mechanism by which DNMT3B7 was functioning in breast cancer cells, two poorly invasive breast cancer cell lines, MCF-7 and T-47D, were stably transfected with a DNMT3B7 expression construct. Expression of DNMT3B7 led to hypermethylation and down-regulation of E-cadherin, altered localization of β-catenin, as well as increased adhesion turnover, cell proliferation, and anchorage-independent growth. The novel results presented in this study suggest a role for DNMT3B7 in the progression of breast cancer to a more aggressive state and the potential for future development of novel therapeutics. PMID:25607950

  10. Family Perspectives on Aggressive Cancer Care Near the End of Life

    PubMed Central

    Wright, Alexi A.; Keating, Nancy L.; Ayanian, John Z.; Chrischilles, Elizabeth A.; Kahn, Katherine L.; Ritchie, Christine S.; Weeks, Jane C.; Earle, Craig C.; Landrum, Mary Beth

    2016-01-01

    Importance Patients with advanced-stage cancer are receiving increasingly aggressive medical care near death, despite growing concerns that this reflects poor quality care. Objective Assess the association of aggressive EOL care with bereaved family members’ perceptions of the quality of EOL care and patients’ goal attainment. Design, Setting, Participants We surveyed 1,146 family members (median [IQR] days after death, 144.5, [IQR 85.0-551.0]) of elderly Medicare patients with advanced-stage lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance study (a multi-regional, prospective, observational study) who died by 2011. Exposures Claims-based quality measures of aggressive EOL care (i.e., ICU admission or repeated hospitalizations or emergency department visits during the last month of life; chemotherapy ≤2 weeks of death; no hospice or ≤3 days of services; and deaths in hospital). Main Outcomes and Measures Family reported “excellent” quality of EOL care. Secondary outcomes included: patient goal attainment (EOL care congruent with patients’ wishes and death in preferred place). Results Of 1,146 cancer patients (median [IQR] age, 76.0 [65.0-87.0] years, 55.8% male), bereaved family members reported excellent EOL care quality for 51.3%. Family of patients who enrolled in hospice >3 days before death reported excellent EOL care quality more often than those receiving no or ≤3 days [58.8% (352/599) vs. 43.1% (236/547); adjusted difference=16.5 percentage points; 95% CI=10.7 to 22.4]. In contrast, family of patients admitted to an ICU ≤30 days before death or who died in the hospital less often reported excellent EOL care quality than those who were not [45.0% (68/151) vs. 52.3% (520/995); adjusted difference=-9.4 percentage points; 95% CI -18.2 to -0.6; and 42.2% (194/460) vs. 57.4% (394/686); adjusted difference=-17.0 percentage points; 95% CI=-22.9 to -11.1, respectively]. Family of patients receiving ≤3 days of

  11. Role of UV light in photodamage, skin aging, and skin cancer: importance of photoprotection.

    PubMed

    Gonzaga, Evelyn R

    2009-01-01

    Solar, and particularly UV, radiation causes molecular and cellular damage with resultant histopathologic and clinical degenerative changes, leading in turn to photosensitivity, photo-aging, and skin cancer. While our bodies have some natural UV defenses, additional protection from the sun is essential, including sun avoidance, physical protection, and sunscreen use. Sun avoidance includes limiting exposure during peak UV times (10am-4pm), avoiding UV-reflective surfaces such as sand, snow and water, and eliminating photosensitizing drugs. Physical protection includes wearing photoprotective clothing such as a broad-brimmed hat and long sleeves and use of UV-blocking films on windows. Sunscreen containing avobenzone, titanium dioxide, zinc oxide or encamsule should be used daily and frequently reapplied. To guard against the UVB spectrum, zinc oxide and titanium dioxide are particularly recommended. Sunscreen is generally under-applied at only 25% of the recommended dose, seriously compromising photoprotection. Dosage guidelines recommend using more than half a teaspoon each on head and neck area and each arm, and more than a teaspoon each on anterior torso, posterior torso, and each leg (approximately 2 mg/cm(2)). PMID:19209950

  12. Insect antimicrobial peptides: potential tools for the prevention of skin cancer.

    PubMed

    Tonk, Miray; Vilcinskas, Andreas; Rahnamaeian, Mohammad

    2016-09-01

    Antimicrobial peptides/proteins (AMPs) are biologically active molecules with diverse structural properties that are produced by mammals, plants, insects, ticks, and microorganisms. They have a range of antibacterial, antifungal, antiviral, and even anticancer activities, and their biological properties could therefore be exploited for therapeutic and prophylactic applications. Cancer and cancer drug resistance are significant current health challenges, so the development of innovative cancer drugs with minimal toxicity toward normal cells and novel modes of action that can evade resistance may provide a new direction for anticancer therapy. The skin is the first line of defense against heat, sunlight, injury, and infection, and skin cancer is thus the most common type of cancer. The skin that has been exposed to sunlight is particularly susceptible, but lesions can occur anywhere on the body. Skin cancer awareness and self-efficacy are necessary to improve sun protection behavior, but more effective preventative approaches are also required. AMPs may offer a new prophylactic approach against skin cancer. In this mini review, we draw attention to the potential use of insect AMPs for the prevention and treatment of skin cancer. PMID:27418360

  13. Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells.

    PubMed

    Xu, Mei; Wang, Siying; Qi, Yuanlin; Chen, Li; Frank, Jacqueline A; Yang, Xiuwei H; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-05-01

    Epidemiological studies demonstrate that alcohol consumption is associated with an increased risk of colorectal cancer (CRC). In addition to promoting carcinogenesis, alcohol may also accelerate the progression of existing CRC. We hypothesized that alcohol may enhance the aggressiveness of CRC. In this study, we investigated the effect of alcohol on the migration/invasion and metastasis of CRC. Alcohol increased the migration/invasion of colorectal cancer cells (DLD1, HCT116, HT29, and SW480) in a concentration-dependent manner. Among these colon cancer cell lines, HCT116 cells were most responsive while HT29 cells were the least responsive to ethanol-stimulated cell migration/invasion. These in vitro results were supported by animal studies which demonstrated that ethanol enhanced the metastasis of colorectal cancer cells to the liver and lung. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in regulating tumor microenvironment and metastasis. Alcohol increased the expression of MCP-1 and its receptor CCR2 at both protein and mRNA levels. The pattern of alcohol-induced alterations in MCP-1 expression was consistent with its effect on migration/invasion; HCT116 cells displayed the highest up-regulation of MCP-1/CCR2 in response to alcohol exposure. An antagonist of CCR2 blocked alcohol-stimulated migration. Alcohol caused an initial cytosolic accumulation of β-catenin and its subsequent nuclear translocation by inhibiting GSK3β activity. Alcohol stimulated the activity of MCP-1 gene promoter in a β-catenin-dependent manner. Furthermore, knock-down of MCP-1/CCR2 or β-catenin was sufficient to inhibit alcohol-induced cell migration/invasion. Together, these results suggested that alcohol may promote the metastasis of CRC through modulating GSK3β/β-catenin/MCP-1 pathway. © 2015 Wiley Periodicals, Inc. PMID:26014148

  14. ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells.

    PubMed

    Jiang, Guiyang; Zhang, Yong; Zhang, Xiupeng; Fan, Chuifeng; Wang, Liang; Xu, Hongtao; Yu, Juanhan; Wang, Enhua

    2015-11-01

    Recent studies have implicated ARMc8 in promoting tumor formation in non-small cell lung cancer and breast cancer; however, so far, no studies have revealed the expression pattern or cellular function of ARMc8 in colon cancer. In this study, we used immunohistochemical staining to measure ARMc8 expression in 206 cases of colon cancer and matched adjacent normal colon tissue. Clinically important behaviors of cells, including invasiveness and migration, were evaluated after upregulation of ARMc8 expression in HT29 cells through gene transfection or downregulation of expression in LoVo cells using RNAi. We found that ARMc8 was primarily located in the membrane and cytoplasm of tumor cells, and its expression level was significantly higher in colon cancer in comparison to that in the adjacent normal colon tissues (p < 0.001). ARMc8 expression was closely related to TNM stage (p = 0.006), lymph node metastasis (p = 0.001), and poor prognosis (p = 0.002) of colon cancer. The invasiveness and migration capacity of HT29 cells transfected with ARMc8 were significantly greater than those of control cells (p < 0.001), while ARMc8 siRNA treatment significantly reduced cell invasion and migration in LoVo cells (p < 0.001). Furthermore, we demonstrated that ARMc8 could upregulate the expression of MMP7 and snail and downregulate the expression of p120ctn and α-catenin. Therefore, ARMc8 probably enhanced invasiveness and metastatic capacity by affecting these tumor-associated factors, thereby playing a role in enhancing the tumorigenicity of colon cancer cells. ARMc8 is likely to become a potential therapeutic target for colon cancer. PMID:26081621

  15. Do non-melanoma skin cancer survivors use tanning beds less often than the general public?

    PubMed

    Wiznia, Lauren; Dai, Feng; Chagpar, Anees B

    2016-01-01

    Purpose Indoor tanning is associated with an increased risk of non-melanoma skin cancers (NMSC), yet little is known about indoor tanning habits of individuals with a history of NMSC. Methods We examined self-reported history of NMSC and tanning bed use among non-Hispanic white respondents in the 2010 National Health Interview Survey (NHIS), a cross-sectional population-based survey designed to be representative of the civilian US population. We computed weighted population estimates and standard errors using the Taylor series linearization method. We then evaluated chi-square tests of independence and conducted weighted logistic regression analyses to evaluate if NMSC status was a predictor of indoor tanning. Results In our analytic sample of 14,400 non-Hispanic white participants, representing 145,287,995 in the population, 543 participants (weighted proportion = 3.45%) self-reported a history of NMSC or "skin cancer type not known." In multivariate analyses, non-melanoma skin cancer survivors were no less likely to use tanning beds in the last 12 months than skin cancer free controls (OR = 0.70, 95% CI: 0.34-1.43, p = 0.33). Conclusions Non-melanoma skin cancer survivors should be educated on their increased risk of recurrence and other skin cancers and in particular the role of indoor tanning in skin tumorigenesis. PMID:27617935

  16. Randomized Trial of Tailored Skin Cancer Prevention for Children: The Project SCAPE Family Study

    PubMed Central

    Glanz, Karen; Steffen, Alana D.; Schoenfeld, Elinor; Tappe, Karyn A.

    2013-01-01

    This study evaluated a tailored intervention to promote sun protection in parents and their children, hypothesizing that the tailored intervention would lead to improved skin cancer prevention behaviors compared to generic materials. Families were recruited through schools and community centers and were included if there was one child in Grades 1–3 at moderate to high risk for skin cancer. Participants were randomized into one of two intervention groups: a tailored intervention, in which they received personalized skin cancer education through the mail; or a control group who received generic skin cancer information materials. Both pre- and post-intervention, parents completed questionnaires about their and their children’s skin cancer risk and prevention knowledge and behaviors. Parents also completed 4-day sun exposure and protection diaries for their child and themselves. Tailored group participants demonstrated significantly greater positive changes in prevention behavior after the intervention, including children’s use of sunscreen, shirts, and hats, and parents’ use of shade, and skin examinations. Effect sizes were small and perceived benefits and social norms mediated intervention effects. Findings from this study support the efficacy of focusing tailored communications to families in order to change skin cancer prevention practices in young children. PMID:23806094

  17. Randomized trial of tailored skin cancer prevention for children: the Project SCAPE family study.

    PubMed

    Glanz, Karen; Steffen, Alana D; Schoenfeld, Elinor; Tappe, Karyn A

    2013-01-01

    This study evaluated a tailored intervention to promote sun protection in parents and their children, hypothesizing that the tailored intervention would lead to improved skin cancer prevention behaviors compared to generic materials. Families were recruited through schools and community centers and were included if there was 1 child in Grades 1-3 at moderate to high risk for skin cancer. Participants were randomized into one of two intervention groups: a tailored intervention, in which they received personalized skin cancer education through the mail; or a control group who received generic skin cancer information materials. Before and after intervention, parents completed questionnaires about their and their children's skin cancer risk and prevention knowledge and behaviors. Parents also completed 4-day sun exposure and protection diaries for their child and themselves. Tailored group participants demonstrated significantly greater positive changes in prevention behavior after the intervention, including children's use of sunscreen, shirts, and hats, and parents' use of shade, and skin examinations. Effect sizes were small and perceived benefits and social norms mediated intervention effects. Findings from this study support the efficacy of focusing tailored communications to families in order to change skin cancer prevention practices in young children. PMID:23806094

  18. Photodynamic therapy of non-melanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Ikram, M.; Khan, R. U.; Firdous, S.; Atif, M.; Nawaz, M.

    2011-02-01

    In this prospective study duly approved from Institutional Ethics Review Committee for research in medicine, PAEC General Hospital Islamabad, Pakistan, we investigate the efficacy, safety and tolerability along with cosmetic outcome of topical 5-aminolaevulinic acid photodynamic therapy for superficial nonmelanoma skin cancers (NMSCs) and their precursors. Patients with Histological diagnosis of NMSCs and their precursors were assessed for PDT, after photographic documentation of the lesions and written consent, underwent two (2) sessions of PDT in one month (4 weeks) according to standard protocol. A freshly prepared 20% 5-ALA in Unguentum base was applied under occlusive dressing for 4-6 h as Drug Light Interval (DLI) and irradiated with light of 630 nm wavelength from a diode laser at standard dose of 90 J/cm2. Approximately 11% patients reported pain during treatment which was managed in different simple ways. In our study we regularly followed up the patients for gross as well as histopathological response and recurrence free periods during median follow-up of 24 months. Regarding Basal cell carcinomas complete response was observed in 86.2% (25/29), partial response in 10.3% (3/29) and recurrence during first year in 3.5% (1/29) lesions. All the lesions which showed partial response or recurrence were nBCCs. Regarding Actinic Keratosis complete response was observed in 95.3% (20/21), partial response in 4.7% (1/21) while Bowen's disease showed 100% (2/2) results. 81.8% (9/11) Squamous Cell Carcinomas showed complete, 9% (1/11) partial response and 9% (1/11) presented with recurrence after 3 months. We observed excellent and good cosmetic results along with tumor clearance in our study. Treatment sessions were well tolerated with high level of patient's satisfaction and only minor side effects of pain during treatment sessions and inflammatory changes post photodynamic therapy were observed. We concluded that 5-ALA PDT is an effective and safe emerging

  19. Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.

    PubMed

    Wu, Jingjing; Zhang, Shizhen; Shan, Jinlan; Hu, Zujian; Liu, Xiyong; Chen, Lirong; Ren, Xingchang; Yao, Lifang; Sheng, Hongqiang; Li, Ling; Ann, David; Yen, Yun; Wang, Jian; Wang, Xiaochen

    2016-07-01

    High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors. PMID:27063096

  20. Diagnosis and Management of Hereditary Basal Cell Skin Cancer.

    PubMed

    Shanley, Susan; McCormack, Christopher

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer in Caucasians worldwide and its incidence is rising. It is generally considered a sporadic tumour, most likely to affect fair-skinned individuals exposed to ultraviolet (UV) radiation. This chapter focusses on the approach to recognising the relatively few individuals in whom a high-risk hereditary susceptibility may be present. Gorlin syndrome is the main consideration and the gene most commonly mutated is PTCH1, a key regulator of the Hedgehog developmental pathway. Recently, loss of function of another gene in the same pathway, SUFU, has been found to explain a subset of families. Understanding the pathogenesis of familial BCCs has advanced the understanding of the biology of sporadic tumours and led to targeted therapy trials. The management of familial BCCs remains a challenge due to significant unmet needs for non-surgical treatments and a high burden of disease for the individual. Together with the prospect of advances in gene discovery and translation, these challenges highlight the need for ongoing review of at-risk and affected individuals by a multidisciplinary team. PMID:27075355

  1. Methodology for diagnosing of skin cancer on images of dermatologic spots by spectral analysis

    PubMed Central

    Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué

    2015-01-01

    In this paper a new methodology for the diagnosing of skin cancer on images of dermatologic spots using image processing is presented. Currently skin cancer is one of the most frequent diseases in humans. This methodology is based on Fourier spectral analysis by using filters such as the classic, inverse and k-law nonlinear. The sample images were obtained by a medical specialist and a new spectral technique is developed to obtain a quantitative measurement of the complex pattern found in cancerous skin spots. Finally a spectral index is calculated to obtain a range of spectral indices defined for skin cancer. Our results show a confidence level of 95.4%. PMID:26504638

  2. U.S. Panel Says Evidence 'Insufficient' to Recommend Skin Cancer Screenings

    MedlinePlus

    ... vice-chairperson of the U.S. Preventive Services Task Force (USPSTF). "We don't know if taking the ... The new report doesn't change the task force's prior statement on skin cancer screening issued in ...

  3. Methodology for diagnosing of skin cancer on images of dermatologic spots by spectral analysis.

    PubMed

    Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué

    2015-10-01

    In this paper a new methodology for the diagnosing of skin cancer on images of dermatologic spots using image processing is presented. Currently skin cancer is one of the most frequent diseases in humans. This methodology is based on Fourier spectral analysis by using filters such as the classic, inverse and k-law nonlinear. The sample images were obtained by a medical specialist and a new spectral technique is developed to obtain a quantitative measurement of the complex pattern found in cancerous skin spots. Finally a spectral index is calculated to obtain a range of spectral indices defined for skin cancer. Our results show a confidence level of 95.4%. PMID:26504638

  4. Green tea prevents non-melanoma skin cancer by enhancing DNA repair

    PubMed Central

    Katiyar, Santosh K.

    2010-01-01

    Excessive exposure of the skin to solar ultraviolet (UV) radiation is one of the major factors for the development of skin cancers, including nonmelanoma. For the last several centuries the consumption of dietary phytochemicals has been linked to numerous health benefits including the photoprotection of the skin. Green tea has been consumed as a popular beverage world-wide and skin photoprotection by green tea polyphenols (GTPs) has been widely investigated. In this article, we have discussed the recent investigations and mechanistic studies which define the potential efficacy of GTPs on the prevention of non-melanoma skin cancer. UV-induced DNA damage, particularly the formation of cyclobutane pyrimidine dimers, has been implicated in immunosuppression and initiation of skin cancer. Topical application or oral administration of green tea through drinking water of mice prevents UVB-induced skin tumor development, and this prevention is mediated, at least in part, through rapid repair of DNA. The DNA repair by GTPs is mediated through the induction of interleukin (IL)-12 which has been shown to have DNA repair ability. The new mechanistic investigations support and explain the anti-photocarcinogenic activity, in particular anti-non-melanoma skin cancer, of green tea and explain the benefits of green tea for human health. PMID:21094124

  5. Skin Cancer Can Strike Anyone | NIH MedlinePlus the Magazine

    MedlinePlus

    ... disease. The development of melanoma is related to sun exposure, particularly to sunburns during childhood. It is most common among people with fair skin, blue or green eyes, and red or blond hair. Fast Facts Skin cancer is the most common form of ...

  6. Cytoplasmic Cyclin E and Phospho-Cyclin-Dependent Kinase 2 Are Biomarkers of Aggressive Breast Cancer.

    PubMed

    Karakas, Cansu; Biernacka, Anna; Bui, Tuyen; Sahin, Aysegul A; Yi, Min; Akli, Said; Schafer, Jolie; Alexander, Angela; Adjapong, Opoku; Hunt, Kelly K; Keyomarsi, Khandan

    2016-07-01

    Cyclin E and its co-activator, phospho-cyclin-dependent kinase 2 (p-CDK2), regulate G1 to S phase transition and their deregulation induces oncogenesis. Immunohistochemical assessments of these proteins in cancer have been reported but were based only on their nuclear expression. However, the oncogenic forms of cyclin E (low molecular weight cyclin E or LMW-E) in complex with CDK2 are preferentially mislocalized to the cytoplasm. Here, we used separate nuclear and cytoplasmic scoring systems for both cyclin E and p-CDK2 expression to demonstrate altered cellular accumulation of these proteins using immunohistochemical analysis. We examined the specificity of different cyclin E antibodies and evaluated their concordance between immunohistochemical and Western blot analyses in a panel of 14 breast cell lines. Nuclear versus cytoplasmic staining of cyclin E readily differentiated full-length from LMW-E, respectively. We also evaluated the expression of cyclin E and p-CDK2 in 1676 breast carcinoma patients by immunohistochemistry. Cytoplasmic cyclin E correlated strongly with cytoplasmic p-CDK2 (P < 0.0001), high tumor grade, negative estrogen/progesterone receptor status, and human epidermal growth factor receptor 2 positivity (all P < 0.0001). In multivariable analysis, cytoplasmic cyclin E plus phosphorylated CDK2 (as one variable) predicted breast cancer recurrence-free and overall survival. These results suggest that cytoplasmic cyclin E and p-CDK2 can be readily detected with immunohistochemistry and used as clinical biomarkers for aggressive breast cancer. PMID:27182644

  7. APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer.

    PubMed

    García-Castro, Araceli; Zonca, Manuela; Florindo-Pinheiro, Douglas; Carvalho-Pinto, Carla E; Cordero, Alex; Gutiérrez del Fernando, Burgo; García-Grande, Aránzazu; Mañes, Santos; Hahne, Michael; González-Suárez, Eva; Planelles, Lourdes

    2015-05-01

    APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL. The inflammatory stimulus poly I:C, a toll-like receptor (TLR) 3 ligand, enhanced APRIL secretion. Silencing experiments decreased cell proliferation, demonstrating that APRIL is a critical autocrine factor for breast tumor growth. Studies of 4T1 orthotopic breast tumors in APRIL transgenic mice showed that an APRIL-enriched environment increased tumor growth and promoted lung metastasis associated with enhanced tumor cell proliferation; BCMA and TACI expression suggests that both participate in these processes. We detected APRIL, BCMA and TACI in human luminal, triple-negative breast carcinomas and HER2 breast carcinomas, with increased levels in more aggressive basal tumors. APRIL was observed near Ki67(+) nuclei and was distributed heterogeneously in the cancer cells, in the leukocyte infiltrate, and in the myoepithelial layer adjacent to the tumor area; these results imply that APRIL provides proliferation signals to tumor cells through paracrine and autocrine signaling. Our study identifies participation of APRIL signaling in breast cancer promotion; we propose impairment of this pathway as a potential therapeutic strategy. PMID:25750171

  8. [Effects of sorting weaner pigs by weight on growth performance, aggressive interactions and skin lesion score after mixing].

    PubMed

    Fels, Michaela; Hoy, Steffen

    2013-01-01

    Weaning piglets at the age of three or four weeks is an integral part of certain production rhythms in modern pig farming. Sorting piglets by weight and mixing them into new groups is a common method in agricultural practice. The aim of this study was to clarify whether the formation of homogeneous weight groups after weaning affects weight development and aggressive behaviour. We compared homogeneous and heterogeneous weight groups and entire litters that were weaned and reared completely. All groups including entire litters were composed of 12 animals. All piglets were weighed the day before weaning, four days later, and on day 38. The number of all aggressive interactions occurring within a group was determined by video analysis for 72 hours after mixing.There during four days after weaning or over the rearing period. Rearing entire litters resulted in significantly higher daily weight gain within four days after weaning and throughout the rearing period. Sorting piglets by weight did not affect the development of weight dispersion in a group. The coefficients of variation of weights in homogeneous and heterogeneous groups which differed significantly at the beginning were on a similar level after 38 days. Neither weight balance of piglet batches at the end of rearing nor growth performance or aggressive interactions were influenced by sorting piglets by weight at weaning. PMID:23540194

  9. Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

    ClinicalTrials.gov

    2016-06-09

    Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

  10. Nuclear Kaiso Indicates Aggressive Prostate Cancers and Promotes Migration and Invasiveness of Prostate Cancer Cells

    PubMed Central

    Jones, Jacqueline; Wang, Honghe; Zhou, Jianjun; Hardy, Shana; Turner, Timothy; Austin, David; He, Qinghua; Wells, Alan; Grizzle, William E.; Yates, Clayton

    2013-01-01

    Kaiso, a p120 catenin-binding protein, is expressed in the cytoplasmic and nuclear compartments of cells; however, the biological consequences and clinical implications of a shift between these compartments have yet to be established. Herein, we report an enrichment of nuclear Kaiso expression in cells of primary and metastatic prostate tumors relative to the normal prostate epithelium. Nuclear expression of Kaiso correlates with Gleason score (P < 0.001) and tumor grade (P < 0.001). There is higher nuclear expression of Kaiso in primary tumor/normal matched samples and in primary tumors from African American men (P < 0.0001). We further found that epidermal growth factor (EGF) receptor up-regulates Kaiso at the RNA and protein levels in prostate cancer cell lines, but more interestingly causes a shift of cytoplasmic Kaiso to the nucleus that is reversed by the EGF receptor–specific kinase inhibitor, PD153035. In both DU-145 and PC-3 prostate cancer cell lines, Kaiso inhibition (short hairpin RNA-Kaiso) decreased cell migration and invasion even in the presence of EGF. Further, Kaiso directly binds to the E-cadherin promoter, and inhibition of Kaiso in PC-3 cells results in increased E-cadherin expression, as well as re-establishment of cell–cell contacts. In addition, Kaiso-depleted cells show more epithelial morphology and a reversal of the mesenchymal markers N-cadherin and fibronectin. Our findings establish a defined oncogenic role of Kaiso in promoting the progression of prostate cancer. PMID:22974583

  11. The β-catenin signaling pathway induces aggressive potential in breast cancer by up-regulating the chemokine CCL5.

    PubMed

    Yasuhara, Rika; Irié, Tarou; Suzuki, Kenya; Sawada, Terumasa; Miwa, Noriko; Sasaki, Akiko; Tsunoda, Yuko; Nakamura, Seigo; Mishima, Kenji

    2015-10-15

    β-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin (CAβ-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAβ-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAβ-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAβ-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of β-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear β-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear β-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that β-catenin expression enhances tumor progression via chemokine production in breast cancers and that β-catenin signaling is a critical regulator of the aggressive traits of breast cancers. PMID:26363360

  12. Immunomics in Skin Cancer - Improvement in Diagnosis, Prognosis and Therapy Monitoring

    PubMed Central

    Bulman, Amanda; Neagu, Monica; Constantin, Carolina

    2013-01-01

    This review will focus on the elements of the skin’s immune system, immune cells and/or non-immune cells that support immune mechanisms, molecules with immune origin and/or immune functions that are involved in skin carcinogenesis. All these immune elements are compulsory in the development of skin tumors and/or sustainability of the neoplastic process. In this light, recent data gathered in this review will acknowledge all immune elements that contribute to skin tumorigenesis; moreover, they can serve as immune biomarkers. These immune markers can contribute to the diagnostic improvement, prognosis forecast, therapy monitoring, and even personalized therapeutical approach in skin cancer. Immune processes that sustain tumorigenesis in non-melanoma and melanoma skin cancers are described in the framework of recent data. PMID:24228023

  13. Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer.

    PubMed

    Yin, Bo; Zhang, Mo; Zeng, Yu; Li, Youqiang; Zhang, Chao; Song, Yongsheng

    2016-04-01

    Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients. PMID:26892177

  14. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    SciTech Connect

    Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting; Kao, Jun-Kai; Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu; Chiu, Husan-Wen; Chang, Chuan-Hsun; Liang, Shu-Mei; Chen, Yi-Ju; Huang, Jau-Ling; Shieh, Jeng-Jer

    2013-02-15

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

  15. Opportunistic screening for skin cancer using a mobile unit in Brazil

    PubMed Central

    2011-01-01

    Background Skin cancer is the most common malignancy in the white population worldwide. In Brazil, the National Cancer Institute (INCA) estimates that in 2010 there will be 119,780 and 5,930 new cases of non-melanoma skin cancer and melanoma, respectively. The aim of this study was to evaluate the use of a mobile unit in the diagnosis and treatment of skin cancer in several poor regions of Brazil. Methods The diagnosis of skin cancer was accomplished through active medical screening in the prevention Mobile Unit (MU) of Barretos Cancer Hospital (BCH). The study population consisted of patients examined in the MU between 2004 and 2007, and their suspicious lesions were subjected to histopathological evaluation. Data were collected prospectively from standardized forms and analyzed. Results During the screening, 17,857 consultations were carried out. A total of 2012 (11.2%) cases of skin cancer were diagnosed. The predominant histological type reported was basal cell carcinoma (n = 1,642 or 81.6%), followed by squamous cell carcinoma (n = 303 or 15.1%), Bowen's disease (n = 25 or 1.2%), malignant melanoma (n = 23 or 1.1%), basosquamous cell carcinoma (n = 3 or 0.1%), miscellaneous lesions (12 or 0.6%), and metatypical carcinoma (n = 4 or 0.2%). Only 0.6% of lesions were stage III. There were no stage IV non-melanoma skin lesions, as well as no melanomas stages III and IV, found. Conclusions It was observed that the MU can be a useful tool for early skin cancer diagnosis and treatment. This program probably is important, especially in developing countries with inadequate public health systems and social inequality. PMID:21645347

  16. The mechanistic basis of arsenicosis: Pathogenesis of skin cancer

    PubMed Central

    Hunt, Katherine M.; Srivastava, Ritesh K.; Elmets, Craig A.; Athar, Mohammad

    2014-01-01

    Significant amounts of arsenic have been found in the groundwater of many countries including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States with an estimated 200 million people at risk of toxic exposure. Although chronic arsenic poisoning damages many organ systems, it usually first presents in the skin with manifestations including hyperpigmentation, hyperkeratoses, Bowen’s disease, squamous cell carcinoma, and basal cell carcinoma. Arsenic promotes oxidative stress by upregulating nicotinamide adenine dinucleotide phosphate oxidase, uncoupling nitric oxide synthase, and by depleting natural antioxidants such as nitric oxide and glutathione in addition to targeting other proteins responsible for the maintenance of redox homeostasis. It causes immune dysfunction and tissue inflammatory responses, which may involve activation of the unfolded protein response signaling pathway. In addition, the dysregulation of other molecular targets such as nuclear factor kappa B, Hippo signaling protein Yap, and the mineral dust-induced proto-oncogene may orchestrate the pathogenesis of arsenic-mediated health effects. The metalloid decreases expression of tumor suppressor molecules and increases expression of pro-inflammatory mitogen-activated protein kinase pathways leading to a tumor-promoting tissue microenvironment. Cooperation of upregulated signal transduction molecules with DNA damage may abrogate apoptosis, promote proliferation, and enhance cell survival. Genomic instability via direct DNA damage and weakening of several cellular DNA repair mechanisms could also be important cancer development mechanisms in arsenic-exposed populations. Thus, arsenic mediates its toxicity by generating oxidative stress, causing immune dysfunction, promoting genotoxicity, hampering DNA repair, and disrupting signal transduction, which may explain the complex disease manifestations seen in arsenicosis. PMID:25173797

  17. The mechanistic basis of arsenicosis: pathogenesis of skin cancer.

    PubMed

    Hunt, Katherine M; Srivastava, Ritesh K; Elmets, Craig A; Athar, Mohammad

    2014-11-28

    Significant amounts of arsenic have been found in the groundwater of many countries including Argentina, Bangladesh, Chile, China, India, Mexico, and the United States with an estimated 200 million people at risk of toxic exposure. Although chronic arsenic poisoning damages many organ systems, it usually first presents in the skin with manifestations including hyperpigmentation, hyperkeratoses, Bowen's disease, squamous cell carcinoma, and basal cell carcinoma. Arsenic promotes oxidative stress by upregulating nicotinamide adenine dinucleotide phosphate oxidase, uncoupling nitric oxide synthase, and by depleting natural antioxidants such as nitric oxide and glutathione in addition to targeting other proteins responsible for the maintenance of redox homeostasis. It causes immune dysfunction and tissue inflammatory responses, which may involve activation of the unfolded protein response signaling pathway. In addition, the dysregulation of other molecular targets such as nuclear factor kappa B, Hippo signaling protein Yap, and the mineral dust-induced proto-oncogene may orchestrate the pathogenesis of arsenic-mediated health effects. The metalloid decreases expression of tumor suppressor molecules and increases expression of pro-inflammatory mitogen-activated protein kinase pathways leading to a tumor-promoting tissue microenvironment. Cooperation of upregulated signal transduction molecules with DNA damage may abrogate apoptosis, promote proliferation, and enhance cell survival. Genomic instability via direct DNA damage and weakening of several cellular DNA repair mechanisms could also be important cancer development mechanisms in arsenic-exposed populations. Thus, arsenic mediates its toxicity by generating oxidative stress, causing immune dysfunction, promoting genotoxicity, hampering DNA repair, and disrupting signal transduction, which may explain the complex disease manifestations seen in arsenicosis. PMID:25173797

  18. Was skin cancer a selective force for black pigmentation in early hominin evolution?

    PubMed Central

    Greaves, Mel

    2014-01-01

    Melanin provides a crucial filter for solar UV radiation and its genetically determined variation influences both skin pigmentation and risk of cancer. Genetic evidence suggests that the acquisition of a highly stable melanocortin 1 receptor allele promoting black pigmentation arose around the time of savannah colonization by hominins at some 1–2 Ma. The adaptive significance of dark skin is generally believed to be protection from UV damage but the pathologies that might have had a deleterious impact on survival and/or reproductive fitness, though much debated, are uncertain. Here, I suggest that data on age-associated cancer incidence and lethality in albinos living at low latitudes in both Africa and Central America support the contention that skin cancer could have provided a potent selective force for the emergence of black skin in early hominins. PMID:24573849

  19. Reducing ultraviolet radiation exposure to prevent skin cancer methodology and measurement.

    PubMed

    Glanz, Karen; Mayer, Joni A

    2005-08-01

    Skin cancer is the most common type of cancer, and is also one of the most preventable. This paper builds on an evidence review of skin cancer prevention interventions that was conducted for the Guide to Community Preventive Services (n=85 studies), and summarizes the state of knowledge about research methodology and measurement in studies of the effectiveness of interventions to reduce ultraviolet radiation (UVR) exposure. As this field advances, researchers should strive to minimize threats to validity in their study designs, as well as to consider the balance between internal and external validity. There is a need for more longer-duration interventions, and follow-up periods that make possible conclusions about the potential of these interventions to affect intermediate markers of skin cancer or at least sustained behavior change. Also, more work is needed to minimize attrition and characterize nonresponders and study dropouts. Verbal report measures of behavior are the most widely used measures of solar protection behavior. Given their limitations, investigators should routinely collect data about reliability and validity of those measures. They should also increase efforts to complement verbal data with objective measures including observations, skin reflectance, personal dosimetry, skin swabbing, and inspection of moles. Measures of environments and policies should incorporate observations, documentation, and direct measures of ambient UVR and shade. This article places the data derived from the evidence review in the context of needs and recommendations for future research in skin cancer prevention. PMID:16005810

  20. Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

    PubMed

    Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

    2015-02-01

    Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN. PMID:25268273

  1. Changing Trends of Skin Cancer: A Tertiary Care Hospital Study in Malwa Region of Punjab

    PubMed Central

    Banipal, Raja Paramjeet Singh; Bhatti, Deepak John; Yadav, Hanuman Prasad

    2016-01-01

    Introduction Skin cancer constitutes a small but significant proportion of patients with cancer. Although the presence of eumelanin in dark skin is protective against the development of skin cancer, it is increasingly being diagnosed in the Indian population. Aim To study the profile of skin cancer patients presenting to a tertiary hospital in Malwa area of Punjab, India. Materials and Methods Retrospective study was done to analyse the profile of skin cancer patients who attended the institution over one year from 1st December 2013 to 30th November 2014. A comprehensive review of aetiology and related risk factors was done to correlate the environmental factors with high skin cancer prevalence in this region. Results Skin cancer constituted (3.18%) 84 out of 2638 patients registered with cancer of all types. The age of the patients was 62±14.2 years and ranged from 27 to 92 yrs. Basal cell carcinoma (BCC) was the most common histological type(46/84, 54.76%) followed by squamous cell carcinoma (SCC) (31/84, 36.91%) and malignant melanoma (MM) (7/84, 8.33%). Male: female ratio was found to be 0.79:1. BCC showed higher female preponderance (p<0.05). Head and Neck was the commonest site involved (p<0.05). Majority (88%) of patients were from rural area. 92% of patients were directly into the profession of agriculture with history of prolonged exposure to sunlight. Conclusion Skin cancer constitutes a small but significant proportion of patients with cancers. This study highlights a paradoxically increasing trend of BCC and female preponderance. Head and neck is the most common site involved. Exposure to Ultra Violet B (UVB) radiation and higher levels of arsenic in drinking water has been reported to be associated with skin cancers. Limited studies show that levels of arsenic and pesticides were higher in the samples of drinking water in Malwa area of Punjab. Therefore a multipronged strategy to provide safe drinking water supply and discouraging the indiscriminate

  2. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    PubMed Central

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated. PMID:26295053

  3. Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

    NASA Astrophysics Data System (ADS)

    Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

    2015-04-01

    To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

  4. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  5. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  6. Synbindin in Extracellular Signal-Regulated Protein Kinase Spatial Regulation and Gastric Cancer Aggressiveness

    PubMed Central

    2013-01-01

    Background The molecular mechanisms that control the aggressiveness of gastric cancer (GC) remain poorly defined. Here we show that synbindin contributes to the aggressiveness of GC by activating extracellular signal-regulated protein kinase (ERK) signaling on the Golgi apparatus. Methods Expression of synbindin was examined in normal gastric mucosa (n = 44), intestinal metaplastic gastric mucosa (n = 66), and GC tissues (n=52), and the biological effects of synbindin on tumor growth and ERK signaling were detected in cultured cells, nude mice, and human tissue samples. The interaction between synbindin and mitogen-activated protein kinase kinase (MEK1)/ERK was determined by immunofluorescence and fluorescence resonance energy transfer assays. The transactivation of synbindin by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was detected using luciferase reporter assay and chromatin immunoprecipitation. Results High expression of synbindin was associated with larger tumor size (120.8 vs 44.8cm3; P = .01), advanced tumor node metastasis (TNM) stage (P = .003), and shorter patient survival (hazard ratio = 1.51; 95% confidence interval [CI] = 1.01 to 2.27; P = .046). Synbindin promotes cell proliferation and invasion by activating ERK2 on the Golgi apparatus, and synbindin is directly transactivated by NF-κB. Synbindin expression level was statistically significantly higher in human GCs with activated ERK2 than those with low ERK2 activity (intensity score of 11.5, 95% CI = 10.4 to 12.4 vs intensity score of 4.6, 95% CI 3.9 to 5.3; P < .001). Targeting synbindin in xenograft tumors decreased ERK2 phosphorylation and statistically significantly reduced tumor volume (451.2mm3, 95% CI = 328.3 to 574.1 vs 726.1mm3, 95% CI = 544.2 to 908.2; P = .01). Conclusions Synbindin contributes to malignant phenotypes of GC by activating ERK on the Golgi, and synbindin is a potential biomarker and therapeutic target for GC. PMID:24104608

  7. Smartphone Mobile Applications to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner.

    PubMed

    Cook, Shane E; Palmer, Louis C; Shuler, Franklin D

    2015-01-01

    Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population. PMID:26521532

  8. Observation and analysis on skin cancer induced by UVB irradiation using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Wang, Yunxia; Wu, Shulian; Li, Hui; Zheng, Xiaoxiao

    2014-09-01

    Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the prevalent skin cancers, which have a quite high incidence in the white race. In recent years, however, their incidences have been increasing in the yellow race, resulting in a great threat to the public health. According to researches, chronics UVB irradiation (280nm~320nm) is the major culprit of skin cancer in humans. In our study, the model of UVB induced skin cancer was established firstly. Optical coherence tomography (OCT) combined with the histopathology was exploited to monitor the morphologic and histological changes of the process of UVB induced skin cancer. Meanwhile, this canceration process was systematically studied and analyzed from the perspective of tissue optics. The attenuation coefficient (μt) has a rising trend in the epidermis, but which shows a downward trend in the dermis. The results are conducive to understand the process of UVB-induced skin cancer and further be able to provide a reference for medical researchers.

  9. Determinants for aggressive end-of-life care for oral cancer patients: a population-based study in an Asian country.

    PubMed

    Chang, Ting-Shou; Su, Yu-Chieh; Lee, Ching-Chih

    2015-01-01

    Few studies have addressed the association between oral cancer and end-of-life (EOL) aggressive care using population data. We investigated the relationship between patient demographics, primary physician's specialty, and hospital characteristics of patients who died from oral cancer in Taiwan from 2009 to 2011 and the aggressiveness of their EOL care. This nationwide population-based, retrospective cohort study identified 5386 patients who died from oral cancer identified from Taiwan's National Register of Deaths Database and collected their claims data from Taiwan's National Health Insurance Research Database. Accepted indicators of aggressiveness of EOL care were examined using a composite measure adapted from Earle et al. Scores ranged from 0 to 6; the higher the score, the more aggressive the EOL care. The impact of each variable on the aggressiveness of EOL care was examined by multivariate analysis using a random-intercept model. The mean composite score for aggressiveness of EOL care was 2.68 ± 1.37. Oral cancer patients who were younger, had a higher level of comorbidity or metastasis, belonged to a lower-level individual socioeconomic status, were cared for by nononcologists, had longer postdiagnosis survival times, or resided in urban areas were more likely to receive aggressive care at EOL. Compared with previous studies, oral cancer patients near death in this nationwide study had a far higher utilization rate (>50%) of chemotherapy, emergency room services, and intensive care unit services. Our findings indicate that oral cancer patients receive extensive aggressive medical care at EOL. Future research may be needed to examine the effect of the means (indicators) of aggressive treatment on survival, quality of life, and medical costs, especially since current research suggests such care may adversely affect quality of life and important preparation of death in these patients. PMID:25634186

  10. LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients.

    PubMed

    Meka, Phanni bhushann; Jarjapu, Sarika; Nanchari, Santhoshi Rani; Vishwakarma, Sandeep Kumar; Edathara, Prajitha Mohandas; Gorre, Manjula; Cingeetham, Anuradha; Vuree, Sugunakar; Annamaneni, Sandhya; Dunna, Nageswara Rao; Mukta, Srinivasulu; B, Triveni; Satti, Vishnupriya

    2015-01-01

    LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients. PMID:26163623

  11. Skin cancer-related prevention and screening behaviors: a review of the literature.

    PubMed

    Kasparian, Nadine A; McLoone, Jordana K; Meiser, Bettina

    2009-10-01

    Primary prevention and early detection continue to be of paramount importance in addressing the public health threat of skin cancer. The aim of this systematic review was to provide a comprehensive overview of the prevalence and correlates of skin cancer-related health behaviors in the general population. To achieve this aim, 91 studies published in international peer-reviewed journals over the past three decades were reviewed and synthesized. Reported estimates of sunscreen use varied considerably across studies, ranging from 7 to 90%. According to self-report, between 23 and 61% of individuals engage in skin self-examination at least once per year, and the documented prevalence of annual clinical skin examination ranges from 8 to 21%. Adherence to sun protection and screening recommendations is associated with a range of factors, including: female gender, sun-sensitive phenotype, greater perceived risk of skin cancer, greater perceived benefits of sun protection or screening, and doctor recommendation for screening. The literature suggests that a large proportion of the general population engage in suboptimal levels of sun protection, although there is substantial variability in findings. The strongest recommendation to emerge from this review is a call for the development and widespread use of standardized measurement scales in future research, in addition to more studies with a population-based, multivariate design. It is also recommended that specific targeted interventions are developed to increase the prevalence of preventative and early intervention behaviors for the control of skin cancer. PMID:19521760

  12. Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells.

    PubMed

    Sumida, Tomoki; Ishikawa, Akiko; Nakano, Hiroyuki; Yamada, Tomohiro; Mori, Yoshihide; Desprez, Pierre-Yves

    2016-08-01

    Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression. PMID:27364596

  13. [The 2003 "Solmobile" prevention campaign for skin cancers of the Swiss League against Cancer: results and stakes].

    PubMed

    Bulliard, Jean-Luc; Levi, Fabio; Panizzon, Renato G

    2004-04-01

    As part of the national skin cancer prevention programme coordinated by the Swiss League against Cancer, a mobile unit visited 29 Swiss towns to inform people on skin type, skin cancer risk and sun protection behaviour. In the summer of 2003, among 6725 visitors, 3662 took the offered possibility of having a cutaneous lesion checked free of charge by a dermatologist present in the mobile unit. The campaign satisfactorily covered, albeit to various degrees, its 3 fields of activity, i.e. (1) primary prevention, (2) secondary prevention and (3) clinical examination. Participants were predominantly females (60%), except for visits on work sites (firms and universities), half were aged 15-44 years, and 40% were considered at increased risk for skin cancer. Sociodemographic and regional differences in the profile of visitors were observed and could largely be attributed to variations in daily availability of the mobile unit. 108 malignant lesions were observed, including 21 cutaneous melanomas. Relative to the number of examinations performed, more cancers were detected in men, those aged 65 or over, and visitors who experienced a prior skin screening and severe sunburns during childhood. Limitations and prospects of this type of preventive campaigns are briefly discussed. PMID:15209058

  14. Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer.

    PubMed

    Sun, Li-Min; Huang, Chih-Jen; Chen, Hsiao-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

    2016-01-01

    We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT. PMID:27158022

  15. Effect of intense THz pulses on expression of genes associated with skin cancer and inflammatory skin conditions

    NASA Astrophysics Data System (ADS)

    Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Purschke, David; Golubov, Andrey; Rodriguez-Juarez, Rocio; Woycicki, Rafal; Hegmann, Frank A.; Kovalchuk, Olga

    2014-03-01

    The growing experimental evidence suggests that broadband, picosecond-duration THz pulses may influence biological systems and functions. While the mechanisms by which THz pulse-induced biological effects are not yet known, experiments using in vitro cell cultures, tissue models, as well as recent in vivo studies have demonstrated that THz pulses can elicit cellular and molecular changes in exposed cells and tissues in the absence of thermal effects. Recently, we demonstrated that intense, picosecond THz pulses induce phosphorylation of H2AX, indicative of DNA damage, and at the same time activate DNA damage response in human skin tissues. We also find that intense THz pulses have a profound impact on global gene expression in human skin. Many of the affected genes have important functions in epidermal differentiation and have been implicated in skin cancer and inflammatory skin conditions. The observed THzinduced changes in expression of these genes are in many cases opposite to disease-related changes, suggesting possible therapeutic applications of intense THz pulses.

  16. In vivo determination of optical properties and fluorophore characteristics of non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Rajaram, Narasimhan; Kovacic, Dianne; Migden, Michael F.; Reichenberg, Jason S.; Nguyen, Tri H.; Tunnell, James W.

    2009-02-01

    Diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques have widely been used as noninvasive tools for early cancer detection in several organs including the cervix, oral cavity and gastrointestinal tract. Using a combined DOS/LIF approach, one can simultaneously measure the morphology and biochemical composition of tissue and use these features to diagnose malignancy. We report for the first time to our knowledge both the optical properties and native fluorophore characteristics of non-melanoma skin cancer in the UV-visible range. We collected in vivo diffuse reflectance and intrinsic fluorescence measurements from 44 skin lesions on 37 patients. The skin sites were further categorized into three groups of non-melanoma skin cancer according to histopathology: 1) pre-cancerous actinic keratosis 2) malignant squamous cell carcinoma (SCC) and 3) basal cell carcinoma (BCC). We used a custom-built probe-based clinical system that collects both white light reflectance and laser-induced fluorescence in the wavelength range of 350-700 nm. We extracted the blood volume fraction, oxygen saturation, blood vessel size, tissue microarchitecture and melanin content from diffuse reflectance measurements. In addition, we determined the native fluorophore contributions of NADH, collagen and FAD from laser-induced fluorescence for all groups. The scattering from tissue decreased with progression from clinically normal to precancerous actinic keratosis to malignant SCC. A similar trend was observed for clinically normal skin and malignant BCC. Statistically significant differences were observed in the collagen contributions, which were lower in malignant SCC and BCC as compared to normal skin. Our data demonstrates that the mean optical properties and fluorophore contributions of normal, benign and malignant nonmelanoma cancers are significantly different from each other and can potentially be used as biomarkers for the early detection of skin cancer.

  17. Patient experiences and outcomes following facial skin cancer surgery: A qualitative study.

    PubMed

    Lee, Erica H; Klassen, Anne F; Lawson, Jessica L; Cano, Stefan J; Scott, Amie M; Pusic, Andrea L

    2016-08-01

    Early melanoma and non-melanoma skin cancer of the facial area are primarily treated with surgery. Little is known about the outcomes of treatment for facial skin cancer patients. The objective of the study was to identify concerns about aesthetics, procedures and health from the patients' perspective after facial skin surgery. Semi-structured in-depth interviews were conducted with 15 participants. Line-by-line coding was used to establish categories and develop themes. We identified five major themes on the impact of skin cancer surgery: appearance-related concerns; psychological (e.g., fear of new cancers or recurrence); social (e.g. impact on social activities and interaction); physical (e.g. pain and swelling) concerns and satisfaction with the experience of care (e.g., satisfaction with surgeon). The priority of participants was the removal of the facial skin cancer, as this reduced their overall worry. The aesthetic outcome was secondary but important, as it had important implications on the participants' social and psychological functioning. The participants' experience with the care provided by the surgeon and staff also contributed to their satisfaction with their treatment. This conceptual framework provides the basis for the development of a new patient-reported outcome instrument. PMID:25833383

  18. Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review.

    PubMed

    Bates, A S; Davis, C R; Takwale, A; Knepil, G J

    2013-06-01

    Nonmelanoma skin cancer (NMSC) is the most common malignancy in the western world, with an incidence of 98,000 in the U.K. Since 2009 the Department of Health (DoH) has collected patient-reported outcome measure (PROM) data following four common surgical procedures. However, a DoH PROM for NMSC does not exist. A systematic review of questionnaires published on patient concerns due to NMSC of the face was conducted. Keywords relevant to PROMs, NMSC and the facial region were comprehensively searched in medical databases. Inclusion criteria stipulated that questionnaires from relevant papers recruited patients with NMSC for both the item formulation and subsequent validation. Questionnaires were then discussed by a multispecialty skin cancer research team. Initially 2548 papers were found; after exclusion criteria were applied, 73 articles were retrieved. Four patient questionnaires for NMSC featured adequate development and validation according to the inclusion criteria. The Facial Skin Cancer Index (FSCI) was the only PROM specific to facial NMSC. Additional questionnaires identified included the Skin Cancer Quality of Life Impact Tool, Skindex, and Dermatology Life Quality Index. There is a scarcity of data relating to NMSC PROMs and appearance concerns. Only one questionnaire--the FSCI--was specific to patients with facial NMSC. We recommend nationally standardized data collection from patients with NMSC in order to create an evidence-based validated PROM for patients with facial skin cancer. PMID:23387431

  19. IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer.

    PubMed

    Lee, Chia-Huei; Chang, Jeffrey Shu-Ming; Syu, Shih-Han; Wong, Thian-Sze; Chan, Jimmy Yu-Wai; Tang, Ya-Chu; Yang, Zhi-Ping; Yang, Wen-Chan; Chen, Chiung-Tong; Lu, Shao-Chun; Tang, Pei-Hua; Yang, Tzu-Ching; Chu, Pei-Yi; Hsiao, Jenn-Ren; Liu, Ko-Jiunn

    2015-04-01

    Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1β) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1β expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1β was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1β secretion in an inflammasome-dependent manner. IL-1β treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-α following IL-1β stimulation. The conditioned medium of IL-1β-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1β increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1β can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. PMID:25204733

  20. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer.

    PubMed

    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment. PMID:26545775

  1. Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer.

    PubMed

    Kirk, Jason S; Schaarschuch, Kevin; Dalimov, Zafardjan; Lasorsa, Elena; Ku, ShengYu; Ramakrishnan, Swathi; Hu, Qiang; Azabdaftari, Gissou; Wang, Jianmin; Pili, Roberto; Ellis, Leigh

    2015-02-20

    Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development. PMID:25605014

  2. Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer

    PubMed Central

    Lasorsa, Elena; Ku, ShengYu; Ramakrishnan, Swathi; Hu, Qiang; Azabdaftari, Gissou; Wang, Jianmin; Pili, Roberto; Ellis, Leigh

    2015-01-01

    Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development. PMID:25605014

  3. LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer.

    PubMed

    Sas-Chen, Aldema; Aure, Miriam R; Leibovich, Limor; Carvalho, Silvia; Enuka, Yehoshua; Körner, Cindy; Polycarpou-Schwarz, Maria; Lavi, Sara; Nevo, Nava; Kuznetsov, Yuri; Yuan, Justin; Azuaje, Francisco; Ulitsky, Igor; Diederichs, Sven; Wiemann, Stefan; Yakhini, Zohar; Kristensen, Vessela N; Børresen-Dale, Anne-Lise; Yarden, Yosef

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal-like subtype associates with increased EGFR signaling, while another, the HER2-enriched subtype, engages a kin of EGFR Based on the premise that EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we identified multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers. PMID:27485121

  4. Chronic Phototoxicity and Aggressive Squamous Cell Carcinoma of the Skin in Children and Adults During Treatment with Voriconazole

    PubMed Central

    Cowen, Edward W.; Nguyen, Josephine C.; Miller, Daniel D.; McShane, Diana; Arron, Sarah T.; Prose, Neil S.; Turner, Maria L.; Fox, Lindy P.

    2009-01-01

    Background Voriconazole is a broad spectrum antifungal agent associated with photosensitivity and accelerated photoaging. A possible link with aggressive squamous cell carcinoma (SCC) has also been reported. Objective To determine the incidence and frequency of cutaneous SCC amongst patients undergoing long-term treatment with voriconazole who also manifest features of chronic phototoxicity. Methods A retrospective review of patients who developed one or more squamous cell neoplasms during long-term treatment with voriconazole at three academic dermatology centers. Results 51 cutaneous SCC were identified in 8 patients (median age 34.5 years, range 9–54) treated with chronic voriconazole (median duration 46.5 months, range 13–60). Underlying diagnoses included graft-versus-host disease, HIV, and Wegener’s granulomatosis. Signs of chronic phototoxicity and accelerated photoaging included erythema, actinic keratoses, and lentigo formation. Limitations The retrospective nature of the study cannot determine the true population risk of SCC associated with voriconazole therapy. A prospective cohort study is needed. Conclusion A high index of suspicion for photosensitivity and SCC may be warranted with chronic voriconazole use when utilized in the setting of concurrent immunosuppression. PMID:19896749

  5. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.

    PubMed

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-04-19

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma.Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines.We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK.Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%.Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression.Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants.In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  6. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    PubMed Central

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  7. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer

    PubMed Central

    Ming, Mei; Han, Weinong; Zhao, Baozhong; Sundaresan, Nagalingam R.; Deng, Chu-Xia; Gupta, Mahesh; He, Yu-Ying

    2014-01-01

    SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival and in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. PMID:25320180

  8. Skin cancer/melanoma public and professional education in Hawaii: an integrated approach to technology transfer.

    PubMed

    Brannon, B R; Wagstaff, D A

    1983-01-01

    The CCPH skin cancer/melanoma education components which have been implemented to date have had an impact on the public and professional target audiences. The comic book/TV/radio media campaign, conducted during the summer months of 1981, appears to have raised public skin cancer/melanoma knowledge levels and positively affected behavior. Results of the physician training sessions also suggest immediate posttraining gains. Follow-up data may provide evidence of long-term knowledge and behavior change. Materials for health and personal services professionals are in final production and, based on the success of completed components, should contribute to improved skin cancer prevention, detection and treatment practices in Hawaii. PMID:6878305

  9. The Impact of Dermatologist Examination and Biometric Feedback Delivered at the Beach on Skin Cancer Prevention

    PubMed Central

    Emmons, Karen M.; Geller, Alan C.; Puleo, Elaine; Savadatti, Sanghamitra S.; Hu, Stephanie W.; Gorham, Sue; Werchniak, Andrew E.

    2011-01-01

    Background There are limited data on the effectiveness of skin cancer prevention education and early detection programs at beaches. Objectives We evaluate four strategies for addressing skin cancer prevention in beach settings. Methods This prospective study at four beaches included 4 intervention conditions: (1) education only; or education plus (2) biometric feedback; (3) dermatologist skin examination; or (4) biometric feedback and dermatologist skin examination. Outcomes included sun protection behaviors, sunburns, and skin self-exams. Results There was a significant increase in hat wearing, sunscreen use, and a reduction in sunburns in the education plus biometric feedback group (OR = 1.97, 1.94, 1.07 respectively), as well as greater improvements in knowing what to look for in skin-self examinations (OR=1.13); there were no differences in frequency of self-examinations. Skin examinations plus biometric feedback led to greater reductions in sunburns. The dermatologist exams identified atypical moles in 28% of participants. Limitations Inclusion of only one beach per condition, use of self-report data, and a limited intervention period. Conclusions Education and biometric feedback may be more effective than education alone for impacting sun protective attitudes and behaviors in beach-going, high-risk populations. PMID:21163550

  10. miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer

    PubMed Central

    Xiong, Yin; Kotian, Shweta; Zeiger, Martha A.; Zhang, Lisa; Kebebew, Electron

    2015-01-01

    Background Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes. Methodology/Principal Findings We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p. Conclusions/Significance To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype. PMID:26244545

  11. Skin cancer risk behaviors among US men: the role of sexual orientation.

    PubMed

    Blashill, Aaron J; Safren, Steven A

    2014-09-01

    The current study assessed skin cancer risk behaviors by sexual orientation in a nationally representative prospective sample of US men (n = 1767), sampled at ages 16 and 29 years. At age 16 years, sexual minority men were 3.9 times as likely as heterosexual men to indoor tan. Participants did not significantly differ in the use of sunscreen or the frequency of outdoor tanning. Thus, sexual minority men might be an at-risk group for developing skin cancers because of their indoor tanning behaviors. PMID:25033138

  12. Non-melanoma skin cancer: importance of gender, immunosuppressive status and vitamin D.

    PubMed

    Oberyszyn, Tatiana M

    2008-03-18

    Ultraviolet light B (UVB) is responsible for the majority of cutaneous damage and is believed to be the single most important etiologic agent in the development of non-melanoma skin cancers (NMSC). These skin tumors are by far the most common form of cancer in humans, with over 1 million new cases identified in the United States each year. Several risk factors exist, which increase the chance of a patient developing NMSC including gender, immunosuppressive status and more controversially vitamin D levels. The present review provides an overview of each of these areas. PMID:18267352

  13. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    SciTech Connect

    Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A.; Kopelovich, Levy; Athar, Mohammad

    2013-05-01

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

  14. The Role of Manganese Superoxide Dismutase in Skin Cancer

    PubMed Central

    Robbins, Delira; Zhao, Yunfeng

    2011-01-01

    Recent studies have shown that antioxidant enzyme expression and activity are drastically reduced in most human skin diseases, leading to propagation of oxidative stress and continuous disease progression. However, antioxidants, an endogenous defense system against reactive oxygen species (ROS), can be induced by exogenous sources, resulting in protective effects against associated oxidative injury. Many studies have shown that the induction of antioxidants is an effective strategy to combat various disease states. In one approach, a SOD mimetic was applied topically to mouse skin in the two-stage skin carcinogenesis model. This method effectively reduced oxidative injury and proliferation without interfering with apoptosis. In another approach, Protandim, a combination of 5 well-studied medicinal plants, was given via dietary administration and significantly decreased tumor incidence and multiplicity by 33% and 57%, respectively. These studies suggest that alterations in antioxidant response may be a novel approach to chemoprevention. This paper focuses on how regulation of antioxidant expression and activity can be modulated in skin disease and the potential clinical implications of antioxidant-based therapies. PMID:21603266

  15. Human papillomavirus and the development of non-melanoma skin cancer.

    PubMed Central

    Harwood, C A; McGregor, J M; Proby, C M; Breuer, J

    1999-01-01

    Human papillomaviruses (HPV) are increasingly recognised as important human carcinogens. The best established association with human malignancy is that of high-risk mucosal HPV types and anogenital cancer. HPV-induced transformation of anogenital epithelia has been the subject of intense research which has identified the cellular tumour suppressor gene products, p53 and pRB, as important targets for the viral oncoproteins E6 and E7 respectively. Certain HPV types are also strongly associated with the development of non-melanoma skin cancer in the inherited disorder epidermodysplasia verruciformis (EV). However, in contrast with anogenital malignancy the oncogenic mechanisms of EV-HPV types remain uncertain, and there appears to be a crucial additional requirement for ultraviolet radiation. Cutaneous HPV types in the general population are predominantly associated with benign viral warts, but a role in non-melanoma skin cancer has recently been postulated. Polymerase chain reaction based HPV detection techniques have shown a high prevalence of HPV DNA, particularly in skin cancers from immunosuppressed patients and to a lesser extent in malignancies from otherwise immunocompetent individuals. No particular HPV type has yet emerged as predominant, and the role of HPV in cutaneous malignancy is unclear at present. It remains to be established whether HPV plays an active or purely a passenger role in the evolution of non-melanoma skin cancer. PMID:10474513

  16. Fernblock, a Nutriceutical with Photoprotective Properties and Potential Preventive Agent for Skin Photoaging and Photoinduced Skin Cancers

    PubMed Central

    Gonzalez, Salvador; Gilaberte, Yolanda; Philips, Neena; Juarranz, Angeles

    2011-01-01

    Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its use as a novel-generation photoprotective nutriceutical of phytochemical origin. PMID:22272084

  17. Cytotoxic Effects of the Ethanol Bane Skin Extract in Human Prostate Cancer Pc3 Cells

    PubMed Central

    Amiri, Maryam; Kazerouni, Faranak; Namaki, Saeed; Darbandi Tamijani, Hassan; Rahimipour, Hooman; Boroumand, Nasrin; Barghi, Siyamak; Ebrahimi, Nazanin; Gheibi Hayat, Seyed Mohammad

    2016-01-01

    Background: It is extensively supposed that vegetarian diet could affect cancer progress and increase the influence of formal chemotherapy. Objectives: The present study was designed to determine the effect of the ethanol Bane skin extract against chemo resistant prostate cancer PC3 cells. Materials and Methods: PC3 and L929 cells were cultivated and then incubated in the ethanol Bane skin extract with various concentrations of 0.78, 1.5, 3.13, 6.25, 12.5 mg/mL in 3 times 24, 48, 72 hours. Cytotoxic effect of the ethanol Bane skin extract on PC3 and L929 cells was examined by MTT assay after 24, 48, and 72 hours. Morphology of PC3 cells was evaluated by Gimsa staining. Results: The ethanol Bane skin extract inhibited proliferation and caused cell death with IC50 values of 2.8 mg/mL on PC3 cells and the IC50 was 6.1 mg/mL on l929 cells. Morphological changes and apoptotic bodies were observed in PC3 cells faced with the ethanol Bane skin extract by staining with Gimsa. Conclusions: The ethanol Bane skin extract could repress the growth of PC3 cell line. This inhibitory effect of the Bane extract depended on the dose and the time on PC3. The result of this study shows that the ethanol Bane skin extract includes photochemical and inhibitory function against proliferation and inducer of apoptosis in human prostate cancer PC3 cells and also has less cytotoxic effect on l929 than PC3 cells. The ethanol Bane skin extract might be a good candidate for the new herbal anticancer drug. PMID:27482333

  18. A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients

    PubMed Central

    Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.

    2013-01-01

    Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306

  19. Cell-type-specific roles for COX-2 in UVB-induced skin cancer

    PubMed Central

    Herschman, Harvey

    2014-01-01

    In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

  20. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    PubMed

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. PMID:24798404

  1. Skin Cancer Protective Behaviors among the Elderly: Explaining Their Response to a Health Education Program Using the Health Belief Model.

    ERIC Educational Resources Information Center

    Carmel, Sara; And Others

    1996-01-01

    In 4 kibbutzim, 43 adults over 60 completed a questionnaire on sun-exposure protective behaviors before and 2 weeks and 4 months after a skin cancer intervention. Beliefs about skin cancer did not change, but beliefs about the value of health and internal health locus of control changed significantly. (SK)

  2. What Influences the Uptake of Information to Prevent Skin Cancer? A Systematic Review and Synthesis of Qualitative Research

    ERIC Educational Resources Information Center

    Garside, Ruth; Pearson, Mark; Moxham, Tiffany

    2010-01-01

    Skin cancer is an increasing problem in Europe, America and Australasia, although largely preventable by avoiding excessive ultraviolet (UV) exposure. This paper presents the findings of a systematic review of qualitative research about the prevention of skin cancer attributable to UV exposure. The aim is to understand elements that may contribute…

  3. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

    PubMed Central

    Kelly, Lindsey M.; Barila, Guillermo; Liu, Pengyuan; Evdokimova, Viktoria N.; Trivedi, Sumita; Panebianco, Federica; Gandhi, Manoj; Carty, Sally E.; Hodak, Steven P.; Luo, Jianhua; Dacic, Sanja; Yu, Yan P.; Nikiforova, Marina N.; Ferris, Robert L.; Altschuler, Daniel L.; Nikiforov, Yuri E.

    2014-01-01

    Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone–independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. PMID:24613930

  4. Risk of skin cancer in patients with diabetes mellitus: A nationwide retrospective cohort study in Taiwan.

    PubMed

    Tseng, Hui-Wen; Shiue, Yow-Ling; Tsai, Kuo-Wang; Huang, Wei-Chun; Tang, Pei-Ling; Lam, Hing-Chung

    2016-06-01

    Increasing evidence suggests that certain types of cancers are more common in people with diabetes mellitus (DM). This study aimed to investigate the risk of skin cancer in patients with DM in Taiwan. In this retrospective cohort study using data from the Taiwan Longitudinal Health Insurance Research Database, the risk of developing overall skin cancer, including nonmelanoma skin cancer (NMSC) and melanoma, was compared by Poisson regression analysis and Cox regression analysis between the DM and non-DM cohorts. The DM cohort with newly diagnosed DM (n = 41,898) and a non-DM cohort were one-to-one matched by age, sex, index date, and comorbidities (coronary artery disease, hyperlipidemia, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and obesity). Compared with non-DM cohort statistically, for the people with DM aged ≥60 years, the incidence rates of overall skin cancer and NMSC were significantly higher (overall: DM/non-DM: number [n] = 99/76, incidence rate ratio [IRR] = 1.44, P = 0.02; NMSC: DM/non-DM: n = 94/66, IRR = 1.57, P = 0.005). By Cox regression analysis, the risk of developing overall skin cancer or NMSC was significantly higher after adjusting for sex, comorbidities, and overall diseases with immunosuppression status (overall: adjusted hazard ratio [AHR] = 1.46, P = 0.01; NMSC: AHR = 1.6, P = 0.003). Other significant risk factors were older males for skin cancer (overall: AHR = 1.68, P = 0.001; NMSC: AHR = 1.59, P = 0.004; melanoma: AHR = 3.25, P = 0.04), chronic obstructive pulmonary disease for NMSC (AHR = 1.44, P = 0.04), and coronary artery disease for melanoma (AHR = 4.22, P = 0.01). The risk of developing melanoma was lower in the DM cohort than in the non-DM cohort, but without significance (AHR = 0.56, P = 0.28; DM/non-DM: n = 5/10). The incidence rate and risk of developing overall skin cancer, including NMSC, was significantly higher in older adults with DM. Other significant risk factors for older adults

  5. Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL.

    PubMed

    Chijiiwa, Yoshiro; Moriyama, Taiki; Ohuchida, Kenoki; Nabae, Toshinaga; Ohtsuka, Takao; Miyasaka, Yoshihiro; Fujita, Hayato; Maeyama, Ryo; Manabe, Tatsuya; Abe, Atsushi; Mizuuchi, Yusuke; Oda, Yoshinao; Mizumoto, Kazuhiro; Nakamura, Masafumi

    2016-04-01

    Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P=0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer. PMID:26892887

  6. Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo

    PubMed Central

    Zhou, P-H; Zheng, J-B; Wei, G-B; Wang, X-L; Wang, W; Chen, N-Z; Yu, J-H; Yao, J-F; Wang, H; Lu, S-Y; Sun, X-J

    2015-01-01

    Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer. PMID:26005859

  7. Development of effective skin cancer treatment and prevention in xeroderma pigmentosum.

    PubMed

    Lambert, W Clark; Lambert, Muriel W

    2015-01-01

    Xeroderma pigmentosum (XP) is a rare, recessively transmitted genetic disease characterized by increasingly marked dyspigmentation and xerosis (dryness) of sun-exposed tissues, especially skin. Skin cancers characteristically develop in sun-exposed sites at very much earlier ages than in the general population; these are often multiple and hundreds or even thousands may develop. Eight complementation groups have been identified. Seven groups, XP-A…G, are associated with defective genes encoding proteins involved in the nucleotide excision DNA repair (NER) pathway that recognizes and excises mutagenic changes induced in DNA by sunlight; the eighth group, XP-V, is associated with defective translesion synthesis (TLS) bypassing such alterations. The dyspigmentation, xerosis and eventually carcinogenesis in XP patients appear to be due to their cells' failure to respond properly to these mutagenic DNA alterations, leading to mutations in skin cells. A subset of cases, especially those in some complementation groups, may develop neurological degeneration, which may be severe. However, in most XP patients, in the past the multiple skin cancers have led to death at an early age due to either metastases or sepsis. Using either topical 5-fluorouracil or imiquimod, we have developed a protocol that effectively prevents most skin cancer development in XP patients. PMID:25382223

  8. Cyclooxygenases: mediators of UV-induced skin cancer and potential targets for prevention.

    PubMed

    Elmets, Craig A; Ledet, Johnathan J; Athar, Mohammad

    2014-10-01

    Non-melanoma skin cancers (NMSCs) are among the most common human malignancies. Current methods for their prevention include avoidance of natural and artificial sources of UV radiation and using photoprotective clothing and sunscreens. However, these methods have proven to be inadequate in stemming the rise in skin cancer incidence over the past several years. There is accumulating evidence that cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis, may be involved in the pathogenesis of NMSC. In preclinical studies, animals genetically deficient in the COX-2 enzyme or that have been treated with pharmacological inhibitors of COX-2 develop significantly fewer tumors when subjected to a UV-induced skin carcinogenesis protocol compared with control mice. Several epidemiological studies in humans support the concept that this enzyme is intimately involved in UV-induced skin cancer development, and UV radiation is known to augment COX-2 expression in human skin. Recent studies suggest that drugs that block COX-2 expression may prevent the development of NMSCs. Thus, pharmacologic agents that inhibit the enzyme COX-2 may be effective chemopreventive agents for NMSCs. PMID:24804836

  9. Protective role of p53 in skin cancer: Carcinogenesis studies in mice lacking epidermal p53.

    PubMed

    Page, Angustias; Navarro, Manuel; Suarez-Cabrera, Cristian; Alameda, Josefa P; Casanova, M Llanos; Paramio, Jesús M; Bravo, Ana; Ramirez, Angel

    2016-04-12

    p53 is a protein that causes cell cycle arrest, apoptosis or senescence, being crucial in the process of tumor suppression in several cell types. Different in vitro and animal models have been designed for the study of p53 role in skin cancer. These models have revealed opposing results, as in some experimental settings it appears that p53 protects against skin cancer, but in others, the opposite conclusion emerges. We have generated cohorts of mice with efficient p53 deletion restricted to stratified epithelia and control littermates expressing wild type p53 and studied their sensitivity to both chemically-induced and spontaneous tumoral transformation, as well as the tumor types originated in each experimental group. Our results indicate that the absence of p53 in stratified epithelia leads to the appearance, in two-stage skin carcinogenesis experiments, of a higher number of tumors that grow faster and become malignant more frequently than tumors arisen in mice with wild type p53 genotype. In addition, the histological diversity of the tumor type is greater in mice with epidermal p53 loss, indicating the tumor suppressive role of p53 in different epidermal cell types. Aging mice with p53 inactivation in stratified epithelia developed spontaneous carcinomas in skin and other epithelia. Overall, these results highlight the truly protective nature of p53 functions in the development of cancer in skin and in other stratified epithelia. PMID:26959115

  10. Protective role of p53 in skin cancer: Carcinogenesis studies in mice lacking epidermal p53

    PubMed Central

    Page, Angustias; Navarro, Manuel; Suarez-Cabrera, Cristian; Alameda, Josefa P.; Casanova, M. Llanos; Paramio, Jesús M.; Bravo, Ana; Ramirez, Angel

    2016-01-01

    p53 is a protein that causes cell cycle arrest, apoptosis or senescence, being crucial in the process of tumor suppression in several cell types. Different in vitro and animal models have been designed for the study of p53 role in skin cancer. These models have revealed opposing results, as in some experimental settings it appears that p53 protects against skin cancer, but in others, the opposite conclusion emerges. We have generated cohorts of mice with efficient p53 deletion restricted to stratified epithelia and control littermates expressing wild type p53 and studied their sensitivity to both chemically-induced and spontaneous tumoral transformation, as well as the tumor types originated in each experimental group. Our results indicate that the absence of p53 in stratified epithelia leads to the appearance, in two-stage skin carcinogenesis experiments, of a higher number of tumors that grow faster and become malignant more frequently than tumors arisen in mice with wild type p53 genotype. In addition, the histological diversity of the tumor type is greater in mice with epidermal p53 loss, indicating the tumor suppressive role of p53 in different epidermal cell types. Aging mice with p53 inactivation in stratified epithelia developed spontaneous carcinomas in skin and other epithelia. Overall, these results highlight the truly protective nature of p53 functions in the development of cancer in skin and in other stratified epithelia. PMID:26959115

  11. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    SciTech Connect

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang

    2012-06-27

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  12. Risk reduction for nonmelanoma skin cancer with childhood sunscreen use

    SciTech Connect

    Stern, R.S.; Weinstein, M.C.; Baker, S.G.

    1986-05-01

    Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care.

  13. Nucleotide Excision Repair and Vitamin D-Relevance for Skin Cancer Therapy.

    PubMed

    Pawlowska, Elzbieta; Wysokinski, Daniel; Blasiak, Janusz

    2016-01-01

    Ultraviolet (UV) radiation is involved in almost all skin cancer cases, but on the other hand, it stimulates the production of pre-vitamin D3, whose active metabolite, 1,25-dihydroxyvitamin D3 (1,25VD3), plays important physiological functions on binding with its receptor (vitamin D receptor, VDR). UV-induced DNA damages in the form of cyclobutane pyrimidine dimers or (6-4)-pyrimidine-pyrimidone photoproducts are frequently found in skin cancer and its precursors. Therefore, removing these lesions is essential for the prevention of skin cancer. As UV-induced DNA damages are repaired by nucleotide excision repair (NER), the interaction of 1,25VD3 with NER components can be important for skin cancer transformation. Several studies show that 1,25VD3 protects DNA against damage induced by UV, but the exact mechanism of this protection is not completely clear. 1,25VD3 was also shown to affect cell cycle regulation and apoptosis in several signaling pathways, so it can be considered as a potential modulator of the cellular DNA damage response, which is crucial for mutagenesis and cancer transformation. 1,25VD3 was shown to affect DNA repair and potentially NER through decreasing nitrosylation of DNA repair enzymes by NO overproduction by UV, but other mechanisms of the interaction between 1,25VD3 and NER machinery also are suggested. Therefore, the array of NER gene functioning could be analyzed and an appropriate amount of 1.25VD3 could be recommended to decrease UV-induced DNA damage important for skin cancer transformation. PMID:27058533

  14. Nucleotide Excision Repair and Vitamin D—Relevance for Skin Cancer Therapy

    PubMed Central

    Pawlowska, Elzbieta; Wysokinski, Daniel; Blasiak, Janusz

    2016-01-01

    Ultraviolet (UV) radiation is involved in almost all skin cancer cases, but on the other hand, it stimulates the production of pre-vitamin D3, whose active metabolite, 1,25-dihydroxyvitamin D3 (1,25VD3), plays important physiological functions on binding with its receptor (vitamin D receptor, VDR). UV-induced DNA damages in the form of cyclobutane pyrimidine dimers or (6-4)-pyrimidine-pyrimidone photoproducts are frequently found in skin cancer and its precursors. Therefore, removing these lesions is essential for the prevention of skin cancer. As UV-induced DNA damages are repaired by nucleotide excision repair (NER), the interaction of 1,25VD3 with NER components can be important for skin cancer transformation. Several studies show that 1,25VD3 protects DNA against damage induced by UV, but the exact mechanism of this protection is not completely clear. 1,25VD3 was also shown to affect cell cycle regulation and apoptosis in several signaling pathways, so it can be considered as a potential modulator of the cellular DNA damage response, which is crucial for mutagenesis and cancer transformation. 1,25VD3 was shown to affect DNA repair and potentially NER through decreasing nitrosylation of DNA repair enzymes by NO overproduction by UV, but other mechanisms of the interaction between 1,25VD3 and NER machinery also are suggested. Therefore, the array of NER gene functioning could be analyzed and an appropriate amount of 1.25VD3 could be recommended to decrease UV-induced DNA damage important for skin cancer transformation. PMID:27058533

  15. Variants in melanogenesis-related genes associate with skin cancer risk among Japanese populations.

    PubMed

    Yoshizawa, Junko; Abe, Yuko; Oiso, Naoki; Fukai, Kazuyoshi; Hozumi, Yutaka; Nakamura, Tomohiro; Narita, Tomohiko; Motokawa, Tomonori; Wakamatsu, Kazumasa; Ito, Shosuke; Kawada, Akira; Tamiya, Gen; Suzuki, Tamio

    2014-04-01

    Human skin color is known to be associated with the risk of cutaneous cancer. Some reports indicated that pigmentation-related gene variants were associated with cutaneous cancer risk in Caucasian populations, but there are no similar reports in East Asian populations. This study aimed to evaluate the association between pigmentation-related genes and the risk of skin cancer in Japanese populations. We studied the associations between 12 variants of four pigmentation-related genes and melanin index variations in 198 Japanese patients with skin cancer and compared these findings to those of 500 Japanese controls by using multiple logistic regression analysis. Furthermore, we analyzed an independent sample of 107 Japanese patients with skin cancer. A non-synonymous variant, H615R in the oculocutaneous albinism 2 gene (OCA2), was associated with the risk of malignant melanoma in the Yamagata group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.86; P = 0.020). Another non-synonymous variant, A481T in OCA2, was associated with the risk of squamous cell carcinoma and actinic keratosis in the Osaka group (OR, 3.16; 95% CI, 1.41-7.04; P = 0.005). In malignant melanoma cases, the minor allele in OCA2 H615R might have induced the development of lesions in sun-exposed skin (OR, 26.32; 95% CI, 1.96-333; P = 0.014). Our results suggest that some OCA2 variants are definite risk factors for the onset of cutaneous cancer in Japanese populations. PMID:24617981

  16. Benefit Cost Analysis of Three Skin Cancer Public Education Mass-Media Campaigns Implemented in New South Wales, Australia.

    PubMed

    Doran, Christopher M; Ling, Rod; Byrnes, Joshua; Crane, Melanie; Shakeshaft, Anthony P; Searles, Andrew; Perez, Donna

    2016-01-01

    Public education mass media campaigns are an important intervention for influencing behaviour modifications. However, evidence on the effectiveness of such campaigns to encourage the population to reduce sun exposure is limited. This study investigates the benefits and costs of three skin cancer campaigns implemented in New South Wales from 2006-2013. This analysis uses Australian dollars (AUD) and 2010-11 as the currency and base year, respectively. Historical data on skin cancer were used to project skin cancer rates for the period 2006-2020. The expected number of skin cancer cases is derived by combining skin cancer rates, sunburn rates and relative risk of skin cancers due to sun exposure. Counterfactual estimates are based on sunburn exposure in the absence of the campaigns. Monetary values are attached to direct (treatment) and indirect (productivity) costs saved due to fewer skin cancer cases. Monetary benefits are compared with the cost of implementing the campaigns and are presented in the form of a benefit-cost ratio. Relative to the counterfactual (i.e., no campaigns) there are an estimated 13,174 fewer skin cancers and 112 averted deaths over the period 2006-2013. The net present value of these benefits is $60.17 million and the campaign cost is $15.63 million. The benefit cost ratio is 3.85, suggesting that for every $1 invested a return of $3.85 is achieved. Skin cancer public education mass media campaigns are a good investment given the likely extent to which they reduce the morbidity, mortality and economic burden of skin cancer. PMID:26824695

  17. Benefit Cost Analysis of Three Skin Cancer Public Education Mass-Media Campaigns Implemented in New South Wales, Australia

    PubMed Central

    2016-01-01

    Public education mass media campaigns are an important intervention for influencing behaviour modifications. However, evidence on the effectiveness of such campaigns to encourage the population to reduce sun exposure is limited. This study investigates the benefits and costs of three skin cancer campaigns implemented in New South Wales from 2006–2013. This analysis uses Australian dollars (AUD) and 2010–11 as the currency and base year, respectively. Historical data on skin cancer were used to project skin cancer rates for the period 2006–2020. The expected number of skin cancer cases is derived by combining skin cancer rates, sunburn rates and relative risk of skin cancers due to sun exposure. Counterfactual estimates are based on sunburn exposure in the absence of the campaigns. Monetary values are attached to direct (treatment) and indirect (productivity) costs saved due to fewer skin cancer cases. Monetary benefits are compared with the cost of implementing the campaigns and are presented in the form of a benefit-cost ratio. Relative to the counterfactual (i.e., no campaigns) there are an estimated 13,174 fewer skin cancers and 112 averted deaths over the period 2006–2013. The net present value of these benefits is $60.17 million and the campaign cost is $15.63 million. The benefit cost ratio is 3.85, suggesting that for every $1 invested a return of $3.85 is achieved. Skin cancer public education mass media campaigns are a good investment given the likely extent to which they reduce the morbidity, mortality and economic burden of skin cancer. PMID:26824695

  18. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    PubMed

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  19. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity

    PubMed Central

    Plikus, Maksim V.; Van Spyk, Elyse Noelani; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S.; Andersen, Bogi

    2015-01-01

    Historically work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as liver, fat and muscle. In recent years, skin is emerging as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging and carcinogenesis. Morphologically skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration -- the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell-type specific circadian mutants. Also, due to the accessibility of the skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar UV radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. The skin also provides opportunities to interrogate clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model for investigating the

  20. Skin Cancer Check? Do Some Sole-Searching

    MedlinePlus

    ... report was published June 16 in the New England Journal of Medicine . SOURCES: Ryuhei Okuyama, M.D., ... Abramson Cancer Center, Philadelphia; June 16, 2016, New England Journal of Medicine HealthDay Copyright (c) 2016 HealthDay . ...

  1. Do We Know What Causes Melanoma Skin Cancer?

    MedlinePlus

    ... become cancer cells. Most UV rays come from sunlight, but some can come from man-made sources ... more likely the result of damage caused by sunlight. In some people, such as those with xeroderma ...

  2. Diet in dermatology: Part I. Atopic dermatitis, acne, and nonmelanoma skin cancer.

    PubMed

    Bronsnick, Tara; Murzaku, Era Caterina; Rao, Babar K

    2014-12-01

    Patients commonly inquire about dietary modifications as a means to prevent or manage skin disease. Answering these questions is often challenging, given the vast and conflicting evidence that exists on this topic. This 2-part continuing medical education article summarizes the evidence to date to enable physicians to answer patients' questions in an evidence-based manner. Part I includes atopic dermatitis, acne, and nonmelanoma skin cancer. The role of dietary supplementation, dietary exclusion, food allergy, maternal diet, and breastfeeding in the development and/or prevention of atopic dermatitis is summarized. The dermatoendocrinologic mechanism for the effects of glycemic index/glycemic load and milk on acne is described, as well as related clinical evidence for dietary modifications. Finally, evidence and recommendations for restriction or supplementation of dietary factors in the prevention of nonmelanoma skin cancer, including fat, vitamins A, C, D, and E, and selenium, are reported. PMID:25454036

  3. An Evaluation of UV-Monitoring Enhanced Skin Cancer Prevention among Farm Youth in Rural Virginia

    ERIC Educational Resources Information Center

    Chen, Yi-Chun; Ohanehi, Donatus C.; Redican, Kerry J.

    2015-01-01

    Background: Health districts in southwest Virginia have one of the highest ultraviolet (UV) radiation exposure and sunburn rate. Due to higher levels of UV exposure, rural farm youth are at higher risk for skin cancer than non-farm youth. Few studies have been published that explore best practices for decreasing UV exposure among this population.…

  4. Estimates of ozone depletion and skin cancer incidence to examine the Vienna Convention achievements

    NASA Astrophysics Data System (ADS)

    Slaper, Harry; Velders, Guus J. M.; Daniel, John S.; de Gruijl, Frank R.; van der Leun, Jan C.

    1996-11-01

    DEPLETION of the ozone layer has been observed on a global scale1, and is probably related to halocarbon emissions. Ozone depletion increases the biologically harmful solar ultraviolet radiation reaching the surface of the Earth, which leads to a variety of adverse effects, including an increase in the incidence of skin cancer. The 1985 Vienna Convention provided the framework for international restrictions on the production of ozone-depleting substances. The consequences of such restrictions have not yet been assessed in terms of effects avoided. Here we present a new method of estimating future excess skin cancer risks which is used to compare effects of a 'no restrictions' scenario with two restrictive scenarios specified under the Vienna Convention: the Montreal Protocol, and the much stricter Copenhagen Amendments. The no-restrictions and Montreal Protocol scenarios produce a runaway increase in skin cancer incidence, up to a quadrupling and doubling, respectively, by the year 2100. The Copenhagen Amendments scenario leads to an ozone minimum around the year 2000, and a peak relative increase in incidence of skin cancer of almost 10% occurring 60 years later. These results demonstrate the importance of the international measures agreed upon under the Vienna Convention.

  5. Fifty years of changes in UV Index and implications for skin cancer in Australia

    NASA Astrophysics Data System (ADS)

    Lemus-Deschamps, Lilia; Makin, Jennifer K.

    2012-07-01

    Surface ultraviolet (UV) radiation plays an important role in human health. Increased exposure to UV radiation increases the risk of skin cancer. In Australia, public campaigns to prevent skin cancer include the promotion of daily UV forecasts. If all other atmospheric factors are equal, stratospheric ozone decreases result in UV increases. Given that Australia still has the highest skin cancer rates in the world, it is important to monitor Australia's stratospheric ozone and UV radiation levels over time because of the effects cumulative exposure can have on humans. In this paper, two long-term ozone datasets derived from surface and satellite measurements, a radiation code and atmospheric meteorological fields are used to calculate clear-sky UV radiation over a 50-year period (1959-2009) for Australia. The deviations from 1970-1980 levels show that clear-sky UV is on the rise. After the 1990s, an overall annual increase from 2 to 6% above the 1970-1980 levels was observed at all latitudes. Examining the summer and winter deviations from 1970-1980 showed that the winter signal dominated the annual changes, with winter increases almost twice those in summer. With ozone levels not expected to recover to pre-depletion levels until the middle of this century, UV levels are expected to continue to rise. Combined with Australians favoring an outdoor life-style, when temperatures are warmer, under high levels of UV, the associated risk of skin cancer will increase.

  6. Fifty years of changes in UV Index and implications for skin cancer in Australia.

    PubMed

    Lemus-Deschamps, Lilia; Makin, Jennifer K

    2012-07-01

    Surface ultraviolet (UV) radiation plays an important role in human health. Increased exposure to UV radiation increases the risk of skin cancer. In Australia, public campaigns to prevent skin cancer include the promotion of daily UV forecasts. If all other atmospheric factors are equal, stratospheric ozone decreases result in UV increases. Given that Australia still has the highest skin cancer rates in the world, it is important to monitor Australia's stratospheric ozone and UV radiation levels over time because of the effects cumulative exposure can have on humans. In this paper, two long-term ozone datasets derived from surface and satellite measurements, a radiation code and atmospheric meteorological fields are used to calculate clear-sky UV radiation over a 50-year period (1959-2009) for Australia. The deviations from 1970-1980 levels show that clear-sky UV is on the rise. After the 1990s, an overall annual increase from 2 to 6% above the 1970-1980 levels was observed at all latitudes. Examining the summer and winter deviations from 1970-1980 showed that the winter signal dominated the annual changes, with winter increases almost twice those in summer. With ozone levels not expected to recover to pre-depletion levels until the middle of this century, UV levels are expected to continue to rise. Combined with Australians favoring an outdoor life-style, when temperatures are warmer, under high levels of UV, the associated risk of skin cancer will increase. PMID:21870202

  7. Estimates of ozone depletion and skin cancer incidence to examine the Vienna Convention achievements.

    PubMed

    Slaper, H; Velders, G J; Daniel, J S; de Gruijl, F R; van der Leun, J C

    1996-11-21

    Depletion of the ozone layer has been observed on a global scale, and is probably related to halocarbon emissions. Ozone depletion increases the biologically harmful solar ultraviolet radiation reaching the surface of the Earth, which leads to a variety of adverse effects, including an increase in the incidence of skin cancer. The 1985 Vienna Convention provided the framework for international restrictions on the production of ozone-depleting substances. The consequences of such restrictions have not yet been assessed in terms of effects avoided. Here we present a new method of estimating future excess skin cancer risks which is used to compare effects of a 'no restrictions' scenario with two restrictive scenarios specified under the Vienna Convention: the Montreal Protocol, and the much stricter Copenhagen Amendments. The no-restrictions and Montreal Protocol scenarios produce a runaway increase in skin cancer incidence, up to a quadrupling and doubling, respectively, by the year 2100. The Copenhagen Amendments scenario leads to an ozone minimum around the year 2000, and a peak relative increase in incidence of skin cancer of almost 10% occurring 60 years later. These results demonstrate the importance of the international measures agreed upon under the Vienna Convention. PMID:8918873

  8. Skin cancer incidence is highly associated with ultraviolet-B radiation history.

    PubMed

    Chang, Ni-Bin; Feng, Rui; Gao, Zhiqiang; Gao, Wei

    2010-09-01

    Recently, the increased amount of ultraviolet-B (UV-B) exposure due to ozone depletion has been found to be associated with increased incidence of skin cancer across the world. The quantification of individual, regional, and historical UV exposure directly affects establishment of the association between skin cancer and UV exposure, but accurate assessment and measurement have been challenging for decades. As a sequence, cumulative studies using different metrics reported conflicting results on whether UV radiation, including sunburns, early childhood sun exposure, and chronic exposure, increases melanoma risk. This paper aims to establish the relationship between UV-B and melanoma incidence across the continental U.S. using an ecological approach that incorporate more accurate UV-B exposure measured by the National Aeronautical and Space Administration Nimbus-7 total ozone mapping spectrometer, and the United State Department of Agriculture ground-based network. Using statistical linear mixed models, we found strong positive associations between the skin cancer and the past UV exposure or the past cumulative 3-year UV exposure 3 or 4 years ago. UV has regional distributions and its regional effects on the skin cancer incidence are still significant after adjusting the effect of UV exposure. Research findings yield deepened understanding of spatiotemporal distribution of melanoma incidence rates and a greater appreciation for the complexity and heterogeneity of melanoma risk factors especially the UV-B exposure at different temporal and spatial scales. PMID:20619731

  9. SunSmart? Skin Cancer Knowledge and Preventive Behaviour in a British Population Representative Sample

    ERIC Educational Resources Information Center

    Miles, A.; Waller, J.; Hiom, S.; Swanston, D.

    2005-01-01

    The incidence of skin cancer has risen rapidly in the UK over the last 20 years, prompting public health organizations to try and raise awareness of the dangers of sun exposure and the need to practice sun-safe behaviour. This study aimed to assess baseline levels of sun-safe knowledge and behaviour in a British population-representative sample,…

  10. Sun Protection is Fun! A Skin Cancer Prevention Program for Preschools.

    ERIC Educational Resources Information Center

    Tripp, Mary K.; Herrmann, Nancy B.; Parcel, Guy S.; Chamberlin, Robert M.; Gritz, Ellen R.

    2000-01-01

    Describes the Sun Protection is Fun! skin cancer prevention program for preschool children that features intervention methods grounded in social cognitive theory and emphasizes symbolic modeling, vicarious learning, enactive mastery experiences, and persuasion. Program components include a curriculum and teacher's guide, videos, newsletters,…

  11. SPECIAL REPORT ON INGESTED INORGANIC ARSENIC: SKIN CANCER; NUTRITIONAL ESSENTIALITY (SAB REVIEW DRAFT)

    EPA Science Inventory

    A technical panel of EPA's Risk Assessment Forum has studied three special issues regarding certain health effects, particularly skin cancer, associated with arsenic ingestion: (1) the validity of the Taiwan study and its use for dose-response assessment in the U.S. population, (...

  12. High School Students' Perceptions of How Major Global Environmental Effects Might Cause Skin Cancer.

    ERIC Educational Resources Information Center

    Boyes, Edward; Stanisstreet, Martin

    1998-01-01

    Quantifies beliefs of high school students about links between skin cancer and global environmental effects. Some students confused the action of heat rays with that of ultraviolet rays and also thought that raised temperatures are culpable. Only one in 10 held the scientifically correct model: that ozone depletion via higher penetration of…

  13. The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

    PubMed Central

    Sharma, Naomi L.; Massie, Charlie E.; Butter, Falk; Mann, Matthias; Bon, Helene; Ramos-Montoya, Antonio; Menon, Suraj; Stark, Rory; Lamb, Alastair D.; Scott, Helen E.; Warren, Anne Y.; Neal, David E.; Mills, Ian G.

    2014-01-01

    In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention. PMID:24753418

  14. Estimating cancer risk from dental cone-beam CT exposures based on skin dosimetry.

    PubMed

    Pauwels, Ruben; Cockmartin, Lesley; Ivanauskaité, Deimante; Urbonienė, Ausra; Gavala, Sophia; Donta, Catherine; Tsiklakis, Kostas; Jacobs, Reinhilde; Bosmans, Hilde; Bogaerts, Ria; Horner, Keith

    2014-07-21

    The aim of this study was to measure entrance skin doses on patients undergoing cone-beam computed tomography (CBCT) examinations, to establish conversion factors between skin and organ doses, and to estimate cancer risk from CBCT exposures. 266 patients (age 8-83) were included, involving three imaging centres. CBCT scans were acquired using the SCANORA 3D (Soredex, Tuusula, Finland) and NewTom 9000 (QR, Verona, Italy). Eight thermoluminescent dosimeters were attached to the patient's skin at standardized locations. Using previously published organ dose estimations on various CBCTs with an anthropomorphic phantom, correlation factors to convert skin dose to organ doses were calculated and applied to estimate patient organ doses. The BEIR VII age- and gender-dependent dose-risk model was applied to estimate the lifetime attributable cancer risk. For the SCANORA 3D, average skin doses over the eight locations varied between 484 and 1788 µGy. For the NewTom 9000 the range was between 821 and 1686 µGy for Centre 1 and between 292 and 2325 µGy for Centre 2. Entrance skin dose measurements demonstrated the combined effect of exposure and patient factors on the dose. The lifetime attributable cancer risk, expressed as the probability to develop a radiation-induced cancer, varied between 2.7 per million (age >60) and 9.8 per million (age 8-11) with an average of 6.0 per million. On average, the risk for female patients was 40% higher. The estimated radiation risk was primarily influenced by the age at exposure and the gender, pointing out the continuing need for justification and optimization of CBCT exposures, with a specific focus on children. PMID:24957710

  15. Estimating cancer risk from dental cone-beam CT exposures based on skin dosimetry

    NASA Astrophysics Data System (ADS)

    Pauwels, Ruben; Cockmartin, Lesley; Ivanauskaité, Deimante; Urbonienė, Ausra; Gavala, Sophia; Donta, Catherine; Tsiklakis, Kostas; Jacobs, Reinhilde; Bosmans, Hilde; Bogaerts, Ria; Horner, Keith; SEDENTEXCT Project Consortium, The

    2014-07-01

    The aim of this study was to measure entrance skin doses on patients undergoing cone-beam computed tomography (CBCT) examinations, to establish conversion factors between skin and organ doses, and to estimate cancer risk from CBCT exposures. 266 patients (age 8-83) were included, involving three imaging centres. CBCT scans were acquired using the SCANORA 3D (Soredex, Tuusula, Finland) and NewTom 9000 (QR, Verona, Italy). Eight thermoluminescent dosimeters were attached to the patient's skin at standardized locations. Using previously published organ dose estimations on various CBCTs with an anthropomorphic phantom, correlation factors to convert skin dose to organ doses were calculated and applied to estimate patient organ doses. The BEIR VII age- and gender-dependent dose-risk model was applied to estimate the lifetime attributable cancer risk. For the SCANORA 3D, average skin doses over the eight locations varied between 484 and 1788 µGy. For the NewTom 9000 the range was between 821 and 1686 µGy for Centre 1 and between 292 and 2325 µGy for Centre 2. Entrance skin dose measurements demonstrated the combined effect of exposure and patient factors on the dose. The lifetime attributable cancer risk, expressed as the probability to develop a radiation-induced cancer, varied between 2.7 per million (age >60) and 9.8 per million (age 8-11) with an average of 6.0 per million. On average, the risk for female patients was 40% higher. The estimated radiation risk was primarily influenced by the age at exposure and the gender, pointing out the continuing need for justification and optimization of CBCT exposures, with a specific focus on children.

  16. Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Ghassemi, Pejhman; Lemaillet, Paul; Germer, Thomas A.; Shupp, Jeffrey W.; Venna, Suraj S.; Boisvert, Marc E.; Flanagan, Katherine E.; Jordan, Marion H.; Ramella-Roman, Jessica C.

    2012-07-01

    Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin--simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.

  17. Disruptive TP53 Mutation is Associated with Aggressive Disease Characteristics in an Orthotopic Murine Model of Oral Tongue Cancer

    PubMed Central

    Sano, Daisuke; Xie, Tong-Xin; Ow, Thomas J.; Zhao, Mei; Pickering, Curtis R.; Zhou, Ge; Sandulache, Vlad C.; Wheeler, David A.; Gibbs, Richard A.; Caulin, Carlos; Myers, Jeffrey N.

    2011-01-01

    Purpose To characterize tumor growth and metastatic potential in head and neck squamous cell carcinoma (HNSCC) cell lines in an orthotopic murine model of oral tongue cancer, and to correlate TP53 mutation status with these findings. Experimental Design Cells from each of 48 HNSCC cell lines were orthotopically injected into the oral tongues of nude mice. Tumor volume, cervical lymph node metastasis, and mouse survival were recorded. Direct sequencing of the TP53 gene and western blot analysis for the p53 protein after induction with 5-fluorouracil was performed. Cell lines were categorized as either mutant TP53 or wild-type TP53, and lines with TP53 mutation were further categorized on the basis of type of mutation (disruptive or non-disruptive), and level of p53 protein expression. The behavior of tumors in these different groups was compared. Results The 48 HNSCC cell lines showed a wide range of behavior from highly aggressive and metastatic to no tumor formation. Mice injected with cells harboring disruptive TP53 mutations had faster tumor growth, greater incidence of cervical lymph node metastasis, and shorter survival than mice injected with cells lacking these mutations. Conclusions HNSCC cell lines display a wide spectrum of behavior in an orthotopic model of oral cancer. Cell lines with disruptive TP53 mutations are more aggressive in this system, corroborating clinical reports that have linked these mutations to poor patient outcome. PMID:21903770

  18. Suppression of invasion and metastasis in aggressive salivary cancer cells through targeted inhibition of ID1 gene expression.

    PubMed

    Murase, Ryuichi; Sumida, Tomoki; Kawamura, Rumi; Onishi-Ishikawa, Akiko; Hamakawa, Hiroyuki; McAllister, Sean D; Desprez, Pierre-Yves

    2016-07-10

    Salivary gland cancer (SGC) represents the most common malignancy in the head and neck region, and often metastasizes to the lungs. The helix-loop-helix ID1 protein has been shown to control metastatic progression in many types of cancers. Using two different approaches to target the expression of ID1 (genetic knockdown and progesterone receptor introduction combined with progesterone treatment), we previously determined that the aggressiveness of salivary gland tumor ACCM cells in culture was suppressed. Here, using the same approaches to target ID1 expression, we investigated the ability of ACCM cells to generate lung metastatic foci in nude mice. Moreover, since both approaches would be challenging for applications in humans, we added a third approach, i.e., treatment of mice with a non-toxic cannabinoid compound known to down-regulate ID1 gene expression. All approaches aimed at targeting the pro-metastatic ID1 gene led to a significant reduction in the formation of lung metastatic foci. Therefore, targeting a key transcriptional regulator using different means results in the same reduction of the metastatic spread of SGC cells in animal models, suggesting a novel approach for the treatment of patients with aggressive SGC. PMID:27087608

  19. Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

    PubMed Central

    Blanchard, Zannel; Mullins, Nicole; Ellipeddi, Pavani; Lage, Janice M.; McKinney, Shawn; El-Etriby, Rana; Zhang, Xu; Isokpehi, Raphael; Hernandez, Brenda; ElShamy, Wael M.

    2014-01-01

    Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10–25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin’s ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl. PMID:24789045

  20. Swiss clinical practice guidelines on field cancerization of the skin.

    PubMed

    Hofbauer, Günther; Anliker, Mark; Boehncke, Wolf-Henning; Brand, Christoph; Braun, Ralph; Gaide, Olivier; Hafner, Jürg; Hunger, Robert; Itin, Peter; Kaeuper, Gina; Lautenschlager, Stephan; Mainetti, Carlo; Streit, Markus

    2014-01-01

    Actinic keratosis (AK) affects millions of people worldwide, and its prevalence continues to increase. AK lesions are caused by chronic ultraviolet radiation exposure, and the presence of two or more AK lesions along with photodamage should raise the consideration of a diagnosis of field cancerization. Effective treatment of individual lesions as well as field cancerization is essential for good long-term outcomes. The Swiss Registry of Actinic Keratosis Treatment (REAKT) Working Group has developed clinical practice guidelines for the treatment of field cancerization in patients who present with AK. These guidelines are intended to serve as a resource for physicians as to the most appropriate treatment and management of AK and field cancerization based on current evidence and the combined practical experience of the authors. Treatment of AK and field cancerization should be driven by consideration of relevant patient, disease, and treatment factors, and appropriate treatment decisions will differ from patient to patient. Prevention measures and screening recommendations are discussed, and special considerations related to management of immunocompromised patients are provided. PMID:25539459

  1. Imaging nonmelanoma skin cancers with combined ultrasound-photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Sunar, Ulas; Rohrbach, Daniel J.; Morgan, Janet; Zeitouni, Natalie

    2013-03-01

    PDT has become a treatment of choice especially for the cases with multiple sites and large areas. However, the efficacy of PDT is limited for thicker and deeper tumors. Depth and size information as well as vascularity can provide useful information to clinicians for planning and evaluating PDT. High-resolution ultrasound and photoacoustic imaging can provide information regarding skin structure and vascularity. We utilized combined ultrasound-photoacoustic microscopy for imaging a basal cell carcinoma (BCC) tumor pre-PDT and the results indicate that combined ultrasound-photoacoustic imaging can be useful tool for PDT planning by providing both structural and functional contrasts.

  2. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer

    PubMed Central

    Lund, Amanda W.; Medler, Terry R.; Leachman, Sancy A.; Coussens, Lisa M.

    2015-01-01

    Skin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, are important contributors to malignancy and potential biomarkers and targets for immunotherapy. PMID:26552413

  3. HLA-G in skin cancer: a wolf in sheep's clothing?

    PubMed

    Urosevic, Mirjana; Dummer, Reinhard

    2003-11-01

    Despite well-defined and immunogenic tumor antigens, and even in the presence of tumor antigen-specific cytotoxic cells, the immune system does not appear to be very effective in eradicating cells that have undergone malignant transformation. Tumor cells, even though invading and representing a threat, are not truly "foreign" but autologous cells that have become transformed in a subtle way, enabling them to escape the host immune system. Melanoma, and to less extent nonmelanoma, skin cancers have developed different strategies to circumvent host immunosurveillance. HLA-G is one of the molecules implicated in cancer immunescape. This review will concentrate on induction and expression of this nonclassical class I molecule in different skin cancer types presenting existing experimental evidence on this topic. PMID:14602238

  4. Identifying mouse models for skin cancer using the Mouse Tumor Biology Database.

    PubMed

    Begley, Dale A; Krupke, Debra M; Neuhauser, Steven B; Richardson, Joel E; Schofield, Paul N; Bult, Carol J; Eppig, Janan T; Sundberg, John P

    2014-10-01

    In recent years, the scientific community has generated an ever-increasing amount of data from a growing number of animal models of human cancers. Much of these data come from genetically engineered mouse models. Identifying appropriate models for skin cancer and related relevant genetic data sets from an expanding pool of widely disseminated data can be a daunting task. The Mouse Tumor Biology Database (MTB) provides an electronic archive, search and analysis system that can be used to identify dermatological mouse models of cancer, retrieve model-specific data and analyse these data. In this report, we detail MTB's contents and capabilities, together with instructions on how to use MTB to search for skin-related tumor models and associated data. PMID:25040013

  5. Handheld confocal Raman microspectrometer for in-vivo skin cancer measurement

    NASA Astrophysics Data System (ADS)

    Lieber, Chad A.; Ellis, Darrel L.; Billheimer, D. D.; Mahadevan-Jansen, Anita

    2004-07-01

    Several studies have demonstrated Raman spectroscopy to be capable of tissue diagnosis with accuracy rivaling that of histopathologic analysis. This technique obtains biochemical-specific information noninvasively, and can eliminate the pain, time, and cost associated with biopsy and pathological analysis. Furthermore, when used in a confocal arrangement, Raman spectra can be obtained from localized regions of the tissue. Skin cancers are an ideal candidate for this emerging technology, due to their obvious accessibility and presentation at specific depths. However, most commercially available confocal Raman microspectrometers are large, rigid systems ill-suited for clinical application. We developed a bench-top confocal Raman microspectrometer using a portable external-cavity diode laser excitation source. This system was used to study several skin lesions in vitro. Results show the depth-resolved Raman spectra can diagnose in vitro skin lesions with 96% sensitivity, 88% specificity, and 86% pathological classification accuracy. Based on the success of this study, a portable Raman system with a handheld confocal microscope was developed for clinical application. Preliminary in vivo data show several distinct spectral differences between skin pathologies. Diagnostic algorithms are planned for this continuing study to assess the capability of Raman spectroscopy for clinical skin cancer diagnosis.

  6. Visual Exemplification and Skin Cancer: The Utility of Exemplars in Promoting Skin Self-Exams and Atypical Nevi Identification.

    PubMed

    King, Andy J

    2016-07-01

    The present article reports an experiment investigating untested propositions of exemplification theory in the context of messages promoting early melanoma detection. The study tested visual exemplar presentation types, incorporating visual persuasion principles into the study of exemplification theory and strategic message design. Compared to a control condition, representative visual exemplification was more effective at increasing message effectiveness by eliciting a surprise response, which is consistent with predictions of exemplification theory. Furthermore, participant perception of congruency between the images and text interacted with the type of visual exemplification to explain variation in message effectiveness. Different messaging strategies influenced decision making as well, with the presentation of visual exemplars resulting in people judging the atypicality of moles more conservatively. Overall, results suggest that certain visual messaging strategies may result in unintended effects of presenting people information about skin cancer. Implications for practice are discussed. PMID:27337542

  7. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

  8. Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

    NASA Astrophysics Data System (ADS)

    Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

    2014-11-01

    The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

  9. Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

    PubMed Central

    Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

    2014-01-01

    Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device. PMID:25375350

  10. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study.

    PubMed

    Shakeel, Faiyaz; Haq, Nazrul; Al-Dhfyan, Abdullah; Alanazi, Fars K; Alsarra, Ibrahim A

    2015-01-01

    Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40 ± 14.56 µg cm(-2) h(-1) and 2.064 × 10(-2) ± 0.050 × 10(-2 )cm h(-1), respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer. PMID:24350612

  11. The barrier function of organotypic non-melanoma skin cancer models.

    PubMed

    Zoschke, Christian; Ulrich, Martina; Sochorová, Michaela; Wolff, Christopher; Vávrová, Kateřina; Ma, Nan; Ulrich, Claas; Brandner, Johanna M; Schäfer-Korting, Monika

    2016-07-10

    Non-melanoma skin cancer (NMSC) is the most frequent human cancer with continuously rising incidences worldwide. Herein, we investigated the molecular basis for the impaired skin barrier function of organotypic NMSC models. We unraveled disturbed epidermal differentiation by reflectance confocal microscopy and histopathological evaluation. While the presence of claudin-4 and occludin were distinctly reduced, zonula occludens protein-1 was more wide-spread, and claudin-1 was heterogeneously distributed within the NMSC models compared with normal reconstructed human skin. Moreover, the cancer altered stratum corneum lipid packing and profile with decreased cholesterol content, increased phospholipid amount, and altered ceramide subclasses. These alterations contributed to increased surface pH and to 1.5 to 2.6-fold enhanced caffeine permeability of the NMSC models. Three topical applications of ingenol mebutate gel (0.015%) caused abundant epidermal cell necrosis, decreased Ki-67 indices, and increased lactate dehydrogenase activity. Taken together, our study provides new biological insights into the microenvironment of organotypic NMSC models, improves the understanding of the disease model by revealing causes for impaired skin barrier function in NMSC models at the molecular level, and fosters human cell-based approaches in preclinical drug evaluation. PMID:27130695

  12. Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice.

    PubMed

    Majed, Ferial; Rashid, Summya; Khan, Abdul Quaiyoom; Nafees, Sana; Ali, Nemat; Ali, Rashid; Khan, Rehan; Hasan, Syed Kazim; Mehdi, Syed Jafar; Sultana, Sarwat

    2015-01-01

    Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent. PMID:25399297

  13. The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors

    PubMed Central

    Campione, Elena; Paternò, Evelin Jasmine; Candi, Eleonora; Falconi, Mattia; Costanza, Gaetana; Diluvio, Laura; Terrinoni, Alessandro; Bianchi, Luca; Orlandi, Augusto

    2015-01-01

    Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein–ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy. PMID:26604686

  14. Dermatocosmetologic aspects of treatment of basal-cell skin cancer

    NASA Astrophysics Data System (ADS)

    Geinitz, A. V.; Stranadko, Ye. F.; Yusupova, Zh. M.; Tkachenko, S. B.

    2005-08-01

    The obtained clinical findings demonstrate excellent results after surgical MSC treatment with the application of modem laser surgical technologies. All the operated patients were under oncologist"s control during 1.5-2.5 years. In 6 cases we observed topical recurrences which needed a repeated intervention. Thus, our experience of applying LPh for surgical treatment of basal-cell carcinomas of the head and neck dem- onstrate that in the analysed cases it is more reasonable to use two models of laser devices different in their physical parameters. These devices are used at different surgical stages so as to provide a precise effect in laser tumour va- porization within the borders of the healthy tissue, to make better vascular coagulation and laser smoothing of wound surface. Immediate, direct and long-term results of modern surgical lasers" application for treating skin BSC almost in all cases give good and excellent cosmetic effect after such intenventions.

  15. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    PubMed

    ElShamy, Wael M; Sinha, Abhilasha; Said, Neveen

    2016-01-01

    The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the "aggressiveness niche" and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche. PMID:27493669

  16. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    PubMed Central

    2016-01-01

    The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the “aggressiveness niche” and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche. PMID:27493669

  17. Pancreatic cancer stem-like cells display aggressive behavior mediated via activation of FoxQ1.

    PubMed

    Bao, Bin; Azmi, Asfar S; Aboukameel, Amro; Ahmad, Aamir; Bolling-Fischer, Aliccia; Sethi, Seema; Ali, Shadan; Li, Yiwei; Kong, Dejuan; Banerjee, Sanjeev; Back, Jessica; Sarkar, Fazlul H

    2014-05-23

    Subpopulations of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) have been identified from most tumors, including pancreatic cancer (PC), and the existence of these cells is clinically relevant. Emerging evidence suggests that CSLCs participate in cell growth/proliferation, migration/invasion, metastasis, and chemo-radiotherapy resistance, ultimately contributing to poor clinical outcome. However, the pathogenesis and biological significance of CSLCs in PC has not been well characterized. In the present study, we found that isolated triple-marker-positive (CD44(+)/CD133(+)/EpCAM(+)) cells of human PC MiaPaCa-2 and L3.6pl cells behave as CSLCs. These CSLCs exhibit aggressive behavior, such as increased cell growth, migration, clonogenicity, and self-renewal capacity. The mRNA expression profiling analysis showed that CSLCs (CD44(+)/CD133(+)/EpCAM(+)) exhibit differential expression of more than 1,600 mRNAs, including FoxQ1, compared with the triple-marker-negative (CD44(-)/CD133(-)/EpCAM(-)) cells. The knockdown of FoxQ1 by its siRNA in CSLCs resulted in the inhibition of aggressive behavior, consistent with the inhibition of EpCAM and Snail expression. Mouse xenograft tumor studies showed that CSLCs have a 100-fold higher potential for tumor formation and rapid tumor growth, consistent with overexpression of CSC-associated markers/mediators, including FoxQ1, compared with its parental MiaPaCa-2 cells. The inhibition of FoxQ1 attenuated tumor formation and growth, and expression of CSC markers in the xenograft tumor derived from CSLCs of MiaPaCa-2 cells. These data clearly suggest the role of differentially expressed genes in the regulation of CSLC characteristics, further suggesting that targeting some of these genes could be important for the development of novel therapies for achieving better treatment outcome of PC. PMID:24719318

  18. Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness*

    PubMed Central

    Liu, Yansheng; Chen, Jing; Sethi, Atul; Li, Qing K.; Chen, Lijun; Collins, Ben; Gillet, Ludovic C. J.; Wollscheid, Bernd; Zhang, Hui; Aebersold, Ruedi

    2014-01-01

    The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa. PMID:24741114

  19. Z skin incision in reduced-port surgery for colorectal cancer

    PubMed Central

    FUJINO, SHIKI; MIYOSHI, NORIKATSU; OHUE, MASAYUKI; NOURA, SHINGO; FUJIWARA, YOSHIYUKI; HIGASHIYAMA, MASAHIKO; YANO, MASAHIKO

    2016-01-01

    Laparoscopic surgery for colorectal cancer (CRC) has recently gained in popularity due to the fewer trocars and shorter incision, leading to reduced wound pain and improved cosmetic outcome. In July, 2013, reduced-port surgery (RPS) was introduced and has been performed thereafter in our hospital. An umbilical incision is used for a main port in RPS, through which the specimen is removed and the anastomosis is performed. In order to make the incision shorter, we introduced the Z skin incision in RPS. In this study, we aimed to discuss this method and evaluate the short-term outcome. Among CRC patients undergoing RPS, Z skin incision (n=14) was compared to conventional skin incision (n=15). The clinical and surgical factors were evaluated and there were no significant differences in terms of gender, age, body mass index, tumor site, procedure, operative time, blood loss or complications between the two groups. The median incision length at the umbilicus was significantly shorter in the Z incision group (P=0.004). Particularly in functional end-to-end anastomosis, the median incision length was 2.5 cm in the Z skin incision group and 4.0 cm in the conventional incision group (P=0.018). In conclusion, Z skin incision is a useful technique for achieving an effective length of skin incision in RPS for CRC. PMID:27073675

  20. European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer.

    PubMed

    Bertino, Giulia; Sersa, Gregor; De Terlizzi, Francesca; Occhini, Antonio; Plaschke, Christina Caroline; Groselj, Ales; Langdon, Cristobal; Grau, Juan J; McCaul, James A; Heuveling, Derrek; Cemazar, Maja; Strojan, Primoz; de Bree, Remco; Leemans, C Renè; Wessel, Irene; Gehl, Julie; Benazzo, Marco

    2016-08-01

    Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427). PMID:27267144

  1. Ultraviolet induced DNA damage and hereditary skin cancer

    SciTech Connect

    Regan, J.D.; Carrier, W.L.; Francis, A.A.

    1984-01-01

    Clearly, cells from normal individuals possess the ability to repair a variety of damage to DNA. Numerous studies indicate that defects in DNA repair may increase an individual's susceptibility to cancer. It is hoped that continued studies of the exact structural changes produced in the DNA by environmental insults, and the correlation of specific DNA changes with particulr cellular events, such as DNA repair, will lead to a better understanding of cell-killing, mutagenesis and carbinogenesis. 1 figure, 2 tables.

  2. Trends in the Frequency of Original Research in Acne Vulgaris, Rosacea, Dermatitis, Psoriasis, Skin Cancer, and Skin Infections, 1970–2010

    PubMed Central

    Choi, Young M; Wu, Jashin J

    2015-01-01

    Context: Medical journals have allowed researchers to share their latest discoveries, especially in the most common diseases affecting patients worldwide. Objective: To analyze trends in the frequency of original research into common dermatologic diseases from 1970 to 2010. Design: A retrospective review of the Journal of the American Academy of Dermatology and the Archives of Dermatology was performed using the MEDLINE database. All original research articles published between 1970 and 2010, by quinquennium, dealing with acne vulgaris, rosacea, skin cancer, dermatitis, psoriasis, or skin infections were included. Main Outcome Measure: Total number of publications dealing with each dermatologic topic considered. Results: The frequency of research into acne vulgaris and rosacea decreased from 24% in 1970 to 5.1% in 2010. Psoriasis research increased in frequency from 17.6% to 26.5% from 2000 to 2010, and skin cancer research increased from 4% in 1970 to 48% in 2010. Conclusions: Topics that experienced early advancements in research, such as acne vulgaris and rosacea, demonstrated a decreasing trend in the frequency of publication. Published psoriasis research has increased in frequency since 2000, most likely because of the discovery of biologics. Finally, skin cancer research has continued to increase in frequency of publication, paralleling the increasing incidence of skin cancer. PMID:25663204

  3. Dye-enhanced multimodal confocal microscopy for noninvasive detection of skin cancers in mouse models

    NASA Astrophysics Data System (ADS)

    Park, Jesung; Mroz, Pawel; Hamblin, Michael R.; Yaroslavsky, Anna N.

    2010-03-01

    Skin cancer is the most common form of human cancer. Its early diagnosis and timely treatment is of paramount importance for dermatology and surgical oncology. In this study, we evaluate the use of reflectance and fluorescence confocal microscopy for detecting skin cancers in an in-vivo trial with B16F10 melanoma and SCCVII squamous cell carcinoma in mice. For the experiments, the mice are anesthetized, then the tumors are infiltrated with aqueous solution of methylene blue and imaged. Reflectance images are acquired at 658 nm. Fluorescence is excited at 658 nm and registered in the range between 690 and 710 nm. After imaging, the mice are sacrificed. The tumors are excised and processed for hematoxylin and eosin histopathology, which is compared to the optical images. The results of the study indicate that in-vivo reflectance images provide valuable information on vascularization of the tumor, whereas the fluorescence images mimic the structural features seen in histopathology. Simultaneous dye-enhanced reflectance and fluorescence confocal microscopy shows promise for the detection, demarcation, and noninvasive monitoring of skin cancer development.

  4. A dose-response analysis of skin cancer from inorganic arsenic in drinking water

    SciTech Connect

    Brown, K.G.; Boyle, K.E.; Chen, C.W.; Gibb, H.J. )

    1989-12-01

    A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3)) if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).

  5. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.

    PubMed

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

  6. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    PubMed Central

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

  7. Behavior Modification and Risk Perception in Patients with Nonmelanoma Skin Cancer

    PubMed Central

    Rhee, John S.; Davis-Malesevich, Melinda; Logan, Brent R.; Neuburg, Marcy; Burzynski, Mary; Nattinger, Ann B.

    2013-01-01

    Context Nonmelanoma skin cancer (NMSC) is the most common cancer among humans; yet risk perceptions and preventive health behaviors in this unique cancer survivorship population is relatively unknown. Objectives To assess the impact of the disease and its treatment on sun-protective behaviors, general preventive health behaviors, and risk perception in NMSC patients, and to determine factors associated with behavioral change. Design and Setting Prospective study of 211 consecutive NMSC patients presenting to a dermatologic surgery clinic at a tertiary care university medical center from February, 2005 to March, 2006. Patients Inclusion criteria consisted of NMSC of the head and neck, adult age, and fluency in English. Of the 211 eligible patients, complete data was obtained for 183 (87%). Most common reasons for dropout were voluntary withdrawal and incompletely answered surveys. Intervention and Outcome Measures Surveys that assessed disease-specific quality of life (QOL), preventive health behaviors (smoking, alcohol use, exercise, diet, skin self exams), sun-protective behaviors (sunscreen, protective clothing use and ultraviolet light exposure minimization), and risk perception (chances of developing another NMSC, melanoma, or other non-skin cancers) were administered before and after surgical treatment of NMSC. Results Sun-protective behaviors improved post-surgery even after controlling for seasons (p<0.001). Predictor factors associated with increased sun-protective behavior included poor skin tanning ability, summer season, no employment, less comorbid conditions and previous NMSC treatment. Baseline QOL was not predictive of behavioral change. As for risk perception, respondents thought they were more likely than someone similar to themselves to develop future NMSC’s but thought they had similar risks of developing melanoma or other non-skin cancers (p<0.001). There was no significant change in any general preventive health behaviors after surgery except

  8. Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17

    PubMed Central

    Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F.

    2012-01-01

    Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α–converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

  9. Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17.

    PubMed

    Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F

    2012-08-01

    Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α-converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

  10. Tumors of the skin and soft tissues

    SciTech Connect

    Weller, R.E.

    1991-10-01

    The majority of the body surface is covered by the skin. Many internal disorders are reflected in the condition of the skin. One of the major functions of the skin is protection of the other organ systems from a variety of environmental insults. In this role, the skin itself is exposed to factors that can ultimately cause chronic diseases and cancer. Since it is relatively easy to recognize skin abnormalities, most skin cancers are brought to professional attention sooner than other types of cancer. However, due to the close resemblance between many skin neoplasms and noncancerous dermatologic disorders, these neoplasms may be mistreated for months or even years. In veterinary oncology, as in human medicine, most cancers can be effectively treated or cured following an accurate diagnosis. Once diagnosed, skin neoplasms should be aggressively treated. If causal factors are known, exposure to these factors should be limited through removal of the agent (for chemical carcinogens) or limiting exposure to the agent (for other carcinogens such as sunlight). 10 tabs. (MHB)

  11. LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling.

    PubMed

    Niu, Ya; Shao, Ziyun; Wang, Hui; Yang, Jiaqi; Zhang, Feifei; Luo, Yuhao; Xu, Lijun; Ding, Yanqing; Zhao, Liang

    2016-01-01

    LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1. PMID:27181092

  12. LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling

    PubMed Central

    Niu, Ya; Shao, Ziyun; Wang, Hui; Yang, Jiaqi; Zhang, Feifei; Luo, Yuhao; Xu, Lijun; Ding, Yanqing; Zhao, Liang

    2016-01-01

    LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1. PMID:27181092

  13. Upregulation of long noncoding RNA LOC100507661 promotes tumor aggressiveness in thyroid cancer.

    PubMed

    Kim, Daham; Lee, Woo Kyung; Jeong, Seonhyang; Seol, Mi-Youn; Kim, Hyunji; Kim, Kyung-Sup; Lee, Eun Jig; Lee, Jandee; Jo, Young Suk

    2016-08-15

    Recent advances in next-generation sequencing have revealed a variety of long noncoding RNAs (lncRNAs). However, studies of lncRNAs are at a very early stage, our knowledge of the biological functions and clinical implications remains limited. To investigate the roles of lncRNAs in thyroid cancers, we verified 56 lncRNAs identified as potential cancer-promoting genes in a previous study that analyzed 2394 tumor SNP arrays from 12 types of cancer. Based on verified sequence information in NCBI and Ensembl, we ultimately selected three candidate lncRNAs for detailed analysis. One of the candidates, LOC100507661, was strongly upregulated in thyroid cancer tissues relative to paired contralateral normal tissue. LOC100507661 was easily detectable in papillary and anaplastic thyroid cancer cell lines such as TPC1, BCPAP, C643, and 8505C, but not in the follicular thyroid cancer cell line FTC133. Stable overexpression of LOC100507661 promoted cell proliferation, migration, and invasion of thyroid cancer cells. Lymph node metastasis and BRAF V600E mutations were more frequent in papillary thyroid cancers with high LOC100507661 expression. Our data demonstrate that LOC100507661 expression is elevated in human thyroid cancer and may play a critical role in thyroid carcinogenesis. PMID:27151833

  14. Computational Intelligence and Image Processing Methods for Applications in Skin Cancer Diagnosis

    NASA Astrophysics Data System (ADS)

    Ogorzałek, Maciej; Surówka, Grzegorz; Nowak, Leszek; Merkwirth, Christian

    Digital photography provides new powerful diagnostic tools in dermatology. Dermoscopy is a special photography technique which enables taking photos of skin lesions in chosen lighting conditions. Digital photography allows for seeing details of the skin changes under various enlargements and coloring. Computer-assisted techniques and image processing methods can be further used for image enhancement and analysis and for feature extraction and pattern recognition in the selected images. Special techniques used in skin-image processing are discussed in detail. Feature extraction methods and automated classification techniques based on statistical learning and model ensembling techniques provide very powerful tools which can assist the doctors in taking decisions. Performance of classifiers will be discussed in specific case of melanoma cancer diagnosis. The techniques have been tested on a large data set of images.

  15. Novel treatment options for nonmelanoma skin cancer: focus on electronic brachytherapy

    PubMed Central

    Kasper, Michael E; Chaudhary, Ahmed A

    2015-01-01

    Nonmelanoma skin cancer (NMSC) is an increasing health care issue in the United States, significantly affecting quality of life and impacting health care costs. Radiotherapy has a long history in the treatment of NMSC. Shortly after the discovery of X-rays and 226Radium, physicians cured patients with NMSC using these new treatments. Both X-ray therapy and brachytherapy have evolved over the years, ultimately delivering higher cure rates and lower toxicity. Electronic brachytherapy for NMSC is based on the technical and clinical data obtained from radionuclide skin surface brachytherapy and the small skin surface applicators developed over the past 25 years. The purpose of this review is to introduce electronic brachytherapy in the context of the history, data, and utilization of traditional radiotherapy and brachytherapy. PMID:26648763

  16. Spectral analysis of delayed luminescence as a tool to discriminate between normal and cancer skin cells

    NASA Astrophysics Data System (ADS)

    Musumeci, F.; Scordino, A.; Tudisco, S.; Privitera, S.; Applegate, L. A.; Niggli, H. J.

    2005-08-01

    Photobiological research in the last decades has shown the existence of Delayed Luminescence in biological tissue, which presents an excitation spectrum with a peak within the UVA region and can be detected with sophisticated photomultiplier systems. Based on these findings, a new and powerful tool able to measure the UV-A-laser-induced Delayed Luminescence emission of cultured cells was developed, with the intention to detect biophysical changes between carcinogenic and normal cells. Indeed noticeable differences have been found in the time resolved emission spectrum of delayed luminescence of cell cultures of human fibroblast and human melanoma. This new, powerful and non-invasive technique, in principle, could be applied in all fields of skin research, such as the investigation of skin abnormalities and to test the effect of products involved in regeneration, anti-aging and UV-light protection in order to prevent skin cancer.

  17. Light - Instead of UV Protection: New Requirements for Skin Cancer Prevention.

    PubMed

    Zastrow, Leonhard; Lademann, Jürgen

    2016-03-01

    The requirements on sunscreens have essentially changed, since some years ago it was demonstrated that approximately 50% of free radicals, that are formed in the skin by solar radiation, originate from the visible and infrared regions of the solar spectrum. In addition, a critical radical concentration threshold could be found. If this concentration, the free radical threshold value (FRTV), is exceeded, sunburn, immunosuppression and skin cancer may develop. Application of sunscreens and lotions protects against sunburn in the UV region of the solar spectrum and therefore is frequently used to extend people's stay in the sun. However, this behaviour can enhance the concentration of free radicals formed in the visible and infrared regions of the solar spectrum, so that the critical radical threshold is exceeded and the skin may be damaged. PMID:26977040

  18. Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue?

    PubMed Central

    Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Golubov, Andrey; Rodriguez-Juarez, Rocio; Woycicki, Rafal; Hegmann, Frank A.; Kovalchuk, Olga

    2013-01-01

    Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum and is non-ionizing. We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes. The ability of intense THz pulses to cause concerted favorable changes in the expression of multiple genes implicated in inflammatory skin diseases and skin cancers suggests potential therapeutic applications of intense THz pulses. PMID:23917523

  19. A systematic review of clinical outcomes for patients diagnosed with skin cancer spinal metastases.

    PubMed

    Goodwin, C Rory; Sankey, Eric W; Liu, Ann; Elder, Benjamin D; Kosztowski, Thomas; Lo, Sheng-Fu L; Fisher, Charles G; Clarke, Michelle J; Gokaslan, Ziya L; Sciubba, Daniel M

    2016-05-01

    OBJECT Surgical procedures and/or adjuvant therapies are effective modalities for the treatment of symptomatic spinal metastases. However, clinical results specific to the skin cancer spinal metastasis cohort are generally lacking. The purpose of this study was to systematically review the literature for treatments, clinical outcomes, and survival following the diagnosis of a skin cancer spinal metastasis and evaluate prognostic factors in the context of spinal skin cancer metastases stratified by tumor subtype. METHODS The authors performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles since 1950 that reported survival, clinical outcomes, and/or prognostic factors for the skin cancer patient population with spinal metastases. The methodological quality of reviews was assessed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) tool. RESULTS Sixty-five studies met the preset criteria and were included in the analysis. Of these studies, a total of 25, 40, 25, and 12 studies included patients who underwent some form of surgery, radiotherapy, chemotherapy, or observation alone, respectively. Sixty-three of the 65 included studies were retrospective in nature (Class of Evidence [CoE] IV), and the 2 prospective studies were CoE II. Based on the studies analyzed, the median overall survival for a patient with a spinal metastasis from a primary skin malignancy is 4.0 months; survival by tumor subtype is 12.5 months for patients with basal cell carcinoma (BCC), 4.0 months for those with melanoma, 4.0 months for those with squamous cell carcinoma, 3.0 months for those with pilomatrix carcinoma, and 1.5 months for those with Merkel cell carcinoma (p < 0.0001). The overall percentage of known continued disease progression after spine metastasis diagnosis was 40.1% (n = 244/608, range 25.0%-88.9%), the rate of known recurrence of the primary skin cancer lesion was 3.5% (n = 21/608, range 0

  20. Current status of pharmacogenomics testing for anti-tumor drug therapies: approaches to non-melanoma skin cancer.

    PubMed

    Grealy, Rebecca; Griffiths, Lyn R

    2009-01-01

    Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment. PMID:19537842

  1. BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization

    PubMed Central

    Song, Shujie; Simon, Jeremy; Parker, Joel; Wilkerson, Matthew D.; Desai, Nisarg; Major, Michael B.; Hayes, D. Neil

    2014-01-01

    SWI/SNF chromatin remodeling complexes regulate critical cellular processes including cell cycle control, programmed cell death, differentiation, genomic instability and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver and pediatric cancers. In particular, ~10% of primary human lung non-small lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes. PMID:25115300

  2. BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization.

    PubMed

    Orvis, Tess; Hepperla, Austin; Walter, Vonn; Song, Shujie; Simon, Jeremy; Parker, Joel; Wilkerson, Matthew D; Desai, Nisarg; Major, Michael B; Hayes, D Neil; Davis, Ian J; Weissman, Bernard

    2014-11-15

    SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non-small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes. PMID:25115300

  3. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

  4. BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

    PubMed

    Zheng, Hua-chuan; Li, Jing; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Wu, Ya-zhou; Takano, Yasuo; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Gou, Wen-feng

    2015-08-14

    Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer. PMID:26050197

  5. Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients.

    PubMed

    Trifa, Fatma; Karray-Chouayekh, Sondes; Jmal, Emna; Jmaa, Zeineb Ben; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

    2013-06-01

    Activation of the Wnt/β-catenin signaling pathway is common in various human cancers. The aim of this study was to investigate the expression of 2 members of the Wnt family (WIF-1 and Wnt5a) in sporadic and hereditary breast cancer tissues. WIF-1, is a secreted antagonist that binds Wnt ligands, and therefore inhibits the canonical Wnt/β-catenin pathway. Wnt5a is one of the members of the noncanonical Wnt family that mainly acts through calcium signaling pathway. The expression of WIF-1 was analyzed by methylation-specific PCR and RT-PCR, and the level of Wnt5a ligand was quantified by RT-QPCR in breast cancer tissues. Methylation of WIF-1 was detected in 71.3 % and 81.8 % of sporadic and hereditary cases, respectively. Aberrant methylation of WIF-1 was associated with advanced TNM stage and triple negative cases in sporadic breast carcinoma (p=0.001 and p=0.037, respectively). In hereditary cases, methylation of WIF-1 correlated with age at diagnosis (p=0.027) and p53 status (p=0.035). Regarding patients' survival, WIF-1 methylated promoter conferred a reduced overall survival rate, and particularly in a group of patients with advanced TNM stage (p log rank=0.006). Furthermore, aberrant CpG methylation of the WIF-1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (p=0.036). On the other hand, in sporadic tumor tissues, the level of Wnt5a mRNA was significantly lower compared to normal tissues (p=0.031) and lower still in those showing more aggressive behavior, suggesting that Wnt5a, a ligand involved in the noncanonical Wnt/β-catenin pathway, could act as a tumor suppressor gene in breast cancer. PMID:23417837

  6. Validating the use of Medicare Australia billing data to examine trends in skin cancer

    PubMed Central

    Perera, Eshini; Gnaneswaran, Neiraja; Perera, Marlon; Sinclair, Rodney

    2015-01-01

    Background:  Epidemiological data surrounding non-melanomatous skin cancer (NMSC) is highly variable, in part due to the lack of government cancer registries. Several studies employ the use of Medical Australia (MA) rebate data in assessing such trends, the validity of which has not been studied in the past. Conversely, melanoma skin cancer is a notifiable disease, and thus, MA and cancer registry data is readily available. The aim of the current study is to assess the use of MA for epidemiological measures for skin cancers, by using melanoma as a disease sample. Methods:  Following ethics approval, data from MA and Victorian Cancer Registry (VCR) from 2004-2008 were extracted. Incidence of MA and VCR unique melanoma cases were compared and stratified by age and local government area (LGA). Regression and a paired-samples t-test were performed. Results: During the study period; 15,150 and 13,886 unique melanoma patients were identified through VCR and MA data sources respectively. An outlier in the >80­ year age group was noted between MA and VCR data. When stratified by age, significant correlation between MA and VCR was observed for all patients (gradient 0.91, R²= 0.936) and following exclusion of >80 patients (gradient 0.96, R²= 0.995). When stratified by LGA, a high degree of observation was observed for all patients (gradient 0.94, R²= 0.977) and following exclusion of >80 patients (gradient 0.996, R²= 0.975). Conclusion: Despite the inclusion of outlier data groups, acceptable correlation between MA and VCR melanoma data was observed, suggesting that MA may be suitable for assessing epidemiological trends. Such principals may be used to validate the use of MA data for similar calculations assessing NMSC trends. PMID:26937270

  7. The Wavelengths in Sunlight Effective in Producing Skin Cancer: A Theoretical Analysis

    PubMed Central

    Setlow, R. B.

    1974-01-01

    DNA is taken as the target for skin cancer induced by ultraviolet light, and the known data on the sensitivity of DNA as a function of wavelength are summarized. The sun's spectrum at the surface of the earth and the DNA action spectrum are used to calculate the carcinogenic effectiveness as a function of wavelength. The most effective wavelengths at 30°N latitude are <305 nm, and a 1% change in atmospheric ozone results in a 2% change in the effective dose of ultraviolet light. Since both the basic biological and physical data are reasonably precise, the major requirement for a quantitative evaluation of the dose response relation for ultraviolet-induced skin cancer in man is better epidemiological data to compare with data from animal models. PMID:4530308

  8. Chromosomal changes in aggressive breast cancers with basal-like features

    PubMed Central

    Yu, Wayne; Kanaan, Yasmine; Bae, Young-Kyung; Gabrielson, Edward

    2009-01-01

    Using high-resolution oligonucleotide CGH arrays, we evaluated chromosomal copy number changes in a series of 16 breast cancers, selected on the basis of highly similar pathological and molecular features characteristic of the “basal-like” phenotype. Each of these cancers showed numerous gains and losses, reflecting multiple chromosomal rearrangements during the development of these high-grade cancers. Chromosomal losses were particularly prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were commonly seen on chromosomal arms 1q, 8q, and 17q. Particularly remarkable were regions of high-level amplification (> 8-fold copy number change) on 4q12, 8q23.3, 19p12, and 19q13.2. These regions included candidate oncogenes cKIT, JUND, and AKT2., and immunohistochemistry confirmed that these particular genes were highly expressed in the cancers harboring the specific amplifications. However, each of these amplifications was observed only in individual cases, and no particular chromosomal alteration appeared to generally characterize this group of cancers. Thus, genomic changes among breast cancers with basal-like features appear to be very heterogeneous. Distinct high-level amplifications may provide new targets for treating some of these cancers, but copy number changes do not reveal a distinctive genomic fingerprint for this proposed class of breast cancers. PMID:19602461

  9. Innate sensing of microbial products promotes wound-induced skin cancer

    PubMed Central

    Hoste, Esther; Arwert, Esther N.; Lal, Rohit; South, Andrew P.; Salas-Alanis, Julio C.; Murrell, Dedee F.; Donati, Giacomo; Watt, Fiona M.

    2015-01-01

    The association between tissue damage, chronic inflammation and cancer is well known. However, the underlying mechanisms are unclear. Here we characterize a mouse model in which constitutive epidermal extracellular-signal-regulated kinase-MAP-kinase signalling results in epidermal inflammation, and skin wounding induces tumours. We show that tumour incidence correlates with wound size and inflammatory infiltrate. Ablation of tumour necrosis factor receptor (TNFR)-1/-2, Myeloid Differentiation primary response gene 88 or Toll-like receptor (TLR)-5, the bacterial flagellin receptor, but not other innate immune sensors, in radiosensitive leukocytes protects against tumour formation. Antibiotic treatment inhibits, whereas injection of flagellin induces, tumours in a TLR-5-dependent manner. TLR-5 is also involved in chemical-induced skin carcinogenesis in wild-type mice. Leukocytic TLR-5 signalling mediates upregulation of the alarmin HMGB1 (High Mobility Group Box 1) in wound-induced papillomas. HMGB1 is elevated in tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease characterized by chronic skin damage. We conclude that in our experimental model the combination of bacteria, chronic inflammation and wounding cooperate to trigger skin cancer. PMID:25575023

  10. Outcome of Glansectomy and Skin Grafting in the Management of Penile Cancer

    PubMed Central

    O'Kane, Hugh F.; Pahuja, Ajay; Ho, K. J.; Thwaini, Ali; Nambirajan, Thaigarajan; Keane, Patrick

    2011-01-01

    Purpose. To report outcome data for patients with penile cancer treated surgically with glansectomy and skin grafting. Materials and Methods. We retrospectively reviewed data on all patients undergoing surgical management of penile cancer by a single surgeon between 1998 and 2008. Outcomes in patients who underwent glansectomy and skin grafting were analysed. Results. Between 1998 and 2008 a total of 25 patients with a mean age 60 (39–83) underwent glansectomy and skin grafting. Six patients had carcinoma in situ (CIS); the stage in the remaining patients ranged from T1G1 to T3G3. Mean followup for patients was 28 months (range 6–66). Disease specific survival was 92% with 2 patients who had positive nodes at lymph node dissection developing groin recurrence. One patient developed a local recurrence requiring a partial penectomy. Conclusions. Penile preserving surgery with glansectomy and skin grafting is a successful technique with minimal complications for local control of penile carcinoma arising on the glans. Careful followup to exclude local recurrence is required. PMID:21603193

  11. Tamoxifen-associated skin reactions in breast cancer patients: from case report to literature review.

    PubMed

    Andrew, Peter; Valiani, Sabira; MacIsaac, Jennifer; Mithoowani, Hamid; Verma, Shailendra

    2014-11-01

    The purpose of this study was to firstly present the maiden case of tamoxifen-induced acute cutaneous lupus erythematosus (ACLE), and secondly, to broaden the discussion into a systematic review of the various tamoxifen-related skin changes documented in patients with breast cancer. We searched PubMed, Cochrane, Embase, CancerLit, Scopus, Web of Science, and Google Scholar databases using keywords to identify reported cases of tamoxifen-related cutaneous adverse events. Outcomes captured included type of cutaneous reaction, time to adverse event, pathologic mechanism, and possible treatment. From 17 clinical studies identified, over ten distinct types of adverse reactions of the skin were itemized. The character of these cutaneous events ranged from the relatively common hot flashes to the rare, but potentially life-threatening, Steven Johnson syndrome. Overall, tamoxifen is generally a well-tolerated hormone therapy with decades of supporting safety data. Based on current medical literature, we present the first case of tamoxifen-induced ACLE. Our clinical experience of managing this case revealed that despite its broad use and the frequency of associated skin reactions, there is a lack of concise information detailing the cutaneous adverse events associated with tamoxifen. The absence of summarized information concerning tamoxifen-related skin changes prompted us to perform a review herein. PMID:25292419

  12. How to Choose the Best Skin Care Products

    MedlinePlus

    ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ...

  13. Vitamin D Intake and Risk of Skin Cancer in US Women and Men.

    PubMed

    Park, Sang Min; Li, Tricia; Wu, Shaowei; Li, Wen-Qing; Qureshi, Abrar A; Cho, Eunyoung

    2016-01-01

    Previous studies suggested a protective effect of vitamin D against skin cancer development. However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few. We prospectively evaluated whether total, dietary and supplemental vitamin D intake were associated with skin cancer risk based on 63,760 women in the Nurses' Health Study (1984-2010) and 41,530 men in the Health Professionals Follow-up Study (1986-2010). Dietary information on vitamin D intake was assessed every 2 to 4 years during the follow-up and cumulative averaged intake was used. We used Cox proportional hazard models to compute the hazard ratios (HR) and 95% confidence intervals (CI). Pooled HR of cohort-specific results were calculated using a random-effects model. During the follow-up, we documented 20,840 BCC, 2,329 SCC and 1,320 melanoma cases. Vitamin D consumption was not associated with the risk of SCC or melanoma but was modestly positively associated with BCC; the pooled HRs of BCC for extreme quintiles of vitamin D intake were 1.10 (95%CI = 1.05-1.15; Ptrend = 0.05) for total vitamin D and 1.13 (95% CI = 1.07 to 1.20; Ptrend <0.01) for dietary vitamin D. Stratified analysis according to sun exposure related factors showed similar results. In conclusion, vitamin D intake was positively associated with risk of BCC, while null associations were found with SCC and melanoma. Our data do not support a beneficial role of orally taken vitamin D on skin cancer carcinogenesis. PMID:27557122

  14. Vitamin D Intake and Risk of Skin Cancer in US Women and Men

    PubMed Central

    Park, Sang Min; Li, Tricia; Wu, Shaowei; Li, Wen-Qing; Qureshi, Abrar A.; Cho, Eunyoung

    2016-01-01

    Previous studies suggested a protective effect of vitamin D against skin cancer development. However, epidemiologic studies on orally taken vitamin D and risk of skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) are few. We prospectively evaluated whether total, dietary and supplemental vitamin D intake were associated with skin cancer risk based on 63,760 women in the Nurses' Health Study (1984–2010) and 41,530 men in the Health Professionals Follow-up Study (1986–2010). Dietary information on vitamin D intake was assessed every 2 to 4 years during the follow-up and cumulative averaged intake was used. We used Cox proportional hazard models to compute the hazard ratios (HR) and 95% confidence intervals (CI). Pooled HR of cohort-specific results were calculated using a random-effects model. During the follow-up, we documented 20,840 BCC, 2,329 SCC and 1,320 melanoma cases. Vitamin D consumption was not associated with the risk of SCC or melanoma but was modestly positively associated with BCC; the pooled HRs of BCC for extreme quintiles of vitamin D intake were 1.10 (95%CI = 1.05–1.15; Ptrend = 0.05) for total vitamin D and 1.13 (95% CI = 1.07 to 1.20; Ptrend <0.01) for dietary vitamin D. Stratified analysis according to sun exposure related factors showed similar results. In conclusion, vitamin D intake was positively associated with risk of BCC, while null associations were found with SCC and melanoma. Our data do not support a beneficial role of orally taken vitamin D on skin cancer carcinogenesis. PMID:27557122

  15. Cutaneous vitamin D synthesis versus skin cancer development: The Janus faces of solar UV-radiation.

    PubMed

    Reichrath, Jörg; Nürnberg, Bernd

    2009-09-01

    In scientific and public communities, there is an ongoing discussion how to balance between positive and negative effects of solar UV-exposure. On the one hand, solar UV-radiation represents the most important environmental risk factor for the development of non-melanoma skin cancer. Consequently, UV protection is an important measure to prevent these malignancies, especially in risk groups. Otherwise, approximately 90% of all vitamin D needed by the human body has to be formed in the skin through the action of UV-radiation. This dilemma represents a serious problem, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer, bone diseases, autoimmune diseases, infectious diseases, cardiovascular diseases and hypertension has now been reported in a large number of investigative and epidemiologic studies. As a consequence, it has been assumed that for the general population in the US, Europe and other countries, the net effects of solar UV B-radiation on human health are beneficial at or near current levels. We and others have shown that strict sun protection causes vitamin D-deficiency/insufficiency and that detection and treatment of vitamin D-deficiency in sun deprived risk groups is of high importance. Although further work is necessary to define an adequate vitamin D-status and adequate guidelines for solar and artificial UV-exposure, it is at present mandatory that public health campaigns and sun protection recommendations to prevent skin cancer consider these facts. In this review, we analyze the present literature to help developing well-balanced recommendations on sun protection that ensure an adequate vitamin D-status. These recommendations will hopefully protect us against adverse effects of UV protection without significantly increasing the risk to develop UV-induced skin cancer. PMID:20808512

  16. Polaroid photographic referral for skin cancer--a potentially useful method of reducing time to surgery.

    PubMed

    Khan, F; McGregor, J C

    1999-06-01

    A prospective trial was conducted on twenty-five patients referred by dermatologists during 1998 using a referral letter and an accompanying polaroid photograph for prospective plastic surgical management of skin cancers. Using the description and the photograph, suitable patients were given dates for operation without requiring a plastic surgery out-patient clinic appointment. This enabled, not only a saving in the cost of an out-patient appointment, but a significant reduction in waiting time to surgery. PMID:10461694

  17. Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging

    PubMed Central

    Rohrbach, Daniel J.; Zeitouni, Nathalie C.; Muffoletto, Daniel; Saager, Rolf; Tromberg, Bruce J.; Sunar, Ulas

    2015-01-01

    The dosimetry of light-based therapies critically depends on both optical and vascular parameters. We utilized spatial frequency domain imaging to quantify optical and vascular parameters, as well as estimated light penetration depth from 17 nonmelanoma skin cancer patients. Our data indicates that there exist substantial spatial variations in these parameters. Characterization of these parameters may inform understanding and optimization of the clinical response of light-based therapies. PMID:26137378

  18. Effects and dose-response relationships of skin cancer and blackfoot disease with arsenic

    PubMed Central

    Tseng, Wen-Ping

    1977-01-01

    In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this “endemic” area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose–response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease. ImagesFIGURE 1.FIGURE 2. PMID:908285

  19. Comparative analysis of combined spectral and optical tomography methods for detection of skin and lung cancers

    NASA Astrophysics Data System (ADS)

    Zakharov, Valery P.; Bratchenko, Ivan A.; Artemyev, Dmitry N.; Myakinin, Oleg O.; Kornilin, Dmitry V.; Kozlov, Sergey V.; Moryatov, Alexander A.

    2015-02-01

    Malignant skin tumors of different types were studied in vivo using optical coherence tomography (OCT), backscattering (BS), and Raman spectroscopy (RS). A multimodal method is proposed for early cancer detection based on complex analysis of OCT images by their relative alteration of scattered-radiation spectral intensities between malignant and healthy tissues. An increase in average accuracy of diagnosis was observed for a variety of cancer types (9% sensitivity, 8% specificity) by a multimodal RS-BS-OCT system in comparison with any of the three methods used separately. The proposed approach equalizes the processing rates for all methods and allows for simultaneous imaging and classification of tumors.

  20. Investigation of In Vivo skin stiffness anisotropy in breast cancer related lymphoedema.

    PubMed

    Coutts, L V; Miller, N R; Mortimer, P S; Bamber, J C

    2016-01-01

    There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/-2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/-16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants. PMID:26684433

  1. Acute Skin Toxicity Following Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer: Who's at Risk?

    SciTech Connect

    Hoppe, Bradford S.; Laser, Benjamin; Kowalski, Alex V.; Fontenla, Sandra C.; Pena-Greenberg, Elizabeth; Yorke, Ellen D.; Lovelock, D. Michael; Hunt, Margie A.; Rosenzweig, Kenneth E.

    2008-12-01

    Purpose: We examined the rate of acute skin toxicity within a prospectively managed database of patients treated for early-stage non-small-cell lung cancer (NSCLC) and investigated factors that might predict skin toxicity. Methods: From May 2006 through January 2008, 50 patients with Stage I NSCLC were treated at Memorial Sloan-Kettering Cancer Center with 60 Gy in three fractions or 44-48 Gy in four fractions. Patients were treated with multiple coplanar beams (3-7, median 4) with a 6 MV linac using intensity-modulated radiotherapy (IMRT) and dynamic multileaf collimation. Toxicity grading was performed and based on the National Cancer Institute Common Terminology Criteria for Adverse Effects. Factors associated with Grade 2 or higher acute skin reactions were calculated by Fisher's exact test. Results: After a minimum 3 months of follow-up, 19 patients (38%) developed Grade 1, 4 patients (8%) Grade 2, 2 patients (4%) Grade 3, and 1 patient Grade 4 acute skin toxicity. Factors associated with Grade 2 or higher acute skin toxicity included using only 3 beams (p = 0.0007), distance from the tumor to the posterior chest wall skin of less than 5 cm (p = 0.006), and a maximum skin dose of 50% or higher of the prescribed dose (p = 0.02). Conclusions: SBRT can be associated with significant skin toxicity. One must consider the skin dose when evaluating the treatment plan and consider the bolus effect of immobilization devices.

  2. Laser induced autofluorescence for diagnosis of non-melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.

    2015-01-01

    Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.

  3. Incorporation of Electronic Brachytherapy for Skin Cancer into a Community Dermatology Practice

    PubMed Central

    Willoughby, Mark; Willoughby, Cole; Mafong, Erick; Han, Amy

    2015-01-01

    Objective: The introduction of an electronic brachytherapy delivery system into an existing general dermatology practice is described. Radiobiologic rational for the dose fractionation schedule is detailed. Design: A miniaturized 50keV x-ray tube and delivery system are United States Food and Drug Administration cleared for nonmelanoma skin cancer. The device is introduced into an existing multi-physician dermatology practice in a standard unshielded treatment room. Setting: A multi-site, multi-physician dermatology practice Results: Fifteen months following introduction of the system, a total of 524 nonmelanoma skin cancer patients have been treated. At 12.5 months follow-up, there have been four recurrences and cosmesis has been excellent. Conclusions: Advances in radiobiology and radiotechnology permit the treatment course to be given in eight fractions over four weeks. Radiation therapy for nonmelanoma skin cancer can now be given in an office setting as an alternative to Mohs surgery for appropriately selected patients. Results are comparable or better than those of surgery. Advances in radiobiology and radiotechnology permit the treatment course to be given in as few as eight fractions over four weeks. Patients are pleased with the convenience of the short course of therapy given in the office. PMID:26705437

  4. Skin cancer in organ transplant recipients: more than the immune system

    PubMed Central

    Wheless, Lee; Jacks, Sarah; Mooneyham, Kathryn Anne; Leach, Brian C.; Cook, Joel

    2014-01-01

    Organ transplant recipients (OTRs) are at increased risk of developing non-melanoma skin cancers (NMSC). This has long been thought to be due to immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian Target of Rapamycin (mTOR) inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with NMSC, and squamous cell carcinoma (SCC) in particular. This finding may help explain the predominance of SCC over basal cell carcinoma in this population. mTOR inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for NMSC. PMID:24725477

  5. Two different approaches in skin cancer therapy: using a photosensitizer/a natural product

    NASA Astrophysics Data System (ADS)

    Abraham, Annie; Gayathri, Devi D.; Cibin, T. R.; Ramaiah, D.

    2010-02-01

    This paper deals with two potential modes for the treatment of skin cancer-one a novel approach using a squaraine dye and the other using a natural product- the flavonoid fraction of Saraca asoka. Squaraine dye is a photosensitizing agent, which is preferentially taken up and retained by the tumor cells and when irradiated with high power visible light results in the selective destruction of the tumor cells by photodynamic therapy. The uniqueness of this mode of treatment lies in the selective destruction of tumor cells without affecting the neighbouring normal cells, which is much advantageous over radiation therapy now frequently used. The chemopreventive and therapeutic effects of the plant component are explored as well. The experimental models were Swiss albino mice in which skin tumor was induced by DMBA. Marked reduction in tumor volume and burden in the treated groups were observed. The reversal of biochemical enzyme markers like rhodanese, myeloperoxidase, β-D glucuronidase, lactate dehydrogenase, hexokinase and sialic acid to near normal levels were observed in the PDT and flavonoid fraction treated groups. The live photographs of the experimental animals and histopathological data further support the obtained results. The study assumes importance as it combines a traditional treatment mode and a novel aspect in cancer therapy using the same experimental models. Also this is the first report on PDT using a squaraine dye for skin cancer therapy in vivo.

  6. Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer

    PubMed Central

    Smith, Steven C.; Baras, Alexander S.; Owens, Charles R.; Dancik, Garrett; Theodorescu, Dan

    2013-01-01

    RalA and RalB are small GTPases which support malignant development and progression in experimental models of bladder, prostate and squamous cancer. However, demonstration of their clinical relevance in human tumors remains lacking. Here, we developed tools to evaluate Ral protein expression, activation and transcriptional output and evaluated their association with clinicopathologic parameters in common human tumor types. In order to evaluate the relevance of Ral activation and transcriptional output, we correlated RalA and RalB activation with the mutational status of key human bladder cancer genes. We also identified and evaluated a “transcriptional signature” of genes that correlates with depletion of RalA and RalB in vivo. The Ral transcriptional signature score, but not protein expression as evaluated by immunohistochemistry, predicted disease stage, progression to muscle invasion, and survival in human bladder cancers, and metastatic and stem cell phenotypes in bladder cancer models. In prostate cancer, the Ral transcriptional signature score was associated with seminal vesicle invasion, androgen-independent progression, and reduced survival. In squamous cell carcinoma, this score was decreased in cancer tissues compared with normal mucosa, validating the experimental findings that Ral acts as a tumor-suppressor in this tumor type. Together, our findings demonstrate the clinical relevance of Ral in human cancer and provide a rationale for the development of Ral-directed therapies. PMID:22586063

  7. A plesiotherapy technique for the post-operative treatment of skin cancer using Ir192 microSelectron.

    PubMed

    Abatzoglou, Ioannis; Tsoutsou, Pelagia; Koukourakis, Michael I

    2008-01-01

    We describe a technique of postoperative irradiation of skin cancer using plesiotherapy with Ir192 high dose rate microSelectron afterloading system (Nucletron, Veenendaal, Netherlands). The clinically defined area is drawn on the skin and the flexible 'skin applicator' is then orientated so that the drawn skin area is encompassed within the catheter defined surface. Using a thin pewter wire, the skin drawn area is copied on the air-adjacent surface of the applicator. Ex vivo CT simulation follows. The data are then transferred to the radiotherapy planning computer and the catheters are virtually reconstructed. The isodose curve chosen to prescribe the dose is 3 mm to 5 mm away from the skin surface. Three fractions of 8Gy are scheduled, 1 week apart, delivering a radiobiological equivalent of 48Gy of standard radiotherapy within 2 weeks. Our preliminary experience shows excellent early skin tolerance. The study is ongoing to assess efficacy and late effects. PMID:19020493

  8. The Skin Cancer and Sun Knowledge (SCSK) Scale: Validity, Reliability, and Relationship to Sun-Related Behaviors among Young Western Adults

    ERIC Educational Resources Information Center

    Day, Ashley K.; Wilson, Carlene; Roberts, Rachel M.; Hutchinson, Amanda D.

    2014-01-01

    Increasing public knowledge remains one of the key aims of skin cancer awareness campaigns, yet diagnosis rates continue to rise. It is essential we measure skin cancer knowledge adequately so as to determine the nature of its relationship to sun-related behaviors. This study investigated the psychometric properties of a new measure of skin cancer…

  9. Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status.

    PubMed Central

    Hsueh, Y. M.; Cheng, G. S.; Wu, M. M.; Yu, H. S.; Kuo, T. L.; Chen, C. J.

    1995-01-01

    In order to evaluate the prevalence and multiple risk factors of arsenic-induced skin cancer among residents in Taiwanese villages in which chronic arseniasis is hyperendemic, a total of 1571 subjects aged 30 or more years were recruited between September 1988 and March 1989. All of them were interviewed personally by a public health nurse using a structured questionnaire, and 1081 interviewed study subjects, including 468 men and 613 women, participated in physical examination, giving a participation rate of 68.8%. The overall prevalence of skin cancer was as high as 6.1%, showing an increase with age in both men and women. There was a significant dose-response relation between skin cancer prevalence and chronic arsenic exposure as indexed by duration of residence in the endemic area, duration of consumption of high-arsenic artesian well water, average arsenic exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.-years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had an increased prevalence of skin cancer. Undernourishment, indexed by a high consumption of dried sweet potato as a staple food, was also significantly associated with an increased prevalence of arsenic-induced skin cancer. All these risk factors remained statistically significant in the multiple logistic regression analysis. Consistent with animal experiments, the findings imply that liver function and nutritional status may affect the metabolism of inorganic arsenic and the development of subsequent skin cancers. PMID:7819025

  10. Hyaluronan degrading silica nanoparticles for skin cancer therapy

    NASA Astrophysics Data System (ADS)

    Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.

    2013-09-01

    We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

  11. An Advertisement and Article Analysis of Skin Products and Topics in Popular Women’s Magazines: Implications for Skin Cancer Prevention

    PubMed Central

    Basch, Corey H.; Mongiovi, Jennifer; Hillyer, Grace Clarke; Fullwood, MD; Ethan, Danna; Hammond, Rodney

    2015-01-01

    Background: In the United States, skin cancer is the most commonly diagnosed cancer, with an estimated 5 million people treated per year and annual medical treatment expenditures that exceed 8 billion dollars. The purpose of this study was two-fold: 1) to enumerate the number of advertisements for skin products with and without Sun Protection Factor (SPF) and to further analyze the specific advertisements for sunblock to determine if models, when present, depict sun safe behaviors and 2) to enumerate the number of articles related to the skin for content. Both aims include an assessment for differences in age and in magazines targeting a Black or Latina population. Methods: The sample for this cross sectional study was comprised of 99 issues of 14 popular United States magazines marketed to women, four of which market to a Black or Latina audience. Results: There were 6,142 advertisements, of which 1,215 (19.8%, 95% CI: 18.8-20.8%) were related to skin products. Among the skin product advertisements, 1,145 (93.8%, 95% CI: 93.9-96.3%) depicted skin products without SPF. The majority of skin articles (91.2%, 95% CI: 91.7-100.0%), skin product advertisements (89.9%, 95% CI: 88.2-91.6%), and sunblock advertisements featuring models (were found in magazines aimed at the older (>24 yr) audience. Conclusion: Future research on this topic could focus on the extent to which images in these magazines translate into risky health behaviors, such as sun seeking, or excessive other harmful effects of UV radiation. PMID:26933645

  12. Skin cancer prevention and UV-protection: how to avoid vitamin D-deficiency?

    PubMed

    Reichrath, J

    2009-11-01

    Because solar UV-radiation represents the most important environmental risk factor for the development of non-melanoma skin cancer, UV protection is important to prevent these malignancies. Consequently, public health campaigns were developed to improve the knowledge of the general population regarding the role of UV-radiation for the development of skin cancer. However, it has to be noted that vitamin D-mediated positive effects of UV light were not adequately considered in most of these campaigns, that often propose a strict 'no sun policy' without giving recommendations how to prevent vitamin D-deficiency. Under our living conditions, approximately 90% of all vitamin D needed by the human body has to be formed in the skin through the action of UV-B-radiation and it has been shown that strict sun protection causes vitamin D-deficiency. This dilemma represents a serious problem, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer, bone diseases, autoimmune diseases, infectious diseases, cardiovascular diseases and hypertension has now been reported in a large number of laboratory and epidemiologic investigations. Although further work is necessary to define an adequate vitamin D-status and adequate guidelines for UV-exposure, it is at present mandatory that guidelines for UV-exposure (e.g. in skin cancer prevention campaigns) consider these facts and give recommendations how to prevent vitamin D-deficiency. At present, most experts in the field agree that the evidence to date suggests that daily intake of 1000-2000 IU vitamin D could reduce the incidence of vitamin D-deficiency-related diseases with minimal risk in Europe, the US, and other countries. In this review, we analyze the present literature to help developing well-balanced guidelines on UV-protection that ensure an adequate vitamin D-status. These recommendations will hopefully protect us against vitamin D-deficiency without increasing the risk

  13. Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways

    PubMed Central

    Slominski, Andrzej T.; Zmijewski, Michal A.; Semak, Igor; Zbytek, Blazej; Pisarchik, Alexander; Li, Wei; Zjawiony, Jordan; Tuckey, Robert C.

    2013-01-01

    Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7-steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu. PMID:23869782

  14. Targeting GRB7/ERK/FOXM1 Signaling Pathway Impairs Aggressiveness of Ovarian Cancer Cells

    PubMed Central

    Chan, David W.; Hui, Winnie W. Y.; Cai, Patty C. H.; Liu, Michelle X.; Yung, Mingo M. H.; Mak, Celia S. L.; Leung, Thomas H. Y.; Chan, Karen K. L.; Ngan, Hextan Y. S.

    2012-01-01

    Ovarian cancer is a highly lethal disease with poor prognosis and especially in high-grade tumor. Emerging evidence has reported that aberrant upregulation and activation of GRB7, ERK as well as FOXM1 are closely associated with aggresivenesss of human cancers. However, the interplay between these factors in the pathogenesis of human cancers still remains unclear. In this study, we found that GRB7 (P<0.0001), ERK phosphorylation (P<0.0001) and FOXM1 (P = 0.001) were frequently increased and associated with high-grade tumors, as well as a high tendency in association with advanced stage ovarian cancer by immunohistochemical analysis. Intriguingly, the expressions of GRB7 (P<0.0001), ERK phosphorylation (P<0.001) and FOXM1 (P<0.001) showed a significant stepwise increase pattern along Grade 1 to Grade 3 ovarian cancers. Biochemical studies using western blot analysis demonstrated that enforced expression or knockdown of GRB7 showed GRB7 could elevate the levels of ERK phosphorylation and FOXM1, whereas enforced expression of FOXM1 could not alter levels of GRB7 and ERK phosphorylation. But inhibition of ERK signaling by U0126 or PD98059 could reduce the level of FOXM1 in GRB7-overexpressing ovarian cancer cells, suggesting that GRB7, ERK and FOXM1 are regulated orderly. Moreover, inhibition of ERK activity by U0126 or PD98059, or decreased FOXM1 expression by Thiostrepton significantly inhibited cell migration/invasion, tumor growth in vitro and in vivo. Collectively, our findings confer that targeting GRB7/ERK/FOXM1 signaling cascade may be a promising molecular therapeutic choice in combating ovarian cancer. PMID:23285101