Science.gov

Sample records for epithelial 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. Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers

    PubMed Central

    Kerkelä, E; Ala-aho, R; Jeskanen, L; Lohi, J; Grénman, R; M-Kähäri, V; Saarialho-Kere, U

    2001-01-01

    Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen's disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-α and keratinocyte growth factor, and by interferon-γ in combination with transforming growth factor-β1 and tumour necrosis factor-α both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11237387

  3. Epithelial skin cancers after kidney transplantation: a retrospective single-centre study of 376 recipients.

    PubMed

    Kaufmann, Robin Adrian; Oberholzer, Patrick Antony; Cazzaniga, Simone; Hunger, Robert Emil

    2016-06-01

    Post-transplant non-melanoma skin cancers (NMSC) are the most common malignancies in kidney transplant recipients. To analyse risk factors associated with the occurrence of basal cell carcinomas (BBC) and squamous cell carcinomas (SCC) in kidney transplant recipients. Statistical analysis was performed on 376 kidney transplant recipients screened for NMSC in 2002-2009 and followed until 2013. NMSC developed in 23.67% of individuals with an SCC/BCC ratio of 2.15:1 and an age-standardised incidence ratio (IR) of 2.71 cases (95% CI: 1.97-3.46) per 100 patients/year. Based on multivariable analysis, NMSC occurrence significantly correlated with higher age (p<0.001), fair skin type (p = 0.01), and particularly SCCs with male gender (p = 0.001). Patients with >10 actinic keratoses were at higher risk of developing NMSCs (IRR = 2.95; 95% CI: 1.97-4.42; p<0.001) and more prone to SCCs, compared to BCCs (p = 0.04). Also, more SCC carriers had high counts of warty lesions (p = 0.006). Calcineurin inhibitors were associated with higher NMSC incidence (IRR = 2.81; 95% CI: 1.1-7.01; p = 0.03), while no difference was seen with the mammalian target of rapamycin (mTOR) inhibitors. Our results confirm an influence of the individual immunosuppressive regimen, in addition to the duration of immunosuppression, and suggest that older patients, males, fair skinned recipients or those affected with high counts of actinic keratoses (field cancerisation) are particularly prone to development of NMSC. PMID:26985913

  4. [Prevention of occupational solar UV radiation-induced epithelial skin cancer].

    PubMed

    Bauer, A; Beissert, S; Knuschke, P

    2015-03-01

    Malignancies of the skin, with an incidence of more than 200,000 newly registered cases/year, are the most frequently notified malignances in Germany. In Europe, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) account for about 30 cases/100,000 persons and 50-100 cases/100,000 persons, respectively. Ultraviolet (UV) exposure is the main risk factor to induce these cancers. Increased incidence rates were shown for persons having red/blonde hair as well as light eye colour, acquire sun burns easily, hardly tan and develop freckles. The majority of the malignancies and precursor lesions are acquired by UV exposure in leisure time. However, in highly occupationally UV-exposed outdoor workers, UV monitoring revealed that exposure levels are 2-3 times higher compared to the general population. Occupations likely to be highly exposed are farmers, forestry workers, gardeners, landscapers, fishermen and seafarers, construction workers, builders, tin smiths, sport teachers, mountain guides, etc. Recent metaanalyses showed that occupational UV exposure is a relevant and independent risk factor for SCC and to a lesser extent also for BCC. To prevent occupationally caused malignancies of the skin a significant reduction of occupationally acquired UV dosages in outdoor workers is mandatory. Relevant factors influencing the cumulative sun exposure in outdoor workers are the amount of UV exposure, the specific tasks to be performed in the sun as well as the UV protection habits of the workers. Besides adequate behavior, textile protection by headgear and clothing as well as the regular use of sunscreens and sun glasses are important.

  5. Translocations in epithelial cancers

    PubMed Central

    Chad Brenner, J.; Chinnaiyan, Arul M.

    2009-01-01

    Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

  6. Skin Cancer Foundation

    MedlinePlus

    ... Cancer Infographics Children For Your Eyes Clothing Shade Sunscreen Sunburn Seal of Recommendation Are You at Risk? ... Defense The Mini Skin Cancer Prevention Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics The Skin Cancer ...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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) ...

  11. 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) ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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.

  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 prevention.

    PubMed

    Kornek, Thomas; Augustin, Matthias

    2013-04-01

    Prevention signifies the avoidance of diseases. It also includes the early detection of diseases and taking measures to avoid worsening of an existing disease. Prevention is divided into primary, secondary and tertiary prevention. The prevention of skin cancer is particularly important due to the rising incidence of skin cancer in recent years. In Germany, 195.000 new cases of skin cancer, including non melanoma skin cancer and melanoma are occurring. Therefore, skin cancer is among the most common cancer diseases. Primary prevention comprises the reduction of skin cancer risk behavior, including education about the danger of UV exposure and the right way of dealing with natural and artificial UV radiation. The implementation of a systematic skin cancer screening in Germany contributes to secondary prevention. First data from the initial project in Schleswig-Holstein, Germany's most northern state, indicate for the first time that the incidence and mortality of melanoma can be reduced by secondary prevention. For tertiary prevention, the national associations recommend a risk-adapted, evidence-based follow-up for all types of skin cancer. From the perspectives of the payers and from the patients, prevention is assessed positively. Prevention can contribute to a reduction of disease burden.

  18. 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 ...

  19. 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) ...

  20. Epithelial cancer detection by oblique-incidence optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Garcia-Uribe, Alejandro; Balareddy, Karthik C.; Zou, Jun; Wang, Kenneth K.; Duvic, Madeleine; Wang, Lihong V.

    2009-02-01

    This paper presents a study on non-invasive detection of two common epithelial cancers (skin and esophagus) based on oblique incidence diffuse reflectance spectroscopy (OIDRS). An OIDRS measurement system, which combines fiber optics and MEMS technologies, was developed. In our pilot studies, a total number of 137 cases have been measured in-vivo for skin cancer detection and a total number of 20 biopsy samples have been measured ex-vivo for esophageal cancer detection. To automatically differentiate the cancerous cases from benign ones, a statistical software classification program was also developed. An overall classification accuracy of 90% and 100% has been achieved for skin and esophageal cancer classification, respectively.

  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. Nonmelanoma Skin Cancer

    PubMed Central

    Samarasinghe, Venura; Madan, Vishal

    2012-01-01

    Nonmelanoma skin cancer (NMSC) represents the most common form of cancer in Caucasians, with continuing increase in incidence worldwide. Basal cell carcinoma (BCC) accounts for 75% of cases of NMSC, and squamous cell carcinoma (SCC) accounts for the remaining majority of NMSC cases. Whilst metastasis from BCC is extremely rare, metastasis from high-risk SCC may be fatal. In this article, we review the aetiology, diagnosis and management of NMSC. PMID:22557848

  4. 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.

  5. 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.

  6. 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.

  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. Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-05-06

    Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  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. 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

  11. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.

    PubMed

    Sand, Michael; Skrygan, Marina; Georgas, Dimitrios; Arenz, Christoph; Gambichler, Thilo; Sand, Daniel; Altmeyer, Peter; Bechara, Falk G

    2012-11-01

    The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA-induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute-1 (AGO1), argonaute-2 (AGO2), as well as double-stranded RNA-binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer.

  12. 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 ...

  13. 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 ...

  14. [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

  15. Epithelial-Mesenchymal Transition and Breast Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  16. Skin cancer, melanoma, and sunlight.

    PubMed

    Fears, T R; Scotto, J; Schneiderman, M A

    1976-05-01

    Recent theoretical studies suggest that the earth's ozone layer which filters ultraviolet radiation may be depleted by a fleet of supersonic transports or by continued use of chlorofluoromethanes. It is now generally accepted that short wavelength ultraviolet radiation leads to the development of skin cancer. In this report we demonstrate an approach to estimating the increase in skin cancer incidence associated with increases in skin cancer incidence associated with increases in ultraviolet radiation. The purpose is to demonstrate the logic used and the assumptions that must be made when such estiamtes are made or cited. We emphasize that such estimates should be considered crude until the many assumptions can be investigated.

  17. 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) ...

  18. 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) ...

  19. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  20. 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.

  1. Folate in skin cancer prevention.

    PubMed

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

    2012-01-01

    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.

  2. [Epithelial-mesenchymal transition in cancer progression].

    PubMed

    Gos, Monika; Miłoszewska, Joanna; Przybyszewska, Małgorzata

    2009-01-01

    According to recently published data, the epithelial-mesenchymal transition--a process important for embryonic development, may be involved in many pathological processes such as wound healing, tissue fibrosis or cancer progression. The EMT process in cell is driven by growth factors (EGF, PDGF, HGF) or other signaling proteins such as TGF-beta, sonic hedgehog (Shh), Wnt/beta-catenin and extracellular matrix (ECM) components that may stimulate cellular growth and migration. During cancer progression, the EMT process is necessary to the conversion of benign tumor to aggressive and highly invasive cancer. This is due to complex changes in cancer cells and their microenvironment that lead to dissolution of intracellular junctions and their detachment from basolateral membrane, and changes in the interactions between cancer cells and ECM. The loss of adhesion is accompanied by molecular and morphologic changes in cancer cells that are essential for the phenotypic change from epithelial to mesenchymal one, and the acquirement of higher migration and invasion potential. During the colonization of distant sites, a reverse process mesenchymal-epithelial transition (MET) takes place and metastatic cancer cells again acquire the epithelial phenotype. The EMT in cancer progression is not only specific for cancer cells. It has been suggested that also cells within tumor microenvironment e.g. cancer associated fibroblasts (CAF) are generated in part from normal epithelial cells in EMT process. The understanding of the role of EMT and MET processes in cancer progression and their relationship with cancer stem cells, cancer associated fibroblasts and other stroma cells might lead to the discovery of new, targeted cancer therapies.

  3. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  4. Studies in human skin epithelial cell carcinogenesis

    SciTech Connect

    Lehman, T.A.

    1987-01-01

    Metabolism and DNA adduct formation of benzo(a)pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and /sup 32/P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the /sup 32/P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts.

  5. Novel approaches to chemoprevention of skin cancer.

    PubMed

    Bickers, D R; Athar, M

    2000-11-01

    Protection against sun-induced damage leading to photocarcinogenesis in skin is a highly desirable goal. Among various strategies, chemopreventive approaches utilizing non-toxic agents to prevent the occurrence of precancerous lesions or their surrogate markers are potentially attractive. Epidemiological and experimental studies provide evidence that some naturally occurring chemical agents in the human diet can diminish cancer risk. Aside from water, tea is the most common beverage consumed worldwide. Black tea accounts for nearly 80% of total tea production. Black tea and green tea are derived from the same plant, Camelia sinensis. Green tea contains monomeric polyphenols known as flavanols and black tea contains dimeric flavanols and polymeric polyphenols known as theaflavins (TFs) and thearubigins (TRs). Over the past fifteen years our laboratory has been exploring the feasibility of using tea and its constitutents as an approach to skin cancer prevention. We demonstrated that green tea, black tea and constituent polyphenols protect against chemical- and ultraviolet B (UVB)-induced carcinogenesis and reduce the growth of established tumors in skin. We have also shown the efficacy of green and black tea extracts against UVB and psoralen + ultraviolet A (PUVA)-induced early damage in skin. Although PUVA is highly effective in treating certain skin diseases, careful follow-up studies of cohorts of patients have shown that similar to UVB, PUVA treatment increases the risk for cutaneous squamous cell carcinoma and melanoma. We have found that oral administration of a standardized green tea extract (SGTE) prior to and during treatment of SKH-1 mice diminished PUVA-induced skin hyperplasia and hyperkeratosis. SGTE-treatment also inhibited PUVA-induced accumulation of c-fos and p53 proteins and epithelial hyperproliferation. Both topical application and oral administration of SGTE after PUVA-treatment reduced skin inflammation and cell hyperproliferation. Topical

  6. Epithelial Ovarian Cancer Experimental Models

    PubMed Central

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

  7. Burden of malignancy after a primary skin cancer: recurrence, multiple skin cancers and second primary cancers.

    PubMed

    Krueger, Hans; Williams, Dan

    2010-01-01

    The current paper summarizes relevant recent research on the high risk of recurrence, multiple skin cancers and second primary cancers in the growing number of people with a history of skin cancer; the ultimate purpose is to better assess the burden of malignancy following skin cancer. A number of challenges exist in identifying and tracking both melanoma and non-melanoma skin cancer (NMSC) cases. Most jurisdictions do not routinely track NMSC cases and, even if they do, it is customary to only include the first diagnosis. There are variable rules for counting multiple melanoma cancers, and recurrences are not considered for either major type of skin cancer. Applying insights from recent studies of this issue to Canadian cancer statistics would increase reported diagnoses of NMSC by about 26% and melanoma by 10% in this country. This approach to a fuller assessment of the burden of skin cancers has been called a "diagnosis-based incidence approach" as compared with a "patient-based incidence approach". A further issue that is not usually taken into account when assessing the burden of skin cancers is the 20% to 30% elevated risk of noncutaneous second primary cancers following a primary skin tumour. In summary, individuals with skin cancer are subject to a high risk of recurrence, multiple skin cancers and second primary cancers. This burden should be a special concern in the large and growing pool of individuals with a history of skin cancer, as well as among prevention planners.

  8. 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.

  9. 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.

  10. Skin cancer prevention in Australia.

    PubMed

    Sinclair, C; Foley, P

    2009-11-01

    Australia has one of the highest skin cancer incidence and mortality rates in the world. The reason for these high rates is due in part to the high ambient UV radiation levels, combined with a predominantly susceptible fair-skinned population. To address this problem, since 1980 Australians have been exposed to social marketing campaigns to raise awareness of skin cancer prevention. These campaigns have used mass media alongside interventions in schools, workplaces, and in community and leisure settings to motivate sun protective behaviour. As a result of these interventions it can be demonstrated that social marketing campaigns can be a very effective method to not only motivate behaviour change, reduce sunburn, and increase awareness but more importantly, reduce melanoma rates and bring positive economic returns to government. However long term investment in this area is required otherwise any population gains in behaviour are very likely to be quickly eroded. PMID:19775367

  11. Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-01-15

    Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  12. 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)

  13. 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. |

  14. Epithelial Skin Biology: Three Decades of Developmental Biology, a Hundred Questions Answered and a Thousand New Ones to Address

    PubMed Central

    Fuchs, Elaine

    2016-01-01

    The mammalian skin epidermis and its hair and sweat gland appendages provide a protective barrier that retains essential body fluids, guards against invasion by harmful microbes, and regulates body temperature through the ability to sweat. At the interface between the external environment and the body, skin is constantly subjected to physical trauma and must also be primed to repair wounds in response to injury. In adults, the skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. This essay focuses on when stem cells become established during skin development and where these cells reside in adult epithelial tissues of the skin. I explore how skin stem cells maintain tissue homeostasis and repair wounds and how they regulate the delicate balance between proliferation and differentiation. Finally, I tackle the relation between skin cancer and mutations that perturb the regulation of stem cells. PMID:26970628

  15. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring. PMID:23746929

  16. Epithelial mechanobiology, skin wound healing, and the stem cell niche.

    PubMed

    Evans, Nicholas D; Oreffo, Richard O C; Healy, Eugene; Thurner, Philipp J; Man, Yu Hin

    2013-12-01

    Skin wound healing is a vital process that is important for re-establishing the epithelial barrier following disease or injury. Aberrant or delayed skin wound healing increases the risk of infection, causes patient morbidity, and may lead to the formation of scar tissue. One of the most important events in wound healing is coverage of the wound with a new epithelial layer. This occurs when keratinocytes at the wound periphery divide and migrate to re-populate the wound bed. Many approaches are under investigation to promote and expedite this process, including the topical application of growth factors and the addition of autologous and allogeneic tissue or cell grafts. The mechanical environment of the wound site is also of fundamental importance for the rate and quality of wound healing. It is known that mechanical stress can influence wound healing by affecting the behaviour of cells within the dermis, but it remains unclear how mechanical forces affect the healing epidermis. Tensile forces are known to affect the behaviour of cells within epithelia, however, and the material properties of extracellular matrices, such as substrate stiffness, have been shown to affect the morphology, proliferation, differentiation and migration of many different cell types. In this review we will introduce the structure of the skin and the process of wound healing. We will then discuss the evidence for the effect of tissue mechanics in re-epithelialisation and, in particular, on stem cell behaviour in the wound microenvironment and in intact skin. We will discuss how the elasticity, mechanical heterogeneity and topography of the wound extracellular matrix impact the rate and quality of wound healing, and how we may exploit this knowledge to expedite wound healing and mitigate scarring.

  17. Epigenetic biomarkers in epithelial ovarian cancer.

    PubMed

    Gloss, Brian S; Samimi, Goli

    2014-01-28

    Ovarian cancer is the most lethal gynecological malignancy and the 5th leading cause of cancer death in women. Women with ovarian cancer are typically diagnosed at late stage, when the cancer has spread into the peritoneal cavity and complete surgical removal is difficult. The 5-year survival time for patients diagnosed at this stage is 30%, in contrast to a 5-year survival of 90% for patients diagnosed at early stage. Cancer screening and early detection have the potential to greatly decrease the mortality and morbidity from cancer. The emerging field of epigenetics offers a valuable opportunity to identify cancer-specific DNA methylation changes that can be used in the clinic to improve early-stage diagnosis and better predict response in treated patients. To date, numerous DNA methylation aberrations have been identified in epithelial ovarian cancer; here we review some candidate genes and pathways with potential clinical utility as biomarkers for diagnosis and/or prognosis. It has become clear that even with the great promise of DNA methylation biomarkers in epithelial ovarian cancer, the identification of highly specific, sensitive and robust panels of markers and the standardization of analysis techniques are still required in order to improve detection, treatment and thus patient outcome.

  18. Sun exposure, skin cancers and related skin conditions.

    PubMed

    Green, A; Whiteman, D; Frost, C; Battistutta, D

    1999-12-01

    Skin cancer is the most commonly occurring cancer in humans. Solar keratoses are related benign tumours that are at least ten times commoner than skin cancers and photoageing of the skin is still more common. Descriptive studies show that incidence rates of the main types of skin cancer, basal cell carcinoma, squamous cell carcinoma and melanoma are maximal in populations in which ambient sun exposure is high and skin (epidermal) transmission of solar radiation is high, suggesting strong associations with sun exposure. Analytic epidemiological studies confirm that exposure to the UV component of sunlight is the major environmental determinant of skin cancers and associated skin conditions and evidence of a causal association between cumulative sun exposure and SCC, solar keratoses and photodamage is relatively straightforward. Results for BCC and melanoma are complicated by several factors including the existence of subgroups of these diseases which do not appear to be caused by sun exposure yet have been included in most aetiological studies to date. Complementary to epidemiological data is the molecular evidence of ultraviolet (UV) mechanisms of carcinogenesis such as UV-specific mutations in the DNA of tumour suppressor genes in skin tumours. With increased UV irradiation resulting from thinning of the ozone layer, skin cancer incidence rates have been predicted to increase in the future--unless, as is hoped, human behaviour to reduce sun exposure can offset these predicted rises.

  19. Mayo Clinic experience with epithelial ovarian cancer.

    PubMed

    Decker, D G

    1983-08-01

    Clinical investigation of epithelial ovarian cancer must involve the precise definition of the lesion, careful application of new techniques, the objective evaluation of such techniques, the comparison of results in a randomized fashion with prior forms of therapy, careful pathological evaluation of the tumour, and the evaluation of toxicity to the patient. The interdisciplinary team approach to the treatment of epithelial ovarian cancer and the development of randomized, prospective trials are essential. Utilizing these two elements, a better integration of surgery, chemotherapy and radiation therapy can be accomplished. Of great importance is the evaluation of response patterns by an observer who is skilled in pelvic examinations and familiar with the natural history of epithelial ovarian cancer. The increasingly important role of surgery in the treatment of this cancer is now more clearly defined. The psychological effects of chemotherapy as well as the response patterns to chemotherapy must be evaluated. During the past 20 years, considerable progress has been made in prolonging the useful, functional life of the patient. The ultimate cure is still a matter for the future and is predicated on more effective combinations of potent chemotherapeutic combinations and a clearer definition of the role of radiation therapy.

  20. Fluorescence polarization imaging for delineating nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Yaroslavsky, A. N.; Neel, V.; Anderson, R. R.

    2004-09-01

    We present a method for detecting nonmelanoma skin cancers using exogenous fluorescence polarization. We built an automated system that permits exogenous fluorescence polarization imaging. It includes a tunable linearly polarized monochromatic light source and a CCD camera equipped with a rotating linear polarizer and a filter to reject excitation light. Two fluorophores that are retained in tumors, toluidine blue and methylene blue, are employed. We demonstrate that fluorescence polarization imaging can be used for accurate delineation of nonmelanoma cancers. The results suggest that this optical technique may be suitable for real-time noninvasive demarcation of epithelial cancers.

  1. Human papillomaviruses and skin cancer.

    PubMed

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  2. Skin Cancer Surveillance Behaviors Among Childhood Cancer Survivors.

    PubMed

    Stapleton, Jerod L; Tatum, Kristina L; Devine, Katie A; Stephens, Sue; Masterson, Margaret; Baig, Amna; Hudson, Shawna V; Coups, Elliot J

    2016-03-01

    The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination (SSE) and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of SSEs did not differ based on treatment history. These findings highlight the need to promote skin cancer surveillance as an important aspect of CCS survivorship care.

  3. 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 ...

  4. Laser speckle and skin cancer: skin roughness assessment

    NASA Astrophysics Data System (ADS)

    Lee, Tim K.; Tchvialeva, Lioudmila; Zeng, Haishan; McLean, David I.; Lui, Harvey

    2009-10-01

    Incidence of skin cancer has been increasing rapidly since the last few decades. Non-invasive optical diagnostic tools may improve the diagnostic accuracy. In this paper, skin structure, skin cancer statistics and subtypes of skin cancer are briefly reviewed. Among the subtypes, malignant melanoma is the most aggressive and dangerous; early detection dramatically improves the prognosis. Therefore, a non-invasive diagnostic tool for malignant melanoma is especially needed. In addition, in order for the diagnostic tool to be useful, it must be able to differentiate melanoma from common skin conditions such as seborrheic keratosis, a benign skin disease that resembles melanoma according to the well known clinical-assessment ABCD rule. The key diagnostic feature between these two diseases is surface roughness. Based on laser speckle contrast, our research team has recently developed a portable, optical, non-invasive, in-vivo diagnostic device for quantifying skin surface roughness. The methodology of our technique is described in details. Examining the preliminary data collected in a pilot clinical study for the prototype, we found that there was a difference in roughness between melanoma and seborrheic keratosis. In fact, there was a perfect cutoff value for the two diseases based on our initial data.

  5. P16 UV mutations in human skin epithelial tumors.

    PubMed

    Soufir, N; Molès, J P; Vilmer, C; Moch, C; Verola, O; Rivet, J; Tesniere, A; Dubertret, L; Basset-Seguin, N

    1999-09-23

    The p16 gene expresses two alternative transcripts (p16alpha and p16beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16alpha and p16beta), in five out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%). These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GG to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions. P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16beta transcript. Our data demonstrate for the first time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.

  6. 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

  7. 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 ...

  8. 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

  9. 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 ...

  10. 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…

  11. Targets for molecular therapy of skin cancer.

    PubMed

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  12. 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.

  13. 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 ...

  14. 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.

  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. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  17. 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

  18. DNA repair, immunosuppression, and skin cancer.

    PubMed

    Yarosh, Daniel B

    2004-11-01

    UV radiation (UVR) produces erythema within the first 24 hours of exposure, suppression of the immune system within the first 10 days, and, for many people, over the course of decades, skin cancer. Although UVR damages many skin targets, DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) is an important mediator of these sequelae. The action spectrum for erythema parallels the action spectrum for CPD formation in skin, and in the absence of repair, as in the genetic disease xeroderma pigmentosum (XP), skin cancer rates are dramatically increased. DNA repair in skin can be enhanced by the delivery of DNA repair enzymes encapsulated in liposomes. Used in this way, photoreactivation of CPDs greatly diminishes erythema and the suppression of contact hypersensitivity (CHS). UV endonucleases delivered by liposomes also prevent UV-induced suppression of delayed-type hypersensitivity. In a clinical study of patients with XP, T4 endonuclease V (T4N5) liposome lotion applied for one year reduced the rates of actinic keratosis (AK) and skin cancer compared with placebo. These results showed that strategies to increase sun protection should include measures to reduce DNA damage and increase the rate of DNA repair.

  19. Expression and localization of epithelial stem cell and differentiation markers in equine skin, eye and hoof

    PubMed Central

    Linardi, Renata L.; Megee, Susan O.; Mainardi, Sarah R.; Senoo, Makoto; Galantino-Homer, Hannah L.

    2015-01-01

    Background The limited characterization of equine skin, eye and hoof epithelial stem cell (ESC) and differentiation markers impedes the investigation of the physiology and pathophysiology of these tissues. Hypothesis/Objectives To characterize ESC and differentiation marker expression in epithelial tissues of the equine eye, haired skin and hoof capsule. Methods Indirect immunofluorescence microscopy and immunoblotting were utilized to detect expression and tissue localization of keratin (K) isoforms K3, K10, K14, and K124, the transcription factor p63 (a marker of ESCs) and phosphorylated p63 (pp63, a marker of ESC to transit-amplifying (TA) cell transition) in epithelial tissues of the foot (haired skin, hoof coronet and hoof lamellae) and the eye (limbus and cornea). Results K14 expression was restricted to the basal layer of epidermal lamellae, and to basal and adjacent suprabasal layers of the haired skin, coronet and corneal limbus. Coronary and lamellar epidermis was negative for both K3 and K10, which were expressed in the cornea/limbus epithelium and haired skin epidermis, respectively. Variable expression of p63 with relatively low to high levels of phosphorylation was detected in individual basal and suprabasal cells of all epithelial tissues examined. Conclusions This is the first report of the characterization of tissue-specific keratin marker expression and the localization of putative epithelial progenitor cell populations, including ESCs (high p63 expression with low pp63 levels) and TA cells (high expression of both p63 and pp63), in the horse. These results will aid further investigation of epidermal and corneal epithelial biology and regenerative therapies in horses. PMID:25963063

  20. Sunlight vitamin D and skin cancer.

    PubMed

    Mason, Rebecca S; Reichrath, Jörg

    2013-01-01

    Today, there is a controversial debate in many scientific and public communities on how much sunlight is appropriate to balance between the positive and negative effects of solar UV-exposure. UV exposure undoubtedly causes DNA damage of skin cells and is a major environmental risk factor for all types of skin cancers. In geographic terms, living in parts of the world with increased erythemal UV or high average annual bright sun results in increased risks of skin cancers, with the greatest increased risk for squamous cell carcinoma, followed by basal cell carcinoma and then melanoma. On the other hand, sunlight exerts positive effects on human health, that are mediated in part via UV-B-mediated cutaneous photosynthesis of vitamin D. It has been estimated that at present, approximately 1 billion people worldwide are vitamin D-deficient or -insufficient. This epidemic causes serious health problems that are still widely under-recognized. Vitamin D deficiency leads to well documented problems for bone and muscle function. There are also associations between vitamin D-deficiency and increased incidence of and/or unfavourable outcome for a broad variety of independent diseases, including various types of malignancies (e.g. colon-, skin-, and breast cancer), autoimmune diseases, infectious diseases, and cardiovascular diseases. In this review, the present literature is analyzed to summarize our present knowledge about the important relationship of sunlight, vitamin D and skin cancer.

  1. 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

  2. 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

  3. 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.

  4. Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.

    PubMed

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kur-Piotrowska, Anna; Kopcewicz, Marta

    2016-01-01

    Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT) was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process.

  5. Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition

    PubMed Central

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kur-Piotrowska, Anna; Kopcewicz, Marta

    2016-01-01

    Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT) was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process. PMID:26938103

  6. Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.

    PubMed

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kur-Piotrowska, Anna; Kopcewicz, Marta

    2016-01-01

    Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT) was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process. PMID:26938103

  7. Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

    ClinicalTrials.gov

    2016-09-20

    Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme

  8. Immune response associated with nonmelanoma skin cancer.

    PubMed

    Strickland, F M; Kripke, M L

    1997-10-01

    It is now clear that UV radiation causes nonmelanoma skin cancer in at least two ways: by causing permanent changes in the genetic code and by preventing immunologic recognition of mutant cells. These are interacting rather than separate mechanisms. Damage to DNA results in disregulation of cellular proliferation and initiates immune suppression by stimulating the production of suppressive cytokines. These cytokines contribute to the loss of immunosurveillance. Ultraviolet radiation has both local and systemic immunosuppressive effects. Locally, it depletes and alters antigen-presenting LC at the site of UV irradiation. Systemic suppression results when Ts cells are induced, by altered LC, by inflammatory macrophages that enter the skin following UV irradiation, or by the action of cytokines. Damage to DNA appears to be one of the triggering events in inducing systemic immunosuppression via the release of immunosuppressive cytokines and mediators. Immunologic approaches to treating skin cancers so far have concentrated on nonspecifically stimulating immune cells that infiltrate these tumors, but induction of specific immune responses against these tumors with antitumor vaccines has received little attention as yet. Preventive measures include sun avoidance and the use of sunscreens to prevent DNA damage by UV light. Future strategies may employ means to reverse UV-induced immunosuppression by using anti-inflammatory agents, biologicals that accelerate DNA repair or prevent the generation of immunosuppressive cytokines, and specific immunotherapy with tumor antigens. New approaches for studying the immunology of human skin cancers are needed to accelerate progress in this field.

  9. 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.

  10. 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

  11. Sunlight and skin cancer: lessons from the immune system.

    PubMed

    Ullrich, Stephen E

    2007-08-01

    The ultraviolet (UV) radiation in sunlight induces skin cancer development. Skin cancer is the most common form of human neoplasia. Estimates suggest that in excess of 1.5 million new cases of skin cancer (www.cancer.org/statistics) will be diagnosed in the United States this year. Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer, and the cost of treating skin cancer in the United States (both melanoma and non-melanoma skin cancer) is estimated to be in excess of $2.9 billion a year. In addition to causing skin cancer, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. Recent studies in my laboratory have focused on understanding the initial molecular events that induce immune suppression. We made two novel observations: first UV-induced keratinocyte-derived platelet activating factor plays a role in the induction of immune suppression. Second, cis-urocanic acid, a skin-derived immunosuppressive compound mediates immune suppression by binding to serotonin receptors on target cells. Recent findings suggest that blocking the binding of these compounds to their receptors not only inhibits UV-induced immune suppression but it also interferes with skin cancer induction.

  12. Optical mapping of nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Yaroslavsky, Anna N.; Neel, Victor; Anderson, Richard R.

    2004-07-01

    More than two million cases of nonmelanoma skin cancers are diagnosed every year. Therefore, there is a strong need for practical, reliable, rapid, and precise methods for tumor delineation, to guide surgery and other treatments of skin cancer. Once developed, such methods may be useful for squamous cell carcinomas of other organs. Non-invasive optical imaging techniques including polarization sensitive reflectance and fluorescence imaging were evaluated for the demarcation of nonmelanoma skin tumors. Thick freshly excised tumor specimens obtained from Mohs surgery were used for the experiments. Imaging was performed using linearly polarized incident light in the visible and near infrared spectral range from 577 nm to 750 nm. Non-toxic absorbing and fluorescent dyes (Toluidine Blue O, Methylene Blue) were employed to enhance tumor contrast in the images. The images were acquired using the remitted light polarized in the directions parallel and perpendicular to the polarization of incident light. Reflectance and fluorescence polarization images were evaluated. The data were processed and analyzed for dependence of the remitted light polarization on the tissue type (cancerous/normal). The data obtained so far from fresh tumor specimens in vitro using dye-enhanced polarized light reflectance, and exogenous fluorescence polarization imaging suggest that optical mapping can become a valuable guidance tool in nonmelanoma cancer surgery.

  13. Targeted Therapy in Nonmelanoma Skin Cancers

    PubMed Central

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio

    2011-01-01

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC. PMID:24212808

  14. The cutting edge of skin cancer in transplant recipients: scientific retreat of international transplant Skin Cancer Collaborative and Skin Cancer in Organ Transplant Patients Europe.

    PubMed

    Hanlon, A; Colegio, O R

    2014-05-01

    The International Transplant Skin Cancer Collaborative (ITSCC) is an organization of more than 300 physicians and scientists focused on the study of dermatologic changes following solid organ transplantation. Transplant patients have a 100-fold increased risk of developing skin cancer. In October 2012, ITSCC and its European counterpart Skin Cancer in Organ Transplant Patients Europe held a joint biennial retreat in Essex, MA to discuss novel findings in the pathogenesis and management of skin cancer in solid organ transplant recipients. This meeting report is a summary of the novel findings discussed.

  15. Wnt-10b promotes differentiation of skin epithelial cells in vitro

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-03-31

    To evaluate the role of Wnt-10b in epithelial differentiation, we investigated the effects of Wnt-10b on adult mouse-derived primary skin epithelial cells (MPSEC). Recombinant Wnt-10b protein (rWnt-10b) was prepared using a gene engineering technique and MPSEC were cultured in its presence, which resulted in morphological changes from cuboidal to spindle-shaped and inhibited their proliferation. Further, involvement of the canonical Wnt signal pathway was also observed. MPSEC treated with rWnt-10b showed characteristics of the hair shaft and inner root sheath of the hair follicle, in results of Ayoub Shklar staining and immunocytochemistry. Further, the cells expressed mRNA for differentiated epithelial cells, including keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5. These results suggest that Wnt-10b promotes the differentiation of MPSEC.

  16. Emerging role of epithelial-mesenchymal transition in hepatic cancer.

    PubMed

    Yoshida, Go J

    2016-01-01

    Accumulating evidence suggests that the phenomenon of epithelial-mesenchymal-transition (EMT) plays a fundamental role in the tumor development. Several research articles have been published from Journal of Experimental and Clinical Cancer Research (JECCR) which have investigated into the molecular machineries underlying the importance of EMT for hepatic cancer. Given those recent publications by JECCR, this commentary focuses on the pathological significance of EMT for liver tumor. PMID:27619936

  17. Non-melanoma skin cancer incidence and impact of skin cancer screening on incidence.

    PubMed

    Eisemann, Nora; Waldmann, Annika; Geller, Alan C; Weinstock, Martin A; Volkmer, Beate; Greinert, Ruediger; Breitbart, Eckhard W; Katalinic, Alexander

    2014-01-01

    Non-melanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized. This analysis has two objectives: first, to provide up-to-date incidence estimates by sex, age group, histological type, and body site; and second, to study the impact of skin cancer screening. The impact of screening on NMSC incidence in Schleswig-Holstein, Germany, is analyzed by comparing four time periods of different screening settings (no screening (1998-2000), pilot project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany, SCREEN, 2003-2004), after SCREEN (2004-2008), and nation-wide skin cancer screening (2008-2010)) to a reference region (Saarland, Germany). Age-standardized (Europe) NMSC incidence was 119/100,000 for women and 145/100,000 for men in the most recent screening period in Schleswig-Holstein (2008-2010). During implementation of SCREEN (2003-2004), incidence increased from 81.5/100,000 to 111.5/100,000 (1998-2000) by 47% for women and 34% for men. All age groups in women were affected by the increase, but increases for men were mostly limited to the older age groups. Incidence in Saarland first increased slowly, but increased steeply with the introduction of the nation-wide skin cancer screening in 2008 (+47% for women and +40% for men, reference 2004-2008). Observed changes are most likely attributed to screening activities.

  18. Wnt-10b secreted from lymphocytes promotes differentiation of skin epithelial cells

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-04-21

    Wnt-10b was originally isolated from lymphoid tissue and is known to be involved in a wide range of biological actions, while recently it was found to be expressed early in the development of hair follicles. However, few studies have been conducted concerning the role of Wnt-10b with the differentiation of skin epithelial cells. To evaluate its role in epithelial differentiation, we purified Wnt-10b from the supernatant of a concanavalin A-stimulated lymphocyte culture using an affinity column and investigated its effects on the differentiation of adult mouse-derived primary skin epithelial cells (MPSEC). MPSEC cultured with Wnt-10b showed morphological changes from cuboidal to spindle-shaped with inhibited proliferation, and also obtained characteristics of the hair shaft and inner root sheath of the hair follicle, represented by red-colored Ayoub Shklar staining, and reactions to AE-13 and AE-15 as seen with immunocytology. Further, RT-PCR analysis demonstrated the expression of mRNA for keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5, in Wnt-10b-treated MPSEC. In addition, involvement of the canonical Wnt signal pathway was demonstrated by a TCF reporter (pTOPFLASH) assay. These results suggest that Wnt-10b promotes the differentiation of MPSEC and may play an important role in hair follicle development by promoting differentiation of epithelial cells.

  19. Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer

  20. Antivascular Therapy for Epithelial Ovarian Cancer

    PubMed Central

    Duhoux, Francois P.; Machiels, Jean-Pascal

    2010-01-01

    Ovarian cancer is the fifth largest cancer killer in women. Improved understanding of the molecular pathways implicated in the pathogenesis of ovarian cancer has led to the investigation of novel targeted therapies. Ovarian cancer is characterized by an imbalance between pro- and antiangiogenic factors in favor of angiogenesis activation. Various antivascular strategies are currently under investigation in ovarian cancer. They can schematically be divided into antiangiogenic and vascular-disrupting therapies. This paper provides a comprehensive review of these new treatments targeting the tumor vasculature in this disease. Promising activities have been detected in phase II trials, and results of phase III clinical trials are awaited eagerly. PMID:20072701

  1. Quantitative changes in human epithelial cancers and osteogenesis imperfecta disease detected using nonlinear multicontrast microscopy

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; D'Souza-Li, Lilia; Assunção, Maria do Carmo; Bottcher-Luiz, Fátima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2012-08-01

    We show that combined multimodal nonlinear optical (NLO) microscopies, including two-photon excitation fluorescence, second-harmonic generation (SHG), third harmonic generation, and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation during the progression of cancer and osteogenesis imperfecta (OI) disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for different types of human breast cancer, mucinous ovarian tumors, and skin dermis of patients with OI. Using a set of scoring methods (anisotropy, correlation, uniformity, entropy, and lifetime components), we found significant differences in the content, distribution and organization of collagen fibrils in the stroma of breast and ovary as well as in the dermis of skin. We suggest that our results provide a framework for using NLO techniques as a clinical diagnostic tool for human cancer and OI. We further suggest that the SHG and FLIM metrics described could be applied to other connective or epithelial tissue disorders that are characterized by abnormal cells proliferation and collagen assembly.

  2. Benign epithelial ovarian tumours-cancer precursors or markers for ovarian cancer risk?

    PubMed

    Jordan, Susan; Green, Adèle; Webb, Penelope

    2006-06-01

    The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

  3. 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.

  4. Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages during Skin Development

    PubMed Central

    McGowan, Kevin M.; Coulombe, Pierre A.

    1998-01-01

    The type I keratin 17 (K17) shows a peculiar localization in human epithelial appendages including hair follicles, which undergo a growth cycle throughout adult life. Additionally K17 is induced, along with K6 and K16, early after acute injury to human skin. To gain further insights into its potential function(s), we cloned the mouse K17 gene and investigated its expression during skin development. Synthesis of K17 protein first occurs in a subset of epithelial cells within the single-layered, undifferentiated ectoderm of embryonic day 10.5 mouse fetuses. In the ensuing 48 h, K17-expressing cells give rise to placodes, the precursors of ectoderm-derived appendages (hair, glands, and tooth), and to periderm. During early development, there is a spatial correspondence in the distribution of K17 and that of lymphoid-enhancer factor (lef-1), a DNA-bending protein involved in inductive epithelial–mesenchymal interactions. We demonstrate that ectopic lef-1 expression induces K17 protein in the skin of adult transgenic mice. The pattern of K17 gene expression during development has direct implications for the morphogenesis of skin epithelia, and points to the existence of a molecular relationship between development and wound repair. PMID:9786956

  5. A distinct molecular profile associated with mucinous epithelial ovarian cancer

    PubMed Central

    Heinzelmann-Schwarz, V A; Gardiner-Garden, M; Henshall, S M; Scurry, J P; Scolyer, R A; Smith, A N; Bali, A; Bergh, P Vanden; Baron-Hay, S; Scott, C; Fink, D; Hacker, N F; Sutherland, R L; O'Brien, P M

    2006-01-01

    Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC. PMID:16508639

  6. Sirtuins and Cancer: Role in the Epithelial-Mesenchymal Transition

    PubMed Central

    Della-Morte, David; Capuani, Barbara; Silvestris, Franco

    2016-01-01

    The human sirtuins (SIRT1–SIRT7) enzymes are a highly conserved family of NAD+-dependent histone deacetylases, which play a critical role in the regulation of a large number of metabolic pathways involved in stress response and aging. Cancer is an age-associated disease, and sirtuins may have a considerable impact on a plethora of processes that regulate tumorigenesis. In particular, growing evidence suggests that sirtuins may modulate epithelial plasticity by inducing transcriptional reprogramming leading to epithelial-mesenchymal transition (EMT), invasion, and metastases. Though commonly regarded as EMT inducers, sirtuins may also suppress this process, and their functional properties seem to largely depend on the cellular context, stage of cancer development, tissue of origin, and microenvironment architecture. Here, we review the role of sirtuins in cancer biology with particular emphasis on their role in EMT. PMID:27379175

  7. 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

  8. Clinical characteristics and awareness of skin cancer in Hispanic patients.

    PubMed

    Javed, Saba; Javed, Syed A; Mays, Rana M; Tyring, Stephen K

    2013-09-01

    Skin cancer in darker skin is associated with considerable morbidity and mortality. We sought to assess the clinical characteristics of cutaneous malignancy amongst Hispanic skin cancer patients and compare them to age-matched non-Hispanic Caucasians. In this retrospective study, 150 Hispanic skin cancer patients were identified from electronic medical records and age-matched to 150 non-Hispanic Caucasian controls with skin cancer. The incidence of actinic keratoses (AKs) in Hispanic skin cancer patients (34.0%) was statistically lower than age-matched non-Hispanic Caucasian skin cancer controls (61.3%, P <0.001; odds ratio, 3.08; 95% confidence interval, 1.92 - 4.93). Moreover, non-Hispanic Caucasian SCC (squamous cell cancer) controls were much more likely to report AKs (36.1%, P = 0.003) than Hispanic SCC patients (25.0%, P = 0.19). This study illustrates a lower incidence of AKs in Hispanic skin cancer patients as compared to their age-matched non-Hispanic Caucasians. The Hispanic skin malignancies present at a more advanced state and there is usually a lack of awareness in such cases. Therefore, patient knowledge and education is crucial for early detection and prevention of skin cancer in the Hispanic population.

  9. 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.

  10. Population education in preventing skin cancer: from childhood to adulthood.

    PubMed

    de Haas, Ellen R M; Nijsten, Tamar; de Vries, Esther

    2010-02-01

    Skin cancer is the most commonly diagnosed cancer in populations of predominantly Caucasian origins. As the main cause of skin cancer is excessive sun exposure among a sun-sensitive population, most skin cancers are theoretically avoidable, and prevention is an important topic for public health purposes. The development of skin cancer may be limited by effective primary prevention campaigns, causing people to protect themselves from the sun. In order to be effective, the right people need to become aware of the risks and benefits; they also need to be convinced that they can take effective protective measures. Secondary skin cancer prevention aims to avoid skin cancer morbidity and mortality and is, therefore, mainly aimed at early detection of cutaneous melanomas. Around the world, elderly men are the worst off in terms of melanoma mortality statistics and would be an important target group for secondary prevention. Several prevention initiatives have been developed, including awareness campaigns and voluntary skin cancer screening days. So far, few of these initiatives have proven to be successful in changing population behavior and/or skin cancer related mortality. Most of these initiatives appealed more to (young) women rather than the elderly males who would benefit most. In this review, various aspects of primary and secondary skin cancer prevention are discussed, including the results of some of the primary and secondary prevention initiatives.

  11. 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.

  12. Effects of sunscreen on skin cancer and photoaging.

    PubMed

    Iannacone, Michelle R; Hughes, Maria Celia B; Green, Adèle C

    2014-01-01

    Application of sunscreen to the skin is widely used as an adjunct strategy, along with wearing protective clothing and seeking shade, to protect against skin cancer and photoaging that result from excessive sun exposure. Many epidemiological studies of case-control and cohort study design have studied the effects of sunscreen use on skin cancer, and more recently photoaging, but their findings have been mostly uninformative. This review of results of randomized controlled trials shows that the evidence, though limited, supports beneficial effects of sunscreen application on the occurrence of skin cancers and skin photoaging.

  13. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  14. Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

    PubMed

    Baandrup, Louise

    2015-07-01

    Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

  15. Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-10-28

    Male Breast Cancer; Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  16. Photocarcinogenesis: an epidemiologic perspective on ultraviolet light and skin cancer.

    PubMed

    Kozma, Bonita; Eide, Melody J

    2014-07-01

    Photocarcinogenesis is the result of a complex interplay between ultraviolet radiation, DNA damage, mutation formation, DNA repair, apoptosis, and the immune system. Recent trends show an increase in incidence of both melanoma and nonmelanoma skin cancers. Some individuals have a genetic predisposition toward increased risk for skin cancer, whereas others experience increased risk through ultraviolet exposure and subsequent mutation formation. The initiation and propagation pathways of melanoma and nonmelanoma skin cancers differ but have some elements in common. The increase in incidence of skin cancer has been discovered to vary among age groups and gender.

  17. 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.

  18. 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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Kim, M. Y.; George, K. A.; Cucinotta, F. A.

    Methods for estimating the probability of excess incidence of skin cancer from space radiation exposure, must consider the variability of skin doses at specific anatomical areas, and the individual factors that may contribute to risk projection models, including skin pigment, and synergistic effects from combined ionizing radiation and UV exposure. Using the multiplicative risk model for transferring the Japanese survivor data to the US population, epidemiological data for the increased risk for skin locations exposed to combined UV and ionizing radiation, and models of space radiation environments, transport, and anatomical shielding, we estimate the skin cancer risk for future lunar and Mars missions. Our model projects that individual variations in the probability for increased skin cancer risk varies more than 10-fold and that an excess cancer risk greater than 1% could occur for astronauts with light skin and hair color exposed to medium class solar particle events during future lunar base operations, or from galactic cosmic rays on Mars missions.

  1. Molecular signature and therapeutic perspective of the epithelial-to-mesenchymal transitions in epithelial cancers.

    PubMed

    Sabbah, Michèle; Emami, Shahin; Redeuilh, Gérard; Julien, Sylvia; Prévost, Grégoire; Zimber, Amazia; Ouelaa, Radia; Bracke, Marc; De Wever, Olivier; Gespach, Christian

    2008-01-01

    The mechanisms involved in the epithelial to mesenchymal transition (EMT) are integrated in concert with master developmental and oncogenic pathways regulating in tumor growth, angiogenesis, metastasis, as well as the reprogrammation of specific gene repertoires ascribed to both epithelial and mesenchymal cells. Consequently, it is not unexpected that EMT has profound impacts on the neoplastic progression, patient survival, as well as the resistance of cancers to therapeutics (taxol, vincristine, oxaliplatin, EGF-R targeted therapy and radiotherapy), independent of the "classical" resistance mechanisms linked to genotoxic drugs. New therapeutic combinations using genotoxic agents and/or EMT signaling inhibitors are therefore expected to circumvent the chemotherapeutic resistance of cancers characterized by transient or sustained EMT signatures. Thus, targeting critical orchestrators at the convergence of several EMT pathways, such as the transcription pathways NF-kappaB, AKT/mTOR axis, MAPK, beta-catenin, PKC and the AP-1/SMAD factors provide a realistic strategy to control EMT and the progression of human epithelial cancers. Several inhibitors targeting these signaling platforms are already tested in preclinical and clinical oncology. In addition, upstream EMT signaling pathways induced by receptor and nonreceptor tyrosine kinases (e.g. EGF-R, IGF-R, VEGF-R, integrins/FAK, Src) and G-protein-coupled receptors (GPCR) constitute practical options under preclinical research, clinical trials or are currently used in the clinic for cancer treatment: e.g. small molecule inhibitors (Iressa: targeting selectively the EGF-R; CP-751,871, AMG479, NVP-AEW541, BMS-536924, PQIP, AG1024: IGF-R; AZD2171, ZD6474: VEGF-R; AZD0530, BMS-354825, SKI606: Src; BIM-46174: GPCR; rapamycin, CCI-779, RAD-001: mTOR) and humanized function blocking antibodies (Herceptin: ErbB2; Avastin: VEGF-A; Erbitux: EGF-R; Abegrin: alphavbeta3 integrins). We can assume that silencing RNA and adenovirus

  2. Skin Cancer in Black Americans: A Review of 126 Cases

    PubMed Central

    Bang, Ki Moon; Halder, Rebat M.; White, Jack E.; Sampson, Calvin C.; Wilson, Jerome

    1987-01-01

    Primary cancer of the skin is rare in blacks. The records of 126 black patients with skin cancer were reviewed. Histopathologic findings included squamous cell carcinomas (43) basal cell carcinomas (39) malignant melanomas (8) dermatofibrosarcomas (16) Bowen's disease (6) mycosis fungoides (14) and sebaceous cell carcinoma (1). There is a higher percentage of skin cancer involving covered areas in blacks than among whites. Squamous cell carcinoma was the most common skin cancer in blacks. The distribution of basal cell carcinoma in blacks was 30 percent in this series, as compared with 80 percent in whites in the 1977 to 1978 survey. The majority of patients with squamous cell carcinoma had associated predisposing conditions and lesions on non-sun-exposed skin. Sunlight and occupational chemical exposure did not appear to be associated with skin cancer in blacks in this series. ImagesFigure 1Figure 2 PMID:3820333

  3. 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.

  4. Assessment of chimerism in epithelial cancers in transplanted patients.

    PubMed

    Leboeuf, Christophe; Ratajczak, Philippe; Vérine, Jérôme; Elbouchtaoui, Morad; Plassa, François; Legrès, Luc; Ferreira, Irmine; Sandid, Wissam; Varna, Mariana; Bousquet, Guilhem; Verneuil, Laurence; Janin, Anne

    2014-01-01

    Cancer is now the most severe complication in the long term in transplant recipients. As most solid-organ or hematopoietic stem-cell transplantations are allogeneic, chimerism studies can be performed on cancers occurring in recipients. We summarize here the different methods used to study chimerism in cancers developing in allogeneic-transplant recipients, analyze their respective advantages and report the main results obtained from these studies. Chimerism analyses of cancers in transplant recipients require methods suited to tissue samples. In the case of gender-mismatched transplantation, the XY chromosomes can be explored using fluorescent in situ hybridization on whole-tissue sections or Y-sequence-specific PCR after the laser microdissection of tumor cells. For cancers occurring after gender-matched transplantation, laser microdissection of tumor cells enables studies of microsatellite markers and high-resolution melting analysis of mitochondrial DNA on genes with marked polymorphism, provided these are different in the donor and the recipient. The results of different studies address the cancers that develop in both recipients and in transplants. The presence of chimeric cells in these two types of cancer implies an exchange of progenitor/stem-cells between transplant and recipient, and the plasticity of these progenitor/stem-cells contributes to epithelial cancers. The presence of chimeric cells in concomitant cancers and preneoplastic lesions implies that the oncogenesis of these cancers progresses through a multistep process.

  5. 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.

  6. 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.

  7. Identifying Risk Factors Using a Skin Cancer Screening Program

    PubMed Central

    Etzkorn, Jeremy Robert; Parikh, Rajiv Prakash; Marzban, Suroosh S.; Law, Kimberly; Davis, Ashley H.; Rawal, Bhupendra; Schell, Michael J.; Sondak, Vernon K.; Messina, Jane L.; Rendina, Lois E.; Zager, Jonathan S.; Lien, Mary H.

    2015-01-01

    Background The incidence of melanoma and nonmelanoma skin cancer continues to increase. To detect lesions at an earlier phase in their progression, skin cancer screening programs have been advocated by some. However, the effectiveness of skin cancer screening and the ideal population that these screenings should target have yet to be firmly established. This study details the relationship of a group of well-known risk factors with presumptive diagnoses in a large series of individuals self-referred for free skin cancer screening. Methods Data obtained during 2007 to 2010 from a descriptive cross-sectional study skin cancer screening program are presented. Participant history was recorded using standardized medical history forms prior to skin examination. Screeners conducted a skin examination varying from whole-body to limited areas (per participant preference) and recorded diagnoses. Diagnoses were assigned to the nonmelanoma cancer (NMC) or suspicious pigmented lesion group for analysis. Results A presumptive diagnosis of NMC was associated with male sex, age ≥ 50 years, personal history of skin cancer, lower skin phototype, increased sunscreen use, and increased chronic sun exposure (all P values ≤ .0001). After controlling for skin phototype, increased sunscreen use was not associated with a presumptive diagnosis of NMC (P = .96). Presumptive diagnosis of a suspicious pigmented lesion was associated with a reported history of “changing mole” (P < .0001) and negatively associated with age ≥ 50 years (P < .0001) and a personal history of skin cancer (P = .0119). Conclusions Several known risk factors for nonmelanoma skin cancer correlated with a presumptive diagnosis of NMC. The yield of presumptive atypical pigmented lesions was increased in participants aged < 50 years, supporting the notion that this population may benefit from screening. PMID:24077401

  8. Predictors of skin cancer in commercial airline pilots

    PubMed Central

    Swearingen, Christopher J.; Kilmer, Jeffrey B.

    2009-01-01

    Background Skin cancers among commercial airline pilots have been reported to occur at increased rates in pilot populations worldwide. The reasons for these increases are unclear, but postulated factors include ionizing radiation, circadian disruption and leisure sun exposure. Aims To investigate the potential association of these occupational and lifestyle factors, as well as medical history and skin type, with non-melanoma skin cancer in pilots. Methods Data were collected using a confidential Internet survey administered in collaboration with the Air Line Pilots Association International to all active pilots in four US commercial airlines. Pilots with non-melanoma skin cancer were compared to those without using multivariable analysis. Results The response rate was 19%. Among pilots flying <20 years prior to diagnosis, factors associated with increased odds of non-melanoma skin cancer were at-risk skin type, childhood sunburns and family history of non-melanoma skin cancer. Off-duty sunscreen use and family history of melanoma were protective. Among pilots with ≥20 years flight time prior to diagnosis, childhood sunburns and family history of non-melanoma skin cancer persisted as risk factors, with the addition of flight time at high latitude. Conclusions Further investigation regarding the potential health impact of long-term flying at high latitudes is recommended. Additionally, occupational health programmes for pilots should stress awareness of and protection against established risk factors for non-melanoma skin cancer. PMID:19465434

  9. SKIN AS A LIVING COLORING BOOK: HOW EPITHELIAL CELLS CREATE PATTERNS OF PIGMENTATION

    PubMed Central

    Weiner, Lorin; Fu, Wenyu; Chirico, William J.; Brissette, Janice L.

    2014-01-01

    Summary The pigmentation of mammalian skin and hair develops through the interaction of two basic cell types — pigment donors and recipients. The pigment donors are melanocytes, which produce and distribute melanin through specialized structures. The pigment recipients are epithelial cells, which acquire melanin and put it to use, collectively yielding the pigmentation visible to the eye. This review will focus on the pigment recipients, the historically less understood cell type. These end-users of pigment are now known to exert a specialized control over the patterning of pigmentation, as they identify themselves as melanocyte targets, recruit pigment donors, and stimulate the transfer of melanin. As such, this review will discuss the evidence that the skin is like a coloring book: the pigment recipients create a “picture,” a blueprint for pigmentation, which is colorless initially but outlines where pigment should be placed. Melanocytes then melanize the recipients and “color in” the picture. PMID:25104547

  10. Skin as a living coloring book: how epithelial cells create patterns of pigmentation.

    PubMed

    Weiner, Lorin; Fu, Wenyu; Chirico, William J; Brissette, Janice L

    2014-11-01

    The pigmentation of mammalian skin and hair develops through the interaction of two basic cell types - pigment donors and recipients. The pigment donors are melanocytes, which produce and distribute melanin through specialized structures. The pigment recipients are epithelial cells, which acquire melanin and put it to use, collectively yielding the pigmentation visible to the eye. This review will focus on the pigment recipients, the historically less understood cell type. These end-users of pigment are now known to exert a specialized control over the patterning of pigmentation, as they identify themselves as melanocyte targets, recruit pigment donors, and stimulate the transfer of melanin. As such, this review will discuss the evidence that the skin is like a coloring book: the pigment recipients create a 'picture,' a blueprint for pigmentation, which is colorless initially but outlines where pigment should be placed. Melanocytes then melanize the recipients and 'color in' the picture.

  11. Mitochondrial function in murine skin epithelium is crucial for hair follicle morphogenesis and epithelial-mesenchymal interactions.

    PubMed

    Kloepper, Jennifer E; Baris, Olivier R; Reuter, Karen; Kobayashi, Ken; Weiland, Daniela; Vidali, Silvia; Tobin, Desmond J; Niemann, Catherin; Wiesner, Rudolf J; Paus, Ralf

    2015-03-01

    Here, we studied how epithelial energy metabolism impacts overall skin development by selectively deleting intraepithelial mtDNA in mice by ablating a key maintenance factor (Tfam(EKO)), which induces loss of function of the electron transport chain (ETC). Quantitative (immuno)histomorphometry demonstrated that Tfam(EKO) mice showed significantly reduced hair follicle (HF) density and morphogenesis, fewer intrafollicular keratin15+ epithelial progenitor cells, increased apoptosis, and reduced proliferation. Tfam(EKO) mice also displayed premature entry into (aborted) HF cycling by apoptosis-driven HF regression (catagen). Ultrastructurally, Tfam(EKO) mice exhibited severe HF dystrophy, pigmentary abnormalities, and telogen-like condensed dermal papillae. Epithelial HF progenitor cell differentiation (Plet1, Lrig1 Lef1, and β-catenin), sebaceous gland development (adipophilin, Scd1, and oil red), and key mediators/markers of epithelial-mesenchymal interactions during skin morphogenesis (NCAM, versican, and alkaline phosphatase) were all severely altered in Tfam(EKO) mice. Moreover, the number of mast cells, major histocompatibility complex class II+, or CD11b+ immunocytes in the skin mesenchyme was increased, and essentially no subcutis developed. Therefore, in contrast to their epidermal counterparts, pilosebaceous unit stem cells depend on a functional ETC. Most importantly, our findings point toward a frontier in skin biology: the coupling of HF keratinocyte mitochondrial function with the epithelial-mesenchymal interactions that drive overall development of the skin and its appendages. PMID:25371971

  12. 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: ...

  13. 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 ...

  14. Immunohistochemical Evaluation of p53 and Ki67 Expression in Skin Epithelial Tumors

    PubMed Central

    Khodaeiani, Effat; Fakhrjou, Ashraf; Amirnia, Mehdi; Babaei-nezhad, Shahla; Taghvamanesh, Farshid; Razzagh-Karimi, Elham; Alikhah, Hossein

    2013-01-01

    Background and Aims: The cellular mechanisms responsible for initiating or limiting the tumors including skin types are of great importance. The p53 is a tumor-inhibiting gene which is believed to be defective in many malignant situations. Ki67 is a non-histonic protein which is mainly interfere with the proliferation and has many controlling effects during the cell cycle. Because of their importance in skin tumor cell growth, this study aimed at evaluating the p53 and Ki67 expression in skin epithelial tumors by immunohistochemical method. Materials and Methods: In a descriptive setting, 50 biopsy samples (30 basal cell carcinomas (BCCs), 10 squamous cell carcinomas (SCCs), 8 keratoacanthomas (KAs), and 2 trichoepitheliomas (TEs)) were immunohistochemically evaluated for p53 and Ki67 expression during a 14-month period. The incidence and expression rate of these two variables were separately reported in each group of samples. Results: The expression rate of p53 was 67.77% for the BCCs, 50.20% for the SCCs, and null for the KAs. For both TEs, it was 50%. The expression rate of Ki67 was 57.33% for the BCCs, 47.70% for the SCCs, 37.5% for the KAs, and 0.0% for TEs. The incidence of P53+ cells was 100% and 90% in the BCC and SCC samples, respectively. The both TEs were positive in this regard. The incidence of Ki67+ cells was 100% for the BCC, SCC, and KA samples. The both TEs were negative in this regard. Conclusion: This study showed that the incidence rate of p53- and Ki67-positive cells is very high in skin malignant epithelial tumors. The expression rate of these two variables is comparable with reports in the literature. Further studies with large sample size are recommended to be carried out for KA and TE samples. PMID:23723466

  15. Drug delivery nanoparticles in skin cancers.

    PubMed

    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.

  16. 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

  17. Skin cancer risk in BRCA1/2 mutation carriers.

    PubMed

    Gumaste, P V; Penn, L A; Cymerman, R M; Kirchhoff, T; Polsky, D; McLellan, B

    2015-06-01

    Women with BRCA1/2 mutations have an elevated risk of breast and ovarian cancer. These patients and their clinicians are often concerned about their risk for other cancers, including skin cancer. Research evaluating the association between BRCA1/2 mutations and skin cancer is limited and has produced inconsistent results. Herein, we review the current literature on the risk of melanoma and nonmelanoma skin cancers in BRCA1/2 mutation carriers. No studies have shown a statistically significant risk of melanoma in BRCA1 families. BRCA2 mutations have been linked to melanoma in large breast and ovarian cancer families, though a statistically significant elevated risk was reported in only one study. Five additional studies have shown some association between BRCA2 mutations and melanoma, while four studies did not find any association. With respect to nonmelanoma skin cancers, studies have produced conflicting results. Given the current state of medical knowledge, there is insufficient evidence to warrant increased skin cancer surveillance of patients with a confirmed BRCA1/2 mutation or a family history of a BRCA1/2 mutation, in the absence of standard risk factors. Nonetheless, suspected BRCA1/2 mutation carriers should be counselled about skin cancer risks and may benefit from yearly full skin examinations.

  18. Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2016-07-25

    Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  19. 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.

  20. 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.

  1. 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

  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%.

  3. Aberrant immune responses in arsenical skin cancers.

    PubMed

    Lee, Chih-Hung; Liao, Wei-Ting; Yu, Hsin-Su

    2011-09-01

    Arsenic is a well-known human carcinogen. It also impairs immune functions and activation in many aspects. However, only a small portion of arsenic-exposed population develops skin abnormalities, including Bowen's disease and skin cancers. Differential immune activation among the individuals might account for the different susceptibilities. In patients with arsenic-induced Bowen's disease, there is a selective CD4 T-cell apoptosis through tumor necrosis factor-alpha pathway, decrease in macrophage differentiation and phagocytosis, reduced Langerhans cell numbers and dendrites, altered regulatory T-cell distribution, and other immune alterations. Several lines of evidence from mouse and fish studies also confirmed the potent and multifaceted effects of arsenic in the immune system. The molecular bases of immunosuppression by arsenic in lymphocytes may include chromosomal and DNA abnormalities, decreased T-cell receptor activation, and the cellular status of oxidation and methylation. This article also reviews the causative and differential role of selective CD4 cell apoptosis and the carcinogenesis of arsenic-induced Bowen's disease.

  4. Ultraviolet radiation and skin cancer: molecular mechanisms.

    PubMed

    Hussein, Mahmoud R

    2005-03-01

    Every living organism on the surface of the earth is exposed to the ultraviolet (UV) fraction of the sunlight. This electromagnetic energy has both life-giving and life-endangering effects. UV radiation can damage DNA and thus mutagenize several genes involved in the development of the skin cancer. The presence of typical signature of UV-induced mutations on these genes indicates that the ultraviolet-B part of sunlight is responsible for the evolution of cutaneous carcinogenesis. During this process, variable alterations of the oncogenic, tumor-suppressive, and cell-cycle control signaling pathways occur. These pathways include (a) mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor-suppressor gene in basal cell carcinomas, (b) an activated mitogenic ras pathway and mutated p53 in squamous cell carcinomas, and (c) an activated ras pathway, inactive p16, and p53 tumor suppressors in melanomas. This review presents background information about the skin optics, UV radiation, and molecular events involved in photocarcinogenesis.

  5. Repetitive DNA alterations in human skin cancers.

    PubMed

    Ribeiro, Gil R H; Francisco, Guilherme; Teixeira, Lúcia V S; Romão-Correia, Rosana F; Sanches, José A; Neto, Cyro Festa; Ruiz, Itamar R G

    2004-11-01

    Repetitive sequences constitute landmarks for genome regulation, evolution, and chromatin architecture. Patterns of specific and non-specific repetitive sequences change in many types and stages of tumor cells, characterized by band loss, gain, and (de) increased staining of pre-existing bands. In this work, repetitive DNA was studied in search of genome instability of skin cancers: basal and squamous cell carcinomas (BCC and SCC), malignant melanoma (MM), melanocytic nevus (MN), and actinic keratosis (AK) lesions. DNAs were extracted from blood and tumor samples from 21 BCC, 7 SCC, 11 MM and 7 lesions. Banding patterns were obtained by random amplification of polymorphic DNA (RAPD), and specific D9S50 and D9S52 microsatellites (9p21). D9S50 patterns revealed microsatellite instability (MSI) and/or loss of heterozygosity (LOH) in 36% BCC, 25% SCC, and 57% MM tumors. D9S52 microsatellite showed 28.5%; 42.8%; and 71.4% altered tumors, respectively. No microsatellite alterations were found in MN and AK. On the other hand, genomic rearrangements detected by RAPD were present in 100% tumors. In BCC, the mean number of tumor DNA alterations showed predominant gain of bands. On the contrary, MM samples presented loss, or decreased intensity signal of RAPD bands. Genome alterations in skin cancers would result from chromosomal rearrangements, aneuploidy and/or polysomies. The low-cost and quick RAPD technique may reveal unknown genes or DNA sequences associated with tumor development and progression, and may be easily implemented in clinical diagnosis.

  6. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

    PubMed

    Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-12-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.

  7. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.

    PubMed

    Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

    2015-12-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  8. Stiffness nanotomography of human epithelial cancer cells

    NASA Astrophysics Data System (ADS)

    Staunton, Jack R.; Doss, Bryant L.; Gilbert, C. Michael; Kasas, Sandor; Ros, Robert

    2012-02-01

    The mechanical stiffness of individual cells is important in both cancer initiation and metastasis. We present atomic force microscopy (AFM) based nanoindentation experiments on various human mammary and esophagus cell lines covering the spectrum from normal immortalized cells to highly metastatic ones. The combination of an AFM with a confocal fluorescence lifetime imaging microscope (FLIM) in conjunction with the ability to move the sample and objective independently allow for precise alignment of AFM probe and laser focus with an accuracy down to a few nanometers. This enables us to correlate the mechanical properties with the point of indentation in the FLIM image. We are using force-volume measurements as well as force indentation curves on distinct points on the cells to compare the elastic moduli of the nuclei, nucleoli, and the cytoplasm, and how they vary within and between individual cells and cell lines. Further, a detailed analysis of the force-indentation curves allows study of the cells' mechanical properties at different indentation depths and to generate 3D elasticity maps.

  9. Chemosensory function of amphibian skin: integrating epithelial transport, capillary blood flow and behaviour.

    PubMed

    Hillyard, S D; Willumsen, N J

    2011-07-01

    Terrestrial anuran amphibians absorb water across specialized regions of skin on the posterioventral region of their bodies. Rapid water absorption is mediated by the insertion of aquaporins into the apical membrane of the outermost cell layer. Water moves out of the epithelium via aquaglyceroporins in the basolateral membrane and into the circulation in conjunction with increased capillary blood flow to the skin and aquaporins in the capillary endothelial cells. These physiological responses are activated by intrinsic stimuli relating to the animals' hydration status and extrinsic stimuli relating to the detection of osmotically available water. The integration of these processes has been studied using behavioural observations in conjunction with neurophysiological recordings and studies of epithelial transport. These studies have identified plasma volume and urinary bladder stores as intrinsic stimuli that activate the formation of angiotensin II (AII) to stimulate water absorption behaviour. The coordinated increase in water permeability and capillary blood flow appears to be mediated primarily by sympathetic stimulation of beta adrenergic receptors, although the neurohypopyseal hormone arginine vasotocin (AVT) may also play a role. Extrinsic stimuli relate primarily to the ionic and osmotic properties of hydration sources. Toads avoid NaCl solutions that have been shown to be harmful in acute exposure, approx. 200-250 mm. The avoidance is partially attenuated by amiloride raising the hypothesis that the mechanism for salt detection by toads resembles that for salt taste in mammals that take in water by mouth. In this model, depolarization of the basolateral membrane of taste cells is coupled to afferent neural stimulation. In toad skin we have identified innervation of skin epithelial cells by branches of spinal nerves and measured neural responses to NaCl solutions that elicit behavioural avoidance. These same concentrations produce depolarization of the

  10. Epithelial Cell Polarity Determinant CRB3 in Cancer Development

    PubMed Central

    Li, Pingping; Mao, Xiaona; Ren, Yu; Liu, Peijun

    2015-01-01

    Cell polarity, which is defined as asymmetry in cell shape, organelle distribution and cell function, is essential in numerous biological processes, including cell growth, cell migration and invasion, molecular transport, and cell fate. Epithelial cell polarity is mainly regulated by three conserved polarity protein complexes, the Crumbs (CRB) complex, partitioning defective (PAR) complex and Scribble (SCRIB) complex. Research evidence has indicated that dysregulation of cell polarity proteins may play an important role in cancer development. Crumbs homolog 3 (CRB3), a member of the CRB complex, may act as a cancer suppressor in mouse kidney epithelium and mouse mammary epithelium. In this review, we focus on the current data available on the roles of CRB3 in cancer development. PMID:25552927

  11. EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

    ClinicalTrials.gov

    2013-01-15

    Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  12. 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.

  13. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer.

  14. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  15. Host epithelial geometry regulates breast cancer cell invasiveness

    PubMed Central

    Boghaert, Eline; Gleghorn, Jason P.; Lee, KangAe; Gjorevski, Nikolce; Radisky, Derek C.; Nelson, Celeste M.

    2012-01-01

    Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment. PMID:23150585

  16. The role of surgery in advanced epithelial ovarian cancer.

    PubMed

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  17. 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

  18. 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 ...

  19. 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

  20. 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.

  1. 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

  2. Periodontal bone loss and risk of epithelial ovarian cancer

    PubMed Central

    Babic, Ana; Poole, Elizabeth M.; Terry, Kathryn L.; Cramer, Daniel W.; Teles, Ricardo P.; Tworoger, Shelley S.

    2015-01-01

    Purpose Periodontitis, a chronic inflammatory response to pathogenic bacteria in the oral microbiome, is common among adults. It is associated with several medical conditions, including cardiovascular diseases, and potentially with esophageal, lung, oral and pancreatic cancer. One of the proposed mechanisms behind these associations is systemic inflammation, which has also been implicated in ovarian cancer etiology. The aim of this study was to evaluate association between ovarian cancer and periodontal bone loss. Methods The association between periodontal bone loss, a marker of periodontitis, and risk of epithelial ovarian cancer was estimated among 60,560 participants of the prospective Nurses’ Health Study using Cox proportional hazards analysis. Competing risks analysis was used to estimate association by histological subtype. Results We did not observe an increased risk of ovarian cancer among participants with periodontal bone loss (HR=0.86, 95% CI: 0.64–1.15). Among women younger than 69 years, periodontal bone loss was associated with a 40% (HR=0.60, 95% CI: 0.36–0.98) decreased ovarian cancer risk, while there was no association in women older than 69 (HR=1.09, 95% CI: 0.75–1.58), although this difference did not reach statistical significance (p-heterogeneity=0.06). We observed a suggestive decreased risk for serous tumors (HR=0.76, 95% CI: 0.53–1.09). The number of natural teeth and root canals, other metrics of oral health, were not associated with ovarian cancer risk. Conclusion Our results do not support an increased ovarian cancer risk in women with periodontal bone loss, however there was a significant decrease in risk in women younger than 69. Given the unexpected association between periodontal bone loss and ovarian cancer risk in younger women, further research is warranted. PMID:25837263

  3. Kindlin-2 inhibits serous epithelial ovarian cancer peritoneal dissemination and predicts patient outcomes.

    PubMed

    Ren, Caixia; Du, Juan; Xi, Chenguang; Yu, Yu; Hu, Ajin; Zhan, Jun; Guo, Hongyan; Fang, Weigang; Liu, Congrong; Zhang, Hongquan

    2014-03-28

    Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.

  4. 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.

  5. Diagnosis of colorectal cancer using Raman spectroscopy of laser-trapped single living epithelial cells

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Qin, Yejun; Zheng, Feng; Sun, Menghong; Shi, Daren

    2006-07-01

    A single-cell diagnostic technique for epithelial cancers is developed by utilizing laser trapping and Raman spectroscopy to differentiate cancerous and normal epithelial cells. Single-cell suspensions were prepared from surgically removed human colorectal tissues following standard primary culture protocols and examined in a near-infrared laser-trapping Raman spectroscopy system, where living epithelial cells were investigated one by one. A diagnostic model was built on the spectral data obtained from 8 patients and validated by the data from 2 new patients. Our technique has potential applications from epithelial cancer diagnosis to the study of cell dynamics of carcinogenesis.

  6. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  7. 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

  8. 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

  9. ABO blood group and incidence of epithelial ovarian cancer

    PubMed Central

    Gates, Margaret A.; Wolpin, Brian M.; Cramer, Daniel W.; Hankinson, Susan E.; Tworoger, Shelley S.

    2010-01-01

    Previous studies have observed an association between ABO blood group and risk of certain malignancies, including ovarian cancer; however, no prospective studies of the association with ovarian cancer risk are available. Using data from 49,153 women in the Nurses’ Health Study, we examined the association between ABO blood group and incidence of epithelial ovarian cancer. Study participants reported their blood type and Rh factor in 1996, and 234 women were diagnosed with incident ovarian cancer during 10 years of follow-up. We used Cox proportional hazards regression to model the incidence rate ratios (RR) and 95% confidence intervals (CI) of ovarian cancer for each blood group category. Compared to women with blood group O, women with blood group AB or B had a non-significant 38% increase in ovarian cancer incidence (95% CI=0.88–2.16 for blood group AB and 0.96–1.99 for blood group B), while blood group A was not associated with risk (RR=0.95, 95% CI=0.70–1.30). Combining blood groups AB and B, we observed a statistically significant positive association with presence versus absence of the B antigen overall (RR=1.41, 95% CI=1.06–1.88) and for the serous invasive subtype (RR=1.53, 95% CI=1.08–2.17). In this large, prospective cohort of women, presence of the B antigen was positively associated with ovarian cancer incidence, while blood group A was not associated with risk. Additional studies are needed to confirm this association and to explore the mechanisms through which blood group may influence ovarian cancer risk. PMID:20309936

  10. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  11. 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)

  12. Evidence that arsenite acts as a cocarcinogen in skin cancer.

    PubMed

    Rossman, Toby G; Uddin, Ahmed N; Burns, Fredric J

    2004-08-01

    Inorganic arsenic (arsenite and arsenate) in drinking water has been associated with skin cancers in several countries such as Taiwan, Chile, Argentina, Bangladesh, and Mexico. This association has not been established in the United States. In addition, inorganic arsenic alone in drinking water does not cause skin cancers in animals. We recently showed that concentrations as low as 1.25 mg/l sodium arsenite were able to enhance the tumorigenicity of solar UV irradiation in mice. The tumors were almost all squamous cell carcinomas (SCCs). These data suggest that arsenic in drinking water may need a carcinogenic partner, such as sunlight, in the induction of skin cancers. Arsenite may enhance tumorigenicity via effects on DNA repair and DNA damage-induced cell cycle effects, leading to genomic instability. Others have found that dimethlyarsinic acid (DMA), a metabolite of arsenite, can induce bladder cancers at high concentrations in drinking water. In those experiments, skin cancers were not produced. Taken together, these data suggest that arsenite (or possibly an earlier metabolite), and not DMA, is responsible for the skin cancers, but a second genotoxic agent may be a requirement. The differences between the US and the other arsenic-exposed populations with regard to skin cancers might be explained by the lower levels of arsenic in the US, less sun exposure, better nutrition, or perhaps genetic susceptibility differences.

  13. Epithelial-Mesenchymal Transition (EMT) gene variants and Epithelial Ovarian Cancer (EOC) risk

    PubMed Central

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chen, Zhihua; Chen, Y. Ann; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E.; Berchuck, Andrew; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N.A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Introduction Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to EOC risk have been based on small sample sizes and none have sought replication in an independent population. Methods We screened 1254 SNPs in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (p<0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A p-value <0.05 and a false discovery rate (FDR) <0.2 was considered statistically significant. Results In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (OR=1.16, 95%CI=1.07–1.25, p=0.0003, FDR=0.19), while F8 rs7053448 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), F8 rs7058826 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), and CAPN13 rs1983383 (OR=0.79, 95%CI=0.69–0.90, p=0.0005, FDR=0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. Conclusion These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219

  14. Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy.

    PubMed

    Lee, Kye-Sung; Zhao, Huimin; Ibrahim, Sherrif F; Meemon, Natthani; Khoudeir, Laura; Rolland, Jannick P

    2012-12-01

    We investigate morphological differences in three-dimensional (3-D) images with cellular resolution between nonmelanoma skin cancer and normal skin using Gabor domain optical coherence microscopy. As a result, we show for the first time cellular optical coherence images of 3-D features differentiating cancerous skin from normal skin. In addition, in vivo volumetric images of normal skin from different anatomic locations are shown and compared.

  15. Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue

    NASA Astrophysics Data System (ADS)

    Woodward, Ruth M.; Cole, Bryan E.; Wallace, Vincent P.; Pye, Richard J.; Arnone, Donald D.; Linfield, Edmund H.; Pepper, Michael

    2002-11-01

    We demonstrate the application of terahertz pulse imaging (TPI) in reflection geometry for the study of skin tissue and related cancers both in vitro and in vivo. The sensitivity of terahertz radiation to polar molecules, such as water, makes TPI suitable for studying the hydration levels in the skin and the determination of the lateral spread of skin cancer pre-operatively. By studying the terahertz pulse shape in the time domain we have been able to differentiate between diseased and normal tissue for the study of basal cell carcinoma (BCC). Basal cell carcinoma has shown a positive terahertz contrast, and inflammation and scar tissue a negative terahertz contrast compared to normal tissue. In vivo measurements on the stratum corneum have enabled visualization of the stratum corneum-epidermis interface and the study of skin hydration levels. These results demonstrate the potential of terahertz pulse imaging for the study of skin tissue and its related disorders, both in vitro and in vivo.

  16. Analgesic drug use and risk of epithelial ovarian cancer.

    PubMed

    Hannibal, Charlotte G; Rossing, Mary Anne; Wicklund, Kristine G; Cushing-Haugen, Kara L

    2008-06-15

    Analgesic use may reduce ovarian cancer risk, possibly through antiinflammatory or antigonadotropic effects. The authors conducted a population-based, case-control study in Washington State that included 812 women aged 35-74 years who were diagnosed with epithelial ovarian cancer between 2002 and 2005 and 1,313 controls. Use of analgesics, excluding use within the previous year, was assessed via in-person interviews. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Overall, acetaminophen and aspirin were associated with weakly increased risks of ovarian cancer. These associations were stronger after more than 10 years of use (acetaminophen: odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.6; aspirin: OR = 1.6, 95% CI: 1.1, 2.2) and were present for indications of headache, menstrual pain, and other pain/injury. Reduced risk was observed among aspirin users who began regular use within the previous 5 years (OR = 0.6, 95% CI: 0.4, 1.0) or used this drug for prevention of heart disease (OR = 0.7, 95% CI: 0.5, 1.0). These results, in the context of prior findings, do not provide compelling evidence of a true increase in risk of ovarian cancer among women who use these drugs. However, they add to the weight of evidence that, in the aggregate, provides little support for the use of analgesic drugs as chemoprevention for this disease.

  17. Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice

    PubMed Central

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M.; Huttner, Wieland; Weidemann, Alexander

    2013-01-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds. PMID:23798557

  18. Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

    ClinicalTrials.gov

    2013-12-17

    Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  19. Spectroscopic methods for the photodiagnosis of nonmelanoma skin cancer.

    PubMed

    Drakaki, Eleni; Vergou, Theognosia; Dessinioti, Clio; Stratigos, Alexander J; Salavastru, Carmen; Antoniou, Christina

    2013-06-01

    The importance of dermatological noninvasive imaging techniques has increased over the last decades, aiming at diagnosing nonmelanoma skin cancer (NMSC). Technological progress has led to the development of various analytical tools, enabling the in vivo/in vitro examination of lesional human skin with the aim to increase diagnostic accuracy and decrease morbidity and mortality. The structure of the skin layers, their chemical composition, and the distribution of their compounds permits the noninvasive photodiagnosis of skin diseases, such as skin cancers, especially for early stages of malignant tumors. An important role in the dermatological diagnosis and disease monitoring has been shown for promising spectroscopic and imaging techniques, such as fluorescence, diffuse reflectance, Raman and near-infrared spectroscopy, optical coherence tomography, and confocal laser-scanning microscopy. We review the use of these spectroscopic techniques as noninvasive tools for the photodiagnosis of NMSC.

  20. Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

    PubMed

    Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

    2014-09-01

    Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours.

  1. Risk factors for epithelial ovarian cancer in Beijing, China.

    PubMed

    Chen, Y; Wu, P C; Lang, J H; Ge, W J; Hartge, P; Brinton, L A

    1992-02-01

    A study in Beijing, China of 112 pathologically confirmed epithelial ovarian cancer cases and 224 age-matched community controls enabled evaluation of risk in relation to reproductive, medical, familial, and selected lifestyle factors. An inverse relationship was observed between the number of full-term pregnancies and ovarian cancer risk. Compared to nulliparous women, subjects with one, two, or three full-term pregnancies were at 50%, 70%, or 90% reduced risks, respectively (P for trend less than 0.01). A positive correlation was found between the number of ovulatory years and risk, with a 2.6-fold increased risk for women with 30 or more compared to less than 10 ovulatory years (P for trend less than 0.01). Infertility, as estimated in various ways, was also found to be an important risk factor. When parity was taken into account, age at first pregnancy was not related to ovarian cancer risk. No protective effect was associated with mumps virus infection. In contrast, risk increased significantly as serum mumps virus antibody titres increased (P for trend less than 0.01). An elevated risk was found in women with a history of long-term (greater than 3 months) application of talc-containing dusting powder to the lower abdomen and perineum (Relative risk 3.9, 95% confidence interval: 0.9-10.63). These findings suggest that Chinese women have risk factors similar to those of occidental women.

  2. Organoid culture systems for prostate epithelial and cancer tissue.

    PubMed

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-02-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth. Starting with the plating of digested tissue material, full-grown organoids can usually be obtained in ∼2 weeks. The culture protocol we describe here is currently the only one that allows the growth of both the luminal and basal prostatic epithelial lineages, as well as the growth of advanced prostate cancers. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.

  3. [Dualistic classification of epithelial ovarian cancer: Is it clinically relevant?].

    PubMed

    Devouassoux-Shisheboran, Mojgan; Genestie, Catherine; Ray-Coquard, Isabelle

    2016-03-01

    Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and the most lethal gynecological malignancies. Based on their heterogeneous morphology, a dualistic model of carcinogenesis was proposed in 2004. Type I carcinomas, composed of low grade serous, endometrioid, mucinous, clear cell carcinomas and malignant Brenner tumors, were distinct from type II carcinomas (high grade serous, undifferentiated carcinomas and carcinosarcomas). However, clinical studies failed to demonstrate the prognostic value of such a classification. The main reproach to this dualistic model was that it lumped together in type I tumors, heterogeneous lesions such as clear cell and mucinous carcinomas. Recent advances on molecular genetic alterations and precursor lesions favor the classification of ovarian carcinomas as five distinct diseases. The dualistic model of carcinogenesis in type I and II can finally be applied only to serous ovarian carcinomas (low grade and high grade).

  4. ESMO World Congress on Gastrointestinal Cancer And European Post-Chicago Melanoma/Skin Cancer Meeting.

    PubMed

    Alexander, Walter

    2016-09-01

    We present sessions on the latest trials and treatments for colorectal cancer from the ESMO World Congress and report on new developments in diagnostics and therapy presented at the European Post-Chicago Melanoma/Skin Cancer Meeting. PMID:27630529

  5. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  6. 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

  7. 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.

  8. Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-07-05

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  9. 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 ...

  10. 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

  11. Recovery of Aging-Related Size Increase of Skin Epithelial Cells: In vivo Mouse and In vitro Human Study

    PubMed Central

    Sokolov, Igor; Guz, Natali V.; Iyer, Swaminathan; Hewitt, Amy; Sokolov, Nina A.; Erlichman, Joseph S.; Woodworth, Craig D.

    2015-01-01

    The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro. Six nude mice were treated by topical application of cytochalasin B on skin of the dorsal left midsection for 140 days (the right side served as control for placebo treatment). An average decrease in cell size of 56±16% resulted. A reduction of cell size was also observed on primary human skin epithelial cells of different in vitro age (passages from 1 to 8). A cell strain obtained from a pool of 6 human subjects was treated with cytochalasin B in vitro for 12 hours. We observed a decrease in cell size that became statistically significant and reached 20–40% for cells of older passage (6–8 passages) whereas no substantial change was observed for younger cells. These results may be important for understanding the aging processes, and for cosmetic treatment of aging skin. PMID:25807526

  12. On the apparent rarity of epithelial cancers in captive chimpanzees

    PubMed Central

    Varki, Nissi M.; Varki, Ajit

    2015-01-01

    Malignant neoplasms arising from epithelial cells are called carcinomas. Such cancers are diagnosed in about one in three humans in ‘developed’ countries, with the most common sites affected being lung, breast, prostate, colon, ovary and pancreas. By contrast, carcinomas are said to be rare in captive chimpanzees, which share more than 99% protein sequence homology with humans (and possibly in other related ‘great apes’—bonobos, gorillas and orangutans). Simple ascertainment bias is an unlikely explanation, as these nonhuman hominids are recipients of excellent veterinary care in research facilities and zoos, and are typically subjected to necropsies when they die. In keeping with this notion, benign tumours and cancers that are less common in humans are well documented in this population. In this brief overview, we discuss other possible explanations for the reported rarity of carcinomas in our closest evolutionary cousins, including inadequacy of numbers surveyed, differences in life expectancy, diet, genetic susceptibility, immune responses or their microbiomes, and other potential environmental factors. We conclude that while relative carcinoma risk is a likely difference between humans and chimpanzees (and possibly other ‘great apes’), a more systematic survey of available data is required for validation of this claim. PMID:26056369

  13. Biodegradable Gelatin Microcarriers Facilitate Re-Epithelialization of Human Cutaneous Wounds - An In Vitro Study in Human Skin

    PubMed Central

    Lönnqvist, Susanna; Rakar, Jonathan; Briheim, Kristina; Kratz, Gunnar

    2015-01-01

    The possibility to use a suspended tridimensional matrix as scaffolding for re-epithelialization of in vitro cutaneous wounds was investigated with the aid of a human in vitro wound healing model based on viable full thickness skin. Macroporous gelatin microcarriers, CultiSpher-S, were applied to in vitro wounds and cultured for 21 days. Tissue sections showed incorporation of wound edge keratinocytes into the microcarriers and thicker neoepidermis in wounds treated with microcarriers. Thickness of the neoepidermis was measured digitally, using immunohistochemical staining of keratins as epithelial demarcation. Air-lifting of wounds enhanced stratification in control wounds as well as wounds with CultiSpher-S. Immunohistochemical staining revealed expression of keratin 5, keratin 10, and laminin 5 in the neoepidermal component. We conclude that the CultiSpher-S microcarriers can function as tissue guiding scaffold for re-epithelialization of cutaneous wounds. PMID:26061630

  14. Perceptions and Portrayals of Skin Cancer among Cultural Subgroups

    PubMed Central

    Miller, Laura E.; Ahn, Ho-Young; Haley, J. Eric

    2014-01-01

    Health communication scholars have a responsibility to be certain that both healthcare practitioners and government agencies accurately communicate health information to the public. In order to carry out this duty, health communication scholars must assess how messages are being received and if they are being received at all by the public. This paper details a two part study which assesses this phenomenon within the context of skin cancer. Study 1 utilized 29 in depth qualitative interviews to identify subcultures among college students whose communication puts them at risk for skin cancer by encouraging poor sun exposure behaviors. The results indicate that farmers, African Americans, and individuals who regularly participate in outdoor athletics are at risk groups. Study 2 reports a content analysis of the known population of skin cancer Public Service Announcements (PSAs) available via the internet in 2013. The aforementioned groups were not present in any of the PSAs. Detailed results and implications are discussed. PMID:24616816

  15. Src is activated by the nuclear receptor peroxisome proliferator-activated receptor β/δ in ultraviolet radiation-induced skin cancer.

    PubMed

    Montagner, Alexandra; Delgado, Maria B; Tallichet-Blanc, Corinne; Chan, Jeremy S K; Sng, Ming K; Mottaz, Hélén; Degueurce, Gwendoline; Lippi, Yannick; Moret, Catherine; Baruchet, Michael; Antsiferova, Maria; Werner, Sabine; Hohl, Daniel; Saati, Talal Al; Farmer, Pierre J; Tan, Nguan S; Michalik, Liliane; Wahli, Walter

    2014-01-01

    Although non-melanoma skin cancer (NMSC) is the most common human cancer and its incidence continues to rise worldwide, the mechanisms underlying its development remain incompletely understood. Here, we unveil a cascade of events involving peroxisome proliferator-activated receptor (PPAR) β/δ and the oncogene Src, which promotes the development of ultraviolet (UV)-induced skin cancer in mice. UV-induced PPARβ/δ activity, which directly stimulated Src expression, increased Src kinase activity and enhanced the EGFR/Erk1/2 signalling pathway, resulting in increased epithelial-to-mesenchymal transition (EMT) marker expression. Consistent with these observations, PPARβ/δ-null mice developed fewer and smaller skin tumours, and a PPARβ/δ antagonist prevented UV-dependent Src stimulation. Furthermore, the expression of PPARβ/δ positively correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma (SCC), and critically, linear models applied to several human epithelial cancers revealed an interaction between PPARβ/δ and SRC and TGFβ1 transcriptional levels. Taken together, these observations motivate the future evaluation of PPARβ/δ modulators to attenuate the development of several epithelial cancers. PMID:24203162

  16. 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.

  17. 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

  18. Vitamin D, ultraviolet exposure, and skin cancer in the elderly.

    PubMed

    Barysch, Marjam Jeanette; Hofbauer, Günther F; Dummer, Reinhard

    2010-01-01

    Ultraviolet (UV) radiation has both beneficial and harmful effects on the human body. Its most important beneficial effect may be vitamin D production in the skin, also known as vitamin D photosynthesis. This is of particular interest for the elderly who often show vitamin D-deficiency. Intentional UV exposure has been recommended by different institutions in order to increase vitamin D levels. Nevertheless, UV radiation directly causes DNA damage and is verifiably responsible for carcinogenesis, potentially resulting in lethal skin cancers. Unfortunately, skin cancer incidence is rising worldwide, and there is still a lack of appropriate treatment for metastasized types. The only proven and avoidable risk factor is UV radiation. It has been shown that the earlier UV protection is started, the greater the benefit in terms of skin cancer prevention. Nevertheless, even if UV protection is started at older ages, individuals will benefit measurably. Because UV radiation is neither a reliable nor a safe method of achieving healthy vitamin D levels, intentional UV radiation is not recommended to increase vitamin D levels. In order to prevent skin cancer, UV protection is to be conducted as commonly recommended, by minimizing sun exposure, and especially sunburn, with appropriate sun protective behaviors, e.g. usage of sunscreen and clothing (hat, sunglasses, long sleeves, and pants). Infants must be protected with extra care. Tanning beds must be avoided.

  19. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

    PubMed

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M

    2016-01-01

    Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance.

  20. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility

    PubMed Central

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M.

    2016-01-01

    Mice lacking three epidermal barrier proteins—envoplakin, periplakin, and involucrin (EPI-/- mice)—have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4+ T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. PMID:26763429

  1. 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.

  2. [Anatomopathological behavior of gallbladder cancer. Frequency and importance of precancerous epithelial lesions of gallbladder cancer].

    PubMed

    Trujillo, C; Olaechea de Careaga, B; Uría, J L; Villagómez, G; Antelo, J

    1986-01-01

    Surgical and autopsy materials were analyzed in a period of six years at La Paz, Bolivia "Bolivian Japanese Gastroenterological Institute" (Instituto de Gastroenterología Boliviano Japonés de La Paz, Bolivia), searching for macro and microscopic appearance of gallbladder cancer. Adenocarcinoma with infiltrative growth was the most frequent finding. Cholecystitis and Cholelithiasis were present in all the cases of gallbladder cancer. Epithelial lesions such hyperplasia, atypical hyperplasia and carcinoma in situ were frequent findings in the surrounding mucosa of invasive gallbladder carcinoma and not so frequent in benign gallbladder lesions. Group V of Nevin classification was common in our cases.

  3. 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

  4. Occupational skin cancer induced by ultraviolet radiation and its prevention.

    PubMed

    Diepgen, T L; Fartasch, M; Drexler, H; Schmitt, J

    2012-08-01

    Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens.

  5. An investigation into the concurrent collection of human scent and epithelial skin cells using a non-contact sampling device.

    PubMed

    Caraballo, Norma Iris; Mendel, Julian; Holness, Howard; La Salvia, Joel; Moroose, Tina; Eckenrode, Brian; Stockham, Rex; Furton, Kenneth; Mills, DeEtta

    2016-09-01

    In criminal investigations, the collection of human scent often employs a non-contact, dynamic airflow device, known as the Scent Transfer Unit 100 (STU-100), to transfer volatile organic compounds (VOCs) from an object/person onto a collection material that is subsequently presented to human scent discriminating canines. Human scent is theorized to be linked to epithelial skin cells that are shed at a relatively constant rate allowing both scent and cellular material to be deposited into the environment and/or onto objects. Simultaneous collection of cellular material, with adequate levels of nuclear deoxyribonucleic acid (nDNA), and human scent using a non-invasive methodology would facilitate criminal investigations. This study evaluated the STU-100 for the concurrent collection of human scent and epithelial skin cells from a porous (paper) and non-porous (stainless steel bar) object that was held for a specified period of time in the dominant hand of twenty subjects (10 females and 10 males). Human scent analysis was performed using headspace static solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME/GC-MS). A polycarbonate filter was used to trap epithelial skin cells which, upon extraction, were subsequently analyzed, inter-laboratory, using the quantitative polymerase chain reaction (qPCR). The STU-100 proved to be inadequate for collecting the minimum number of epithelial skin cells required to obtain nuclear DNA concentrations above the limit of detection for the qPCR kit. With regard to its use for human scent collection, a reduction in the number and mass of compounds was observed when compared to samples that were directly collected. However, when the indirect collection of human scent from the two different objects was compared, a greater number and mass of compounds was observed from the non-porous object than from the porous object. This outcome suggests that the matrix composition of the scent source could affect the

  6. An investigation into the concurrent collection of human scent and epithelial skin cells using a non-contact sampling device.

    PubMed

    Caraballo, Norma Iris; Mendel, Julian; Holness, Howard; La Salvia, Joel; Moroose, Tina; Eckenrode, Brian; Stockham, Rex; Furton, Kenneth; Mills, DeEtta

    2016-09-01

    In criminal investigations, the collection of human scent often employs a non-contact, dynamic airflow device, known as the Scent Transfer Unit 100 (STU-100), to transfer volatile organic compounds (VOCs) from an object/person onto a collection material that is subsequently presented to human scent discriminating canines. Human scent is theorized to be linked to epithelial skin cells that are shed at a relatively constant rate allowing both scent and cellular material to be deposited into the environment and/or onto objects. Simultaneous collection of cellular material, with adequate levels of nuclear deoxyribonucleic acid (nDNA), and human scent using a non-invasive methodology would facilitate criminal investigations. This study evaluated the STU-100 for the concurrent collection of human scent and epithelial skin cells from a porous (paper) and non-porous (stainless steel bar) object that was held for a specified period of time in the dominant hand of twenty subjects (10 females and 10 males). Human scent analysis was performed using headspace static solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME/GC-MS). A polycarbonate filter was used to trap epithelial skin cells which, upon extraction, were subsequently analyzed, inter-laboratory, using the quantitative polymerase chain reaction (qPCR). The STU-100 proved to be inadequate for collecting the minimum number of epithelial skin cells required to obtain nuclear DNA concentrations above the limit of detection for the qPCR kit. With regard to its use for human scent collection, a reduction in the number and mass of compounds was observed when compared to samples that were directly collected. However, when the indirect collection of human scent from the two different objects was compared, a greater number and mass of compounds was observed from the non-porous object than from the porous object. This outcome suggests that the matrix composition of the scent source could affect the

  7. Free tissue transfer in the reconstruction of massive skin cancer.

    PubMed

    Wax, Mark K

    2009-05-01

    Skin cancer arising in the head and neck is a common occurrence. Although the vast majority of these cancers can be treated with simple excision and local reconstruction there is a subset of patients who have massive tumors that require composite tissue resection. These patients are best reconstructed with free tissue transfer. Acceptable functional and cosmetic results can be expected. Long-term survival is excellent in patients who have negative margins.

  8. 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

  9. 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 ...

  10. 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

  11. 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

  12. Beta genus papillomaviruses and skin cancer.

    PubMed

    Howley, Peter M; Pfister, Herbert J

    2015-05-01

    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.

  13. 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.

  14. 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

  15. NPPB is a Novel Candidate Biomarker Expressed by Cancer-Associated Fibroblasts In Epithelial Ovarian Cancer

    PubMed Central

    Lawrenson, Kate; Grun, Barbara; Lee, Nathan; Mhawech-Fauceglia, Paulette; Kan, Jenny; Swenson, Steve; Lin, Yvonne G.; Pejovic, Tanja; Millstein, Joshua; Gayther, Simon A

    2014-01-01

    Most solid tumours contain cancer-associated fibroblasts (CAFs) that support tumourigenesis and malignant progression. However the cellular origins of CAFs in epithelial ovarian cancers (EOCs) remain poorly understood, and their utility as a source of clinical biomarkers for cancer diagnosis has not been explored in great depth. Here, we report establishing in vitro and in vivo models of CAFs in ovarian cancer development. Normal ovarian fibroblasts and mesenchymal stem cells cultured in the presence of EOC cells acquired a CAF-like phenotype, and promoted EOC cell migration in vitro. CAFs also promoted ovarian cancer growth in vivo in both subcutaneous and intraperitoneal murine xenograft assays. Molecular profiling of CAFs identified gene expression signatures that were highly enriched for extracellular and secreted proteins. We identified novel candidate CAF specific biomarkers for ovarian cancer including NPPB, which was expressed in the stroma of 60% primary ovarian cancer tissues (n=145) but not in the stroma of normal ovaries (n=4). NPPB is a secreted protein that was also elevated in the blood of 50% of women with ovarian cancer (n=8). Taken together these data suggest that the tumor stroma is a novel source of biomarkers, including NPPB, that may be of clinical utility for detection of EOC. PMID:25047817

  16. Molecular signaling of the epithelial to mesenchymal transition in generating and maintaining cancer stem cells.

    PubMed

    Ouyang, Gaoliang; Wang, Zhe; Fang, Xiaoguang; Liu, Jia; Yang, Chaoyong James

    2010-08-01

    The epithelial to mesenchymal transition (EMT) is a highly conserved cellular program that allows polarized, well-differentiated epithelial cells to convert to unpolarized, motile mesenchymal cells. EMT is critical for appropriate embryogenesis and plays a crucial role in tumorigenesis and cancer progression. Recent studies revealed that there is a direct link between the EMT program and the gain of epithelial stem cell properties. EMT is sufficient to induce a population with stem cell characteristics from well-differentiated epithelial cells and cancer cells. In this review, we briefly introduce the biology of EMT inducers and transcription factors in tumorigenesis and then focus on the role of these key players of the EMT in generating and maintaining cancer stem cells.

  17. Preventing skin cancer through reduction of indoor tanning: current evidence.

    PubMed

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

    2013-06-01

    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.

  18. 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…

  19. Preventing skin cancer through reduction of indoor tanning: current evidence.

    PubMed

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

    2013-06-01

    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

  20. 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…

  1. 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.

  2. 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

  3. 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.

  4. The role of antioxidants in skin cancer prevention and treatment.

    PubMed

    Godic, Aleksandar; Poljšak, Borut; Adamic, Metka; Dahmane, Raja

    2014-01-01

    Skin cells are constantly exposed to reactive oxygen species (ROS) and oxidative stress from exogenous and endogenous sources. UV radiation is the most important environmental factor in the development of skin cancer and skin aging. The primary products caused by UV exposure are generally direct DNA oxidation or generation of free radicals which form and decompose extremely quickly but can produce effects that can last for hours, days, or even years. UV-induced generation of ROS in the skin develops oxidative stress when their formation exceeds the antioxidant defense ability. The reduction of oxidative stress can be achieved on two levels: by lowering exposure to UVR and/or by increasing levels of antioxidant defense in order to scavenge ROS. The only endogenous protection of our skin is melanin and enzymatic antioxidants. Melanin, the pigment deposited by melanocytes, is the first line of defense against DNA damage at the surface of the skin, but it cannot totally prevent skin damage. A second category of defense is repair processes, which remove the damaged biomolecules before they can accumulate and before their presence results in altered cell metabolism. Additional UV protection includes avoidance of sun exposure, usage of sunscreens, protective clothes, and antioxidant supplements.

  5. Multiple aggressive squamous skin cancers in association with nonbullous congenital ichthyosiform erythroderma.

    PubMed

    Brown, V L; Farrant, P B J; Turner, R J; Price, M L; Burge, S M

    2008-05-01

    Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. Celtic ancestry, HLA phenotype and increased risk of skin cancer.

    PubMed

    Long, C C; Darke, C; Marks, R

    1998-04-01

    Individuals of Celtic ancestry are claimed to be at greater risk of skin cancer than non-Celts, and various positive and negative associations between certain human leucocyte antigen (HLA) phenotypes and the development of skin cancer have been described. The aims of this study were to determine whether any HLA phenotypes are associated either with Celtic or non-Celtic ancestry, or skin type. One thousand and ten members of the Welsh Bone Marrow Donor Registry (WBMDR), whose HLA phenotypes are known, were asked to complete a questionnaire which enquired as to their family origins and their 'Index of Celtic Ancestry' scored out of 12. Three groups were identified: non-Celts (score < 3), Celts (score > 9), and a subset of the Celts--'high scoring' Celts (score > 10). Details of hair and eye colour and skin type were also requested. Skin type and HLA-A, -B, -DR and -DQ frequencies were compared between the three groups (Celts, non-Celts and 'high scoring' Celts), and a random indigenous population of 9196 members of the WBMDR. Seven hundred and thirty-six replies were received (279 male, 457 female, mean age 31 years). One hundred and forty-four Celts, 51 'high scoring' Celts and 170 non-Celts were identified. Forty-six (32%) Celts had skin type I or II compared with 36 (21%) non-Celts (P = 0.039), and 37 (73%) 'high scoring' Celts had skin type I or II (P < 0.0001). However, there were no significant differences between the groups with regard to hair colour, eye colour or number of episodes of painful sunburn. The frequency of HLA-DR4 was 32% in the non-Celtic group, 44% in the Celtic group (not significant), and 53% in the 'high scoring' Celts (P = 0.008). However, the difference was not significant after correction. There were no significant associations between skin type and HLA phenotype. HLA-DR4 is known to be associated with an increased risk of both basal cell carcinoma and malignant melanoma and its increased frequency in Celts may be an independent risk

  11. Comparison of stubbing and the double swab method for collecting offender epithelial material from a victim's skin.

    PubMed

    de Bruin, Karla G; Verheij, Saskia M; Veenhoven, Martine; Sijen, Titia

    2012-03-01

    After manual strangulation, epithelial cells originating from the offender can often be found on the skin of the victim. In order to obtain a conclusive DNA profile, it is important to secure as many epithelial cells from the offender and as few epithelial cells from the victim as possible. In this study, two methods for securing offender DNA were compared: the double swab method and an adapted tape-lifting method, so-called stubbing. 50 male volunteers were asked to simulate manual strangulation on the forearm of a female volunteer. After securing the epithelial material, DNA profiles were generated. The contribution of both donors to the samples was determined from the number of detected alleles, specific for each donor, and the average peak height of the donor-specific alleles. For the offender, in all cases except one, partial or full profiles were obtained and no difference between the double swab and the stubbing method was observed. For the victim, fewer alleles were detected by means of double swab than by means of stubbing. In conclusion, the double swab method performs slightly better than the stubbing method. However, from a practical point of view, the stubbing method may be preferred over the double swab technique.

  12. Prospective, double-blinded, randomised controlled trial assessing the effect of an Octenidine-based hydrogel on bacterial colonisation and epithelialization of skin graft wounds in burn patients

    PubMed Central

    W, Eisenbeiß; F, Siemers; G, Amtsberg; P, Hinz; B, Hartmann; T, Kohlmann; A, Ekkernkamp; U, Albrecht; O, Assadian; A, Kramer

    2012-01-01

    Background: Moist wound treatment improves healing of skin graft donor site wounds. Microbial colonised wounds represent an increased risk of wound infection; while antimicrobially active, topical antiseptics may impair epithelialization. Objectives: The aim of this prospective randomised controlled clinical trial was to examine the influence of an Octenidine-dihydrochloride (OCT) hydrogel on bacterial colonisation and epithelialization of skin graft donor sites. Methods: The study was designed as a randomised, double-blinded, controlled clinical trial. Skin graft donor sites from a total of 61 patients were covered either with 0.05% OCT (n=31) or an OCT-free placebo wound hydrogel (n=30). Potential interaction with wound healing was assessed by measuring the time until 100% re-epithelialization. In addition, microbial wound colonisation was quantitatively determined in all skin graft donor sites. Results: There was no statistically significant difference in the time for complete epithelialization of skin graft donor sites in the OCT and the placebo group (7.3±0.2 vs. 6.9±0.2 days; p=0.236). Microbial wound colonisation was significantly lower in the OCT group than in the placebo group (p=0.014). Conclusions: The OCT-based hydrogel showed no delay in wound epithelialization and demonstrated a significantly lower bacterial colonisation of skin graft donor site wounds. PMID:23071904

  13. Familial skin cancer syndromes: Increased melanoma risk.

    PubMed

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

  14. Ultraviolet light exposure influences skin cancer in association with latitude.

    PubMed

    Rivas, Miguel; Araya, María C; Caba, Fresia; Rojas, Elisa; Calaf, Gloria M

    2011-04-01

    The increase in the amount of solar ultraviolet (UV) light that reaches the earth is considered to be responsible for the worldwide increase in skin cancer. It has been reported that excessive levels of UVA and UVB light have multiple effects, which can be harmful to humans. Experimental measurements were obtained using wide-band solar light YES biometers from 2006 to 2009 in Arica, Chile and from 2003 to 2006 in Valdivia, Chile, both instruments having been calibrated according to the World Health Organization (WHO) criteria and integrated into the Chilean Meteorological Organization network. To explain the possible effect of radiation on skin cancer, revised pathological reports in Arica and Valdivia were analyzed. In Arica, data on men and women were collected between 1997 and 1998-2002, and in Valdivia, between 1997-2000 and 2001-2007. In this study, comparative values of ultraviolet index (UVI) from the above datasets, were analyzed. Arica is a city located in the subtropical zone of northern Chile, 25 meters above sea level, with a latitude of 18˚49'S and a longitude of 70˚19'W. It has a microclimate characterized by stable meteorological conditions throughout the year, including low precipitation (<5 mm per decade), predictable winds, a high percentage of clear sky days and high ground reflectivity due to the presence of light sand. Due to its location near sea level, the population performs a great number of outdoor activities. Valdivia is a city located in the southern part of Chile, 19 meters above sea level with a latitude of 39˚38'S and a longitude of 73˚5'W. The aim of the present study was to determine the relationship between latitude and the risk of skin cancer in two cities with different latitudes. The incidence of skin cancer per 100,000 persons significantly (P<0.05) increased in both genders between the periods 1997-2000 and 2001-2007 in Arica. However, it decreased in men between the periods 1993-1997 and 1998-2002 in Valdivia. The results

  15. 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,…

  16. A cross-reactive antigen of thymus and skin epithelial cells common with the polysaccharide of group A streptococci.

    PubMed Central

    Lyampert, I M; Beletskaya, L V; Borodiyuk, N A; Gnezditskaya, E V; Rassokhina, I I; Danilova, T A

    1976-01-01

    Investigation of antibodies to the specific determinant of streptococcal group A polysaccharide in indirect immunofluorescence experiments has revealed the existence of a cross-reactive antigen in the epithelial cells of the thymus and skin. This CR antigen is contained by the epithelial cells of man and animals of different species. It has been demonstrated in all the individuals studied including animals producing antibodies to the polysaccharide of Group A streptococci. The principal cause of autoimmune thymitis characteristic of rheumatic fever and other autoimmune processes is probably damage done to the thymus by autoantibodies resulting from immunization with microbial cross-reactive antigens shared by the thymus. Reaction of the autoantibodies with thymic antigens may affect the immunosuppressive function of the thymus and the maturation process of suppressor T cells. These events probably constitute the basic stage in the development of an autoimmune process. Images Figure 1 Figure 2 Figures 3-6 PMID:800402

  17. Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation

    PubMed Central

    WINSHIP, AMY LOUISE; RAINCZUK, KATE; TON, AMANDA; DIMITRIADIS, EVA

    2016-01-01

    Endometrial cancer is the most common invasive gynaecological malignancy. While endocrine, genetic and inflammatory factors are thought to contribute to its pathogenesis, its precise etiology and molecular regulators remain poorly understood. Fibulin-5 is an extracellular matrix (ECM) protein that inhibits cell growth and invasion in several cancer cell types and is downregulated in a number of types of human cancer. However, it is unknown whether fibulin-5 plays a role in endometrial tumourigenesis. In the current report, the expression and localisation of fibulin-5 in type I endometrioid human endometrial cancers of grades (G) 1–3 was investigated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Fibulin-5 mRNA was found to be significantly reduced in whole tumour tissues from women across G1-3 compared with benign endometrium (P<0.0001). Consistently, fibulin-5 protein was also reduced in the tumour epithelial compartment across increasing tumour grades. By contrast, increased protein localisation to the tumour stroma was observed with increasing grade. Knockdown by small interfering RNA in Ishikawa endometrial epithelial cancer cells expressing fibulin-5 stimulated cell adhesion and proliferation in vitro. Fibulin-5 mRNA expression in Ishikawa cells was induced by transforming growth factor-β and fibulin-5 in turn activated extracellular signal-regulated kinases (ERK1/2), suggesting that it may act via the mitogen-activated protein kinase pathway. In summary, the present study identified fibulin-5 as a downregulated ECM gene in human endometrial cancer and observed a shift from epithelial to stromal protein localisation with increasing tumour grade in women. These data suggest that loss of fibulin-5 function may promote endometrial cancer progression by enhancing epithelial cell adhesion and proliferation. PMID:27347195

  18. A targeted genetic association study of epithelial ovarian cancer susceptibility

    PubMed Central

    Earp, Madalene; Winham, Stacey J.; Larson, Nicholas; Permuth, Jennifer B.; Sicotte, Hugues; Chien, Jeremy; Anton-Culver, Hoda; Bandera, Elisa V.; Berchuck, Andrew; Cook, Linda S.; Cramer, Daniel; Doherty, Jennifer A.; Goodman, Marc T.; Levine, Douglas A.; Monteiro, Alvaro N.A.; Ness, Roberta B.; Pearce, Celeste L.; Rossing, Mary Anne; Tworoger, Shelley S.; Wentzensen, Nicolas; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E.; Cunningham, Julie M.; Edwards, Robert P.; Fogarty, Zachary C.; Iversen, Edwin S.; Kraft, Peter; Larson, Melissa C.; Le, Nhu D.; Lin, Hui-Yi; Lissowska, Jolanta; Modugno, Francesmary; Moysich, Kirsten B.; Olson, Sara H.; Pike, Malcolm C.; Poole, Elizabeth M.; Rider, David N.; Terry, Kathryn L.; Thompson, Pamela J.; van den Berg, David; Vierkant, Robert A.; Vitonis, Allison F.; Wilkens, Lynne R.; Wu, Anna H.; Yang, Hannah P.; Ziogas, Argyrios; Phelan, Catherine M.; Schildkraut, Joellen M.; Chen, Yian Ann; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.

    2016-01-01

    Background Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. Results At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5×10−8), nor were any significant after Bonferroni correction for 17,000 variants (p< 3×10-6). Methods A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. Conclusion Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance. PMID:26848776

  19. Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer

    PubMed Central

    Roca, Hernan; Hernandez, James; Weidner, Savannah; McEachin, Richard C.; Fuller, David; Sud, Sudha; Schumann, Taibriana; Wilkinson, John E.; Zaslavsky, Alexander; Li, Hangwen; Maher, Christopher A.; Daignault-Newton, Stephanie; Healy, Patrick N.; Pienta, Kenneth J.

    2013-01-01

    Cell plasticity regulated by the balance between the mesenchymal to epithelial transition (MET) and the opposite program, EMT, is critical in the metastatic cascade. Several transcription factors (TFs) are known to regulate EMT, though the mechanisms of MET remain unclear. We demonstrate a novel function of two TFs, OVOL1 and OVOL2, as critical inducers of MET in human cancers. Our findings indicate that the OVOL-TFs control MET through a regulatory feedback loop with EMT-inducing TF ZEB1, and the regulation of mRNA splicing by inducing Epithelial Splicing Regulatory Protein 1 (ESRP1). Using mouse prostate tumor models we show that expression of OVOL-TFs in mesenchymal prostate cancer cells attenuates their metastatic potential. The role of OVOL-TFs as inducers of MET is further supported by expression analyses in 917 cancer cell lines, suggesting their role as crucial regulators of epithelial-mesenchymal cell plasticity in cancer. PMID:24124593

  20. 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.

  1. Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery∗

    PubMed Central

    Hunsicker, Oliver; Fotopoulou, Christina; Pietzner, Klaus; Koch, Mandy; Krannich, Alexander; Sehouli, Jalid; Spies, Claudia; Feldheiser, Aarne

    2015-01-01

    Abstract Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery. This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [<500 mL] vs HAS: high ascites group [>500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study. A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced

  2. 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.

  3. 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

  4. [UV exposure, skin cancer and decrease in the ozone layer].

    PubMed

    Rauterberg, A; Jung, E G

    1993-12-01

    All over the world a remarkable increase in malignant tumors of the skin is reported. More than 90% of them are localized in areas of the skin exposed to sunlight. The incidence of malignant melanomas of the skin is tenfold higher today than 40 years ago. Experimental data and results of epidemiological studies indicate two different risk patterns of UV exposure for the development of skin cancer. The cumulative UV-light exposure during lifetime induces--especially in light-sensitive individuals older than 60 years--actinic elastosis, precanceroses and squamous cell carcinomas as well as lentigo maligna melanomas. Intense UV exposure in childhood and youth may lead to development of superficial spreading melanomas and nodular melanomas between the age of 20 and 40. The reduction of ozone in the stratosphere could still contribute to a higher incidence of tumors of the skin in the next decades. The evident role of UVB light in the induction of tumors of the skin offers the possibility for preventive strategies.

  5. Whole-cell and single channel K+ and Cl- currents in epithelial cells of frog skin

    PubMed Central

    1991-01-01

    Whole-cell and single channel currents were studied in cells from frog (R. pipiens and R. catesbiana) skin epithelium, isolated by collagenase and trypsin treatment, and kept in primary cultures up to three days. Whole-cell currents did not exhibit any significant time-dependent kinetics under any ionic conditions used. With an external K gluconate Ringer solution the currents showed slight inward rectification with a reversal potential near zero and an average conductance of 5 nS at reversal. Ionic substitution of the external medium showed that most of the cell conductance was due to K and that very little, if any, Na conductance was present. This confirmed that most cells originate from inner epithelial layers and contain membranes with basolateral properties. At voltages more positive than 20 mV outward currents were larger with K in the medium than with Na or N-methyl-D-glucamine. Such behavior is indicative of a multi-ion transport mechanism. Whole-cell K current was inhibited by external Ba and quinidine. Blockade by Ba was strongly voltage dependent, while that by quinidine was not. In the presence of high external Cl, a component of outward current that was inhibited by the anion channel blocker diphenylamine-2-carboxylate (DPC) appeared in 70% of the cells. This component was strongly outwardly rectifying and reversed at a potential expected for a Cl current. At the single channel level the event most frequently observed in the cell-attached configuration was a K channel with the following characteristics: inward-rectifying I-V relation with a conductance (with 112.5 mM K in the pipette) of 44 pS at the reversal potential, one open and at least two closed states, and open probability that increased with depolarization. Quinidine blocked by binding in the open state and decreasing mean open time. Several observations suggest that this channel is responsible for most of the whole-cell current observed in high external K, and for the K conductance of the

  6. Whole-cell and single channel K+ and Cl- currents in epithelial cells of frog skin.

    PubMed

    García-Díaz, J F

    1991-07-01

    Whole-cell and single channel currents were studied in cells from frog (R. pipiens and R. catesbiana) skin epithelium, isolated by collagenase and trypsin treatment, and kept in primary cultures up to three days. Whole-cell currents did not exhibit any significant time-dependent kinetics under any ionic conditions used. With an external K gluconate Ringer solution the currents showed slight inward rectification with a reversal potential near zero and an average conductance of 5 nS at reversal. Ionic substitution of the external medium showed that most of the cell conductance was due to K and that very little, if any, Na conductance was present. This confirmed that most cells originate from inner epithelial layers and contain membranes with basolateral properties. At voltages more positive than 20 mV outward currents were larger with K in the medium than with Na or N-methyl-D-glucamine. Such behavior is indicative of a multi-ion transport mechanism. Whole-cell K current was inhibited by external Ba and quinidine. Blockade by Ba was strongly voltage dependent, while that by quinidine was not. In the presence of high external Cl, a component of outward current that was inhibited by the anion channel blocker diphenylamine-2-carboxylate (DPC) appeared in 70% of the cells. This component was strongly outwardly rectifying and reversed at a potential expected for a Cl current. At the single channel level the event most frequently observed in the cell-attached configuration was a K channel with the following characteristics: inward-rectifying I-V relation with a conductance (with 112.5 mM K in the pipette) of 44 pS at the reversal potential, one open and at least two closed states, and open probability that increased with depolarization. Quinidine blocked by binding in the open state and decreasing mean open time. Several observations suggest that this channel is responsible for most of the whole-cell current observed in high external K, and for the K conductance of the

  7. [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

  8. [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.

  9. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness.

    PubMed

    Giannoni, Elisa; Bianchini, Francesca; Masieri, Lorenzo; Serni, Sergio; Torre, Eugenio; Calorini, Lido; Chiarugi, Paola

    2010-09-01

    Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread.

  10. Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-12-21

    Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  11. The role of optical radiations in skin cancer.

    PubMed

    Ayala, Fabrizio; 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.

  12. Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1.

    PubMed

    Zhang, Yongjian; Liu, Wei; He, Wenbo; Zhang, Yuanyuan; Deng, Xiuling; Ma, Yanmin; Zeng, Jin; Kou, Bo

    2016-05-01

    Hedgehog (Hh) signaling pathway is considered to play a crucial role in vertebrate development and carcinogenesis. Additionally, epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, facilitating cancer metastasis and invasion. Accumulating evidence has indicated that the Hh signaling pathway could potentiate the epithelial-mesenchymal transition (EMT). In the present study, we demonstrated that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephaniae, exerts its anti-metastatic ability in bladder cancer cells by regulating GLI family zinc finger 1 (Gli-1), a key factor of Hedgehog signaling pathway. In our study, we confirmed that tetrandrine could impede migration and invasion in bladder cancer 5637 and T24 cells. Additionally, tetrandrine reverses EMT by increasing the expression of E-cadherin and reducing the N-cadherin, vimentin and Slug expression in a dose-dependent manner. Interestingly, tetrandrine also decreases mobility and reduces the expression of Gli-1 in bladder cancer cells. Moreover, we verified that tetrandrine inhibits metastasis and induces mesenchymal-epithelial transition (MET) of bladder cancer through downregulation of Gli-1, which could be partially reversed by Gli-1 overexpression. In conclusion, our findings show that tetrandrine inhibits migration and invasion, and reverses EMT of bladder cancer cells through negatively regulating Gli-1. It indicates that Gli-1 may be a potential therapeutic target of tetrandrine against bladder cancer. PMID:26983576

  13. 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.

  14. 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

  15. 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

  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. Metabolic Reprogramming and Dependencies Associated with Epithelial Cancer Stem Cells Independent of the Epithelial-Mesenchymal Transition Program.

    PubMed

    Aguilar, Esther; Marin de Mas, Igor; Zodda, Erika; Marin, Silvia; Morrish, Fionnuala; Selivanov, Vitaly; Meca-Cortés, Óscar; Delowar, Hossain; Pons, Mònica; Izquierdo, Inés; Celià-Terrassa, Toni; de Atauri, Pedro; Centelles, Josep J; Hockenbery, David; Thomson, Timothy M; Cascante, Marta

    2016-05-01

    In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analyses that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics, and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis. Stem Cells 2016;34:1163-1176. PMID:27146024

  18. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation

    PubMed Central

    Ciminale, Vincenzo; Silic-Benussi, Micol; Guzzo, Giulia; Rasola, Andrea; Frasson, Chiara; Nardo, Giorgia; Zulato, Elisabetta; Nicoletto, Maria Ornella; Manicone, Mariangela

    2014-01-01

    We investigated the metabolic profile of cancer stem cells (CSC) isolated from patients with epithelial ovarian cancer. CSC overexpressed genes associated with glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid β-oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle. Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher mitochondrial reactive oxygen species (ROS) production and elevated membrane potential, and underwent apoptosis upon inhibition of the mitochondrial respiratory chain. The CSC also had a high rate of pentose phosphate pathway (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis, and may rather reflect the PPP role in recharging scavenging enzymes. Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while maintaining their CSC phenotype and OXPHOS profile. These observations may explain the CSC resistance to anti-angiogenic therapies, and indicate this peculiar metabolic profile as a possible target of novel treatment strategies. PMID:24946808

  19. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation.

    PubMed

    Pastò, Anna; Bellio, Chiara; Pilotto, Giorgia; Ciminale, Vincenzo; Silic-Benussi, Micol; Guzzo, Giulia; Rasola, Andrea; Frasson, Chiara; Nardo, Giorgia; Zulato, Elisabetta; Nicoletto, Maria Ornella; Manicone, Mariangela; Indraccolo, Stefano; Amadori, Alberto

    2014-06-30

    We investigated the metabolic profile of cancer stem cells (CSC) isolated from patients with epithelial ovarian cancer. CSC overexpressed genes associated with glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid β-oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle. Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher mitochondrial reactive oxygen species (ROS) production and elevated membrane potential, and underwent apoptosis upon inhibition of the mitochondrial respiratory chain. The CSC also had a high rate of pentose phosphate pathway (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis, and may rather reflect the PPP role in recharging scavenging enzymes. Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while maintaining their CSC phenotype and OXPHOS profile. These observations may explain the CSC resistance to anti-angiogenic therapies, and indicate this peculiar metabolic profile as a possible target of novel treatment strategies. PMID:24946808

  20. Novel vitamin D compounds and skin cancer prevention

    PubMed Central

    Tongkao-on, Wannit; Gordon-Thomson, Clare; Dixon, Katie M.; Song, Eric J.; Luu, Tan; Carter, Sally E.; Sequeira, Vanessa B.; Reeve, Vivienne E.; Mason, Rebecca S.

    2013-01-01

    As skin cancer is one of the most costly health issues in many countries, particularly in Australia, the possibility that vitamin D compounds might contribute to prevention of this disease is becoming increasingly more attractive to researchers and health communities. In this article, important epidemiologic, mechanistic and experimental data supporting the chemopreventive potential of several vitamin D-related compounds are explored. Evidence of photoprotection by the active hormone, 1α,25dihydroxyvitamin D3, as well as a derivative of an over-irradiation product, lumisterol, a fluorinated analog and bufalin, a potential vitamin D-like compound, are provided. The aim of this article is to understand how vitamin D compounds contribute to UV adaptation and potentially, skin cancer prevention. PMID:24494039

  1. [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.

  2. 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

  3. The epithelial-mesenchymal transition in cancer: a potential critical topic for translational proteomic research.

    PubMed

    Bottoni, Patrizia; Isgrò, Maria Antonietta; Scatena, Roberto

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a morphogenetic process that results in a loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. First described in embryogenesis, the EMT has been recently implicated in carcinogenesis and tumor progression. In addition, recent evidence has shown that stem-like cancer cells present the hallmarks of the EMT. Some of the molecular mechanisms related to the interrelationships between cancer pathophysiology and the EMT are well-defined. Nevertheless, the precise molecular mechanism by which epithelial cancer cells acquire the mesenchymal phenotype remains largely unknown. This review focuses on various proteomic strategies with the goal of better understanding the physiological and pathological mechanisms of the EMT process.

  4. CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

    PubMed Central

    Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

    2014-01-01

    The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

  5. Dynamic cohesin-mediated chromatin architecture controls epithelial-mesenchymal plasticity in cancer.

    PubMed

    Yun, Jiyeon; Song, Sang-Hyun; Kim, Hwang-Phill; Han, Sae-Won; Yi, Eugene C; Kim, Tae-You

    2016-09-01

    Epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET) are important interconnected events in tumorigenesis controlled by complex genetic networks. However, the cues that activate EMT-initiating factors and the mechanisms that reversibly connect EMT/MET are not well understood. Here, we show that cohesin-mediated chromatin organization coordinates EMT/MET by regulating mesenchymal genes. We report that RAD21, a subunit of the cohesin complex, is expressed in epithelial breast cancer cells, whereas its expression is decreased in mesenchymal cancer. Depletion of RAD21 in epithelial cancer cells causes transcriptional activation of TGFB1 and ITGA5, inducing EMT. Reduced binding of RAD21 changes intrachromosomal chromatin interactions within the TGFB1 and ITGA5 loci, creating an active transcriptional environment. Similarly, stem cell-like cancer cells also show an open chromatin structure at both genes, which correlates with high expression levels and mesenchymal fate characteristics. Conversely, overexpression of RAD21 in mesenchymal cancer cells induces MET-specific expression patterns. These findings indicate that dynamic cohesin-mediated chromatin structures are responsible for the initiation and regulation of essential EMT-related cell fate changes in cancer. PMID:27466323

  6. 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.

  7. Protective actions of vitamin D in UVB induced skin cancer.

    PubMed

    Bikle, Daniel D

    2012-12-01

    Non-melanoma skin cancers (NMSC) are the most common type of cancer, occurring at a rate of over 1 million per year in the United States. Although their metastatic potential is generally low, they can and do metastasize, especially in the immune compromised host, and their surgical treatment is often quite disfiguring. Ultraviolet radiation (UVR) as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVR is also required for vitamin D synthesis in the skin. Based on our own data and that reported in the literature, we hypothesize that the vitamin D produced in the skin serves to suppress UVR epidermal tumor formation. In this review we will first discuss the evidence supporting the conclusion that the vitamin D receptor (VDR), with or without its ligand 1,25-dihydroxyvitamin D, limits the propensity for cancer formation following UVR. We will then explore three potential mechanisms for this protection: inhibition of proliferation and stimulation of differentiation, immune regulation, and stimulation of DNA damage repair (DDR).

  8. 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

  9. 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%.

  10. Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

    PubMed

    Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

    2015-09-01

    Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

  11. Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

    PubMed

    Gordon, Sarah; Daneshian, Mardas; Bouwstra, Joke; Caloni, Francesca; Constant, Samuel; Davies, Donna E; Dandekar, Gudrun; Guzman, Carlos A; Fabian, Eric; Haltner, Eleonore; Hartung, Thomas; Hasiwa, Nina; Hayden, Patrick; Kandarova, Helena; Khare, Sangeeta; Krug, Harald F; Kneuer, Carsten; Leist, Marcel; Lian, Guoping; Marx, Uwe; Metzger, Marco; Ott, Katharina; Prieto, Pilar; Roberts, Michael S; Roggen, Erwin L; Tralau, Tewes; van den Braak, Claudia; Walles, Heike; Lehr, Claus-Michael

    2015-01-01

    Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

  12. Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology.

    PubMed

    Gordon, Sarah; Daneshian, Mardas; Bouwstra, Joke; Caloni, Francesca; Constant, Samuel; Davies, Donna E; Dandekar, Gudrun; Guzman, Carlos A; Fabian, Eric; Haltner, Eleonore; Hartung, Thomas; Hasiwa, Nina; Hayden, Patrick; Kandarova, Helena; Khare, Sangeeta; Krug, Harald F; Kneuer, Carsten; Leist, Marcel; Lian, Guoping; Marx, Uwe; Metzger, Marco; Ott, Katharina; Prieto, Pilar; Roberts, Michael S; Roggen, Erwin L; Tralau, Tewes; van den Braak, Claudia; Walles, Heike; Lehr, Claus-Michael

    2015-01-01

    Models of the outer epithelia of the human body - namely the skin, the intestine and the lung - have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report. PMID:26536291

  13. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer.

    PubMed

    Funasaka, Tatsuyoshi; Hogan, Victor; Raz, Avraham

    2009-07-01

    Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is a housekeeping gene product/cytokine that catalyzes a step in glycolysis and gluconeogenesis, and acts as a multifunctional cytokine associated with aggressive tumors. PGI/AMF has been correlated significantly with breast cancer progression and poor prognosis in breast cancer. We show here that ectopic expression of PGI/AMF induced epithelial-to-mesenchymal transition (EMT) in MCF10A normal human breast epithelial cells, and inhibition of PGI/AMF expression triggered mesenchymal-to-epithelial transition (MET) in aggressive mesenchymal-type human breast cancer MDA-MB-231 cells. EMT in MCF10A cells was shown by morphologic changes and loss of E-cadherin/beta-catenin-mediated cell-cell adhesion, which is concomitant with the induction of the E-cadherin transcriptional repressor Snail and proteosome-dependent degradation of beta-catenin protein. Molecular analysis showed that PGI/AMF suppressed epithelial marker expressions and enhanced mesenchymal marker expressions. Silencing of PGI/AMF expression by RNA interference in MDA-MB-231 cells induced the reverse processes of EMT including altered cell shape, gain of epithelial marker, and reduction of mesenchymal marker, e.g., MET. Taken together, the results show the involvement of PGI/AMF in both EMT and MET: overexpression of PGI/AMF induces EMT in normal breast epithelial cells and reduction of PGI/AMF expression led to MET in aggressive breast cancer cells. These results suggest for the first time that PGI/AMF is a key gene to both EMT in the initiating step of cancer metastasis and MET in the later stage of metastasis during breast cancer progression.

  14. Annexin A9 (ANXA9) biomarker and therapeutic target in epithelial cancer

    DOEpatents

    Hu, Zhi; Kuo, Wen-Lin; Neve, Richard M.; Gray, Joe W.

    2012-06-12

    Amplification of the ANXA9 gene in human chromosomal region 1q21 in epithelial cancers indicates a likelihood of both in vivo drug resistance and metastasis, and serves as a biomarker indicating these aspects of the disease. ANXA9 can also serve as a therapeutic target. Interfering RNAs (iRNAs) (such as siRNA and miRNA) and shRNA adapted to inhibit ANXA9 expression, when formulated in a therapeutic composition, and delivered to cells of the tumor, function to treat the epithelial cancer.

  15. 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

  16. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion.

    PubMed

    Mariotti, Sara; Barravecchia, Ivana; Vindigni, Carla; Pucci, Angela; Balsamo, Michele; Libro, Rosaliana; Senchenko, Vera; Dmitriev, Alexey; Jacchetti, Emanuela; Cecchini, Marco; Roviello, Franco; Lai, Michele; Broccoli, Vania; Andreazzoli, Massimiliano; Mazzanti, Chiara M; Angeloni, Debora

    2016-01-12

    The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy. PMID:26689989

  17. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion

    PubMed Central

    Vindigni, Carla; Pucci, Angela; Balsamo, Michele; Libro, Rosaliana; Senchenko, Vera; Dmitriev, Alexey; Jacchetti, Emanuela; Cecchini, Marco; Roviello, Franco; Lai, Michele; Broccoli, Vania; Andreazzoli, Massimiliano; Mazzanti, Chiara M.; Angeloni, Debora

    2016-01-01

    The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy. PMID:26689989

  18. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion.

    PubMed

    Mariotti, Sara; Barravecchia, Ivana; Vindigni, Carla; Pucci, Angela; Balsamo, Michele; Libro, Rosaliana; Senchenko, Vera; Dmitriev, Alexey; Jacchetti, Emanuela; Cecchini, Marco; Roviello, Franco; Lai, Michele; Broccoli, Vania; Andreazzoli, Massimiliano; Mazzanti, Chiara M; Angeloni, Debora

    2016-01-12

    The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy.

  19. Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer

    PubMed Central

    Dokukin, M. E.; Guz, N. V.; Woodworth, C.D.; Sokolov, I.

    2015-01-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation. PMID:25844044

  20. Emergence of fractal geometry on the surface of human cervical epithelial cells during progression towards cancer

    NASA Astrophysics Data System (ADS)

    Dokukin, M. E.; Guz, N. V.; Woodworth, C. D.; Sokolov, I.

    2015-03-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation.

  1. Alterations of skin-associated lymphoid tissue in the carcinogenesis of arsenical skin cancer.

    PubMed

    Yu, H S; Chen, G S; Sheu, H M; Kao, J S; Chang, K L; Yu, C L

    1992-01-01

    We investigated the skin-associated lymphoid tissue in arsenical skin cancers, including 14 Bowen's disease, 6 basal cell carcinoma and 6 squamous cell carcinoma patients from an endemic area by immunohistochemical and morphometric methods. There was a progressive decrease of Langerhans cells in the order of normal skin, normal appearing edge and arsenical cancers. A disruption of the uniform Langerhans cell dendrites was also noticed. The Langerhans cell density in arsenical tumors did not correlate with the peritumoral infiltrates. The prominent infiltrated cells in the peritumoral area had T cell markers. The number of peritumoral T lymphocytes in squamous cell carcinoma was significantly less than that of Bowen's disease and basal cell carcinoma. Peritumoral mononuclear infiltrates in Bowen's disease and squamous cell carcinoma showed a higher helper/suppressor T cell ratio than that in basal cell carcinoma. This may be accounted for by a selective increased recruitment of helper T cells to the tumor infiltrates in Bowen's disease and squamous cell carcinoma.

  2. 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 ...

  3. 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

  4. Epithelial to mesenchymal transition and the cancer stem cell phenotype: Insights from cancer biology with therapeutic implications for colorectal cancer

    PubMed Central

    Findlay, Victoria J.; Wang, Cindy; Watson, Dennis K.; Camp, E. Ramsay

    2014-01-01

    Although mortality from colorectal cancer (CRC) is decreasing, colorectal cancer is still the second highest cause of cancer related deaths in America. Chemotherapy and radiation therapy now play central roles in our strategies to fight cancer, although we continue to lack novel strategies overcoming therapeutic resistance. Molecular mechanisms of therapeutic resistance in CRC continue to be under intense investigation. In this review, we highlight the recent evidence linking epithelial-to-mesenchymal transition (EMT) with aggressive tumor biology as well as with the cancer stem cells (CSC) across multiple organ systems including colon cancer. Furthermore, in the era of neo-adjuvant treatment, the clinical implications are concerning that our treatments may have the potential to induce more aggressive cancer cells through EMT, perhaps even generating CSCs more capable of metastasis and further resistant to treatment. This concern and potential reality highlights the critical need for further understanding the impact of clinical therapy on the pathobiology of cancer and further supports the need to therapeutically target the CSC. Besides serving as potential biomarkers for aggressive tumor biology and therapeutic resistance, EMT and CSC molecular pathways may highlight novel therapeutic targets as strategies for improving the response to conventional anti-neoplastic agents translating into improved oncologic outcomes. PMID:24787239

  5. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  6. 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.

  7. The role of skin cancer knowledge in sun-related behaviours: a systematic review.

    PubMed

    Day, Ashley K; Wilson, Carlene J; Hutchinson, Amanda D; Roberts, Rachel M

    2014-09-01

    Skin cancer is the most commonly diagnosed cancer in many Western countries. This systematic review provides a comprehensive overview of the relationship between skin cancer knowledge and sun-protective, exposure and tanning behaviours in the general population. A total of 34 studies, published in peer-reviewed journals over three decades, were reviewed and synthesised. Sun-protective behaviour was positively associated with skin cancer knowledge in most cases. Findings were inconsistent regarding other sun-related behaviours. Heterogeneity in measurement compromised the capacity to definitively link knowledge and sun-related behaviours. There is a need for development and utilisation of a standardised skin cancer knowledge scale, and guidelines are suggested.

  8. Gene Expression Correlations in Human Cancer Cell Lines Define Molecular Interaction Networks for Epithelial Phenotype

    PubMed Central

    Kohn, Kurt W.; Zeeberg, Barry M.; Reinhold, William C.; Pommier, Yves

    2014-01-01

    Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute’s CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1); interactions at adherens junctions (CDH1, ADAP1, CAMSAP3); interactions at desmosomes (PPL, PKP3, JUP); transcription regulation of cell-cell junction complexes (GRHL1 and 2); epithelial RNA splicing regulators (ESRP1 and 2); epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B); epithelial Ca(+2) signaling (ATP2C2, S100A14, BSPRY); terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2); maintenance of apico-basal polarity (RAB25, LLGL2, EPN3). The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets. PMID:24940735

  9. Evidence of epithelial-mesenchymal transition in canine prostate cancer metastasis.

    PubMed

    Fonseca-Alves, Carlos Eduardo; Kobayashi, Priscila Emiko; Rivera-Calderón, Luis Gabriel; Laufer-Amorim, Renée

    2015-06-01

    The epithelial-mesenchymal transition (EMT) is a fundamental event responsible for the invasiveness and metastasis of epithelial tumours. The EMT has been described in many human cancers, but there are few reports of this phenomenon in veterinary oncology. Due to the importance of this process, the current study evaluated mesenchymal and epithelial marker protein expression in prostate lesions from dogs. Our results indicate both a loss of E-cadherin and translocation of β-catenin from the membrane to the cytoplasm and nucleus in the tumour group. Vimentin expression in the tumour group was higher than in normal tissue. All of the metastases were positive for prostate-specific antigen, pan-cytokeratin and E-cadherin, although fewer positive cells were present than in the primary tumours. The immunohistochemical results showed a loss of epithelial markers and a gain of a mesenchymal marker among metastatic cells, suggesting that the EMT occurs during the metastatic process of canine prostate carcinoma.

  10. Nonsurgical Innovations in the Treatment of Nonmelanoma Skin Cancer

    PubMed Central

    Amini, Sadegh; Viera, Martha H.; Valins, Whitney

    2010-01-01

    Basal cell carcinoma and squamous cell carcinoma are the most frequent types of cancer in the United States and represent 75 percent and 20 percent, respectively, of all nonmelanoma skin cancers. Since ultraviolet radiation is implicated in their development, photoprotection is fundamental in their prevention. Additional preventive measures include identifying high-risk individuals for early detection along with using agents, such as retinoids, that are effective in decreasing the risk of premalignant cells further developing into carcinomas. Newer agents achieving this goal include perillyl alcohol, T4 endonuclease 5, DL-α-tocopherol, and α-difluoromethylornithine. Procedural modalities are currently the standard of treatment, but recent evidence has consistently shown that newer (nonsurgical) therapies, such as interferon, imiquimod, retinoids, and 5-fluorouracil, can be used effectively either as monotherapies or as adjuvants to those surgical modalities for the treatment of superficial nonmelanoma skin cancers and premalignant lesions. These newer therapies have achieved significant reductions in morbidity and mortality. Procedural modalities that have been evolving into important tools for the treatment of actinic keratosis and nonmelanoma skin cancers include photodynamic therapy and lasers. Nonsurgical therapies currently proving to be effective in clinical trials include ingenol mebutate and cyclooxygenase-2 inhibitors. Agents that are showing promising results in early phases of clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, such as cyclopamine and GDC-0449; α-melanocyte–stimulating hormone analogs, such as afamelanotide; epidermal growth factor receptor inhibitors, such as gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug capecitabine. PMID:20725548

  11. Non-melanoma skin cancers and glucocorticoid therapy

    PubMed Central

    Karagas, M R; Cushing, G L; Greenberg, E R; Mott, L A; Spencer, S K; Nierenberg, D W

    2001-01-01

    Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term mortality in organ transplant recipients receiving immunosuppressive drugs such as azathioprine and cyclosporin, often combined with adrenocortical steroids (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other conditions including musculoskeletal, connective tissue and respiratory disorders. Presently, it is unknown whether patients taking glucocorticoids are at an increased risk of skin malignances. In a population-based case-control study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and gender matched controls; neither cases nor controls had a history of organ transplantation. Participants underwent a structured personal interview regarding history of medication use and skin cancer risk factors. We used unconditional logistic regression analysis to compute odds ratios associated with glucocorticoid use for 1 month or longer while controlling for potential confounding factors. Risk of SCC was increased among users of oral glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC in particular, among patients other than organ transplant recipients. We hypothesize that immunosuppression induced by oral glucocorticoids may allow these cancers to emerge from immunosurveillance. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531252

  12. Immunohistochemical Expression of Leptin in Non Melanoma Skin Cancer

    PubMed Central

    Farag, Azza G.A.; El-Dien, Marwa Mohammed Serag

    2016-01-01

    Introduction Obesity in adults is associated with numerous health disorders including some forms of cancer. Various epidemiological studies have found a link between excess adiposity and malignant melanoma; however, the association with non melanoma skin cancer is questionable. Leptin is a hormone produced mainly by the adipose tissue and its serum level may reflect body mass index. Leptin is reported to promote proliferation and angiogenesis and deregulate apoptosis, therefore facilitates the process of carcinogenesis. Aim The current study tried to assess leptin localization and expression in non melanoma skin cancer to verify its possible role in pathogenesis of this cancer. Materials and Methods This study was carried out on 13 Basal Cell Carcinoma (BCC) cases and 14 Squamous Cell Carcinoma (SCC) cases together with 19 normal skin biopsies as a control group using immunohistochemical method. Results Leptin was expressed in 52.6% of the normal epidermis with pure cytoplasmic and both cytoplasmic and nuclear staining patterns. All cases of SCC (100%) and two cases of BCC (15.4%) showed leptin expression in tumour cells whereas nuclear expression was in favour of SCC. Stromal expression of leptin was seen in both SCC (57.1%) and BCC (38.5%) without significant differences. Percentage of leptin expression by tumour cells in SCC showed positive linear correlation with tumour size (p=0.02) and microvessel density (p=0.000). Stromal expression of leptin in SCC was associated with large tumour size (p=0.04), advanced stage (p=0.01) and tumours arising in sites other than head and neck (p=0.01). Conclusion Leptin could have a more important role in pathogenesis of cutaneous SCC rather than BCC that may reflect the trivial role of obesity in induction of BCC. The expression of leptin by tumour and stromal cells of SCC could co-operate in its progression by promoting angiogenesis with subsequently acquiring large tumour size and then advanced stage. PMID:27656540

  13. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    ClinicalTrials.gov

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  14. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  15. Emerging role of cystic fibrosis transmembrane conductance regulator - an epithelial chloride channel in gastrointestinal cancers.

    PubMed

    Hou, Yuning; Guan, Xiaoqing; Yang, Zhe; Li, Chunying

    2016-03-15

    Cystic fibrosis transmembrane conductance regulator (CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers. PMID:26989463

  16. Emerging role of cystic fibrosis transmembrane conductance regulator - an epithelial chloride channel in gastrointestinal cancers

    PubMed Central

    Hou, Yuning; Guan, Xiaoqing; Yang, Zhe; Li, Chunying

    2016-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers. PMID:26989463

  17. Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair.

    PubMed

    Katiyar, Suchitra; Elmets, Craig A; Katiyar, Santosh K

    2007-05-01

    Human skin is constantly exposed to numerous noxious physical, chemical and environmental agents. Some of these agents directly or indirectly adversely affect the skin. Cutaneous overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) has a variety of adverse effects on human health, including the development of melanoma and nonmelanoma skin cancers. Therefore, there is a need to develop measures or strategies, and nutritional components are increasingly being explored for this purpose. The polyphenols present in green tea (Camellia sinensis) have been shown to have numerous health benefits, including protection from UV carcinogenesis. (-)-Epigallocatechin-3-gallate (EGCG) is the major and most photoprotective polyphenolic component of green tea. In this review article, we have discussed the most recent investigations and mechanistic studies that define and support the photoprotective efficacy of green tea polyphenols (GTPs) against UV carcinogenesis. The oral administration of GTPs in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in mice, and this prevention is mediated through: (a) the induction of immunoregulatory cytokine interleukin (IL) 12; (b) IL-12-dependent DNA repair following nucleotide excision repair mechanism; (c) the inhibition of UV-induced immunosuppression through IL-12-dependent DNA repair; (d) the inhibition of angiogenic factors; and (e) the stimulation of cytotoxic T cells in a tumor microenvironment. New mechanistic information strongly supports and explains the chemopreventive activity of GTPs against photocarcinogenesis.

  18. Friend or foe: Endoplasmic reticulum protein 29 (ERp29) in epithelial cancer

    PubMed Central

    Chen, Shaohua; Zhang, Daohai

    2015-01-01

    The endoplasmic reticulum (ER) protein 29 (ERp29) is a molecular chaperone that plays a critical role in protein secretion from the ER in eukaryotic cells. Recent studies have also shown that ERp29 plays a role in cancer. It has been demonstrated that ERp29 is inversely associated with primary tumor development and functions as a tumor suppressor by inducing cell growth arrest in breast cancer. However, ERp29 has also been reported to promote epithelial cell morphogenesis, cell survival against genotoxic stress and distant metastasis. In this review, we summarize the current understanding on the biological and pathological functions of ERp29 in cancer and discuss the pivotal aspects of ERp29 as “friend or foe” in epithelial cancer. PMID:25709888

  19. The Extracellular Matrix in Epithelial Ovarian Cancer – A Piece of a Puzzle

    PubMed Central

    Cho, Angela; Howell, Viive M.; Colvin, Emily K.

    2015-01-01

    Epithelial ovarian cancer is the fifth leading cause of cancer-related deaths in women and the most lethal gynecological malignancy. Extracellular matrix (ECM) is an integral component of both the normal and tumor microenvironment. ECM composition varies between tissues and is crucial for maintaining normal function and homeostasis. Dysregulation and aberrant deposition or loss of ECM components is implicated in ovarian cancer progression. The mechanisms by which tumor cells induce ECM remodeling to promote a malignant phenotype are yet to be elucidated. A thorough understanding of the role of the ECM in ovarian cancer is needed for the development of effective biomarkers and new therapies. PMID:26579497

  20. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    SciTech Connect

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-12-17

    Research highlights: {yields} Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. {yields} Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. {yields} PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. {yields} This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated {beta}-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered

  1. [Prevalence of skin tears among hospitalized patients with cancer].

    PubMed

    Amaral, Ana Flávia dos Santos; Pulido, Kelly Cristina Strazzieri; Santos, Vera Lucia Conceição de Gouveia

    2012-10-01

    This study aimed to analyze the prevalence of skin tears (ST) among hospitalized oncology patients and associated demographic and clinical variables. This is an epidemiological cross-sectional study type, performed at Octavio Frias de Oliveira State of São Paulo Cancer Institute. All adult patients hospitalized from April 10th to 18th 2010 were evaluated by interview and physical examination. Chi-square test was used to compare demographic and clinical variables between patients with and without ST. Five patients among 157 had nine skin tears, resulting in a prevalence of 3.3%. Among demographic variables, only number of children showed statistically significant difference (p=0.027) between groups. Clinically, patients with ST had lower Karnofsky scores (p=0.031), lower scores at Braden Scale (p=0.026) and less collaborative behaviors (p=0.042) when compared to patients with no lesions. This study contributes to a better knowledge of ST in oncology patients.

  2. 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 %.

  3. Mesenchymal to Epithelial Transition Induced by Reprogramming Factors Attenuates the Malignancy of Cancer Cells

    PubMed Central

    Takaishi, Mikiro; Tarutani, Masahito; Takeda, Junji; Sano, Shigetoshi

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is a biological process of metastatic cancer. However, an effective anticancer therapy that directly targets the EMT program has not yet been discovered. Recent studies have indicated that mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is observed in fibroblasts during the generation of induced pluripotent stem cells. In the present study, we investigated the effects of reprogramming factors (RFs) on squamous cell carcinoma (SCC) cells. RFs-introduced cancer cells (RICs) demonstrated the enhanced epithelial characteristics in morphology with altered expression of mRNA and microRNAs. The motility and invasive activities of RICs in vitro were significantly reduced. Furthermore, xenografts of RICs exhibited no lymph node metastasis, whereas metastasis was detected in parental SCC-inoculated mice. Thus, we concluded that RICs regained epithelial properties through MET and showed reduced cancer malignancy in vitro and in vivo. Therefore, the understanding of the MET process in cancer cells by introduction of RFs may lead to the designing of a novel anticancer strategy. PMID:27258152

  4. Nuclear medicine for imaging of epithelial ovarian cancer.

    PubMed

    Abedi, Seyed Mohammad; Mardanshahi, Alireza; Shahhosseini, Roza; Hosseinimehr, Seyed Jalal

    2016-05-01

    Cancer is one of the leading causes of mortality worldwide. Usually, the diagnosis of cancer at an early stage is important to facilitate proper treatment and survival. Nuclear medicine has been successfully used in the diagnosis, staging, therapy and monitoring of cancers. Single-photon emission computed tomography and PET-based companion imaging agents are in development for use as a companion diagnostic tool for patients with ovarian cancer. The present review discusses the basic and clinical studies related to the use of radiopharmaceuticals in the diagnosis and management of ovarian cancer, focusing on their utility and comparing them with other imaging techniques such as computed tomography and MRI.

  5. GM130 regulates epithelial-to-mesenchymal transition and invasion of gastric cancer cells via snail

    PubMed Central

    Zhao, Jianquan; Yang, Chun; Guo, Shujun; Wu, Yonggang

    2015-01-01

    Gastric cancer is one of the most common causes of digestive tract tumor. Despite of recent advances in surgical techniques and development of adjuvant therapy, the underlying mechanisms of gastric cancer remain poorly understood and relevant insight into novel treatment strategies using gene target remains incomplete. Recently, several studies report that epithelial to mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors; however, the molecular mechanisms underlying this transition are unknown. As a cis-Golgi matrix protein, GM130 plays an important role in cell cycle progression and transport of protein in the secretory pathway. In this study, we found that GM130 expression has a positive correlation with the pathological differentiation and tumor node metastasis (TNM) stage of gastric cancer. High GM130 expression levels also predict shorter overall survival of gastric cancer patients. RNA interference-mediated knockdown of GM130 expression increased epithelial marker (E-cadherin) and decreased mesenchymal marker (N-cadherin and vimentin) expression in gastric cancer cells, suppressing cell invasion, and tumor formation. Furthermore, we found that GM130 upregulated expression of the key EMT regulator Snail (SNAI1), which mediated EMT activation and cell invasion by GM130. Taken together, our study indicates GM130 may be a promising therapeutic biomarker for gastric cancer. PMID:26617790

  6. GM130 regulates epithelial-to-mesenchymal transition and invasion of gastric cancer cells via snail.

    PubMed

    Zhao, Jianquan; Yang, Chun; Guo, Shujun; Wu, Yonggang

    2015-01-01

    Gastric cancer is one of the most common causes of digestive tract tumor. Despite of recent advances in surgical techniques and development of adjuvant therapy, the underlying mechanisms of gastric cancer remain poorly understood and relevant insight into novel treatment strategies using gene target remains incomplete. Recently, several studies report that epithelial to mesenchymal transition (EMT) is a crucial process for the invasion and metastasis of epithelial tumors; however, the molecular mechanisms underlying this transition are unknown. As a cis-Golgi matrix protein, GM130 plays an important role in cell cycle progression and transport of protein in the secretory pathway. In this study, we found that GM130 expression has a positive correlation with the pathological differentiation and tumor node metastasis (TNM) stage of gastric cancer. High GM130 expression levels also predict shorter overall survival of gastric cancer patients. RNA interference-mediated knockdown of GM130 expression increased epithelial marker (E-cadherin) and decreased mesenchymal marker (N-cadherin and vimentin) expression in gastric cancer cells, suppressing cell invasion, and tumor formation. Furthermore, we found that GM130 upregulated expression of the key EMT regulator Snail (SNAI1), which mediated EMT activation and cell invasion by GM130. Taken together, our study indicates GM130 may be a promising therapeutic biomarker for gastric cancer. PMID:26617790

  7. CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer.

    PubMed

    Zeng, Qiqun; Li, Weidong; Lu, Di; Wu, Zhenzhen; Duan, Hongxia; Luo, Yongting; Feng, Jing; Yang, Dongling; Fu, Li; Yan, Xiyun

    2012-01-24

    The epithelial-mesenchymal transition (EMT) plays an important role in breast cancer metastasis, especially in the most aggressive and lethal subtype, "triple-negative breast cancer" (TNBC). Here, we report that CD146 is a unique activator of EMTs and significantly correlates with TNBC. In epithelial breast cancer cells, overexpression of CD146 down-regulated epithelial markers and up-regulated mesenchymal markers, significantly promoted cell migration and invasion, and induced cancer stem cell-like properties. We further found that RhoA pathways positively regulated CD146-induced EMTs via the key EMT transcriptional factor Slug. An orthotopic breast tumor model demonstrated that CD146-overexpressing breast tumors showed a poorly differentiated phenotype and displayed increased tumor invasion and metastasis. We confirmed these findings by conducting an immunohistochemical analysis of 505 human primary breast tumor tissues and found that CD146 expression was significantly associated with high tumor stage, poor prognosis, and TNBC. CD146 was expressed at abnormally high levels (68.9%), and was strongly associated with E-cadherin down-regulation in TNBC samples. Taken together, these findings provide unique evidence that CD146 promotes breast cancer progression by induction of EMTs via the activation of RhoA and up-regulation of Slug. Thus, CD146 could be a therapeutic target for breast cancer, especially for TNBC. PMID:22210108

  8. 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

  9. In vivo study for the discrimination of cancerous and normal skin using fibre probe-based Raman spectroscopy.

    PubMed

    Schleusener, Johannes; Gluszczynska, Patrycja; Reble, Carina; Gersonde, Ingo; Helfmann, Jürgen; Fluhr, Joachim W; Lademann, Jürgen; Röwert-Huber, Joachim; Patzelt, Alexa; Meinke, Martina C

    2015-10-01

    Raman spectroscopy has proved its capability as an objective, non-invasive tool for the detection of various melanoma and non-melanoma skin cancers (NMSC) in a number of studies. Most publications are based on a Raman microspectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fibre-coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma (MM) (n = 36), basal cell carcinoma (BCC) (n = 39) and squamous cell carcinoma (SCC) (n = 29). NMSC were discriminated from normal skin with a balanced accuracy of 73% (BCC) and 85% (SCC) using partial least squares discriminant analysis (PLS-DA). Discriminating MM and pigmented nevi (PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy. PMID:26010742

  10. 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.

  11. 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%.

  12. New Agents for Prevention of Ultraviolet-Induced Nonmelanoma Skin Cancer

    PubMed Central

    Camp, William L.; Turnham, Jennifer W.; Athar, Mohammad; Elmets, Craig A.

    2012-01-01

    With the incidence of nonmelanoma skin cancer on the rise, current prevention methods, such as the use of sunscreens, have yet to prove adequate to reverse this trend. There has been considerable interest in identifying compounds that will inhibit or reverse the biochemical changes required for skin cancers to develop, either by pharmacologic intervention or by dietary manipulation. By targeting different pathways identified as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or the addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. PMID:21540016

  13. Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts

    PubMed Central

    Liu, Suling; Cong, Yang; Wang, Dong; Sun, Yu; Deng, Lu; Liu, Yajing; Martin-Trevino, Rachel; Shang, Li; McDermott, Sean P.; Landis, Melissa D.; Hong, Suhyung; Adams, April; D’Angelo, Rosemarie; Ginestier, Christophe; Charafe-Jauffret, Emmanuelle; Clouthier, Shawn G.; Birnbaum, Daniel; Wong, Stephen T.; Zhan, Ming; Chang, Jenny C.; Wicha, Max S.

    2013-01-01

    Summary Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24−CD44+ are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites. PMID:24511467

  14. CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

    PubMed Central

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

  15. CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

    PubMed

    El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

    2014-01-01

    Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

  16. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients.

    PubMed

    Zwald, Fiona O'Reilly; Brown, Marc

    2011-08-01

    Skin cancer is the most frequent malignancy in organ transplant recipients, 95% of which are nonmelanoma skin cancer, especially squamous cell and basal cell carcinomas. This paper also discusses the incidence of other tumors (eg, melanoma, Merkel cell carcinoma, and Kaposi sarcoma) that are also increased in organ transplant patients compared to the general population. Part I of this two-part series describes the latest data concerning the epidemiologic and pathogenic aspects of nonmelanoma skin cancer development in solid organ transplant recipients. This review also highlights the concept of "field cancerization," represented by extensive areas of actinic damage and epidermal dysplasia, which accounts for increased risk of aggressive skin cancer development in susceptible patients. PMID:21763561

  17. 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'.

  18. 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

  19. Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ

    PubMed Central

    Whitaker-Menezes, Diana; Martinez-Outschoorn, Ubaldo E; Flomenberg, Neal; Birbe, Ruth C; Witkiewicz, Agnieszka K; Howell, Anthony; Pavlides, Stephanos; Tsirigos, Aristotelis; Ertel, Adam; Pestell, Richard G; Broda, Paolo; Minetti, Carlo

    2011-01-01

    We have recently proposed a new mechanism for explaining energy transfer in cancer metabolism. In this scenario, cancer cells behave as metabolic parasites, by extracting nutrients from normal host cells, such as fibroblasts, via the secretion of hydrogen peroxide as the initial trigger. Oxidative stress in the tumor microenvironment then leads to autophagy-driven catabolism, mitochondrial dys-function and aerobic glycolysis. This, in turn, produces high-energy nutrients (such as L-lactate, ketones and glutamine) that drive the anabolic growth of tumor cells, via oxidative mitochondrial metabolism. A logical prediction of this new “parasitic” cancer model is that tumor-associated fibroblasts should show evidence of mitochondrial dys-function (mitophagy and aerobic glycolysis). In contrast, epithelial cancer cells should increase their oxidative mitochondrial capacity. To further test this hypothesis, here we subjected frozen sections from human breast tumors to a staining procedure that only detects functional mitochondria. This method detects the in situ enzymatic activity of cytochrome C oxidase (COX), also known as Complex IV. Remarkably, cancer cells show an over-abundance of COX activity, while adjacent stromal cells remain essentially negative. Adjacent normal ductal epithelial cells also show little or no COX activity, relative to epithelial cancer cells. Thus, oxidative mitochondrial activity is selectively amplified in cancer cells. Although COX activity staining has never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. Similar results were obtained with NADH activity staining, which measures Complex I activity, and succinate dehydrogenase (SDH) activity staining, which measures Complex II activity. COX and NADH activities were blocked by electron transport inhibitors, such as Metformin. This has mechanistic and clinical implications

  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. 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

  2. Epithelial cells in bone marrow of oesophageal cancer patients: a significant prognostic factor in multivariate analysis

    PubMed Central

    Thorban, S; Rosenberg, R; Busch, R; Roder, R J

    2000-01-01

    The detection of epithelial cells in bone marrow, blood or lymph nodes indicates a disseminatory potential of solid tumours. 225 patients with squamous cell carcinoma of the oesophagus were prospectively studied. Prior to any therapy, cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and correlated with established histopathologic and patient-specific prognosis factors. The prognosis factors were assessed by multivariate analysis. Twenty-nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in bone marrow. The analyses of the mean and median overall survival time showed a significant difference between patients with and without epithelial cells in bone marrow (P< 0.001). Multivariate analysis in the total patient population and in patients with curative resection of the primary tumour confirmed the curative resection rate and the bone marrow status as the strongest independent prognostic factors, besides the T-category. The detection of epithelial cells in bone marrow of oesophageal cancer patients is a substantial prognostic factor proved by multivariate analysis and is helpful for exact preoperative staging, as well as monitoring of neoadjuvant therapy. © 2000 Cancer Research Campaign PMID:10883665

  3. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.

    PubMed

    Chen, Xue; Bode, Ann M; Dong, Zigang; Cao, Ya

    2016-09-01

    The epithelial-mesenchymal transition (EMT), defined as transdifferentiation of epithelial cells into mesenchymal cells, is critical for embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. Recently, the role of EMT in carcinogenesis has attracted much attention. Oncoviruses, including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and hepatitis B and C viruses (HBVs, HCVs), are known to be involved in the etiology of cancer and have been found to play important roles in cancer metastasis, especially in the EMT process. The HPV encoded oncoproteins E6 and E7 (E6/E7), EBV latent membrane protein-1 and -2A, EBV nuclear antigen, HBV-encoded X antigen, and nonstructural HCV protein 5A are all involved in the regulation of EMT. This review primarily focuses on the role of oncoviruses and their encoded proteins or signaling pathways in the EMT process. Understanding their roles will help us in the development of effective strategies for prevention and treatment of virus-related cancers.-Chen, X., Bode, A. M., Dong, Z., Cao, Y. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.

  4. Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer.

    PubMed

    Gunasinghe, N P A Devika; Wells, Alan; Thompson, Erik W; Hugo, Honor J

    2012-12-01

    As yet, there is no cure for metastatic breast cancer. Historically, considerable research effort has been concentrated on understanding the processes of metastasis, how a primary tumour locally invades and systemically disseminates using the phenotypic switching mechanism of epithelial to mesenchymal transition (EMT); however, much less is understood about how metastases are then formed. Breast cancer metastases often look (and may even function) as 'normal' breast tissue, a bizarre observation against the backdrop of the organ structure of the lung, liver, bone or brain. Mesenchymal to epithelial transition (MET), the opposite of EMT, has been proposed as a mechanism for establishment of the metastatic neoplasm, leading to questions such as: Can MET be clearly demonstrated in vivo? What factors cause this phenotypic switch within the cancer cell? Are these signals/factors derived from the metastatic site (soil) or expressed by the cancer cells themselves (seed)? How do the cancer cells then grow into a detectable secondary tumour and further disseminate? And finally--Can we design and develop therapies that may combat this dissemination switch? This review aims to address these important questions by evaluating long-standing paradigms and novel emerging concepts in the field of epithelial mesencyhmal plasticity.

  5. Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer

    PubMed Central

    Best, Sarah; Ledger, Anita; Mooney, Anne-Marie; Ferguson, Alison; Shore, Paul; Swarbrick, Alexander; Ormandy, Christopher J; Simpson, Peter T; Carroll, Jason S; Visvader, Jane; Naylor, Matthew J

    2014-01-01

    Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally-regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differentiation in a manner that disrupted alveolar progenitor cell populations. Conversely, exogenous transgenic expression of Runx2 in mammary epithelial cells blocked milk production, suggesting that the decrease in endogenous Runx2 observed late in pregnancy is necessary for full differentiation. In addition, overexpression of Runx2 drove EMT-like changes in normal mammary epithelial cells, while Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor latency and enhanced overall survival in a mouse model of breast cancer, with Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our results establish a novel function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions. PMID:25056120

  6. Proteomics analysis of E-cadherin knockdown in epithelial breast cancer cells.

    PubMed

    Vergara, Daniele; Simeone, Pasquale; Latorre, Dominga; Cascione, Francesca; Leporatti, Stefano; Trerotola, Marco; Giudetti, Anna Maria; Capobianco, Loredana; Lunetti, Paola; Rizzello, Antonia; Rinaldi, Rosaria; Alberti, Saverio; Maffia, Michele

    2015-05-20

    E-cadherin is the core protein of the epithelial adherens junction. Through its cytoplasmic domain, E-cadherin interacts with several signaling proteins; among them, α- and β-catenins mediate the link of E-cadherin to the actin cytoskeleton. Loss of E-cadherin expression is a crucial step of epithelial-mesenchymal transition (EMT) and is involved in cancer invasion and metastatization. In human tumors, down-regulation of E-cadherin is frequently associated with poor prognosis. Despite the critical role of E-cadherin in cancer progression, little is known about proteome alterations linked with its down-regulation. To address this point, we investigated proteomics, biophysical and functional changes of epithelial breast cancer cell lines upon shRNA-mediated stable knockdown of E-cadherin expression (shEcad). shEcad cells showed a distinct proteomic signature including altered expression of enzymes and proteins involved in cytoskeletal dynamic and migration. Moreover, these results suggest that, besides their role in mechanical adhesion, loss of E-cadherin expression may contribute to cancer progression by modifying a complex network of pathways that tightly regulate fundamental processes as oxidative stress, immune evasion and cell metabolism. Altogether, these results extend our knowledge on the cellular modifications associated with E-cadherin down-regulation in breast cancer cells.

  7. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer.

    PubMed

    Chen, Xue; Bode, Ann M; Dong, Zigang; Cao, Ya

    2016-09-01

    The epithelial-mesenchymal transition (EMT), defined as transdifferentiation of epithelial cells into mesenchymal cells, is critical for embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. Recently, the role of EMT in carcinogenesis has attracted much attention. Oncoviruses, including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and hepatitis B and C viruses (HBVs, HCVs), are known to be involved in the etiology of cancer and have been found to play important roles in cancer metastasis, especially in the EMT process. The HPV encoded oncoproteins E6 and E7 (E6/E7), EBV latent membrane protein-1 and -2A, EBV nuclear antigen, HBV-encoded X antigen, and nonstructural HCV protein 5A are all involved in the regulation of EMT. This review primarily focuses on the role of oncoviruses and their encoded proteins or signaling pathways in the EMT process. Understanding their roles will help us in the development of effective strategies for prevention and treatment of virus-related cancers.-Chen, X., Bode, A. M., Dong, Z., Cao, Y. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer. PMID:27279361

  8. Nonmelanoma Skin Cancer and Risk for Subsequent Malignancy

    PubMed Central

    Chen, Jiping; Ruczinski, Ingo; Jorgensen, Timothy J.; Yenokyan, Gayane; Yao, Yin; Alani, Rhoda; Liégeois, Nanette J.; Hoffman, Sandra C.; Hoffman-Bolton, Judith; Strickland, Paul T.; Helzlsouer, Kathy J.

    2008-01-01

    Background Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study. Methods In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18 405) a personal history of NMSC (total n = 19 174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided. Results The crude incidence rate (per 10 000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups (P for interaction = .022). Conclusions This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased

  9. DNA methylation changes in epithelial ovarian cancer histotypes

    PubMed Central

    Earp, Madalene A.; Cunningham, Julie M.

    2016-01-01

    Survival after a diagnosis of ovarian cancer has not improved, and despite histological differences, treatment is similar for all cases. Understanding the molecular basis for ovarian cancer risk and prognosis is fundamental, and to this end much has been gleaned about genetic changes contributing to risk, and to a lesser extent, survival. There’s considerable evidence for genetic differences between the four pathologically defined histological subtypes; however, the contribution of epigenetics is less well documented. In this report, we review alterations in DNA methylation in ovarian cancer, focusing on histological subtypes, and studies examining the roles of methylation in determining therapy response. As epigenetics is making its way into clinical care, we review the application of cell free DNA methylation to ovarian cancer diagnosis and care. Finally, we comment on recurrent limitations in the DNA methylation literature for ovarian cancer, which can and should be addressed to mature this field. PMID:26363302

  10. Sheep, wolf, or werewolf: cancer stem cells and the epithelial-to-mesenchymal transition.

    PubMed

    Chang, Jeffrey T; Mani, Sendurai A

    2013-11-28

    Multiple cancers contain subpopulations that exhibit characteristics of cancer stem cells (CSCs), the ability to self-renew and seed heterogeneous tumors. Recent evidence suggests two potentially overlapping models for these phenotypes: one where stem cells arise from multipotent progenitor cells, and another where they are created via an epithelial to mesenchymal transition. Unraveling this issue is critical, as it underlies phenomena such as metastasis and therapeutic resistance. Therefore, there is intense interest in understanding these two types of CSSs, how they differ from differentiated cancer cells, the mechanisms that drive their phenotypes, and how that knowledge can be incorporated into therapeutics.

  11. Circular polarization terahertz imaging 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.

  12. 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.

  13. 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

  14. DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis.

    PubMed

    Lee, Eunsohl; Wang, Jingcheng; Yumoto, Kenji; Jung, Younghun; Cackowski, Frank C; Decker, Ann M; Li, Yan; Franceschi, Renny T; Pienta, Kenneth J; Taichman, Russell S

    2016-09-01

    Cancer metastasis is a multistep process associated with the induction of an epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Although significant progress has been made in understanding the molecular mechanisms regulating EMT and the CSC phenotype, little is known of how these processes are regulated by epigenetics. Here we demonstrate that reduced expression of DNA methyltransferase 1 (DNMT1) plays an important role in the induction of EMT and the CSC phenotype by prostate cancer (PCa) cells, with enhanced tumorigenesis and metastasis. First, we observed that reduction of DNMT1 by 5-azacitidine (5-Aza) promotes EMT induction as well as CSCs and sphere formation in vitro. Reduced expression of DNMT1 significantly increased PCa migratory potential. We showed that the increase of EMT and CSC activities by reduction of DNMT1 is associated with the increase of protein kinase C. Furthermore, we confirmed that silencing DNMT1 is correlated with enhancement of the induction of EMT and the CSC phenotype in PCa cells. Additionally, chromatin immunoprecipitation assay reveals that reduction of DNMT1 promotes the suppression of H3K9me3 and H3K27me3 on the Zeb2 and KLF4 promoter region in PCa cells. Critically, we found in an animal model that significant tumor growth and more disseminated tumor cells in most osseous tissues were observed following injection of 5-Aza pretreated-PCa cells compared with vehicle-pretreated PCa cells. Our results suggest that epigenetic alteration of histone demethylation regulated by reduction of DNMT1 may control induction of EMT and the CSC phenotype, which facilitates tumorigenesis in PCa cells and has important therapeutic implications in targeting epigenetic regulation. PMID:27659015

  15. Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer

    PubMed Central

    Chen, Guangyuan; Xie, Jiabin; Huang, Ping; Yang, Zhihong

    2016-01-01

    The Hippo pathway is dysregulated in multiple types of human cancer, including ovarian cancer. Nuclear expression of yes-associated protein 1 (YAP1), a downstream transcription coactivator of the Hippo pathway, has been demonstrated to promote tumorigenesis in ovarian cancer and may serve as a poor prognostic indicator. However, transcriptional coactivator with PDZ binding motif (TAZ), a downstream target of the Hippo pathway and paralog of YAP in mammalian cells, has not been fully investigated in ovarian cancer. The present study aimed to investigate the dysregulation and biological function of TAZ in ovarian cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that TAZ mRNA and protein levels, respectively, were upregulated in ovarian cancer, and a meta-analysis of ovarian cancer microarray datasets identified that increased expression of TAZ mRNA is correlated with poor prognosis in patients with ovarian cancer. In addition, TAZ-knockdown in ovarian cancer cells demonstrated that TAZ regulates the migration, proliferation and epithelial-mesenchymal transition of ovarian cancer cells. Furthermore, pharmacological disruption of the YAP/TAZ/TEA domain protein complex resulted in a decrease in ovarian cancer cell migration, proliferation and vimentin expression. The results of the present study indicate that the overexpression of TAZ is important in the development and progression of ovarian cancer, and may function as a potential drug target for treatment of this disease entity. PMID:27588129

  16. Inflammatory microenvironment contributes to epithelial-mesenchymal transition in gastric cancer.

    PubMed

    Ma, Hui-Ying; Liu, Xin-Zhou; Liang, Chun-Min

    2016-08-01

    Gastric cancer (GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori (H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition (EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT. PMID:27547005

  17. Inflammatory microenvironment contributes to epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    Ma, Hui-Ying; Liu, Xin-Zhou; Liang, Chun-Min

    2016-01-01

    Gastric cancer (GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori (H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition (EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT. PMID:27547005

  18. Dihydroartiminisin inhibits the growth and metastasis of epithelial ovarian cancer.

    PubMed

    Wu, Buchu; Hu, Ke; Li, Shu; Zhu, Jing; Gu, Liying; Shen, Haoran; Hambly, Brett D; Bao, Shisan; Di, Wen

    2012-01-01

    Dihydroartiminisin (DHA), the active component of a Chinese herb (Artemisia annua), has been utilised as an anti-malarial drug since ancient China. DHA has also been shown to inhibit proliferation of cancer in vitro. However, the capacity of DHA to inhibit the development of ovarian cancer is still unclear. The adhesion, invasion, and migration of human ovarian cancer cell line (HO8910PM) was determined following DHA treatment in vitro, using Matrigel coated plate, transwell membrane chamber, and wound healing models, respectively. A mouse ovarian cancer model was established by orthotopic inoculation of HO8910PM cell line in nude mice. The growth and metastasis in vivo was determined 8 weeks post-implantation in response to DHA treatment. The expression of phosphorylated focal adhesion kinase (pFAK) and matrix metalloproteinases (MMP-2 and MMP-9) was evaluated using Western blotting. The expression of Von Willebrand factor (vWF) and infiltration of macrophages were determined, using immunohistochemistry. DHA inhibits ovarian cancer cell proliferation, adhesion, migration and invasion in vitro in a dose-dependent manner, consistent with decreased expression of pFAK and MMP-2, but not MMP-9. DHA inhibited metastasis significantly in vivo, associated with reduced vWF expression and macrophage infiltration. In conclusion, DHA inhibits the development of ovarian cancer, in part via down-regulating pFAK, MMP-2, vWF and macrophage infiltration. PMID:22025319

  19. Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To-Mesenchymal-Transition and Tumor Cell Migration

    PubMed Central

    Mayer, Christine; Darb-Esfahani, Silvia; Meyer, Anne-Sophie; Hübner, Katrin; Rom, Joachim; Sohn, Christof; Braicu, Ioana; Sehouli, Jalid; Hänsch, G. Maria; Gaida, Matthias M.

    2016-01-01

    Background: Ovarian cancer (OvCa) is a highly aggressive malignoma with a tumor-promoting microenvironment. Infiltration of polymorphonuclear neutrophils (PMN) is frequently seen, raising the question of their impact on tumor development. In that context, effects of PMN on human ovarian cancer cells were assessed. Methods: Human epithelial ovarian cancer cells were incubated with human PMN, lysate of PMN, or neutrophil elastase. Morphological alterations were observed by time-lapse video-microscopy, and the underlying molecular mechanism was analyzed by flow cytometry and Western blotting. Functional alternations were assessed by an in vitro wound healing assay. In parallel, a large cohort of n=334 primary OvCa tissue samples of various histological subtypes was histologically evaluated. Results: Co-cultivation of cancer cells with either PMN or PMN lysate causes a change of the polygonal epithelial phenotype of the cells towards a spindle shaped morphology, causing a cribriform cell growth. The PMN-induced alteration could be attributed to elastase, a major protease of PMN. Elastase-induced shape change was most likely due to the degradation of membranous E-cadherin, which results in loss of cell contacts and polarity. Moreover, in response to elastase, epithelial cytokeratins were downmodulated, in parallel with a nuclear translocation of β-catenin. These PMN-elastase induced alterations of cells are compatible with an epithelial-to-mesenchymal transition (EMT) of the cancer cells. Following EMT, the cells displayed a more migratory phenotype. In human biopsies, neutrophil infiltration was seen in 72% of the cases. PMN infiltrates were detected preferentially in areas with low E-cadherin expression. Conclusion: PMN in the microenvironment of OvCa can alter tumor cells towards a mesenchymal and migratory phenotype. PMID:27053953

  20. Actinic Keratosis Treatment as a Key Component of Preventive Strategies for Nonmelanoma Skin Cancer

    PubMed Central

    2010-01-01

    Actinic keratosis is responsible for more than eight million visits to dermatologists and primary care physicians annually. Actinic keratosis, the result of chronic sun damage to the skin, is closely linked to nonmelanoma skin cancer, both histologically and pathophysiologically. Clinical evidence shows that not only does actinic keratosis have the potential to progress and transform into nonmelanoma skin cancer, but it also may in fact be an early stage of cancer. The treatment of actinic keratosis is evolving from a “treat-as-you-go” strategy to a more preventive approach to curtail the potential emergence of nonmelanoma skin cancer. As the interrelationship between actinic keratosis and nonmelanoma skin cancer, squamous cell carcinoma, and basal cell carcinoma continues to strengthen, treating actinic keratosis as part of a preventive strategy to reduce nonmelanoma skin cancer is coming to the forefront. The following review of the relationship between actinic keratosis and nonmelanoma skin cancer discusses the rationale for early actinic keratosis treatment to prevent or reduce nonmelanoma skin cancer occurrence. PMID:20725550

  1. Possible role of ovarian epithelial inflammation in ovarian cancer.

    PubMed

    Ness, R B; Cottreau, C

    1999-09-01

    Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

  2. 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

  3. Negative Appearance Evaluation Is Associated With Skin Cancer Risk Behaviors Among American Men and Women

    PubMed Central

    Blashill, Aaron J.; Williams, Alison; Grogan, Sarah; Clark-Carter, David

    2015-01-01

    Objective The current study aimed to examine links between appearance evaluation and skin cancer risk behaviors in men and women. Method Data (N = 1,535; men, n = 873; women, n = 662) were extracted from Wave 4 of the National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal dataset of U.S. adolescents and young adults. Results Skin cancer risk (i.e., number of hours spent outside for those with a history of severe sunburn and who were unlikely to use sunscreen) was significantly associated with participant gender, appearance evaluation, and their interaction. Both men and women who negatively evaluated their appearance were at significantly increased skin cancer risk, and this was particularly true for men. Conclusions Negative appearance evaluation appears to be a correlate of engaging in behaviors that place individuals at risk of developing skin cancer. Future research may benefit from skin cancer prevention interventions that directly address appearance-based evaluations. PMID:25133823

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

    PubMed Central

    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

  5. Neuromedin B receptor antagonism inhibits migration, invasion, and epithelial-mesenchymal transition of breast cancer cells.

    PubMed

    Park, Hyun-Joo; Kim, Mi-Kyoung; Choi, Kyu-Sil; Jeong, Joo-Won; Bae, Soo-Kyung; Kim, Hyung Joon; Bae, Moon-Kyoung

    2016-09-01

    Neuromedin B (NMB) acts as an autocrine growth factor and a pro-angiogenic factor. Its receptor, NMB receptor (NMB-R), is overexpressed in solid tumors. In the present study, we showed that an NMB-R antagonist, PD168368, suppresses migration and invasion of the human breast cancer cell line MDA-MB-231. In addition, PD168368 reduced epithelial-mesenchymal transition (EMT) of breast cancer cells by E-cadherin upregulation and vimentin downregulation. Moreover, we found that PD168368 potently inhibits in vivo metastasis of breast cancer. Taken together, these findings suggest that NMB-R antagonism may be an alternative approach to prevent breast cancer metastasis, and targeting NMB-R may provide a novel therapeutic strategy for breast cancer treatment. PMID:27571778

  6. The comparison of glycosphingolipids isolated from an epithelial ovarian cancer cell line and a nontumorigenic epithelial ovarian cell line using MALDI-MS and MALDI-MS/MS.

    PubMed

    Rajanayake, Krishani K; Taylor, William R; Isailovic, Dragan

    2016-08-01

    Glycosphingolipids (GSLs) are important biomolecules, which are linked to many diseases such as GSL storage disorders and cancer. Consequently, the expression of GSLs may be altered in ovarian cancer cell lines in comparison to apparently healthy cell lines. Here, differential expressions of GSLs in an epithelial ovarian cancer cell line SKOV3 and a nontumorigenic epithelial ovarian cell line T29 were studied using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and MALDI-MS/MS. The isolation of GSLs from SKOV3 and T29 cell lines was carried out using Folch partition. GSLs were successfully detected by MALDI-MS, and structurally assigned by a comparison of their MALDI-MS/MS fragmentation patterns with MS/MS data found in SimLipid database. Additionally, LIPID MAPS was used to assign GSL ion masses in MALDI-MS spectra. Seventeen neutral GSLs were identified in Folch partition lower (chloroform/methanol) phases originating from both cell lines, while five globo series neutral GSLs were identified only in the Folch partition lower phase of SKOV3 cell line. Several different sialylated GSLs were detected in Folch partition upper (water/methanol) phases of SKOV3 and T29 cell lines. Overall, this study demonstrates the alteration and increased glycosylation of GSLs in an epithelial ovarian cancer cell line in comparison to a nontumorigenic epithelial ovarian cell line. PMID:27267063

  7. Effectiveness of an employee skin cancer screening program for secondary prevention.

    PubMed

    Uslu, Ugur; Hees, Felix; Winnik, Eva; Uter, Wolfgang; Sticherling, Michael

    2016-08-01

    Incidences of UV-induced skin cancer are continuously increasing. For this reason, early diagnosis is becoming more important. In this study, 783 employees of a technical company participated in an employee skin cancer screening program, which consisted of a physical examination for benign and malignant skin lesions and premalignant conditions. To ensure the quality of the examinations, screening was only performed by 5 trained dermatologists. Participants also were asked to complete a standardized questionnaire prior to examination. A total of 661 skin lesions were diagnosed among 48% of participants; 12.8% of participants exhibited 50 or more melanocytic nevi and the risk for developing skin cancer was categorized as at least moderate for 64.9%. Additionally, 84.4% of participants with at least 1 skin lesion were advised to have a checkup within 1 year. The high rate of suspicious nevi detected in this study suggested that employee skin cancer screening programs are effective and also should be recommended at companies where employees are not at increased risk for developing skin cancer due to the nature of their work (eg, those who work outdoors). Despite the comparatively selective and young study population, these examinations provide evidence of the importance of skin cancer screening for the wider population. PMID:27622254

  8. 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

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

    PubMed

    Nonaka, Taichiro; Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Yamamoto, Norio; Asato, Ryo; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro; Kinoshita, Kazuo

    2016-04-01

    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.

  10. 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

  11. SSRI use and clinical outcomes in epithelial ovarian cancer.

    PubMed

    Christensen, Desiré K; Armaiz-Pena, Guillermo N; Ramirez, Edgardo; Matsuo, Koji; Zimmerman, Bridget; Zand, Behrouz; Shinn, Eileen; Goodheart, Michael J; Bender, David; Thaker, Premal H; Ahmed, Amina; Penedo, Frank J; DeGeest, Koen; Mendez, Luis; Domann, Frederick; Sood, Anil K; Lutgendorf, Susan K

    2016-05-31

    Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications. PMID:27121207

  12. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  13. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery.

  14. TGFβ signaling regulates epithelial-mesenchymal plasticity in ovarian cancer ascites-derived spheroids.

    PubMed

    Rafehi, Samah; Ramos Valdes, Yudith; Bertrand, Monique; McGee, Jacob; Préfontaine, Michel; Sugimoto, Akira; DiMattia, Gabriel E; Shepherd, Trevor G

    2016-03-01

    Epithelial-mesenchymal transition (EMT) serves as a key mechanism driving tumor cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFβ) signaling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFβ signaling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a substratum. CDH1/E-cadherin expression was markedly reduced in spheroids compared with adherent cells, in concert with an up-regulation of several transcriptional repressors, i.e., SNAI1/Snail, TWIST1/2, and ZEB2. Treatment of EOC spheroids with the TGFβ type I receptor inhibitor, SB-431542, potently blocked the endogenous activation of EMT in spheroids. Furthermore, treatment of spheroids with SB-431542 upon re-attachment enhanced the epithelial phenotype of dispersing cells and significantly decreased cell motility and Transwell migration. Spheroid formation was significantly compromised by exposure to SB-431542 that correlated with a reduction in cell viability particularly in combination with carboplatin treatment. Thus, our findings are the first to demonstrate that intact TGFβ signaling is required to control EMT in EOC ascites-derived cell spheroids, and it promotes the malignant characteristics of these structures. As such, we show the therapeutic potential for targeted inhibition of this pathway in ovarian cancer patients with late-stage disease. PMID:26647384

  15. Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells.

    PubMed

    Unahabhokha, Thitita; Chanvorachote, Pithi; Sritularak, Boonchoo; Kitsongsermthon, Jutarat; Pongrakhananon, Varisa

    2016-01-01

    Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT). Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT), thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis. PMID:27651818

  16. Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells

    PubMed Central

    Unahabhokha, Thitita; Chanvorachote, Pithi; Kitsongsermthon, Jutarat

    2016-01-01

    Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT). Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT), thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis. PMID:27651818

  17. Gigantol Inhibits Epithelial to Mesenchymal Process in Human Lung Cancer Cells

    PubMed Central

    Unahabhokha, Thitita; Chanvorachote, Pithi; Kitsongsermthon, Jutarat

    2016-01-01

    Lung cancer remains a leading public health problem as evidenced by its increasing death rate. The main cause of death in lung cancer patients is cancer metastasis. The metastatic behavior of lung cancer cells becomes enhanced when cancer cells undergo epithelial to mesenchymal transition (EMT). Gigantol, a bibenzyl compound extracted from the Thai orchid, Dendrobium draconis, has been shown to have promising therapeutic potential against cancer cells, which leads to the hypothesis that gigantol may be able to inhibit the fundamental EMT process in cancer cells. This study has demonstrated for the first time that gigantol possesses the ability to suppress EMT in non-small cell lung cancer H460 cells. Western blot analysis has revealed that gigantol attenuates the activity of ATP-dependent tyrosine kinase (AKT), thereby inhibiting the expression of the major EMT transcription factor, Slug, by both decreasing its transcription and increasing its degradation. The inhibitory effects of gigantol on EMT result in a decrease in the level of migration in H460 lung cancer cells. The results of this study emphasize the potential of gigantol for further development against lung cancer metastasis.

  18. 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

  19. Photodynamic Therapy for Non-Melanoma Skin Cancers

    PubMed Central

    Cohen, Diana K.; Lee, Peter K.

    2016-01-01

    Non-melanoma skin cancer (NMSC) is traditionally treated with surgical excision. Non-surgical methods such as cryotherapy and topical chemotherapeutics, amongst other treatments, are other options. Actinic keratosis (AKs) are considered precancerous lesions that eventually may progress to squamous cell carcinoma (SCC). Photodynamic therapy (PDT) offers an effective treatment for AKs, and is also effective for superficial basal cell carcinoma (BCC). Nodular BCC and Bowen’s disease (SCC in situ) have shown acceptable response rates with PDT, although recurrence rates are higher for these two NMSC subtypes. Methylaminolevulinate (MAL) PDT is a more effective treatment option than 5-aminolevulinic acid (ALA) PDT for nodular BCC. Several studies have shown that PDT results in superior cosmetic outcomes compared to surgical treatment. PDT is overall well-tolerated, with pain being the most common side effect. PMID:27782043

  20. Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer

    PubMed Central

    2014-01-01

    An important clinical challenge in prostate cancer therapy is the inevitable transition from androgen-sensitive to castration-resistant and metastatic prostate cancer. Albeit the androgen receptor (AR) signaling axis has been targeted, the biological mechanism underlying the lethal event of androgen independence remains unclear. New emerging evidences indicate that epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) play crucial roles during the development of castration-resistance and metastasis of prostate cancer. Notably, EMT may be a dynamic process. Castration can induce EMT that may enhance the stemness of CSCs, which in turn results in castration-resistance and metastasis. Reverse of EMT may attenuate the stemness of CSCs and inhibit castration-resistance and metastasis. These prospective approaches suggest that therapies target EMT and CSCs may cast a new light on the treatment of castration-resistant prostate cancer (CRPC) in the future. Here we review recent progress of EMT and CSCs in CRPC. PMID:24618337

  1. Regulatory Roles of Dclk1 in Epithelial Mesenchymal Transition and Cancer Stem Cells

    PubMed Central

    Chandrakesan, P; Panneerselvam, J; Qu, D; Weygant, N; May, R; Bronze, MS; Houchen, CW

    2016-01-01

    The identification of functionally relevant subpopulations of therapy-resistant cancer cells is a challenge. These cells, intrinsically resistant to conventional therapy, can cause recurrence. Evidence has suggested that therapy-resistant cancer cells are likely epithelial–mesenchymal transition (EMT) cells and/or stem-like cells called cancer stem cells (CSCs). EMT, a normal embryological process that converts epithelial cells into mesenchymal cells, is frequently activated during cancer development and progression. CSCs are a small subpopulation of cancer cells within a tumor mass that have the ability to self-renew and maintain tumor-initiating capacity by giving rise to heterogeneous lineages of cancer cells that comprise the whole tumor. Although the origin of CSCs and EMT cells remains to be fully explored, a growing body of evidence has indicated that the biology of EMT and CSCs is strongly linked. Doublecortin-like kinase 1 (DCLK1), a cancer stem cell marker, is functionally involved in maintaining cancer stemness and the process of EMT important for cancer initiation, cancer metastasis, and secondary tumor formation. Therefore, targeting these cells may provide new strategies to overcome tumor heterogeneity, therapeutic resistance, and cancer relapse. In this review, we will provide a potential mechanistic link between EMT induction and the emergence of CSCs for the origin and progression of cancer. We will highlight the functional activity of DCLK1 in supporting EMT and cancer cell self-renewal, which will lead us to a better understanding of DCLK1 expression in cancer development and progression, and help us to develop targeted therapies for effective cancer treatment. PMID:27335684

  2. Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

    PubMed Central

    Yun, Rongna; Yu, Xiaolin; Huang, Genhua; Tan, Buzhen

    2016-01-01

    Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p < 0.01). In tumor tissues, Notch3 expression and pS6 expression were negatively associated with age (p > 0.05) but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p < 0.05 or p < 0.01). A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p < 0.01), in which the clinical stage (p < 0.05) and Notch3 expression (p < 0.01) played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis. PMID:27445438

  3. Non-melanoma skin cancer, sun exposure and sun protection.

    PubMed

    Calzavara-Pinton, P; Ortel, B; Venturini, M

    2015-08-01

    The incidence of skin tumors including squamous cell carcinoma (SCC), and its biological precursor, the actinic keratosis, and basal cell carcinoma (BCC) often named together non-melanoma skin cancer (NMSC) is growing all over the world in people of Caucasian ancestry. A plenty of clinical and epidemiological studies have demonstrated the causal relationship with high cumulative solar dosages and number of sunburns, although the hazard may be different for different tumors according to the modalities of ultraviolet (UV) exposure. BCC is much more strongly related to measures of intermittent ultraviolet exposure (particularly those of childhood or adolescence) than to measures of cumulative exposure. In contrast, SCC is more strongly related to constant or cumulative sun exposure. Photobiological studies have clarified that sunlight and UVB radiation are complete carcinogens for AK and SCC although the relationship with UVA exposure is much less known. Also the likelihood of BCC has been related to either sunburns and high lifetime solar, UVA and UVB cumulative doses but the pathogenetic pathways of both UVB and UVA radiation for BCC development need to be clarified so far. The lack of a complete knowledge of the photocarcinogenic pathways of keratinocytes has contributed to the limited results of solar photoprotection strategies, beside the limitations of the available sunscreens and present EU regulations.

  4. Arsenic-related Bowen's disease, palmar keratosis, and skin cancer.

    PubMed

    Cöl, M; Cöl, C; Soran, A; Sayli, B S; Oztürk, S

    1999-08-01

    Chronic arsenical intoxication can still be found in environmental and industrial settings. Symptoms of chronic arsenic intoxication include general pigmentation or focal "raindrop" pigmentation of the skin and the appearance of hyperkeratosis of the palms of the hands and soles of the feet. In addition to arsenic-related skin diseases including keratosis, Bowen's disease, basal-cell-carcinoma, and squamous-cell carcinoma, there is also an increased risk of some internal malignancies. Arsenic-related diseases are common in areas of the world where the drinking water has a high arsenic content. In this paper, we describe a 35-year-old male patient who had arsenic-related keratosis, squamous-cell carcinoma in the palmar area of his left hand, and Bowen's disease on his left thigh. The patient worked in a borax mine for 15 years, so he was exposed to arsenic in drinking water, airborne arsenic in his workplace, and had direct contact. The patient was treated for 11 months for arsenic-related keratosis until an axillary lymph node metastasis occurred; the lesion was excised and diagnosed to be malignant. Bowen's disease was detected when the patient was being treated for cancer. No other malignancy was found. The patient is still receiving regular follow-up care.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Tubal ligation, hysterectomy, and epithelial ovarian cancer in the New England Case-Control Study

    PubMed Central

    Rice, Megan S.; Murphy, Megan A.; Vitonis, Allison F.; Cramer, Daniel W.; Titus, Linda J.; Tworoger, Shelley S.; Terry, Kathryn L.

    2013-01-01

    Previous studies have observed that tubal ligation and hysterectomy are associated with a decreased risk of ovarian cancer; however little is known about whether these associations vary bysurgical characteristics, individual characteristics, or tumor histology. We used logistic regression to examine tubal ligation, simple hysterectomy, and hysterectomy with unilateral oophorectomy in relation to risk of epithelial ovarian cancer in the New England Case-Control study. Our primary analysis included 2,265 cases and 2,333 controls. Overall, tubal ligation was associated with a lower risk of epithelial ovarian cancer (OR: 0.82, 95%CI: 0.68-0.97), especially for endometrioid tumors (OR=0.45, 95%CI: 0.29-0.69). The inverse association between tubal ligation and ovarian cancer risk was stronger for women who had undergone the procedure at the time of last delivery (OR=0.60, 95%CI: 0.42-0.84) rather than at a later time (OR=0.93, 95%CI: 0.75-1.15). Overall, simple hysterectomy was not associated with ovarian cancer risk (OR: 1.09, 95%CI: 0.83, 1.42), although it was associated with a non-significant decreased risk of ovarian cancer among women who underwent the procedure at age 45 or older (RR: 0.64, 95%CI: 0.40, 1.02) or within the last 10 years (OR=0.65, 95%CI: 0.38, 1.13). Overall, women who had a hysterectomy with a unilateral oophorectomy had significantly lower risk of ovarian cancer (OR=0.65, 95%CI: 0.45-0.94). In summary, tubal ligation and hysterectomy with unilateral oophorectomy were inversely associated with ovarian cancer risk in a large population-based case-control study. Additional research is necessary to understand the potential biologic mechanisms by which these procedures may reduce ovarian cancer risk. PMID:23650079

  10. OCT4 mediates FSH-induced epithelial-mesenchymal transition and invasion through the ERK1/2 signaling pathway in epithelial ovarian cancer.

    PubMed

    Liu, Lei; Zhang, Jing; Fang, Chi; Zhang, Zhenbo; Feng, Youji; Xi, Xiaowei

    2015-06-01

    Our previous study showed that Octamer-binding transcription factor 4 (OCT4) expression was upregulated and significantly associated with histological grade through the analysis of OCT4 expression in 159 ovarian cancer tissue samples, and OCT4 mediated follicle-stimulating hormone (FSH)-induced anti-apoptosis in epithelial ovarian cancer. Nevertheless, whether OCT4 participates in FSH-induced invasion in ovarian cancer is still unknown. Therefore, the present study aimed to define whether FSH-induced ovarian cancer invasion is mediated by OCT4. In present study, we showed that FSH induced not only the epithelial-mesenchymal transition (EMT) and invasive phenotype but also the upregulation of OCT4 expression in a dose- and time-dependent manner in epithelial ovarian cancer cells. In addition, the expression of FSH receptor (FSHR) was upregulated by FSH induction, and knockdown of FSHR inhibited FSH-stimulated OCT4 expression. ERK1/2 signaling pathway participated in the enhanced expression of OCT4 and Snail induced by FSH. We further showed that the activated expression of Snail and N-cadherin, the suppressed expression of E-cadherin and the morphological change of the cells stimulated by FSH were blocked by OCT4-specific small interfering RNA. Moreover, our results showed that OCT4 mediated the increase in invasive capacity induced by FSH in ovarian cancer cells. Taken together, our work reveals that OCT4 is an essential mediator in FSH-induced EMT and invasion in epithelial ovarian cancer and may act as a potential therapeutic target.

  11. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Jammal, Millena Prata; Martins-Filho, Agrimaldo; Silveira, Thales Parenti; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2016-01-01

    INTRODUCTION Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors. METHOD The study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05. RESULTS TNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently. CONCLUSION IL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies. PMID:27512342

  12. Diurnal Cortisol and Survival in Epithelial Ovarian Cancer

    PubMed Central

    Schrepf, Andrew; Thaker, Premal H.; Goodheart, Michael J.; Bender, David; Slavich, George M.; Dahmoush, Laila; Penedo, Frank; DeGeest, Koen; Mendez, Luis; Lubaroff, David M.; Cole, Steven W.; Sood, Anil K.; Lutgendorf, Susan K.

    2015-01-01

    Introduction Hypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment. Materials and Methods Participants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables. Results Each cortisol measure was associated with decreased survival time, adjusting for covariates (all p<.041). A one standard deviation increase in night cortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r >.36, all p<.017). Discussion Abnormal cortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity. PMID:25647344

  13. CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype.

    PubMed

    Tan, Tuan Zea; Yang, He; Ye, Jieru; Low, Jeffrey; Choolani, Mahesh; Tan, David Shao Peng; Thiery, Jean-Paul; Huang, Ruby Yun-Ju

    2015-12-22

    Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research. PMID:26549805

  14. CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype.

    PubMed

    Tan, Tuan Zea; Yang, He; Ye, Jieru; Low, Jeffrey; Choolani, Mahesh; Tan, David Shao Peng; Thiery, Jean-Paul; Huang, Ruby Yun-Ju

    2015-12-22

    Databases pertaining to various diseases provide valuable resources on particular genes of interest but lack the molecular subtype and epithelial-mesenchymal transition status. CSIOVDB is a transcriptomic microarray database of 3,431 human ovarian cancers, including carcinoma of the ovary, fallopian tube, and peritoneum, and metastasis to the ovary. The database also comprises stroma and ovarian surface epithelium from normal ovary tissue, as well as over 400 early-stage ovarian cancers. This unique database presents the molecular subtype and epithelial-mesenchymal transition status for each ovarian cancer sample, with major ovarian cancer histologies (clear cell, endometrioid, mucinous, low-grade serous, serous) represented. Clinico-pathological parameters available include tumor grade, surgical debulking status, clinical response and age. The database has 1,868 and 1,516 samples with information pertaining to overall and disease-free survival rates, respectively. The database also provides integration with the copy number, DNA methylation and mutation data from TCGA. CSIOVDB seeks to provide a resource for biomarker and therapeutic target exploration for ovarian cancer research.

  15. Targeted agents in epithelial ovarian cancer: review on emerging therapies and future developments

    PubMed Central

    Lokadasan, Rajitha; James, Francis V; Narayanan, Geetha; Prabhakaran, Pranab K

    2016-01-01

    Epithelial ovarian cancer (EOC) remains a clinical challenge and there is a need to optimise the currently available treatment and to urgently develop new therapeutic strategies. Recently, there has been improved understanding of the molecular characteristics and tumour microenvironment of ovarian cancers. This has facilitated the development of various targeted agents used concurrently with chemotherapy or as maintenance. Most of the studies have explored the tumour angiogenesis pathways. In phase-III trials, bevacizumab showed a statistically significant improvement in progression-free survival, although there was no improvement in overall survival in selected high-risk cases. Although several multi-targeted tyrosine kinase inhibitors were found to be useful, the toxicity and survival benefit has to be weighed. Poly ADP ribose polymerase (PARP) inhibitors have been another marvellous molecule found to be effective in breast cancer 1, early onset (BRCA)-positive ovarian cancers. Several newer molecules targeting Her 2, Wee tyrsine kinases, PIP3/AKT/mTR-signalling pathways, folate receptors are under development and may provide additional opportunities in the future. This article focuses on the targeted agents that have successfully paved the way in the management of epithelial ovarian cancer and the newer molecules that may offer therapeutic opportunities in the future. PMID:27110282

  16. Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis.

    PubMed

    Tong, Jessica G; Valdes, Yudith Ramos; Barrett, John W; Bell, John C; Stojdl, David; McFadden, Grant; McCart, J Andrea; DiMattia, Gabriel E; Shepherd, Trevor G

    2015-01-01

    Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-Myxoma virus, double-deleted vaccinia virus, and Maraba virus-using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and with slightly slower kinetics in tumor spheroids. Myxoma virus and vaccinia viruses infect and kill adherent cells to a much lesser extent than Maraba virus, and their oncolytic potential is almost completely attenuated in spheroids. Myxoma virus and vaccinia are able to infect and spread throughout spheroids, but are blocked in the final stages of the lytic cycle, and oncolytic-mediated cell killing is reactivated upon spheroid reattachment. Alternatively, Maraba virus has a remarkably reduced ability to initially enter spheroid cells, yet rapidly infects and spreads throughout spheroids generating significant cell killing effects. We show that low-density lipoprotein receptor expression in ovarian cancer spheroids is reduced and this controls efficient Maraba virus binding and entry into infected cells. Taken together, these results are the first to implicate the potential impact of differential viral oncolytic properties at key steps of ovarian cancer metastasis.

  17. 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

  18. 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).

  19. Hemicellulose dressing versus rayon dressing in the re-epithelialization of split-thickness skin graft donor sites: a multicenter study.

    PubMed

    Ferreira, Lydia M; Blanes, Leila; Gragnani, Alfredo; Veiga, Daniela F; Veiga, Frederico P; Nery, Gilka B; Rocha, Gustavo Henrique H R; Gomes, Heitor C; Rocha, Mario G; Okamoto, Regina

    2009-08-01

    The aim of this study was to compare the effectiveness of a hemicellulose dressing with that of rayon dressing in the healing of split-thickness skin graft donor sites. Twenty-eight patients were selected from five different hospitals and randomized into two groups: hemicellulose dressing group and rayon dressing group. All patients underwent split-thickness skin grafting for various reasons, and the skin graft donor site wounds were covered with hemicellulose dressing (n=14) or rayon dressing (n=14). The donor site was assessed on postoperative days 1, 7, 14, 21, and 28 for hyperemia, pruritus, pain, exudate level, and adherence of the wound dressing. At the 60-day follow-up visit, the donor site was assessed again for pruritus and pain. Touch-pressure, thermal, and pain sensibility tests were performed preoperatively and on postoperative day 60 together with the assessment of color and texture of the re-epithelialized area. In all patients, re-epithelialization was completed between 14 and 21 days after surgery. There were no significant differences between the two groups with regard to pain, hyperemia, pruritus, exudate, and final appearance (color and texture) of the skin graft donor site. The rayon dressing provided significantly better adherence than the hemicellulose dressing, and both dressings showed similar results with regard to the parameters evaluated when used in the treatment of split-thickness skin graft donor sites.

  20. MAL-PDT for difficult to treat nonmelanoma skin cancer.

    PubMed

    Stebbins, William G; Hanke, C William

    2011-01-01

    With an incidence of over 3.5 million nonmelanoma skin cancers (NMSCs) per year in the United States, there is an increasing need for effective, cost-effective treatments for NMSC. When surgical excision is impractical or not feasible, methyl aminolevulinate photodynamic therapy (MAL-PDT) has demonstrated consistently high long-term cure rates ranging from 70-90%, with superior cosmetic outcomes compared with other treatment modalities. With the exception of invasive squamous cell carcinoma, MAL-PDT has been successful in treating all types of NMSC, especially in patients with multiple comorbidities, field cancerization, and lesions in cosmetically sensitive locations. Herein, a step-by-step description of the procedure for MAL-PDT is provided, followed by a review of outcomes from large clinical trials performed over the past 15 years for each variant of NMSC. After reading this review, clinicians should have a thorough understanding of the benefits and limits of MAL-PDT, and should be able to add this valuable procedure to their armamentarium of therapies for NMSC.

  1. Validation of claims data algorithms to identify nonmelanoma skin cancer

    PubMed Central

    Eide, Melody J.; Tuthill, J. Mark; Krajenta, Richard; Jacobsen, Gordon; Levine, Marc; Johnson, Christine C

    2012-01-01

    Health maintenance organization (HMO) administrative databases have been used as sampling frames for ascertaining nonmelanoma skin cancer (NMSC). However, because of the lack of tumor registry information on these cancers, these ascertainment methods have not been previously validated. NMSC cases arising from patients served by a staff model medical group and diagnosed between 1/1/07 to 12/31/08 were identified from claims data using three ascertainment strategies. These claims-data cases were then compared to NMSC identified using natural language processing (NLP) of electronic pathology reports (EPR), and sensitivity, specificity, positive (PPV) and negative predictive values (NPV) calculated. Comparison of claims data ascertained cases to the NLP demonstrated sensitivities ranging from 48-65% and specificities from 85-98%, with ICD-9-CM ascertainment demonstrating the highest case sensitivity though the lowest specificity. HMO health plan claims data had a higher specificity than all payer claims data. A comparison of EPR and clinic log registry cases showed sensitivity of 98% and specificity of 99%. Validation of administrative data to ascertain NMSC demonstrates respectable sensitivity and specificity though NLP ascertainment was superior. There is a substantial difference in cases identified by NLP compared to claims data suggesting that formal surveillance efforts should be considered. PMID:22475754

  2. Human papillomaviruses and non-melanoma skin cancer.

    PubMed

    McLaughlin-Drubin, Margaret E

    2015-04-01

    Human papillomaviruses (HPVs) infect the squamous epithelium and can induce benign and malignant lesions. To date, more than 200 different HPV types have been identified and classified into five genera, α, β, γ, μ, and ν. While high-risk α mucosal HPVs have a well-established role in cervical carcinoma and a significant percentage of other anogenital tract and oral carcinomas, the biology of the cutaneous β HPVs and their contribution to non-melanoma skin cancer (NMSC) has been less studied. Although the association of β HPV infection with NMSC in patients with a rare, genetically determined condition, epidermodysplasia verruciformis has been well established, the role of β HPV infection with NMSC in the normal population remains controversial. In stark contrast to α HPV-associated cancers, the presence of the β HPV genome does not appear to be mandatory for the maintenance of the malignant phenotype. Moreover, the mechanism of action of the β HPV E6 and E7 oncoproteins differs from the β HPV oncoproteins.

  3. Pilot clinical study for quantitative spectral diagnosis of non-melanoma skin cancer

    PubMed Central

    Rajaram, Narasimhan; Reichenberg, Jason S.; Migden, Michael R.; Nguyen, Tri H.

    2010-01-01

    Background Several research groups have demonstrated the non-invasive diagnostic potential of diffuse optical spectroscopy (DOS) and laser-induced fluorescence (LIF) techniques for early cancer detection. By combining both modalities, one can simultaneously measure quantitative parameters related to the morphology, function and biochemical composition of tissue and use them to diagnose malignancy. The objective of this study was to use a quantitative reflectance/fluorescence spectroscopic technique to determine the optical properties of normal skin and non-melanoma skin cancers and the ability to accurately classify them. An additional goal was to determine the ability of the technique to differentiate non-melanoma skin cancers from normal skin. Study Design The study comprised 48 lesions measured from 40 patients scheduled for a biopsy of suspected non-melanoma skin cancers. White light reflectance and laser-induced fluorescence spectra (wavelength range = 350–700 nm) were collected from each suspected lesion and adjacent clinically normal skin using a custom-built, optical fiber-based clinical instrument. After measurement, the skin sites were biopsied and categorized according to histopathology. Using a quantitative model, we extracted various optical parameters from the measured spectra that could be correlated to the physiological state of tissue. Results Scattering from cancerous lesions was significantly lower than normal skin for every lesion group, whereas absorption parameters were significantly higher. Using numerical cut-offs for our optical parameters, our clinical instrument could classify basal cell carcinomas with a sensitivity and specificity of 94 and 89%, respectively. Similarly, the instrument classified actinic keratoses and squamous cell carcinomas with a sensitivity of 100% and specificity of 50%. Conclusion The measured optical properties and fluorophore contributions of normal skin and non-melanoma skin cancers are significantly different

  4. p53 codon 72 polymorphism and human papillomavirus associated skin cancer

    PubMed Central

    O'Connor, D; Kay, E; Leader, M; Atkins, G; Murphy, G; Mabruk, M

    2001-01-01

    Background/Aims—Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC. Methods—Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV. Results—The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant differences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts. Conclusions—These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer. Key Words: p53 codon 72 polymorphism • human papillomavirus • skin cancer PMID:11429426

  5. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  6. Identification of Key Proteins in Human Epithelial Cells Responding to Bystander Signals From Irradiated Trout Skin

    PubMed Central

    Smith, Richard; Wang, Jiaxi; Seymour, Colin; Mothersill, Carmel; Howe, Orla

    2015-01-01

    Radiation-induced bystander signaling has been found to occur in live rainbow trout fish (Oncorhynchus mykiss). This article reports identification of key proteomic changes in a bystander reporter cell line (HaCaT) grown in low-dose irradiated tissue-conditioned media (ITCM) from rainbow trout fish. In vitro explant cultures were generated from the skin of fish previously exposed to low doses (0.1 and 0.5 Gy) of X-ray radiation in vivo. The ITCM was harvested from all donor explant cultures and placed on recipient HaCaT cells to observe any change in protein expression caused by the bystander signals. Proteomic methods using 2-dimensional (2D) gel electrophoresis and mass spectroscopy were employed to screen for novel proteins expressed. The proteomic changes measured in HaCaT cells receiving the ITCM revealed that exposure to 0.5 Gy induced an upregulation of annexin A2 and cingulin and a downregulation of Rho-GDI2, F-actin-capping protein subunit beta, microtubule-associated protein RP/EB family member, and 14-3-3 proteins. The 0.1 Gy dose also induced a downregulation of Rho-GDI2, hMMS19, F-actin-capping protein subunit beta, and microtubule-associated protein RP/EB family member proteins. The proteins reported may influence apoptotic signaling, as the results were suggestive of an induction of cell communication, repair mechanisms, and dysregulation of growth signals. PMID:26673684

  7. UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer

    PubMed Central

    Pfeifer, Gerd P.; Besaratinia, Ahmad

    2012-01-01

    Ultraviolet (UV) irradiation from the sun has been epidemiologically and mechanistically linked to skin cancer, a spectrum of diseases of rising incidence in many human populations. Both non-melanoma and melanoma skin cancers are associated with sunlight exposure. In this review, we discuss the UV wavelength-dependent formation of the major UV-induced DNA damage products, their repair and mutagenicity and their potential involvement in sunlight-associated skin cancers. We emphasize the major role played by the cyclobutane pyrimidine dimers (CPDs) in skin cancer mutations relative to that of (6-4) photoproducts and oxidative DNA damage. Collectively, the data implicate the CPD as the DNA lesion most strongly involved in human cancers induced by sunlight. PMID:21804977

  8. The role of the cutaneous microbiome in skin cancer: lessons learned from the gut.

    PubMed

    Yu, Yang; Champer, Jackson; Beynet, David; Kim, Jenny; Friedman, Adam J

    2015-05-01

    The human microbiome has recently gained prominence as a major factor in health and disease. Here we review the literature regarding the microbiome and cancer and suggest how the microbiome may be manipulated for improved health outcomes. The gut microbiome has been relatively well studied, and the mechanisms of how it may increase or decrease the risk of certain cancers may apply to the skin microbiome. Additionally, the gut microbiome may directly impact the risk of cancer in the skin and other organs by promoting systemic inflammation. The skin microbiome itself is as diverse as the gut microbiome, but research has just begun to unravel its influence on the host. Like the gut microbiome, it affects the risk for several diseases, including cancer. By using healthpromoting strains from the microbiome in oral or topical probiotics, it may be possible to reduce the risk of skin cancer and perhaps even increase the likelihood of successful treatment.

  9. Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition

    PubMed Central

    Khan, Md. Asaduzzaman; Tania, Mousumi; Wei, Chunli; Mei, Zhiqiang; Fu, Shelly; Cheng, Jingliang; Xu, Jianming; Fu, Junjiang

    2015-01-01

    Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis. PMID:26023736

  10. 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

  11. 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.

  12. Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?

    PubMed Central

    Brivio, Simone; Cadamuro, Massimiliano; Fabris, Luca; Strazzabosco, Mario

    2015-01-01

    In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. In CCA, several reports indicate that cancer cells acquire a number of EMT biomarkers and functions. These phenotypic changes are likely induced by both autocrine and paracrine signals released in the tumor microenvironment (cytokines, growth factors, morphogens) and intracellular stimuli (microRNAs, oncogenes, tumor suppressor genes) variably associated with specific disease mechanisms, including chronic inflammation and hypoxia. Nevertheless, evidence supporting a complete EMT of neoplastic cholangiocytes into stromal cells is lacking, and the gain of EMT-like changes by CCA cells rather reflects a shift towards an enhanced pro-invasive phenotype, likely induced by the tumor stroma. This concept may help to identify new biomarkers of early metastatic behavior along with potential therapeutic targets. PMID:26703747

  13. Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

    PubMed Central

    2013-01-01

    Background Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. PMID:23574945

  14. Effect of Cigarette Smoking on Epithelial to Mesenchymal Transition (EMT) in Lung Cancer

    PubMed Central

    Vu, Trung; Jin, Lin; Datta, Pran K.

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is a process that allows an epithelial cell to acquire a mesenchymal phenotype through multiple biochemical changes resulting in an increased migratory capacity. During cancer progression, EMT is found to be associated with an invasive or metastatic phenotype. In this review, we focus on the discussion of recent studies about the regulation of EMT by cigarette smoking. Various groups of active compounds found in cigarette smoke such as polycyclic aromatic hydrocarbons (PAH), nicotine-derived nitrosamine ketone (NNK), and reactive oxygen specicies (ROS) can induce EMT through different signaling pathways. The links between EMT and biological responses to cigarette smoke, such as hypoxia, inflammation, and oxidative damages, are also discussed. The effect of cigarette smoke on EMT is not only limited to cancer types directly related to smoking, such as lung cancer, but has also been found in other types of cancer. Altogether, this review emphasizes the importance of understanding molecular mechanisms of the induction of EMT by cigarette smoking and will help in identifying novel small molecules for targeting EMT induced by smoking. PMID:27077888

  15. Uncertainty in the Utility of Immunohistochemistry in Mismatch Repair Protein Expression in Epithelial Ovarian Cancer

    PubMed Central

    Copppola, Domenico; Nicosia, Santo V.; Doty, Andrea; Sellers, Thomas A; Lee, Ji-Hyun; Fulp, Jimmy; Thompson, Zachary; Galeb, Sanja; McLaughlin, John; Narod, Steven A; Schildkraut, Joellen; Pal, Tuya

    2014-01-01

    Background Utility of immunohistochemistry (IHC) for mismatch repair (MMR) protein expression has been demonstrated in colorectal cancer but remains incompletely defined in ovarian cancer. We evaluated MMR protein expression in three population-based samples of epithelial ovarian cancers. Methods IHC staining was performed on full section (FS) or tissue microarray (TMA) slides for MLH1, MSH2, and MSH6 expression. Results Of 487 cases, 147 and 340 were performed through FS and TMA, respectively. Overall, Loss of Expression (LoE) of at least one MMR protein was observed in 12.7% based on an expression score of ≤3 (on a scale of 9). Notably, LoE was significantly higher in TMAs (17.9%) compared to FS cases (0.7%) (p <0.001). Conclusions A substantial proportion of epithelial ovarian cancers have a loss of MMR protein expression. Protein expression results vary significantly by the tissue sampling methodology utilized, raising concerns about the clinical utility of this test for ovarian tumors. PMID:23155266

  16. Glycosylation in Cancer: Interplay between Multidrug Resistance and Epithelial-to-Mesenchymal Transition?

    PubMed Central

    da Fonseca, Leonardo Marques; da Silva, Vanessa Amil; Freire-de-Lima, Leonardo; Previato, José Osvaldo; Mendonça-Previato, Lucia; Capella, Márcia Alves Marques

    2016-01-01

    The expression of unusual glycan structures is a hallmark of cancer progression, and their functional roles in cancer biology have been extensively investigated in epithelial-to-mesenchymal transition (EMT) models. EMT is a physiological process involved in embryonic development and wound healing. It is characterized by loss of epithelial cell polarity and cell adhesion, permitting cell migration, and thus formation of new epithelia. However, this process is unwanted when occurring outside their physiological limit, resulting in fibrosis of organs and progression of cancer and metastasis. Several studies observed that EMT is related to the acquisition of multidrug resistance (MDR) phenotype, a condition in which cancer cells acquire resistance to multiple different drugs, which has virtually nothing in common. However, although some studies suggested interplay between these two apparently distinct phenomena, almost nothing is known about this possible relationship. A common pathway to them is the need for glycosylation, a post-translational modification that can alter biological function. Thus, this review intends to compile the main facts obtained until now in these two areas, as an effort to unravel the relationship between EMT and MDR. PMID:27446804

  17. Effect of Cigarette Smoking on Epithelial to Mesenchymal Transition (EMT) in Lung Cancer.

    PubMed

    Vu, Trung; Jin, Lin; Datta, Pran K

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is a process that allows an epithelial cell to acquire a mesenchymal phenotype through multiple biochemical changes resulting in an increased migratory capacity. During cancer progression, EMT is found to be associated with an invasive or metastatic phenotype. In this review, we focus on the discussion of recent studies about the regulation of EMT by cigarette smoking. Various groups of active compounds found in cigarette smoke such as polycyclic aromatic hydrocarbons (PAH), nicotine-derived nitrosamine ketone (NNK), and reactive oxygen specicies (ROS) can induce EMT through different signaling pathways. The links between EMT and biological responses to cigarette smoke, such as hypoxia, inflammation, and oxidative damages, are also discussed. The effect of cigarette smoke on EMT is not only limited to cancer types directly related to smoking, such as lung cancer, but has also been found in other types of cancer. Altogether, this review emphasizes the importance of understanding molecular mechanisms of the induction of EMT by cigarette smoking and will help in identifying novel small molecules for targeting EMT induced by smoking. PMID:27077888

  18. EpCAM Aptamer-siRNA Chimera Targets and Regress Epithelial Cancer

    PubMed Central

    Subramanian, Nithya; Kanwar, Jagat R.; Kanwar, Rupinder K.; Sreemanthula, JagadeeshBabu; Biswas, Jyotirmay; Khetan, Vikas; Krishnakumar, Subramanian

    2015-01-01

    Epithelial cell adhesion molecule (EpCAM), a cancer stem cell (CSC) marker is over expressed in epithelial cancers and in retinoblastoma (RB). We fabricated an EpCAM targeting aptamer-siRNA chimera and investigated its anti-tumor property and EpCAM intracellular domain (EpICD) mediated signaling in epithelial cancer. The anti-tumor efficacy of EpCAM aptamer-siEpCAM chimera (EpApt-siEp) was evaluated by qPCR, northern and Western blotting in WERI-Rb1- RB cell line, primary RB tumor cells and in MCF7- breast cancer cell line. Anti-tumor activity of EpApt-siEp was studied in vivo using epithelial cancer (MCF7) mice xenograft model. The mechanism and pathways involved in the anti-tumor activity was further studied using protein arrays and qPCR. EpApt-siEp chimera was processed in vitro by dicer enzyme. Treatment of the WERI-Rb1 and MCF7 cells with EpApt-siEp revealed statistically significant down regulation of EpCAM expression (P<0.005) and concomitant reduction in cellular proliferation. In primary RB cells cultured from RB tumors, EpApt-siEp silenced EpCAM, significantly inhibited (P<0.01) cell proliferation and induced cytotoxicity. Knockdown of EpICD expressed in RB primary tumors led to repression of pluripotency markers, SOX2, OCT4, NANOG, and CD133. In vivo studies showed complete tumor growth regression without any toxicity in animals (P<0.001) and tumor tissues showed significant downregulation (P<0.05) of EpCAM, MRP1, ABCG2, stathmin, survivin and upregulation of ATM (P<0.05) leading to apoptosis by intrinsic pathway with minor alteration in cytokines. Our results revealed that EpApt-siEp potentially eradicated EpCAM positive cancer cells through CSC marker suppression and apoptosis, while sparing normal EpCAM negative adjacent cells. PMID:26176230

  19. Changes in biophysical properties of the skin following radiotherapy for breast cancer.

    PubMed

    Hu, Stephen Chu-Sung; Hou, Ming-Feng; Luo, Kuei-Hau; Chuang, Hung-Yi; Wei, Shu-Yi; Chen, Gwo-Shing; Chiang, Wenchang; Huang, Chih-Jen

    2014-12-01

    Acute radiation dermatitis is a common adverse effect in patients undergoing radiotherapy for breast cancer. However, the effects of radiotherapy on biophysical properties of the skin have rarely been investigated. In this prospective cohort study, we seek to determine the effects of radiotherapy for breast cancer on skin biophysical parameters. We measured various skin biophysical parameters (skin hydration, pH, sebum level, pigmentation, and blood flow) in 144 breast cancer patients by non-invasive techniques before and after radiotherapy. The measurements were simultaneously performed on the irradiated breast and the corresponding contralateral unirradiated breast for comparison. Following radiotherapy, the irradiated breast showed a significant decrease in skin hydration, increase in skin pH, increase in pigmentation, and increase in cutaneous blood flow. The contralateral unirradiated breast showed a slight increase in pigmentation but no significant changes in any of the other biophysical parameters after radiotherapy. No significant associations were found between patient characteristics (diabetes mellitus, hypertension, type of surgery, chemotherapy, hormone therapy) and changes in skin biophysical parameters following radiotherapy. In conclusion, radiation therapy for breast cancer induces measurable and significant changes in biophysical properties of the skin including hydration, pH, pigmentation, and blood flow. These findings give us a greater understanding of the effects of ionizing radiation on skin physiology, and provide non-invasive and objective methods to assess radiation dermatitis.

  20. Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis

    PubMed Central

    Lee, Geum-A.; Hwang, Kyung-A.; Choi, Kyung-Chul

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy. PMID:27231938

  1. Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer

    NASA Astrophysics Data System (ADS)

    Sundaram, Karthik M.

    Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecologic malignant tumors. Diagnosis of epithelial ovarian cancer (EOC) presents two main challenges. The first challenge is detecting low volume (< 1 g) and early stage (≤ stage II) masses to prevent rapid progression to late stages and ultimately death. The second challenge is differentiating malignant from benign tissue to avoid costly and invasive surgeries (19.5 surgeries are required to find 1 cancer even with multiple screenings). First-line diagnostic tests such as ultrasound and serum marker tests (e.g. CA-125) aid in diagnosis but they lack the sensitivity and specificity required to overcome both challenges. Magnetic resonance imaging (MRI), a second-line diagnostic aided by gadolinium based contrast agents (CAs), offers higher resolution pictures for classifying indeterminate ovarian masses. But as currently practiced, MRI still lacks the sensitivity and specificity required to alter patient outcomes. In this work we develop a new paradigm for EOC diagnosis that targets the prolactin receptor (PRLR) - a cell surface tyrosine kinase receptor that is over-expressed in moderate to high levels on > 98% of epithelial ovarian cancers. Upon binding of native ligands to PRLR, the ligand:PRLR complex is internalized by cells. By conjugating gadolinium-chelates, molecules normally used as contrast agents diagnostically, to human placental lactogen (hPL), a native ligand of PRLR, we show that MRI becomes highly sensitive and specific for detecting PRLR (+) tumors in a nude mouse model of EOC. We further establish the adaptability of this approach for fluorescence-based imaging techniques using an hPL conjugated Cy5.5 dye. We conclude that molecular imaging of PRLR with hPL-conjugated imaging agents can address the current challenges that limit EOC diagnosis.

  2. A Randomized Controlled Trial of an Appearance-focused Intervention to Prevent Skin Cancer

    PubMed Central

    Hillhouse, Joel; Turrisi, Rob; Stapleton, Jerod; Robinson, June

    2014-01-01

    BACKGROUND Skin cancer represents a significant health threat with over 1.3 million diagnoses, 8000 melanoma deaths, and more than $1 billion spent annually for skin cancer healthcare in the US. Despite findings from laboratory, case-control, and prospective studies that indicate a link between youthful indoor tanning (IT) and skin cancer, IT is increasing among US youth. Appearance-focused interventions represent a promising method to counteract these trends. METHODS A total of 430 female indoor tanners were randomized into intervention or no intervention control conditions. Intervention participants received an appearance-focused booklet based on decision-theoretical models of health behavior. Outcome variables included self-reports of IT behavior and intentions, as well as measures of cognitive mediating variables. RESULTS Normative increases in springtime IT rates were significantly lower (ie, over 35%) at 6-month follow-up in intervention versus control participants with similar reductions in future intentions. Mediation analyses revealed 6 cognitive variables (IT attitudes, fashion attitudes, perceived susceptibility to skin cancer and skin damage, subjective norms, and image norms) that significantly mediated change in IT behavior. CONCLUSIONS The appearance-focused intervention demonstrated strong effects on IT behavior and intentions in young indoor tanners. Appearance-focused approaches to skin cancer prevention need to present alternative behaviors as well as alter IT attitudes. Mediational results provide guides for strengthening future appearance-focused interventions directed at behaviors that increase risk of skin cancer. PMID:18937268

  3. 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

  4. 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

  5. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  6. Circulating tumour cells and the epithelial mesenchymal transition in colorectal cancer.

    PubMed

    Lim, S H S; Becker, T M; Chua, W; Ng, W L; de Souza, P; Spring, K J

    2014-10-01

    Circulating tumour cells (CTCs) hold great potential as liquid biopsies to prognosticate disease and guide treatment in colorectal cancer. However, their emerging role in determining the molecular phenotype of tumour metastasis carries even more promising clinical use in the provision of comprehensive biomarker detection for targeted therapies and determination of drug resistance. The isolation of CTCs is technology dependent, and in the case of epithelial cell adhesion molecule-based platforms, the ability to detect cells that have undergone the epithelial to mesenchymal transition (EMT) is ineffective. CTCs displaying a mesenchymal phenotype are believed to have an increased metastatic potential. The rarity of CTCs provides another challenge in the enumeration of these cells. The future will likely involve the analysis of individual CTCs at any stage of the EMT in order to provide real-time phenotypic and molecular snapshots capable of tracking the dynamic evolution of tumour progression over time.

  7. Overexpression of MACC1 and the association with hepatocyte growth factor/c-Met in epithelial ovarian cancer

    PubMed Central

    LI, HONGYU; ZHANG, HUI; ZHAO, SHUJUN; SHI, YUN; YAO, JUNGE; ZHANG, YANYAN; GUO, HUANHUAN; LIU, XINGSUO

    2015-01-01

    Metastasis-associated in colon cancer-1 (MACC1) is a gene that has been newly identified by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases and normal tissues. MACC1 exerts an important role in colon cancer metastasis through upregulation of the c-Met proto-oncogene. The tyrosine kinase receptor encoded by the c-Met oncogene exhibits the unusual property of mediating the invasive growth of epithelial cells upon binding with the hepatocyte growth factor (HGF). MACC1 has been investigated with regard to colon carcinoma and MACC1 expression is associated with metastasis in various types of human cancer. However, the value of MACC1 as a potential biomarker for ovarian cancer remains unknown, although the c-Met/HGF receptor has been shown to be overexpressed in epithelial ovarian cancer tissues. To investigate the role of MACC1 in epithelial ovarian tumors, the expression levels of MACC1 mRNA in ovarian tumor specimens were analyzed together with the prognostic significance. MACC1 protein expression was also detected in the epithelial ovarian tissue specimens, and the effects of MACC1 overexpression on ovarian cancer migration, invasion and prognosis were evaluated. Due to the close association between MACC1 and c-Met expression levels in colon cancer, the expression levels of HGF/c-Met in the ovarian specimens were also examined to determine whether such a correlation is also present in epithelial ovarian cancer. A total of 92 epithelial ovarian tissue samples were used to assess the expression levels of MACC1 mRNA and protein using reverse transcription-polymerase chain reaction and immunohistochemical methods, respectively. The serum levels of MACC1 protein expression in patients with epithelial ovarian cancer were detected by enzyme-linked immunosorbent assay. The results indicated that MACC1 may be important in the malignant progression of epithelial ovarian tumors, in particular for early stage patients. Thus, MACC

  8. 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

  9. Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

    PubMed

    Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

    2013-01-01

    The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

  10. The Development of Combined Raman Spectroscopy-Optical Coherence Tomography and Application for Skin Cancer Diagnosis

    NASA Astrophysics Data System (ADS)

    Patil, Chetan

    2009-11-01

    Optical spectroscopy and imaging have shown promise for performing rapid, non-invasive disease detection and diagnosis in vivo. Independently, Raman Spectroscopy (RS) has demonstrated the ability to perform diagnosis of epithelial cancers such the cervix with excellent overall classification accuracy due to the inherent biochemical specificity of the technique, however relating features of tissue morphology with techniques such as Raman mapping is clinically impractical due to the weak nature of the scattering phenomena resulting in prohibitively long acquisition times. Optical Coherence Tomography (OCT), on the other hand, has demonstrated the ability to perform real-time, high-resolution, cross-sectional imaging of the microstructural characteristics of disease, but typically lacks molecularly specific information that can assist in classifying pathological lesions. We present the development of a combined Raman Spectroscopy-OCT (RS-OCT) instrument capable of compensating for the limitations of each technique individually and performing both biochemical and microstructural evaluation of tissues. We will include the design and development of benchtop RS-OCT implementations based on independent 785 nm Raman and 1310 nm time-domain OCT system backbones, as well as with a 785nm Raman / 850nm spectral-domain OCT setup employing an integrated detection arm. These systems motivated the ultimate design of a clinical RS-OCT system for application in dermatology. In order to aid in the development of our Raman spectral processing and classification methods, we conducted a simultaneous pilot study in which RS alone was used to measure basal and squamous cell carcinomas. We will present the initial results from our clinical experiences with the combined RS-OCT device, and include a discussion of spectral classification and the ultimate potential of combined RS-OCT for skin cancer diagnosis.

  11. MicroRNAs involved in regulating epithelial-mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics.

    PubMed

    Xia, H; Hui, K M

    2012-11-01

    One of the major challenges in cancer gene therapy is the identification of functionally relevant tumor-specific genes as the therapeutic targets. MicroRNAs (miRNAs) are a class of small, 22-25 nucleotides, endogenously expressed noncoding RNA. miRNAs are important genetic regulators: one miRNA can possibly target multiple genes and they can function as tumor promoters (oncogenic miRNAs, oncomirs) or tumor suppressors (anti-oncomirs). Therefore, the identification of misregulated miRNAs in cellular signaling pathways related to oncogenesis can have profound implications for cancer therapy. The epithelial-mesenchymal transition (EMT) converts epithelial cells into mesenchymal cells, a normal embryological process that frequently get activated during cancer invasion and metastasis. Recent evidence also supports the presence of a small subset of self-renewing, stem-like cells within the tumor mass that possess the capacity to seed new tumors and they have been termed 'cancer stem cells (CSC)'. Conceivably, these CSCs could provide a resource for cells that cause therapy resistance. Although the cell origin of CSCs remains to be fully elucidated, a growing body of evidence has demonstrated that the biology of EMT and CSCs is tightly linked with the sequences and compositions of miRNA molecules. Therefore, targeting miRNAs involved in EMT and CSCs regulation can provide novel miRNA-based therapeutic strategies in oncology.

  12. Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers.

    PubMed

    Lo, Pui-Chi; Chen, Juan; Stefflova, Klara; Warren, Michael S; Navab, Roya; Bandarchi, Bizhan; Mullins, Stefanie; Tsao, Ming; Cheng, Jonathan D; Zheng, Gang

    2009-01-22

    Fibroblast activation protein (FAP) is a cell-surface serine protease highly expressed on cancer-associated fibroblasts of human epithelial carcinomas but not on normal fibroblasts, normal tissues, and cancer cells. We report herein a novel FAP-triggered photodynamic molecular beacon (FAP-PPB) comprising a fluorescent photosensitizer and a black hole quencher 3 linked by a peptide sequence (TSGPNQEQK) specific to FAP. FAP-PPB was effectively cleaved by both human FAP and murine FAP. By use of the HEK293 transfected cells (HEK-mFAP, FAP(+); HEK-vector, FAP(-)), systematic in vitro and in vivo experiments validated the FAP-specific activation of FAP-PPB in cancer cells and mouse xenografts, respectively. FAP-PPB was cleaved by FAP, allowing fluorescence restoration in FAP-expressing cells while leaving non-expressing FAP cells undetectable. Moreover, FAP-PPB showed FAP-specific photocytotoxicity toward HEK-mFAP cells whereas it was non-cytotoxic toward HEK-Vector cells. This study suggests that the FAP-PPB is a potentially useful tool for epithelial cancer detection and treatment.

  13. HDAC Inhibition Impedes Epithelial-Mesenchymal Plasticity and Suppresses Metastatic, Castration-Resistant Prostate Cancer

    PubMed Central

    Ruscetti, Marcus; Dadashian, Eman L.; Guo, Weilong; Quach, Bill; Mulholland, David J.; Park, Juw Won; Tran, Linh M.; Kobayashi, Naoko; Bianchi-Frias, Daniella; Xing, Yi; Nelson, Peter S.; Wu, Hong

    2015-01-01

    PI3K/AKT and RAS/MAPK pathway co-activation in the prostate epithelium promotes both epithelial-mesenchymal transition (EMT) and metastatic castration-resistant prostate cancer (mCRPC), which is currently incurable. To study the dynamic regulation of the EMT process, we developed novel genetically-defined cellular and in vivo model systems from which epithelial, EMT, and mesenchymal-like tumor cells with Pten deletion and Kras activation can be isolated. When cultured individually, each population has the capacity to regenerate all three tumor cell populations, indicative of epithelial-mesenchymal plasticity. Despite harboring the same genetic alterations, mesenchymal-like tumor cells are resistant to PI3K and MAPK pathway inhibitors, suggesting that epigenetic mechanisms may regulate the EMT process, as well as dictate the heterogeneous responses of cancer cells to therapy. Among differentially expressed epigenetic regulators, the chromatin remodeling protein HMGA2 is significantly upregulated in EMT and mesenchymal-like tumors cells, as well as in human mCRPC. Knockdown of HMGA2, or suppressing HMGA2 expression with the histone deacetylase (HDAC) inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and dramatically reduces tumor growth and metastasis in vivo through successful targeting of EMT and mesenchymal-like tumor cells. Importantly, LBH589 treatment in combination with castration prevents mCRPC development and significantly prolongs survival following castration by enhancing p53 and AR acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to ADT. Taken together, these findings demonstrate that cellular plasticity is regulated epigenetically, and that mesenchymal-like tumor cell populations in mCRPC that are resistant to conventional and targeted therapies can be effectively treated with the epigenetic inhibitor LBH589. PMID:26640144

  14. Connecting epithelial polarity, proliferation and cancer in Drosophila: the many faces of lgl loss of function.

    PubMed

    Grifoni, Daniela; Froldi, Francesca; Pession, Annalisa

    2013-01-01

    Loss of cell polarity is a prominent feature of epithelial cancers. Several tumour-suppressor genes are indeed involved in establishing and maintaining a correct apical-basal polarity suggesting that a link exists between disruption of epithelial polarity and the control of cell proliferation. Nevertheless, the molecular basis of this link is only beginning to be unveiled. In Drosophila, the tumour suppressor gene lethal giant larvae (lgl) is widely used as a genetic tool in cancer modelling: its loss of function causes neoplastic growth of the imaginal tissues, larval epithelial organs from which adult structures originate. These mutant epithelia are characterised by loss of cell polarity and tissue architecture as well as hyperproliferation. We observed that in a clonal context, the ability of lgl mutant cells to express their neoplastic potential correlates with the levels of the oncoprotein Myc, a master regulator of cell growth and proliferation. Malignant, polarity-deficient mutant cells upregulate Myc and are able to overcome the tumour-suppressive defences imposed by the surrounding wild-type tissue. How does the loss of lgl function induce an increase in Myc levels? The answer to this question came from the finding that Lgl is an upstream regulator of the Hippo pathway, a highly conserved signalling network that controls proliferation of epithelial cells and organ size. The core of this pathway responds to several upstream regulators and converges on the inhibition of a transcriptional co-factor, Yorkie, which, as we and others have shown, is a direct regulator of the myc promoter. In this review we discuss the key findings that contributed to the identification of this regulatory network that links cell polarity to cell proliferation control. PMID:24395559

  15. Epithelial-Mesenchymal Plasticity of Breast Cancer Stem Cells: Implications for Metastasis and Therapeutic Resistance

    PubMed Central

    Luo, Ming; Brooke, Michael; Wicha, Max S.

    2015-01-01

    Over the past several decades the traditional view of cancer being a homogeneous mass of rapid proliferating malignant cells is being replaced by a model of ever increasing complexity, which points out that cancers are complex tissues composed of multiple cell types. A large variety of immune and other host cells constitute the tumor microenvironment, which supports the growth and progression of the tumor where individual cancer cells evolve with increasing phenotypic and genetic heterogeneity. Furthermore, it has also become clear that, in addition to this cellular and genetic heterogeneity, most tumors exhibit a hierarchical organization composed of tumor cells displaying divergent lineage markers and at the apex of this hierarchy are cells capable of self-renewal. These “cancer stem cells” not only drive tumor growth, but also mediate metastasis and contribute to treatment resistance. Besides displaying remarkable genetic and phenotypic heterogeneity, cancer stem cells maintain plasticity to transition between mesenchymal-like (EMT) and epithelial-like (MET) states in a process regulated by the tumor microenvironment. These stem cell state transitions may play a fundamental role in the process of tumor metastasis. In this review, we will discuss emerging knowledge regarding the plasticity of cancer stem cells and the role that this plasticity plays in tumor metastasis. We also discuss the implications of these findings for the development of cancer stem cell targeted therapeutics. PMID:25506895

  16. KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer

    PubMed Central

    Gumireddy, Kiranmai; Li, Anping; Gimotty, Phyllis A.; Klein-Szanto, Andres J.; Showe, Louise C.; Katsaros, Dionyssios; Coukos, George; Zhang, Lin; Huang, Qihong

    2009-01-01

    Metastasis is a complex multi-step process requiring the concerted action of many genes and is the primary cause of cancer deaths. Pathways that regulate metastasis enhancement and suppression both contribute to tumor dissemination process. In order to identify novel metastasis suppressors, we set up a forward genetic screen in a mouse model. We transduced a genome-wide RNAi library into the non-metastatic 168FARN breast cancer cell line, orthotopically transplanted the cells into mouse mammary fat pads, and then selected for cells that could metastasize to the lung and identified an RNAi for the KLF17 gene. Conversely, we demonstrate that ectopic expression of KLF17 in highly metastatic 4T1 breast cancer cell line inhibited their ability to metastasize from the mammary fat pad to the lung. We also show that suppression of KLF17 expression promotes breast cancer cell invasion and epithelial-mesenchymal transition (EMT) and that KLF17 functions by directly binding to the promoter of Id-1, a key metastasis regulator in breast cancer, to inhibit its transcription. Finally, we demonstrate that KLF17 expression is significantly down-regulated in primary human breast cancer samples and that the combined expression patterns of KLF17 and Id-1 can serve as a potential biomarker for lymph node metastasis in breast cancer. PMID:19801974

  17. Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels

    PubMed Central

    Lanitis, Evripidis; Dangaj, Denarda; Hagemann, Ian S.; Song, De-Gang; Best, Andrew; Sandaltzopoulos, Raphael; Coukos, George; Powell, Daniel J.

    2012-01-01

    The breadth of HER2 expression by primary human ovarian cancers remains controversial, which questions its suitability as a universal antigen in this malignancy. To address these issues, we performed extensive HER2 expression analysis on a wide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical (IHC) analysis of multiple tumor sites in 50 cases of high-grade ovarian serous carcinomas revealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumors as well as all established and short-term cultured cancer cell lines. Cancer cells generally expressed HER2 at higher levels than that found in normal ovarian surface epithelial (OSE) cells. Accordingly, genetically-engineered human T cells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovarian cancer cells tested with minimal or no reactivity against normal OSE cells. In conclusion, all human ovarian cancers express immunologically-detectable levels of HER2, indicating that IHC measurement underestimates the true frequency of HER2-expressing ovarian cancers and may limit patient access to otherwise clinically meaningful HER2-targeted therapies. PMID:23189165

  18. Predictive testing of the melanocortin 1 receptor for skin cancer and photoaging.

    PubMed

    Lynde, C W; Sapra, S

    2010-01-01

    Genetic predisposition to melanoma and nonmelanoma skin cancer extends far beyond the Fitzpatrick phenotype classification scheme. Specific alleles of the gene that codes for the malnocortin 1 receptor are predictive of skin cancer risk independent of skin type and hair color. The ability to identify high risk patients independent of the red hair phenotype may help to modify routine sun and skin monitoring behaviors. In addition, as this increased skin cancer risk is likely due to impaired UVA and UVB defence mechanisms, consideration of genetic predisposition may also be appropriate for patients undergoing psoralen + UVA (PUVA) or UVB treatments for various cutaneous disorders, such as psoriasis, eczema, and vitiligo. Testing aimed at improving prognostication may serve to limit the influence of certain risk factors.

  19. Epidemiological overview, advances in diagnosis, prevention, treatment and management of epithelial ovarian cancer in Mexico.

    PubMed

    Gallardo-Rincón, Dolores; Espinosa-Romero, Raquel; Muñoz, Wendy Rosemary; Mendoza-Martínez, Roberto; Villar-Álvarez, Susana Del; Oñate-Ocaña, Luis; Isla-Ortiz, David; Márquez-Manríquez, Juan Pablo; Apodaca-Cruz, Ángel; Meneses-García, Abelardo

    2016-04-01

    The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease. PMID:27557390

  20. Spy1 participates in the proliferation and apoptosis of epithelial ovarian cancer.

    PubMed

    Lu, Shumin; Liu, Rong; Su, Min; Wei, Yingze; Yang, Shuyun; He, Song; Wang, Xia; Qiang, Fulin; Chen, Chen; Zhao, Shuyang; Zhang, Weiwei; Xu, Pan; Mao, Guoxin

    2016-02-01

    This study focused on determining the role of Spy1 in human epithelial ovarian cancer (EOC). Speedy is a novel cell cycle protein capable of promoting cell proliferation. In this study, western blot and immunohistochemistrical analyses were performed to detect the expression of Spy1 in ovarian cancer. Spy1 protein levels increased with ovarian cancer grade, and Kaplan-Meier curve showed that overexpression of Spy1 was significantly correlated with reduced patient survival. In vitro, Spy1 depletion in ovarian cell lines led to reduced proliferation according to CCK8 and plate colony assays. The expression of Spy1 was positively related to pThr187-p27. Flow cytometry revealed that the reduced expression of Spy1 induced the apoptosis of the EOC cells. In summary, our findings suggested that Spy1 may be a novel independent prognostic predictor of survival for ovarian patients.

  1. Cancer Risk-Assessment of Radiation Damage in Ataxia Telangiectasia Heterozygous Human Breast Epithelial Cell Cultures

    NASA Technical Reports Server (NTRS)

    Applewhite, Lisa C.

    2002-01-01

    This paper describes the study of the markers of cellular changes that are found during the onset of carcinogenesis. Several of the biological factors are markers of stress response, oncoprotein expression, and differentiation factors. Oxidative stress response agents such as heat shock proteins (HSPs) protect cells from oxidative stresses such as ionizing radiation. The onocoprotein HER-2/neu, a specific breast cancer marker, indicates early onset of cancer. Additional structural and morphogenetic markers of differentiation were considered in order to determine initial cellular changes at the initial onset of cancer. As an additional consideration, all-trans retinoic acid (RA), a differentiation agent, was considered because of its known role in regulating normal differentiation and inhibiting tumor proliferation via specific nuclear receptors. This paper discusses study and results of the preliminary analyses of gamma irradiation of AT heterozygous human breast epithelial cells (WH). Comparisons are also made of the effects various RA concentrations post-irradiation.

  2. Design and technical evaluation of fibre-coupled Raman probes for the image-guided discrimination of cancerous skin

    NASA Astrophysics Data System (ADS)

    Schleusener, J.; Reble, C.; Helfmann, J.; Gersonde, I.; Cappius, H.-J.; Glanert, M.; Fluhr, J. W.; Meinke, M. C.

    2014-03-01

    Two different designs for fibre-coupled Raman probes are presented that are optimized for discriminating cancerous and normal skin by achieving high epithelial sensitivity to detect a major component of the Raman signal from the depth range of the epithelium. This is achieved by optimizing Raman spot diameters to the range of ≈200 µm, which distinguishes this approach from the common applications of either Raman microspectroscopy (1-5 µm) or measurements on larger sampling volume using spot sizes of a few mm. Video imaging with a depicted area in the order of a few cm, to allow comparing Raman measurements to the location of the histo-pathologic findings, is integrated in both designs. This is important due to the inhomogeneity of cancerous lesions. Video image acquisition is achieved using white light LED illumination, which avoids ambient light artefacts. The design requirements focus either on a compact light-weight configuration, for pen-like handling, or on a video-visible measurement spot to enable increased positioning accuracy. Both probes are evaluated with regard to spot size, Rayleigh suppression, background fluorescence, depth sensitivity, clinical handling and ambient light suppression. Ex vivo measurements on porcine ear skin correlates well with findings of other groups.

  3. Quantitative approach to skin field cancerization using a nanoencapsulated photodynamic therapy agent: a pilot study

    PubMed Central

    Passos, Simone K; de Souza, Paulo EN; Soares, Priscila KP; Eid, Danglades RM; Primo, Fernando L; Tedesco, Antonio Cláudio; Lacava, Zulmira GM; Morais, Paulo C

    2013-01-01

    Background This paper introduces a new nanoformulation of 5-aminolevulinic acid (nano-ALA) as well as a novel quantitative approach towards evaluating field cancerization for actinic keratosis and/or skin photodamage. In this pilot study, we evaluated field cancerization using nano-ALA and methyl aminolevulinate (MAL), the latter being commercialized as Metvix®. Methods and results Photodynamic therapy was used for the treatment of patients with selected skin lesions, whereas the fluorescence of the corresponding photosensitizer was used to evaluate the time evolution of field cancerization in a quantitative way. Field cancerization was quantified using newly developed color image segmentation software. Using photodynamic therapy as the precancer skin treatment and the approach introduced herein for evaluation of fluorescent area, we found that the half-life of field cancerization reduction was 43.3 days and 34.3 days for nano-ALA and MAL, respectively. We also found that nano-ALA targeted about 45% more skin lesion areas than MAL. Further, we found the mean reduction in area of skin field cancerization was about 10% greater for nano-ALA than for MAL. Conclusion Although preliminary, our findings indicate that the efficacy of nano-ALA in treating skin field cancerization is higher than that of MAL. PMID:23450821

  4. Rotating Night Shifts and Risk of Skin Cancer in the Nurses’ Health Study

    PubMed Central

    Razavi, Pedram; Qureshi, Abrar A.

    2011-01-01

    Night shift work is associated with increased risk of several cancers, but the risk of skin cancer among night shift workers is unknown. We documented 10 799 incident skin cancers in 68 336 women in the Nurses’ Health Study from June 1988 to June 2006 and examined the relationship between rotating night shifts and skin cancer. We used Cox proportional hazard models, adjusted for confounding variables (phenotypic and established risk factors of skin cancer), and performed stratified analysis to explore the modifying effect of hair color. Working 10 years or more on rotating night shifts was associated with a 14% decreased risk of skin cancer compared with never working night shifts (age-standardized incidence rate: 976 per 100 000 person-years (PY) vs 1070 per 100 000 PY, respectively; adjusted hazard ratios = 0.86, 95% confidence interval = 0.81 to 0.92, Ptrend < .001). This association was strongest for cutaneous melanoma; working 10 years or more of rotating night shifts was associated with 44% decreased risk of melanoma, after adjustment for melanoma risk factors (age-standardized incidence rate: 20 per 100 000 PY vs 35 per 100 000 PY, respectively; adjusted hazard ratios = 0.56, 95% confidence interval = 0.36 to 0.87, Ptrend = .005). Hair color, a surrogate for an individual’s susceptibility to skin cancer, was a statistically significant effect modifier for the observed associations; darker-haired women had the lowest risk (Pinteraction = .02). PMID:21335547

  5. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    PubMed Central

    Jim, Heather S.L.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Vierkant, Robert A.; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Schernhammer, Eva; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M.; Kelemen, Linda E.; Ramus, Susan J.; Monteiro, Alvaro N.A.; Goode, Ellen L.; Narod, Steven A.; Gayther, Simon A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID:26807442

  6. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

    PubMed Central

    Hearn, Jessica M.; Romero-Canelón, Isolda; Munro, Alison F.; Fu, Ying; Pizarro, Ana M.; Garnett, Mathew J.; McDermott, Ultan; Carragher, Neil O.; Sadler, Peter J.

    2015-01-01

    The organometallic “half-sandwich” compound [Os(η6-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance. PMID:26162681

  7. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.

    PubMed

    Hearn, Jessica M; Romero-Canelón, Isolda; Munro, Alison F; Fu, Ying; Pizarro, Ana M; Garnett, Mathew J; McDermott, Ultan; Carragher, Neil O; Sadler, Peter J

    2015-07-21

    The organometallic "half-sandwich" compound [Os(η(6)-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance.

  8. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.

    PubMed

    Hearn, Jessica M; Romero-Canelón, Isolda; Munro, Alison F; Fu, Ying; Pizarro, Ana M; Garnett, Mathew J; McDermott, Ultan; Carragher, Neil O; Sadler, Peter J

    2015-07-21

    The organometallic "half-sandwich" compound [Os(η(6)-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance. PMID:26162681

  9. Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis.

    PubMed

    Ruscetti, Marcus; Quach, Bill; Dadashian, Eman L; Mulholland, David J; Wu, Hong

    2015-07-01

    The epithelial-mesenchymal transition (EMT) has been postulated as a mechanism by which cancer cells acquire the invasive and stem-like traits necessary for distant metastasis. However, direct in vivo evidence for the role of EMT in the formation of cancer stem-like cells (CSC) and the metastatic cascade remains lacking. Here we report the first isolation and characterization of mesenchymal-like and EMT tumor cells, which harbor both epithelial and mesenchymal characteristics, in an autochthonous murine model of prostate cancer. By crossing the established Pb-Cre(+/-);Pten(L/L);Kras(G12D) (/+) prostate cancer model with a vimentin-GFP reporter strain, generating CPKV mice, we were able to isolate epithelial, EMT, and mesenchymal-like cancer cells based on expression of vimentin and EpCAM. CPKV mice (but not mice with Pten deletion alone) exhibited expansion of cells with EMT (EpCAM(+)/Vim-GFP(+)) and mesenchymal-like (EpCAM(-)/Vim-GFP(+)) characteristics at the primary tumor site and in circulation. These EMT and mesenchymal-like tumor cells displayed enhanced stemness and invasive character compared with epithelial tumor cells. Moreover, they displayed an enriched tumor-initiating capacity and could regenerate epithelial glandular structures in vivo, indicative of epithelia-mesenchyme plasticity. Interestingly, while mesenchymal-like tumor cells could persist in circulation and survive in the lung following intravenous injection, only epithelial and EMT tumor cells could form macrometastases. Our work extends the evidence that mesenchymal and epithelial states in cancer cells contribute differentially to their capacities for tumor initiation and metastatic seeding, respectively, and that EMT tumor cells exist with plasticity that can contribute to multiple stages of the metastatic cascade. PMID:25948589

  10. 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

  11. [Carcinogenic viruses in etiopathogenesis of skin cancers in patients after organ transplantation].

    PubMed

    Piesiaków, Maria Luiza; Imko-Walczuk, Beata; Osiecka, Karolina; Kiełbowicz, Marta; Dębska-Ślizień, Alicja

    2016-02-14

    The latest literature report specifies multifactoral etiology of skin cancer in population of patients after organs transplats. Carcirogenic viruses are one of etiopathogenesis components. Viruses of a vital meaning for skin oncogenesis are called Human papillomavirus - HPV, Human herpesvirus 8 - HHV8 i Merkel cell polyomavirus - MCV. Report on connections exisisting between viruses HPV and skin cancers in the population of patients after organs transplants confirms clinical connection between viruses papillas and cancers centres occuring in similar locations and more frequent appearance of attributes characteristic for HPV infection within the limits of changes in the type of Squamous cell carcinoma (SCC). What's more, coexisting of viruses papillas and SCC is more often noticed in the population of organ recipients than in the population of healthy people. It is not confirmed yet that any specific correlation between subtypes of HPV and greater frequency of morbidity in skin cancers really exist. However, in the population of organ recipients infections of different types of HPV are found within the limits of cancers centres in the case of SCC (63%) as well as in basal cell carcinoma-BCC (55%). DNA of HPV was also fund in healthy parts of organ recipients skin (92-94%). HHV8 is also an oncogenic viruse that influences the development of lymphoma. Infection of that virus may cause ocuuring of Kaposi's sarkoma, which is one of the most frequent types of cancer appearing in population of patients treating by long-term immunosuppression in particular geographical zones. MCV, which belongs to the group called Polyomaviriade, owes a particular meaning in etiopathogenesis of Merkel cell carcinoma - MCC. It is a rare cancer derived from neuroendocrine cells of the basic layers of epidermie. For over 30 years it was supposed that correlation between viruses and skin cancers in population of organ recipient exist. Knowledge of the total viruses influence on skin cancers

  12. [Carcinogenic viruses in etiopathogenesis of skin cancers in patients after organ transplantation].

    PubMed

    Piesiaków, Maria Luiza; Imko-Walczuk, Beata; Osiecka, Karolina; Kiełbowicz, Marta; Dębska-Ślizień, Alicja

    2016-01-01

    The latest literature report specifies multifactoral etiology of skin cancer in population of patients after organs transplats. Carcirogenic viruses are one of etiopathogenesis components. Viruses of a vital meaning for skin oncogenesis are called Human papillomavirus - HPV, Human herpesvirus 8 - HHV8 i Merkel cell polyomavirus - MCV. Report on connections exisisting between viruses HPV and skin cancers in the population of patients after organs transplants confirms clinical connection between viruses papillas and cancers centres occuring in similar locations and more frequent appearance of attributes characteristic for HPV infection within the limits of changes in the type of Squamous cell carcinoma (SCC). What's more, coexisting of viruses papillas and SCC is more often noticed in the population of organ recipients than in the population of healthy people. It is not confirmed yet that any specific correlation between subtypes of HPV and greater frequency of morbidity in skin cancers really exist. However, in the population of organ recipients infections of different types of HPV are found within the limits of cancers centres in the case of SCC (63%) as well as in basal cell carcinoma-BCC (55%). DNA of HPV was also fund in healthy parts of organ recipients skin (92-94%). HHV8 is also an oncogenic viruse that influences the development of lymphoma. Infection of that virus may cause ocuuring of Kaposi's sarkoma, which is one of the most frequent types of cancer appearing in population of patients treating by long-term immunosuppression in particular geographical zones. MCV, which belongs to the group called Polyomaviriade, owes a particular meaning in etiopathogenesis of Merkel cell carcinoma - MCC. It is a rare cancer derived from neuroendocrine cells of the basic layers of epidermie. For over 30 years it was supposed that correlation between viruses and skin cancers in population of organ recipient exist. Knowledge of the total viruses influence on skin cancers

  13. 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

  14. Photodynamic Therapy and Non-Melanoma Skin Cancer

    PubMed Central

    Griffin, Liezel L.; Lear, John T.

    2016-01-01

    Non-melanoma skin cancer (NMSC) is the most common malignancy among the Caucasian population. Photodynamic therapy (PDT) is gaining popularity for the treatment of basal cell carcinoma (BCC), Bowen’s disease (BD) and actinic keratosis (AK). A topical or systemic exogenous photosensitiser, results in selective uptake by malignant cells. Protoporphyrin IX (PpIX) is produced then activated by the introduction of a light source. Daylight-mediated MAL (methyl aminolaevulinate) PDT for AKs has the advantage of decreased pain and better patient tolerance. PDT is an effective treatment for superficial BCC, BD and both individual and field treatment of AKs. Excellent cosmesis can be achieved with high patient satisfaction. Variable results have been reported for nodular BCC, with improved outcomes following pretreatment and repeated PDT cycles. The more aggressive basisquamous, morphoeic infiltrating subtypes of BCC and invasive squamous cell carcinoma (SCC) are not suitable for PDT. Prevention of “field cancerization” in organ transplant recipients on long-term immunosuppression and patients with Gorlin syndrome (naevoid basal cell carcinoma syndrome) is a promising development. The optimisation of PDT techniques with improved photosensitiser delivery to target tissues, new generation photosensitisers and novel light sources may expand the future role of PDT in NMSC management. PMID:27782094

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

    PubMed

    Katiyar, Santosh K

    2011-04-15

    Excessive exposure of the skin to solar ultraviolet (UV) radiation is one of the major factors for the development of skin cancers, including non-melanoma. 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.

  16. A Randomized Trial of Tailored Skin Cancer Prevention Messages for Adults: Project SCAPE

    PubMed Central

    Schoenfeld, Elinor R.; Steffen, Alana

    2010-01-01

    Objectives. We evaluated the impact of a mailed, tailored intervention on skin cancer prevention and skin self-examination behaviors of adults at moderate and high risk for skin cancer. Methods. Adults at moderate and high risk for skin cancer were recruited in primary health care settings in Honolulu, HI, and Long Island, NY. After completing a baseline survey, participants were randomized to 2 groups. The treatment group received tailored materials, including personalized risk feedback, and the control group received general educational materials. Multivariate analyses compared sun protection and skin self-examination between groups, controlling for location, risk level, gender, and age. Results. A total of 596 adults completed the trial. The tailored materials had a significant effect on overall sun-protection habits, the use of hats, the use of sunglasses, and the recency of skin self-examination. Some effects were moderated by location and risk level. Conclusions. Tailored communications including personalized risk feedback can improve sun-protection behaviors and skin self-examination among adults at increased risk for skin cancer. These convenient, low-cost interventions can be implemented in a variety of settings and should be tested further to assess their long-term effectiveness. PMID:20167900

  17. Computer simulations of the mechanical response of brushes on the surface of cancerous epithelial cells

    PubMed Central

    Goicochea, A. Gama; Guardado, S. J. Alas

    2015-01-01

    We report a model for atomic force microscopy by means of computer simulations of molecular brushes on surfaces of biological interest such as normal and cancerous cervical epithelial cells. Our model predicts that the force needed to produce a given indentation on brushes that can move on the surface of the cell (called “liquid” brushes) is the same as that required for brushes whose ends are fixed on the cell’s surface (called “solid” brushes), as long as the tip of the microscope covers the entire area of the brush. Additionally, we find that cancerous cells are softer than normal ones, in agreement with various experiments. Moreover, soft brushes are found to display larger resistance to compression than stiff ones. This phenomenon is the consequence of the larger equilibrium length of the soft brushes and the cooperative association of solvent molecules trapped within the brushes, which leads to an increase in the osmotic pressure. Our results show that a careful characterization of the brushes on epithelial cells is indispensable when determining the mechanical response of cancerous cells. PMID:26315877

  18. Ultrashort cationic lipopeptides and lipopeptoids: Evaluation and mechanistic insights against epithelial cancer cells.

    PubMed

    Domalaon, Ronald; Findlay, Brandon; Ogunsina, Makanjuola; Arthur, Gilbert; Schweizer, Frank

    2016-10-01

    Peptides present an attractive scaffold for the development of new anticancer lead agents due to their accessibility and ease of modification. Synthetic ultrashort cationic lipopeptides, with four amino acids or less conjugated to a fatty acid, were developed to retain the biological activity of longer peptides in a smaller molecular size. Herein, we report the activity of amphiphilic lipotripeptides, lipotripeptoids and lipotetrapeptides against breast (MDA-MB-231, JIMT-1), prostate (DU145) and pancreas (MiaPaCa2) epithelial cancer cell lines. The lipotripeptide C16-KKK-NH2 and lipotetrapeptide C16-PCatPHexPHexPCat-NH2 were identified to possess anticancer activity. The latter lipotetrapeptide possess a short polyproline scaffold consisting of only two L-4R-aminoproline (PCat) and two L-4R-hexyloxyproline (PHex). However, all the prepared lipotripeptoids lack anticancer activity. The amphiphilic C16-PCatPHexPHexPCat-NH2 exhibited similar anticancer potency to the surfactant benzethonium chloride while superior activity was observed in comparison to myristylamine. Mechanistic studies revealed that the peptides do not lyse ovine erythrocytes nor epithelial cancer cells, thus ruling out necrosis as the mechanism of cell death. Surprisingly, the two lipopeptides exhibit different mechanisms of action that result in cancer cell death. The lipotripeptide C16-KKK-NH2 was found to induce caspase-mediated apoptosis while C16-PCatPHexPHexPCat-NH2 kills tumor cells independent of caspases.

  19. Epithelial junction opener JO-1 improves monoclonal antibody therapy of cancer.

    PubMed

    Beyer, Ines; van Rensburg, Ruan; Strauss, Robert; Li, ZongYi; Wang, Hongjie; Persson, Jonas; Yumul, Roma; Feng, Qinghua; Song, Hui; Bartek, Jiri; Fender, Pascal; Lieber, André

    2011-11-15

    The efficacy of monoclonal antibodies (mAb) used to treat solid tumors is limited by intercellular junctions which tightly link epithelial tumor cells to each another. In this study, we define a small, recombinant adenovirus serotype 3-derived protein, termed junction opener 1 (JO-1), which binds to the epithelial junction protein desmoglein 2 (DSG2). In mouse xenograft models employing Her2/neu- and EGFR-positive human cancer cell lines, JO-1 mediated cleavage of DSG2 dimers and activated intracellular signaling pathways which reduced E-cadherin expression in tight junctions. Notably, JO-1-triggered changes allowed for increased intratumoral penetration of the anti-Her2/neu mAb trastuzumab (Herceptin) and improved access to its target receptor, Her2/neu, which is partly trapped in tight junctions. This effect translated directly into increased therapeutic efficacy of trastuzumab in mouse xenograft models using breast, gastric, and ovarian cancer cells that were Her2/neu-positive. Furthermore, combining JO-1 with the EGFR-targeting mAb cetuximab (Erbitux) greatly improved therapeutic outcomes in a metastatic model of EGFR-positive lung cancer. A combination of JO-1 with an approach that triggered transient degradation of tumor stroma proteins elicited eradication of tumors. Taken together, our findings offer preclinical proof of concept to employ JO-1 in combination with mAb therapy.

  20. Computer simulations of the mechanical response of brushes on the surface of cancerous epithelial cells

    NASA Astrophysics Data System (ADS)

    Goicochea, A. Gama; Guardado, S. J. Alas

    2015-08-01

    We report a model for atomic force microscopy by means of computer simulations of molecular brushes on surfaces of biological interest such as normal and cancerous cervical epithelial cells. Our model predicts that the force needed to produce a given indentation on brushes that can move on the surface of the cell (called “liquid” brushes) is the same as that required for brushes whose ends are fixed on the cell’s surface (called “solid” brushes), as long as the tip of the microscope covers the entire area of the brush. Additionally, we find that cancerous cells are softer than normal ones, in agreement with various experiments. Moreover, soft brushes are found to display larger resistance to compression than stiff ones. This phenomenon is the consequence of the larger equilibrium length of the soft brushes and the cooperative association of solvent molecules trapped within the brushes, which leads to an increase in the osmotic pressure. Our results show that a careful characterization of the brushes on epithelial cells is indispensable when determining the mechanical response of cancerous cells.

  1. Resveratrol sensitizes tamoxifen in antiestrogen-resistant breast cancer cells with epithelial-mesenchymal transition features.

    PubMed

    Shi, Xiao-Peng; Miao, Shan; Wu, Yin; Zhang, Wei; Zhang, Xiao-Fang; Ma, Hua-Zhao; Xin, Hai-Li; Feng, Juan; Wen, Ai-Dong; Li, Yan

    2013-07-26

    Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-β/Smad signaling. Ectopic supplement of TGF-β promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-β production and Smad phosphorylation. In particular, 50 μM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-β production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-β/Smad-dependent.

  2. ARP2, a novel pro-apoptotic protein expressed in epithelial prostate cancer LNCaP cells and epithelial ovary CHO transformed cells.

    PubMed

    Mas-Oliva, Jaime; Navarro-Vidal, Enrique; Tapia-Vieyra, Juana Virginia

    2014-01-01

    Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+)-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2) associated to a lethal influx of Ca(2+) in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line) transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event. PMID:24465888

  3. ARP2, a novel pro-apoptotic protein expressed in epithelial prostate cancer LNCaP cells and epithelial ovary CHO transformed cells.

    PubMed

    Mas-Oliva, Jaime; Navarro-Vidal, Enrique; Tapia-Vieyra, Juana Virginia

    2014-01-01

    Neoplastic epithelial cells generate the most aggressive types of cancers such as those located in the lung, breast, colon, prostate and ovary. During advanced stages of prostate cancer, epithelial cells are associated to the appearance of androgen-independent tumors, an apoptotic-resistant phenotype that ultimately overgrows and promotes metastatic events. We have previously identified and electrophysiologically characterized a novel Ca(2+)-permeable channel activated during apoptosis in the androgen-independent prostate epithelial cancer cell line, LNCaP. In addition, we reported for the first time the cloning and characterization of this channel-like molecule named apoptosis regulated protein 2 (ARP2) associated to a lethal influx of Ca(2+) in Xenopus oocytes. In the present study, LNCaP cells and Chinese hamster ovary cells (CHO cell line) transfected with arp2-cDNA are induced to undergo apoptosis showing an important impact on cell viability and activation of caspases 3 and 7 when compared to serum deprived grown cells and ionomycin treated cells. The subcellular localization of ARP2 in CHO cells undergoing apoptosis was studied using confocal microscopy. While apoptosis progresses, ARP2 initially localized in the peri-nuclear region of cells migrates with time towards the plasma membrane region. Based on the present results and those of our previous studies, the fact that ARP2 constitutes a novel cation channel is supported. Therefore, ARP2 becomes a valuable target to modulate the influx and concentration of calcium in the cytoplasm of epithelial cancer cells showing an apoptotic-resistant phenotype during the onset of an apoptotic event.

  4. [Risk factors for skin cancer development in patients after organ transplantation].

    PubMed

    Imko-Walczuk, Beata; Piesiaków, Maria Luiza; Okuniewska, Aleksandra; Jaśkiewicz, Janusz; Lizakowski, Sławomir; Dębska-Ślizień, Alicja; Rutkowski, Bolesław

    2012-11-13

    Cancer has become the second most common cause of death in patients after organ transplantation. Among all cancers arising de novo after transplantation skin cancers are the most common, accounting for 95% of all skin neoplasms. Due to the significantly higher morbidity, aggressive, rapid progression of cancer and unfavorable prognosis, the population requires a specific oncological approach. Therefore, special attention should be paid to factors predisposing to the development of cancer, including skin cancer, in patients after organ transplantation. Some of these factors are well understood, while the role of others is still ambiguous. Among the etiological factors mentioned are those that are associated with the recipient. These include genetic factors such as male sex, fair skin and inability to be tanned, and compatibility of the HLA system, and non genetic factors such as patient age, chronic skin ulcers and scars, the type of transplanted organ, immunosuppression, and particularly the type and cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced by environmental factors such as exposure to sunlight and therefore latitude, ionizing radiation, chemical carcinogens and viral infections. Knowledge of etiological factors and mechanisms of etiopathogenesis allow for indication and observation of patients with increased risk of cancer as well as faster healing in these patients.  

  5. Microcalcifications in breast cancer: an active phenomenon mediated by epithelial cells with mesenchymal characteristics

    PubMed Central

    2014-01-01

    Background Mammary microcalcifications have a crucial role in breast cancer detection, but the processes that induce their formation are unknown. Moreover, recent studies have described the occurrence of the epithelial–mesenchymal transition (EMT) in breast cancer, but its role is not defined. In this study, we hypothesized that epithelial cells acquire mesenchymal characteristics and become capable of producing breast microcalcifications. Methods Breast sample biopsies with microcalcifications underwent energy dispersive X-ray microanalysis to better define the elemental composition of the microcalcifications. Breast sample biopsies without microcalcifications were used as controls. The ultrastructural phenotype of breast cells near to calcium deposits was also investigated to verify EMT in relation to breast microcalcifications. The mesenchymal phenotype and tissue mineralization were studied by immunostaining for vimentin, BMP-2, β2-microglobulin, β-catenin and osteopontin (OPN). Results The complex formation of calcium hydroxyapatite was strictly associated with malignant lesions whereas calcium-oxalate is mainly reported in benign lesions. Notably, for the first time, we observed the presence of magnesium-substituted hydroxyapatite, which was frequently noted in breast cancer but never found in benign lesions. Morphological studies demonstrated that epithelial cells with mesenchymal characteristics were significantly increased in infiltrating carcinomas with microcalcifications and in cells with ultrastructural features typical of osteoblasts close to microcalcifications. These data were strengthened by the rate of cells expressing molecules typically involved during physiological mineralization (i.e. BMP-2, OPN) that discriminated infiltrating carcinomas with microcalcifications from those without microcalcifications. Conclusions We found significant differences in the elemental composition of calcifications between benign and malignant lesions

  6. The Incidence of Nonmelanoma Skin Cancers and Actinic Keratoses in South Florida

    PubMed Central

    Zarraga, Matthew B.

    2012-01-01

    Background: Incidence of nonmelanoma skin cancer and actinic keratoses appears to be increasing worldwide due to increasing levels of ultraviolet radiation, lifestyle changes, and an aging population. Because of its demographics and geographic location, the population of South Florida is at risk for high rates of nonmelanoma skin cancer and actinic keratoses. Objective: To determine the incidence of nonmelanoma skin cancer and actinic keratoses in two populations in South Florida by measuring treatments by dermatologists in health maintenance organization gatekeeper populations. Methods: The incidence of nonmelanoma skin cancer and actinic keratoses in South Florida was determined by evaluating the number of nonmelanoma skin cancers and actinic keratoses treated by dermatologists (Current Procedural Terminology [CPT] Code Analysis) in two health maintenance organization populations; “commercial” (age 0–65, mean 27) and Medicare (age 65+, mean 68) in the calendar year 1996. Results: The incidence of treatment of nonmelanoma skin cancer was 466.5 per 100,000 people per year in the “commercial” (age 0 to 65) population and 10,689.8 per 100,000 people per year in the Medicare age population. The incidence of treated actinic keratoses was 4,464.6 per 100,000 people per year and 110,450.3 in each population respectively. Conclusion: The studied populations in South Florida appear to have some of the highest incidence rates of nonmelanoma skin cancer in the world and extremely high rates of actinic keratoses. The findings suggest that there is an epidemic of nonmelanoma skin cancer in the South Florida community, which has significant implications for the future medical needs of both “commercial” and Medicare-age populations. PMID:22708003

  7. Concise Review: Stem Cells and Epithelial-Mesenchymal Transition in Cancer: Biological Implications and Therapeutic Targets.

    PubMed

    Sato, Ryo; Semba, Takashi; Saya, Hideyuki; Arima, Yoshimi

    2016-08-01

    Cancer stem cells (CSCs) constitute a small subpopulation of cancer cells with stem-like properties that are able to self-renew, generate differentiated daughter cells, and give rise to heterogeneous tumor tissue. Tumor heterogeneity is a hallmark of cancer and underlies resistance to anticancer therapies and disease progression. The epithelial-mesenchymal transition (EMT) is a reversible phenomenon that is mediated by EMT-inducing transcription factors (EMT-TFs) and plays an important role in normal organ development, wound healing, and the invasiveness of cancer cells. Recent evidence showing that overexpression of several EMT-TFs is associated with stemness in cancer cells has suggested the existence of a link between EMT and CSCs. In this review, we focus on the roles of CSCs and EMT signaling in driving tumor heterogeneity. A better understanding of the dynamics of both CSCs and EMT-TFs in the generation of tumor heterogeneity may provide a basis for the development of new treatment options for cancer patients. Stem Cells 2016;34:1997-2007. PMID:27251010

  8. Concise Review: Stem Cells and Epithelial-Mesenchymal Transition in Cancer: Biological Implications and Therapeutic Targets.

    PubMed

    Sato, Ryo; Semba, Takashi; Saya, Hideyuki; Arima, Yoshimi

    2016-08-01

    Cancer stem cells (CSCs) constitute a small subpopulation of cancer cells with stem-like properties that are able to self-renew, generate differentiated daughter cells, and give rise to heterogeneous tumor tissue. Tumor heterogeneity is a hallmark of cancer and underlies resistance to anticancer therapies and disease progression. The epithelial-mesenchymal transition (EMT) is a reversible phenomenon that is mediated by EMT-inducing transcription factors (EMT-TFs) and plays an important role in normal organ development, wound healing, and the invasiveness of cancer cells. Recent evidence showing that overexpression of several EMT-TFs is associated with stemness in cancer cells has suggested the existence of a link between EMT and CSCs. In this review, we focus on the roles of CSCs and EMT signaling in driving tumor heterogeneity. A better understanding of the dynamics of both CSCs and EMT-TFs in the generation of tumor heterogeneity may provide a basis for the development of new treatment options for cancer patients. Stem Cells 2016;34:1997-2007.

  9. DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation

    PubMed Central

    Pellacani, D; Kestoras, D; Droop, A P; Frame, F M; Berry, P A; Lawrence, M G; Stower, M J; Simms, M S; Mann, V M; Collins, A T; Risbridger, G P; Maitland, N J

    2014-01-01

    Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. Here we clarify the origin and function of CpG island hypermethylation in CaP, in the context of a cancer cell hierarchy and epithelial differentiation, by analysis of separated basal and luminal cells from cancers. For a set of genes (including GSTP1) that are hypermethylated in CaP, gene downregulation is the result of cell differentiation and is not cancer specific. Hypermethylation is however seen in more differentiated cancer cells and is promoted by hyperproliferation. These genes are maintained as actively expressed and methylation-free in undifferentiated CaP cells, and their hypermethylation is not essential for either tumour development or expansion. We present evidence for the causes and the dynamics of CpG island hypermethylation in CaP, showing that, for a specific set of genes, promoter methylation is downstream of gene downregulation and is not a driver of gene repression, while gene repression is a result of tissue-specific differentiation. PMID:24464224

  10. WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail.

    PubMed

    Yue, Z; Feng, W; Xiangke, L; Liuxing, W; Qingxia, F; Jianbo, G

    2014-12-01

    WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of cancers, has been associated with a lot of metastatic diseases. However, the role and mechanisms of the high expression of WAVE3 in human gastric cancer has not been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and MKN45. Furthermore, a correlation was found between aggressiveness of these cell lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC-7901 cells and found that upregulating WAVE3 could promote the migration, invasion and proliferation of SGC-7901 cells in vitro. It has been reported that WAVE3 could induce cancer invasion and metastasis by participating epithelial-mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901 cells by dampening the expression of E-cadherin while increasing the expression of vimentin. Elevated WAVE3 levels could also improve the expression of transcription factor Snail. In addition, downregulating Snail could particularly reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901 cells elevated by overexpression of WAVE3. Taken together, we demonstrated that WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer prevention and therapy. PMID:25378074

  11. Skin Cancer Knowledge, Beliefs, Self-Efficacy, and Preventative Behaviors among North Mississippi Landscapers

    PubMed Central

    Ford, M. Allison; Hallam, Jeffrey S.; Bass, Martha A.; Vice, Michael A.

    2013-01-01

    There are slightly over one million workers in the landscape service industry in the US. These workers have potential for high levels of solar ultraviolet radiation exposure, increasing their risk of skin cancer. A cross-sectional sample of 109 landscapers completed a self-administered questionnaire based on Health Belief Model (HBM). The participants correctly answered 67.1% of the knowledge questions, 69.7% believed they were more likely than the average person to get skin cancer, and 87.2% perceived skin cancer as a severe disease. Participants believed that the use of wide-brimmed hats, long sleeved shirts/long pants, and sunscreen was beneficial but reported low usage of these and other sun protective strategies. The primary barriers to using sun protection were “I forget to wear it” and “it is too hot to wear.” Of the HBM variables, perceived benefits outweighing perceived barrier (r = .285, P = .003) and self-efficacy (r = .538, P = .001) were correlated with sun protection behaviors. The reasons for absence of the relationship between perceived skin cancer threat and sun protection behaviors could be lack of skin cancer knowledge and low rate of personal skin cancer history. PMID:24223037

  12. Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer.

    PubMed

    Merritt, Melissa A; Green, Adèle C; Nagle, Christina M; Webb, Penelope M

    2008-01-01

    Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer.

  13. Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment.

    PubMed

    Scott, Clare L; Becker, Marc A; Haluska, Paul; Samimi, Goli

    2013-12-04

    Despite increasing evidence that precision therapy targeted to the molecular drivers of a cancer has the potential to improve clinical outcomes, high-grade epithelial ovarian cancer (OC) patients are currently treated without consideration of molecular phenotype, and predictive biomarkers that could better inform treatment remain unknown. Delivery of precision therapy requires improved integration of laboratory-based models and cutting-edge clinical research, with pre-clinical models predicting patient subsets that will benefit from a particular targeted therapeutic. Patient-derived xenografts (PDXs) are renewable tumor models engrafted in mice, generated from fresh human tumors without prior in vitro exposure. PDX models allow an invaluable assessment of tumor evolution and adaptive response to therapy. PDX models have been applied to pre-clinical drug testing and biomarker identification in a number of cancers including ovarian, pancreatic, breast, and prostate cancers. These models have been shown to be biologically stable and accurately reflect the patient tumor with regards to histopathology, gene expression, genetic mutations, and therapeutic response. However, pre-clinical analyses of molecularly annotated PDX models derived from high-grade serous ovarian cancer (HG-SOC) remain limited. In vivo response to conventional and/or targeted therapeutics has only been described for very small numbers of individual HG-SOC PDX in conjunction with sparse molecular annotation and patient outcome data. Recently, two consecutive panels of epithelial OC PDX correlate in vivo platinum response with molecular aberrations and source patient clinical outcomes. These studies underpin the value of PDX models to better direct chemotherapy and predict response to targeted therapy. Tumor heterogeneity, before and following treatment, as well as the importance of multiple molecular aberrations per individual tumor underscore some of the important issues addressed in PDX models.

  14. Chidamide alleviates TGF-β-induced epithelial-mesenchymal transition in lung cancer cell lines.

    PubMed

    Lin, Sheng-Hao; Wang, Bing-Yen; Lin, Ching-Hsiung; Chien, Peng-Ju; Wu, Yueh-Feng; Ko, Jiunn-Liang; Chen, Jeremy J W

    2016-07-01

    Transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-β-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-β induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-β-induced SMAD2 phosphorylation and attenuated TGF-β-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-β-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-β-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-β suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-β-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis.

  15. Laminin-binding integrin gene copy number alterations in distinct epithelial-type cancers

    PubMed Central

    Harryman, William L; Pond, Erika; Singh, Parminder; Little, Andrew S; Eschbacher, Jennifer M; Nagle, Raymond B; Cress, Anne E

    2016-01-01

    Background: The laminin-binding integrin (LBI) family are cell adhesion molecules that are essential for invasion and metastasis of human epithelial cancers and cell adhesion mediated drug resistance. We investigated whether copy number alteration (CNA) or mutations of a five-gene signature (ITGB4, ITGA3, LAMB3, PLEC, and SYNE3), representing essential genes for LBI adhesion, would correlate with patient outcomes within human epithelial-type tumor data sets currently available in an open access format. Methods: We investigated the relative alteration frequency of an LBI signature panel (integrin β4 (ITGB4), integrin α3 (ITGA3), laminin β3 chain (LAMB3), plectin (PLEC), and nesprin 3 (SYNE3)), independent of the epithelial cancer type, within publically available and published data using cBioPortal and Oncomine software. We rank ordered the results using a 20% alteration frequency cut-off and limited the analysis to studies containing at least 100 samples. Kaplan-Meier survival curves were analyzed to determine if alterations in the LBI signature correlated with patient survival. The Oncomine data mining tool was used to compare the heat map expression of the LBI signature without SYNE3 (as this was not included in the Oncomine database) to drug resistance patterns. Results: Twelve different cancer types, representing 5,647 samples, contained at least a 20% alteration frequency of the five-gene LBI signature. The frequency of alteration ranged from 38.3% to 19.8%. Within the LBI signature, PLEC was the most commonly altered followed by LAMB3, ITGB4, ITGA3, and SYNE3 across all twelve cancer types. Within cancer types, there was little overlap of the individual amplified genes from each sample, suggesting different specific amplicons may alter the LBI adhesion structures. Of the twelve cancer types, overall survival was altered by CNA presence in bladder urothelial carcinoma (p=0.0143*) and cervical squamous cell carcinoma and endocervical adenocarcinoma (p=0

  16. EphB2 promotes cervical cancer progression by inducing epithelial-mesenchymal transition.

    PubMed

    Gao, Qing; Liu, Wei; Cai, Jiangyi; Li, Mu; Gao, Yane; Lin, Wenjing; Li, Zongfang

    2014-02-01

    EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various cancers and plays an important role in tumor progression. However, the expression and functions of EphB2 in cervical cancer remain unknown. In this study, we performed immunohistochemistry in clinical cervical specimens and found that EphB2 was overexpressed in the cervical cancer specimens, and its expression correlated with cancer progression. The percentage of EphB2-positive cells increased gradually from 28% in the normal cervix to 40% in high-grade squamous intraepithelial lesions, and ultimately to 69.8% in squamous cell carcinomas (P < .05). We overexpressed EphB2 in HeLa cells and silenced EphB2 in cervical cancer (C33A) cells, which expressed low and high levels of EphB2, respectively. Exogenous EphB2 promoted cell migration, invasion, and an epithelial-mesenchymal transition (EMT) signature, which is a complex process that occurs during organogenesis and cancer metastasis, whereas EphB2 silencing had the opposite effect (P < .05). Furthermore, HeLa cells with exogenous EphB2 exhibited a stem cell-like state that promoted tumorsphere formation in vitro and exhibited tumorigenesis potential in vivo (P < .05), whereas EphB2 silencing in C33A cells inhibited these stem cell properties (P < .05). In addition, we investigated the intracellular signaling pathways in cervical cancer and found that R-Ras expression correlated positively with EphB2 in clinical samples, and its activity was regulated by EphB2 in cervical cancer. These findings demonstrate that EphB2 plays an important role in cervical cancer progression by orchestrating an EMT program through R-Ras activation.

  17. Interplay Between Transcription Factors and MicroRNAs Regulating Epithelial-Mesenchymal Transitions in Colorectal Cancer.

    PubMed

    Kaller, Markus; Hermeking, Heiko

    2016-01-01

    The epithelial-mesenchymal-transition (EMT) represents a morphogenetic program involved in developmental processes such as gastrulation and neural crest formation. The EMT program is co-opted by epithelial tumor cells and endows them with features necessary for spreading to distant sites, such as invasion, migration, apoptosis resistance and stemness. Thereby, EMT facilitates metastasis formation and therapy resistance. A growing number of transcription factors has been implicated in the regulation of EMT. These include EMT-inducing transcription factors (EMT-TFs), the most prominent being SNAIL, SLUG, ZEB1, ZEB2 and TWIST, and negative regulators of EMT, such as p53. Furthermore, a growing number of microRNAs, such as members of the miR-200 and miR-34 family, have been characterized as negative regulators of EMT. EMT-TFs and microRNAs, such as ZEB1/2 and miR-200 or SNAIL and miR-34, are often engaged in double-negative feedback loops forming bistable switches controlling the transitions from epithelial to the mesenchymal cell states. Within this chapter, we will provide a comprehensive overview over the transcription factors and microRNAs that have been implicated in the regulation of EMT in colorectal cancer. Furthermore, we will highlight the regulatory connections between EMT-TFs and miRNAs to illustrate common principles of their interaction that regulate EMTs. PMID:27573895

  18. Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-03-17

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  19. Vitamin D receptor, UVR, and skin cancer: a potential protective mechanism.

    PubMed

    Bikle, Daniel D

    2008-10-01

    More than 1 million skin cancers occur annually in the United States--of which 80% are basal-cell carcinoma (BCC), 16% are squamous-cell carcinoma (SCC), and 4% are melanomas--making skin cancer by far the most common cancer (Greenlee et al., 2001). UVR is the major etiologic agent. UV wavelengths shorter than 280 nm (UVC) are absorbed by the ozone layer and do not reach the earth. UV wavelengths longer than 320 nm (UVA) have limited ability to induce the characteristic mutations in DNA seen in epidermal cancers. Thus, UVB, with a spectrum between 280 and 320 nm, is the major cause of these cancers (Freeman et al., 1989), but this is the same spectrum required for vitamin D production in the skin. Is there a link?

  20. Worry about skin cancer mediates the relation of perceived cancer risk and sunscreen use.

    PubMed

    Kiviniemi, Marc T; Ellis, Erin M

    2014-12-01

    Preventive health behaviors are believed to be motivated in part by a person's perception of risk for a particular health problem. Risk contains a cognitive component, beliefs about the chances of a health problem occurring, and an affective component, fear or worry about the health problem. Although both have been shown to influence behavior, the nature of their interrelation as an influence on behavior has not been examined. Data from the 2005 Health Information National Trends Survey, a US nationally-representative telephone survey was analyzed. Participants reported perceived absolute and comparative risk for skin cancer, feelings of worry about skin cancer, and sunscreen use behavior. Analyses examined main effects models for the relation between perceived risk, worry, and sunscreen use, as well as both moderated and mediated models. For both absolute and comparative risk, the relation between cognitively-based perceived risk for skin cancer and sunscreen use was fully mediated by feelings of worry, as evidenced by significant direct effects of worry (bs > 0.046, ps < 0.01) and indirect effects of risk through worry (bs > 0.19, ps < 0.01). When worry was included in the models, direct effects of risk perceptions were non-significant (bs < 0.11, ps < 0.10). No evidence was found for moderated effects of worry on the relation between risk and behavior. While cognitive risk appraisals do influence decision making and may be addressed by interventions, these findings demonstrate that affectively-based risk components play a key role in behavior regulation. Affectively-based risk might be an effective target for interventions and should be incorporated more fully in decision-making models.

  1. Alterations of mitogenic responses of mononuclear cells by arsenic in arsenical skin cancers.

    PubMed

    Yu, H S; Chang, K L; Wang, C M; Yu, C L

    1992-11-01

    We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non-arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non-endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 x 10(-7) M) was added to PHA-stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology--arsenic. Arsenic seems to play a role as a co-stimulant of PHA similar to interleukin-1.

  2. [Disappearance of the ozone layer and skin cancer: attempt at risk assessment].

    PubMed

    Schaart, F M; Garbe, C; Orfanos, C E

    1993-02-01

    The increased incidence of skin cancer recorded worldwide is alarming. The incidence of malignant melanoma has doubled in Germany every 10-15 years during recent decades, for example, as documented in the population-based cancer registry of the Saarland. In 1989, the incidence was 8.3 cases/100,000 inhabitants a year equally for both sexes. Non-melanoma skin cancer (basal cell and squamous cell carcinomas) showed a similar dramatic increase like melanoma and ranged in second place in the Saarland Cancer Registry in 1989, exceeded in men only by lung cancers and in women only by breast cancer. Their incidence was 93.4/100,000 in men and 55.8/100,000 in women. Epidemiological studies worldwide revealed a correlation between the increase of skin cancer incidence and UV exposure in white populations, and Caucasians living in regions near the equator are predominantly affected by this increase. Recently, incidence values for non-melanoma skin cancer in the USA were reported to be 232/100,000, whereas, for Queensland/Australia even numbers as high as 2398/100,000 (males) and 1908/100,000 (females) have been published. So far, the increase in skin cancer incidence has been related to changes in leisure time habits with increasing UV exposure. In this paper, an attempt is made to estimate any additional future risks for the development of skin cancer as a result of increasing UV radiation caused by stratospheric ozone depletion. Its reduction has been reported to be 3% over large areas of the globe (65 degrees North to 65 degrees South) according to the latest study of the United Nations Environment Programme.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 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

  4. 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.

  5. Gigapixel photography for skin cancer surveillance: a novel alternative to total-body photography.

    PubMed

    Mikailov, Anar; Blechman, Adam

    2013-11-01

    There is substantial evidence supporting the use of cutaneous imaging in combination with standard total-body skin examinations for early detection and treatment of melanoma. In the last 2 decades, total-body photography (TBP) has been widely used in combination with standard total-body skin examinations for active skin cancer surveillance with proven clinical utility; however, the groundbreaking image detail provided by gigapixel photography (GP) could improve dermatologists' ability to monitor suspicious lesions and therefore could serve a critical role in supplementing traditional total-body skin examinations for skin cancer surveillance. Although it has been successfully implemented in other fields, future studies are required to determine the effectiveness of GP in dermatology.

  6. 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

  7. Interferometric detection of early markers for epithelial ovarian cancer and prognostic markers for acute lymphocytic leukemia

    NASA Astrophysics Data System (ADS)

    O'Neil, P.; Zhao, M.; Wang, X.; Nolte, D. D.

    2010-02-01

    We are developing fluorescence-free interferometric biosensors for the early detection of epithelial ovarian cancer (EOC) and prognosis of acute lymphocytic leukemia (ALL). We can detect potential early markers for EOC (CA125, human epididymus protein 4, osteopontin) spiked into serum as well as elevated CA125 in EOC patient serum. For ALL prognosis we are focusing on three intracellular protein markers (p73, p57/Kip2, and p15/Ink4b), the down-regulation of any two being indicative of a more aggressive cancer. We have detected p15 and p57 spiked into buffer and are preparing to test positive and negative control lysates from bone marrow biopsies.

  8. The ubiquitin–proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer

    PubMed Central

    2012-01-01

    Epithelial to Mesenchymal transition (EMT) in cancer, a process permitting cancer cells to become mobile and metastatic, has a signaling hardwire forged from development. Multiple signaling pathways that regulate carcinogenesis enabling characteristics in neoplastic cells such as proliferation, resistance to apoptosis and angiogenesis are also the main players in EMT. These pathways, as almost all cellular processes, are in their turn regulated by ubiquitination and the Ubiquitin-Proteasome System (UPS). Ubiquitination is the covalent link of target proteins with the small protein ubiquitin and serves as a signal to target protein degradation by the proteasome or to other outcomes such as endocytosis, degradation by the lysosome or specification of cellular localization. This paper reviews signal transduction pathways regulating EMT and being regulated by ubiquitination. PMID:22827778

  9. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers

    PubMed Central

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-01-01

    Abstract Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients’ survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76–2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58–2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75–2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05–3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41–2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46–2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42–4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30–4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46–3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40–5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95

  10. A Human Espophageal Epithelial Cell Model for Study of Radiation Induced Cancer and DNA Damage Repair

    NASA Technical Reports Server (NTRS)

    Huff, Janice L.; Patel, Zarana S.; Hada, Megumi; Cucinotta, Francis A.

    2008-01-01

    For cancer risk assessment in astronauts and for countermeasure development, it is essential to understand the molecular mechanisms of radiation carcinogenesis and how these mechanisms are influenced by exposure to the types of radiation found in space. We are developing an in vitro model system for the study of radiation-induced initiation and progression of esophageal carcinoma, a type of cancer found to have a significant enhancement in incidence in the survivors of the atomic bomb detonations in Japan. Here we present the results of our preliminary characterization of both normal and hTERT immortalized esophageal epithelial cells grown in 2-dimensional culture. We analyzed DNA repair capacity by measuring the kinetics of formation and loss of - H2AX foci following radiation exposure. Additionally, we analyzed induction of chromosomal aberrations using 3-color fluorescence in situ hybridization (FISH). Data were generated using both low LET (gamma rays) and high LET ions (1000 MeV/nucleon iron).

  11. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells.

    PubMed

    Jeon, Min Ji; Kim, Won Gu; Lim, Seonhee; Choi, Hyun-Jeung; Sim, Soyoung; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2016-01-01

    The naturally occurring short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant which is clinically used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. In this study, we evaluate the effects of ALA on thyroid cancer cell proliferation, migration and invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62 and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2 and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways in thyroid cancer cells. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for treatment of advanced thyroid cancer, possibly as an adjuvant therapy with other systemic therapeutic agents.

  12. Overexpression of piRNA Pathway Genes in Epithelial Ovarian Cancer

    PubMed Central

    Lim, Shu Ly; Ricciardelli, Carmela; Oehler, Martin K.; De Arao Tan, Izza M. D.; Russell, Darryl; Grützner, Frank

    2014-01-01

    The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and

  13. Genotypes of cancer stem cells characterized by epithelial-to-mesenchymal transition and proliferation related functions.

    PubMed

    Hsu, Chueh-Lin; Chung, Feng-Hsiang; Chen, Chih-Hao; Hsu, Tzu-Ting; Liu, Szu-Mam; Chung, Dao-Sheng; Hsu, Ya-Fen; Chen, Chien-Lung; Ma, Nianhan; Lee, Hoong-Chien

    2016-01-01

    Cancer stem cells (CSCs), or cancer cells with stem cell-like properties, generally exhibit drug resistance and have highly potent cancer inducing capabilities. Genome-wide expression data collected at public repositories over the last few years provide excellent material for studies that can lead to insights concerning the molecular and functional characteristics of CSCs. Here, we conducted functional genomic studies of CSC based on fourteen PCA-screened high quality public CSC whole genome gene expression datasets and, as control, four high quality non-stem-like cancer cell and non-cancerous stem cell datasets from the Gene Expression Omnibus database. A total of 6,002 molecular signatures were taken from the Molecular Signatures Database and used to characterize the datasets, which, under two-way hierarchical clustering, formed three genotypes. Type 1, consisting of mainly glia CSCs, had significantly enhanced proliferation, and significantly suppressed epithelial-mesenchymal transition (EMT), related functions. Type 2, mainly breast CSCs, had significantly enhanced EMT, but not proliferation, related functions. Type 3, composed of ovarian, prostate, and colon CSCs, had significantly suppressed proliferation related functions and mixed expressions on EMT related functions. PMID:27597445

  14. Genotypes of cancer stem cells characterized by epithelial-to-mesenchymal transition and proliferation related functions

    PubMed Central

    Hsu, Chueh-Lin; Chung, Feng-Hsiang; Chen, Chih-Hao; Hsu, Tzu-Ting; Liu, Szu-Mam; Chung, Dao-Sheng; Hsu, Ya-Fen; Chen, Chien-Lung; Ma, Nianhan; Lee, Hoong-Chien

    2016-01-01

    Cancer stem cells (CSCs), or cancer cells with stem cell-like properties, generally exhibit drug resistance and have highly potent cancer inducing capabilities. Genome-wide expression data collected at public repositories over the last few years provide excellent material for studies that can lead to insights concerning the molecular and functional characteristics of CSCs. Here, we conducted functional genomic studies of CSC based on fourteen PCA-screened high quality public CSC whole genome gene expression datasets and, as control, four high quality non-stem-like cancer cell and non-cancerous stem cell datasets from the Gene Expression Omnibus database. A total of 6,002 molecular signatures were taken from the Molecular Signatures Database and used to characterize the datasets, which, under two-way hierarchical clustering, formed three genotypes. Type 1, consisting of mainly glia CSCs, had significantly enhanced proliferation, and significantly suppressed epithelial-mesenchymal transition (EMT), related functions. Type 2, mainly breast CSCs, had significantly enhanced EMT, but not proliferation, related functions. Type 3, composed of ovarian, prostate, and colon CSCs, had significantly suppressed proliferation related functions and mixed expressions on EMT related functions. PMID:27597445

  15. Hyperglycemia Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer via Hydrogen Peroxide

    PubMed Central

    Jiang, Zhengdong

    2016-01-01

    Diabetes mellitus (DM) and pancreatic cancer are intimately related, as approximately 85% of patients diagnosed with pancreatic cancer have impaired glucose tolerance or even DM. Our previous studies have indicated that high glucose could promote the invasive and migratory abilities of pancreatic cancer cells. We therefore explored the underlying mechanism that hyperglycemia modulates the metastatic potential of pancreatic cancer. Our data showed that streptozotocin- (STZ-) treated diabetic nude mice exhibit larger tumor size than that of the euglycemic mice. The number of nude mice that develop liver metastasis or ascites is much more in the STZ-treated group than that in the euglycemic group. Hyperglycemic mice contain a higher plasma H2O2-level than that from euglycemic mice. The injection of polyethylene glycol-conjugated catalase (PEG-CAT), an H2O2 scavenger, may reverse hyperglycemia-induced tumor metastasis. In addition, hyperglycemia could also modulate the expression of epithelial-mesenchymal transition- (EMT-) related factors in pancreatic tumor tissues, as the E-cadherin level is decreased and the expression of mesenchymal markers N-cadherin and vimentin as well as transcription factor snail is strongly increased. The injection of PEG-CAT could also reverse hyperglycemia-induced EMT. These results suggest that the association between hyperglycemia and poor prognosis of pancreatic cancer can be attributed to the alterations of EMT through the production of hydrogen peroxide. PMID:27433288

  16. Paeoniflorin prevents hypoxia-induced epithelial-mesenchymal transition in human breast cancer cells.

    PubMed

    Zhou, Zhenyu; Wang, Shunchang; Song, Caijuan; Hu, Zhuang

    2016-01-01

    Paeoniflorin (PF) is a monoterpene glycoside extracted from the root of Paeonia lactiflora Pall. Previous studies have demonstrated that PF inhibits the growth, invasion, and metastasis of tumors in vivo and in vitro. However, the effect of PF on hypoxia-induced epithelial-mesenchymal transition (EMT) in breast cancer cells remains unknown. Therefore, the objective of this study was to investigate the effect of PF on hypoxia-induced EMT in breast cancer cells, as well as characterize the underlying mechanism. The results presented in this study demonstrate that PF blocks the migration and invasion of breast cancer cells by repressing EMT under hypoxic conditions. PF also significantly attenuated the hypoxia-induced increase in HIF-1α level. Furthermore, PF prevented hypoxia-induced expression of phosphorylated PI3K and Akt in MDA-MB-231 cells. In conclusion, PF prevented hypoxia-induced EMT in breast cancer cells by inhibiting HIF-1α expression via modulation of PI3K/Akt signaling pathway. This finding provides evidence that PF can serve as a therapeutic agent for the treatment of breast cancer. PMID:27175085

  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.

  18. 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

  19. 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

  20. The effect of an arginine-glycine-aspartic acid peptide and hyaluronate synthetic matrix on epithelialization of meshed skin graft interstices.

    PubMed

    Cooper, M L; Hansbrough, J F; Polarek, J W

    1996-01-01

    Keratinocytes and fibroblasts interact with proteins of the extracellular matrix such as fibronectin and vitronectin through RGD (arginine-glycine-aspartic acid) cell-attachment sequences. This study evaluated the ability of a provisional synthetic matrix composed of an RGD peptide and hyaluronic acid to accelerate the epithelialization of the interstices of meshed, human, split-thickness skin when placed on full-thickness wounds of athymic mice. Full-thickness skin defects, sparing the panniculus carnosus, were created on athymic mice and 3:1 meshed, human skin was placed on them. The grafts had four central, isolated interstices, which epithelialized by migration of human keratinocytes. Conditions were either the addition to the wound of the synthetic matrix or a matrix of hyaluronic acid alone. The time to closure of the graft interstices was decreased (p < 0.02) in the wounds treated with the RGD peptide-hyaluronic acid provisional matrix. The resultant epithelium of the closed interstices was significantly thicker 8 days after surgery for the RGD-treated wounds. Basement membrane proteins (laminin and type IV collagen) were also found to be present at the dermoepidermal junction earlier in the RGD-treated wounds. These results imply that use of the RGD peptide conjugate to effect cell-matrix interactions may have clinical significance in the field of wound healing.