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. Skin Cancer

    MedlinePlus

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

  3. [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. PMID:25687945

  4. 6 Common Cancers - Skin Cancer

    MedlinePlus

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

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. 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) ...

  9. 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) ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. Squamous cell skin cancer

    MedlinePlus

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

  14. Skin Cancer in Skin of Color

    PubMed Central

    Bradford, Porcia T.

    2009-01-01

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

  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. Skin cancer and photoaging in ethnic skin.

    PubMed

    Halder, Rebat M; Ara, Collette J

    2003-10-01

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

  17. 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 ...

  18. Skin Cancer Foundation

    MedlinePlus

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

  19. Skin Cancer Prevention

    MedlinePlus

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

  20. Skin Cancer Screening

    MedlinePlus

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

  1. Drugs Approved for Skin Cancer

    MedlinePlus

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

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

    MedlinePlus

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

  3. Skin cancer in skin of color.

    PubMed

    Bradford, Porcia T

    2009-01-01

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

  4. Epithelial ovarian cancer: An overview

    PubMed Central

    Desai, Arpita; Xu, Jingyao; Aysola, Kartik; Qin, Yunlong; Okoli, Chika; Hariprasad, Ravipati; Chinemerem, Ugorji; Gates, Candace; Reddy, Avinash; Danner, Omar; Franklin, Geary; Ngozi, Anachebe; Cantuaria, Guilherme; Singh, Karan; Grizzle, William; Landen, Charles; Partridge, Edward E; Rice, Valerie Montgomery; Reddy, E Shyam P; Rao, Veena N

    2014-01-01

    Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions. PMID:25525571

  5. Skin Cancers of the Feet

    MedlinePlus

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

  6. Ultraviolet radiation and skin cancer.

    PubMed

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

    2010-09-01

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

  7. Discovery – Preventing Skin Cancer

    Cancer.gov

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

  8. Drugs Approved for Skin Cancer

    Cancer.gov

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

  9. Epithelial deletion of podoplanin is dispensable for re-epithelialization of skin wounds.

    PubMed

    Baars, Sebastian; Bauer, Christine; Szabowski, Sibylle; Hartenstein, Bettina; Angel, Peter

    2015-10-01

    The mucin-like transmembrane protein podoplanin (PDPN) is prominently represented in tumor-associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain-of-function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss-of-function approach by generating a novel transgenic mouse line with keratinocyte-specific podoplanin deficiency. Performing cutaneous full-thickness excisional wounds to examine re-epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN-deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate-limiting for re-epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology. PMID:26121181

  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. 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 ...

  12. 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 ...

  13. [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

  14. Skin cancer prevention and screening.

    PubMed

    Holm, Richard P

    2015-01-01

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

  15. 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) ...

  16. 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) ...

  17. 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.

  18. Ultraviolet Light and Skin Cancer in Athletes

    PubMed Central

    Harrison, Shannon C.; Bergfeld, Wilma F.

    2009-01-01

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

  19. Epithelial-Mesenchymal Transition and Breast Cancer.

    PubMed

    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

  20. 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

  1. Folate in Skin Cancer Prevention

    PubMed Central

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

    2013-01-01

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

  2. Epithelial antimicrobial defence of the skin and intestine

    PubMed Central

    2012-01-01

    Surface tissues of the body such as the skin and intestinal tract are in direct contact with the external environment and are thus continuously exposed to large numbers of microorganisms. To cope with the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins that directly kill or inhibit the growth of microorganisms. In this Review, we highlight new advances in our understanding of how epithelial antimicrobial proteins protect against pathogens and contribute to microbiota–host homeostasis at the skin and gut mucosae. Further, we discuss recent insights into the regulatory mechanisms that control antimicrobial protein expression. Finally, we consider how impaired antimicrobial protein expression and function can contribute to disease. PMID:22728527

  3. 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 ...

  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. Skin Cancer in the Crosshairs

    PubMed Central

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

    2015-01-01

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

  6. Minced Skin for Tissue Engineering of Epithelialized Subcutaneous Tunnels

    PubMed Central

    Fossum, Magdalena; Zuhaili, Baraa; Hirsch, Tobias; Spielmann, Malte; Reish, Richard G.; Mehta, Priyesh

    2009-01-01

    We used minced, autologous skin for neoepithelialization of surgically created subcutaneous tunnels in a large animal model. Partial-thickness skin grafts were harvested from the back region of five 50–60 kg Yorkshire pigs. The skin was minced to 0.8 × 0.8 × 0.3 mm particles. Silicone-latex tubes were covered with fibrin, rolled in minced skin, and placed in subcutaneous tunnels created in the abdominal area. For comparison, single cell suspensions of keratinocytes and fibroblasts in fibrin or fibrin only were transplanted on tubes. Tunnels were extracted after 14, 21, and 28 days for microscopic evaluation. All tubes transplanted with minced skin particles showed neoepithelialization. The epithelium was stratified and differentiated after 2 weeks in vivo, and the stratum corneum was directed toward the implanted tube. No epithelium formed from tubes transplanted with single cell suspensions, and only sparse keratinocytes could be detected by serial sectioning and immunostaining on day 14, but not later. No epithelial lining was found in tunnels with fibrin-only-coated tubes. Epithelial cysts could be found the first 2 weeks after transplantation in the minced skin group but not later. In conclusion, a minced skin technique could serve as a potential source for tissue engineering of tubular conduits for reconstructive purposes of the urethra and for cutaneous stomas for bladder catheterization, or intestinal irrigations. The method would have the advantage of being simple and expeditious and not requiring in vitro culturing. PMID:19292681

  7. 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

  8. Skin cancer in the elderly

    SciTech Connect

    Pollack, S.V.

    1987-11-01

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

  9. Climate change and skin cancer.

    PubMed

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

    2002-05-01

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

  10. [Skin cancers and environmental factors].

    PubMed

    Autier, P

    1998-09-01

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

  11. For Better Skin Cancer Checks, Partner Up

    MedlinePlus

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

  12. 'Sunscreen' Gene May Guard Against Skin Cancer

    MedlinePlus

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

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

    PubMed

    Hensler, Sabine; Mueller, Margareta M

    2013-01-01

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

  14. 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)

  15. Review - Skin cancer: Etiology and management.

    PubMed

    Qadir, Muhammad Imran

    2016-05-01

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

  16. Hedgehog signaling in skin cancers

    PubMed Central

    Li, Chengxin; Chi, Sumin; Xie, Jingwu

    2011-01-01

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

  17. 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. |

  18. 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

  19. 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

  20. 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 ...

  1. [The molecular biology of epithelial ovarian cancer].

    PubMed

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research. PMID:23238064

  2. Epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    Huang, Lei; Wu, Ruo-Lin; Xu, A-Man

    2015-01-01

    Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-β, Wnt/β-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID:26807164

  3. Defining a tissue stem cell-driven Runx1/Stat3 signalling axis in epithelial cancer

    PubMed Central

    Scheitz, Cornelia Johanna Franziska; Lee, Tae Seung; McDermitt, David James; Tumbar, Tudorita

    2012-01-01

    Cancers and tissue stem cells (SCs) share similar molecular pathways for their self-renewal and differentiation. The race is on to identify unique pathways to specifically target the cancer, while sparing normal SCs. Here, we uncover the transcription factor Runx1/AML1, a known haematopoietic and leukaemia factor, albeit dispensable for normal adult SC homeostasis, as being important for some mouse and human epithelial cancers. We implicate Runx1 as a SC-intrinsic gene in mouse hair follicle and oral epithelia by genetic lineage tracing in adulthood. Runx1-expressing SCs, but not other cells that ectopically upregulate Runx1 by injury and inflammation, are at the skin tumour origin. Runx1 loss impairs tumour initiation and maintenance and the growth of oral, skin, and ovarian epithelial human cancer cells. Runx1 stimulates Stat3 signalling via direct transcriptional repression of SOCS3 and SOCS4 and this is essential for cancer cell growth. Thus, Runx1 is a broader epithelial SC and cancer factor than previously recognized, and qualifies as an attractive potential target for both prevention and therapy of several epithelial cancers. PMID:23034403

  4. Non-melanoma skin cancer.

    PubMed

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

    2016-02-01

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

  5. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  6. Skin cancer - an overview for dentists.

    PubMed

    Steel, B J

    2014-05-01

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

  7. Downregulation of miR-205 in migrating epithelial tongue facilitates skin wound re-epithelialization by derepressing ITGA5.

    PubMed

    Wang, Tao; Zhao, Na; Long, Shuang; Ge, Lan; Wang, Aiping; Sun, Huiqin; Ran, Xinze; Zou, Zhongmin; Wang, Junping; Su, Yongping

    2016-08-01

    Keratinocyte migration is essential for re-epithelialization during skin wound healing, but the molecular mechanisms regulating this cellular response remain to be completely clarified. Here we show that keratinocyte-specific miR-205 is significantly downregulated in the leading edge of the migrating epithelial tongue after skin injury in mice. In HaCaT keratinocytes, miR-205 could be downregulated by TGF-β1 stimulation. And similar to the effect of TGF-β1, miR-205 knockdown could promote keratinocyte migration in wound scratch model in vitro. Furthermore, topical inhibition of miR-205 by administrating Pluronic gel containing antagomir-205 could accelerate re-epithelialization in mouse skin wound model in vivo. Moreover, we identified integrin alpha 5 (ITGA5) as one key functional miR-205 target in the re-epithelialization process and epidermal downregulation of miR-205 may desilence ITGA5 to promote keratinocyte migration. And knockdown of ITGA5 would abolish the pro-migratory effects of miR-205 inhibition in vitro. What's more, we found dysregulation of miR-205 and its target ITGA5 in epidermis of clinical chronic wound samples with persistence of high level miR-205 and absence of ITGA5. Our findings indicate that downregulation of miR-205 in the leading migrating keratinocytes is critical for re-epithelialization and miR-205 may be a potential therapeutic target for chronic wounds. PMID:27169579

  8. 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

  9. 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 ...

  10. 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

  11. 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 ...

  12. Global controversies and advances in skin cancer.

    PubMed

    Baldwin, Louise; Dunn, Jeff

    2013-01-01

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

  13. Climate change and human skin cancer.

    PubMed

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

    2008-06-01

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

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

    PubMed

    Siegel, Victoria; Stone, Alicia; George, Anna

    2016-01-01

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

  15. Noncontraceptive estrogen use and epithelial ovarian cancer.

    PubMed

    Kaufman, D W; Kelly, J P; Welch, W R; Rosenberg, L; Stolley, P D; Warshauer, M E; Lewis, J; Woodruff, J; Shapiro, S

    1989-12-01

    The relation of noncontraceptive estrogen use to epithelial ovarian cancer was evaluated in a case-control study conducted in hospitals mainly in the northeastern United States. There were 377 cases diagnosed within the year before hospital admission and 2,030 hospital controls; data were collected by interview in the hospital. Compared with women who never took noncontraceptive estrogens, the overall relative risk estimate for women whose estrogen use lasted at least one year and was not combined with progestogens or testosterone was 1.2 (95% confidence interval (CI) 0.8-1.9), after taking into account risk factors for ovarian cancer. There were 55 cases of the endometrioid, clear cell, or malignant mixed mesodermal cell type; the corresponding relative risk estimate was 0.9 (95% CI 0.3-3.0). There were 26 cases of undifferentiated cell type, with a relative risk estimate of 3.6 (95% CI 1.2-11). Relative risk estimates were similar in a subset of the cases (57%) for which pathology slides were reviewed. For estrogen use of long duration, use of high-dose preparations, or use in the distant past, the relative risk estimates were not significantly different from 1.0. The estimates were elevated for some categories of use, but not consistently--for example, for an interval of 5-9 years since estrogen use began (relative risk (RR) = 2.7), but not after shorter or longer intervals, and for use of conjugated estrogens with a dose of 0.3 mg (RR = 3.2) or 1.25 mg (RR = 2.4), but not for doses of 0.625 mg or 2.5 mg. The relative risk estimate was also elevated for use by nulliparous women (RR = 2.4). The results suggest that, overall, noncontraceptive estrogen use is not associated with the risk of epithelial ovarian cancer. Furthermore, our data do not support the hypothesis that estrogens increase the risk of endometrioid ovarian cancer. The elevated estimates could be due to multiple stratification of the data, but they should be explored in further studies, given the

  16. 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…

  17. 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.

  18. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    PubMed Central

    Sölétormos, György; Duffy, Michael J.; Othman Abu Hassan, Suher; Verheijen, René H.M.; Tholander, Bengt; Bast, Robert C.; Gaarenstroom, Katja N.; Sturgeon, Catharine M.; Bonfrer, Johannes M.; Petersen, Per Hyltoft; Troonen, Hugo; CarloTorre, Gian; Kanty Kulpa, Jan; Tuxen, Malgorzata K.; Molina, Raphael

    2016-01-01

    Objective To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. Methods Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. Results Because of its low sensitivity (50–62% for early stage epithelial ovarian cancer) and limited specificity (94–98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended for the differential diagnosis of a pelvic mass. Because human epididymis protein 4 has been reported to have superior specificity to CA125, especially in premenopausal women, it may be considered either alone or as part of the risk of ovarian malignancy algorithm, in the differential diagnosis of pelvic masses, especially in such women. CA125 should be used to monitor response to first-line chemotherapy using the previously published criteria of the Gynecological Cancer Intergroup, that is, at least a 50% reduction of a pretreatment sample of 70 kU/L or greater. The value of CA125 in posttherapy surveillance is less clear. Although a prospective randomized trial concluded that early administration of chemotherapy based on increasing CA125 levels had no effect on survival, European Group on Tumor Markers state that monitoring with CA125 in this situation should occur, especially if the patient is a candidate for secondary cytoreductive surgery. Conclusions At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin. PMID:26588231

  19. 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 ...

  20. Evaluating the use of optical coherence tomography for the detection of epithelial cancers in vitro

    NASA Astrophysics Data System (ADS)

    Smith, Louise E.; Hearnden, Vanessa; Lu, Zenghai; Smallwood, Rod; Hunter, Keith D.; Matcher, Stephen J.; Thornhill, Martin H.; Murdoch, Craig; MacNeil, Sheila

    2011-11-01

    Optical coherence tomography (OCT) is a noninvasive imaging methodology that is able to image tissue to depths of over 1 mm. Many epithelial conditions, such as melanoma and oral cancers, require an invasive biopsy for diagnosis. A noninvasive, real-time, point of care method of imaging depth-resolved epithelial structure could greatly improve early diagnosis and long-term monitoring in patients. Here, we have used tissue-engineered (TE) models of normal skin and oral mucosa to generate models of melanoma and oral cancer. We have used these to determine the ability of OCT to image epithelial differences in vitro. We report that while in vivo OCT gives reasonable depth information for both skin and oral mucosa, in vitro the information provided is less detailed but still useful. OCT can provide reassurance on the development of TE models of skin and oral mucosa as they develop in vitro. OCT was able to detect the gross alteration in the epithelium of skin and mucosal models generated with malignant cell lines but was less able to detect alteration in the epithelium of TE models that mimicked oral dysplasia or, in models where tumor cells had penetrated into the dermis.

  1. 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.

  2. 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 ...

  3. In vivo multiphoton tomography of skin cancer

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  4. 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

  5. Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer

    PubMed Central

    Goruppi, Sandro; Dotto, G. Paolo

    2013-01-01

    Multifocal and recurrent epithelial tumors, originating from either dormant or de novo cancer cells, are major causes of morbidity and mortality. The age-dependent increase of cancer incidence has long been assumed to result from the sequential accumulation of cancer driving or facilitating mutations with induction of cellular senescence as a protective mechanism. However, recent evidence suggests that the initiation and development of epithelial cancer results from a close interplay with its altered tissue microenvironment, with chronic inflammation, stromal senescence, autophagy, and activation of cancer associated fibroblasts (CAFs) playing possible primary roles. We will discuss recent progress in these areas, and highlight how this understanding may be used for devising novel preventive and therapeutic approaches to the epithelial cancer problem. PMID:24074947

  6. Cell volume regulation in epithelial physiology and cancer

    PubMed Central

    Pedersen, Stine F.; Hoffmann, Else K.; Novak, Ivana

    2013-01-01

    The physiological function of epithelia is transport of ions, nutrients, and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume regulation both rely on the spatially and temporally coordinated function of ion channels and transporters. In healthy epithelia, specific ion channels/transporters localize to the luminal and basolateral membranes, contributing to functional epithelial polarity. In pathophysiological processes such as cancer, transepithelial and cell volume regulatory ion transport are dys-regulated. Furthermore, epithelial architecture and coordinated ion transport function are lost, cell survival/death balance is altered, and new interactions with the stroma arise, all contributing to drug resistance. Since altered expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed. PMID:24009588

  7. Topical therapies for skin cancer and actinic keratosis.

    PubMed

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

    2015-09-18

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

  8. Clinical implications of epithelial cell plasticity in cancer progression.

    PubMed

    Aparicio, Luis A; Blanco, Moisés; Castosa, Raquel; Concha, Ángel; Valladares, Manuel; Calvo, Lourdes; Figueroa, Angélica

    2015-09-28

    In the last few years, the role of epithelial cell plasticity in cancer biology research has gained increasing attention. This concept refers to the ability of the epithelial cells to dynamically switch between different phenotypic cellular states. This programme is particularly relevant during the epithelial-to-mesenchymal transition (EMT) in cancer progression. During colonization, epithelial cells first activate the EMT programme to disseminate from a primary tumour to reach a distant tissue site. During this process, cells are transported into the circulation and are able to escape the immune system of the host. Then, a reverse process called mesenchymal-to-epithelial transition (MET) occurs on cells that settle in the distant organs. Although epithelial cell plasticity has an important impact on tumour biology, the clinical relevance of this concept remains to be recapitulated. In this review, we will update the current state of epithelial cell plasticity in cancer progression and its clinical implications for the design of therapeutic strategies, the acquisition of multidrug resistance, and future perspectives for the management of cancer patients. PMID:26099173

  9. 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.

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

    PubMed Central

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

    2016-01-01

    Summary Cellular senescence suppresses cancer by arresting cells at risk of 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. Furthermore, 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. PMID:15657080

  11. Generation of bioengineered feather buds on a reconstructed chick skin from dissociated epithelial and mesenchymal cells.

    PubMed

    Ishida, Kentaro; Mitsui, Toshiyuki

    2016-04-01

    Various kinds of in vitro culture systems of tissues and organs have been developed, and applied to understand multicellular systems during embryonic organogenesis. In the research field of feather bud development, tissue recombination assays using an intact epithelial tissue and mesenchymal tissue/cells have contributed to our understanding the mechanisms of feather bud formation and development. However, there are few methods to generate a skin and its appendages from single cells of both epithelium and mesenchyme. In this study, we have developed a bioengineering method to reconstruct an embryonic dorsal skin after completely dissociating single epithelial and mesenchymal cells from chick skin. Multiple feather buds can form on the reconstructed skin in a single row in vitro. The bioengineered feather buds develop into long feather buds by transplantation onto a chorioallantoic membrane. The bioengineered bud sizes were similar to those of native embryo. The number of bioengineered buds was increased linearly with the initial contact length of epithelial and mesenchymal cell layers where the epithelial-mesenchymal interactions occur. In addition, the bioengineered bud formation was also disturbed by the inhibition of major signaling pathways including FGF (fibroblast growth factor), Wnt/β-catenin, Notch and BMP (bone morphogenetic protein). We expect that our bioengineering technique will motivate further extensive research on multicellular developmental systems, such as the formation and sizing of cutaneous appendages, and their regulatory mechanisms. PMID:27019985

  12. An Update on Nonmelanoma Skin Cancer

    PubMed Central

    Patel, Rita V.; Frankel, Amylynne

    2011-01-01

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

  13. 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

  14. 'Sunscreen' Gene May Guard Against Skin Cancer

    MedlinePlus

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

  15. 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

  16. 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

  17. 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

  18. Phototoxic aptamers selectively enter and kill epithelial cancer cells

    PubMed Central

    Ferreira, Cátia S. M.; Cheung, Melissa C.; Missailidis, Sotiris; Bisland, Stuart; Gariépy, Jean

    2009-01-01

    The majority of cancers arise from malignant epithelial cells. We report the design of synthetic oligonucleotides (aptamers) that are only internalized by epithelial cancer cells and can be precisely activated by light to kill such cells. Specifically, phototoxic DNA aptamers were selected to bind to unique short O-glycan-peptide signatures on the surface of breast, colon, lung, ovarian and pancreatic cancer cells. These surface antigens are not present on normal epithelial cells but are internalized and routed through endosomal and Golgi compartments by cancer cells, thus providing a focused mechanism for their intracellular delivery. When modified at their 5′ end with the photodynamic therapy agent chlorin e6 and delivered to epithelial cancer cells, these aptamers exhibited a remarkable enhancement (>500-fold increase) in toxicity upon light activation, compared to the drug alone and were not cytotoxic towards cell types lacking such O-glycan-peptide markers. Our findings suggest that these synthetic oligonucleotide aptamers can serve as delivery vehicles in precisely routing cytotoxic cargoes to and into epithelial cancer cells. PMID:19103663

  19. 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

  20. 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.

  1. Cell-type-specific roles for COX-2 in UVB-induced skin cancer

    PubMed Central

    Herschman, Harvey

    2014-01-01

    In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

  2. Isolation of Cancer Epithelial Cells from Mouse Mammary Tumors

    PubMed Central

    Johnson, Sara; Chen, Hexin; Lo, Pang-Kuo

    2016-01-01

    The isolation of cancer epithelial cells from mouse mammary tumor is accomplished by digestion of the solid tumor. Red blood cells and other contaminates are removed using several washing techniques such that primary epithelial cells can further enriched. This procedure yields primary tumor cells that can be used for in vitro tissue culture, fluorescence-activated cell sorting (FACS) and a wide variety of other experiments (Lo et al., 2012).

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

    PubMed

    Saladi, Rao N; Persaud, Andrea N

    2005-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Photodynamic therapy for skin cancer

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

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

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

    ClinicalTrials.gov

    2016-07-29

    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

  7. Cyfip1 is a putative invasion suppressor in epithelial cancers

    PubMed Central

    Silva, Jose M.; Ezhkova, Elena; Silva, Javier; Heart, Stephen; Castillo, Mireia; Campos, Yolanda; Castro, Veronica; Bonilla, Felix; Cordon-Cardo, Carlos; Muthuswamy, Senthil K.; Powers, Scott; Fuchs, Elaine; Hannon, Gregory J.

    2009-01-01

    Summary Identification of bona fide tumor suppressors is often challenging because of the large number of alterations present in most human cancers. To evaluate candidates present within regions recurrently deleted in human cancers we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of Cyfip1 is commonly observed during invasion of epithelial tumors and it associated with poor prognosis in same tumor types. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene. PMID:19524508

  8. Epithelial cell cultures from normal and cancerous human tissues.

    PubMed

    Owens, R B; Smith, H S; Nelson-Rees, W A; Springer, E L

    1976-04-01

    Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal. PMID:176412

  9. 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.

  10. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer

    PubMed Central

    Ming, Mei; Han, Weinong; Zhao, Baozhong; Sundaresan, Nagalingam R.; Deng, Chu-Xia; Gupta, Mahesh; He, Yu-Ying

    2014-01-01

    SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer. Here we challenge this concept by presenting evidence that skin-specific deletion of SIRT6 in the mouse inhibits skin tumorigenesis. SIRT6 promoted expression of COX-2 by repressing AMPK signaling, thereby increasing cell proliferation and survival and in the skin epidermis. SIRT6 expression in skin keratinocytes was increased by exposure to UVB light through activation of the AKT pathway. Clinically, we found that SIRT6 was upregulated in human skin squamous cell carcinoma. Taken together, our results provide evidence that SIRT6 functions an oncogene in the epidermis and suggest greater complexity to its role in epithelial carcinogenesis. PMID:25320180

  11. 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.

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

    PubMed Central

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

    2014-01-01

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

  13. ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.

    PubMed

    Chang, Hsiao-Min; Huang, Wen-Yen; Lin, Sung-Jan; Huang, Wei-Chao; Shen, Chia-Rui; Mao, Wan-Yu; Shen, Chia-Ning

    2016-05-01

    The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing. PMID:26739701

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. EGEN-001 and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-08-11

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

  19. 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

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

    PubMed

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

    2013-02-01

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

  1. Skin manifestations associated with kidney cancer.

    PubMed

    Amin, Asim; Burgess, Earle F

    2016-06-01

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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Targeted Therapies in Epithelial Ovarian Cancer

    PubMed Central

    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer. PMID:24281034

  7. 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

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

    PubMed

    Palmirotta, Raffaele; Cives, Mauro; Della-Morte, David; Capuani, Barbara; Lauro, Davide; Guadagni, Fiorella; 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

  9. FYN promotes breast cancer progression through epithelial-mesenchymal transition.

    PubMed

    Xie, Ye-Gong; Yu, Yue; Hou, Li-Kun; Wang, Xin; Zhang, Bin; Cao, Xu-Chen

    2016-08-01

    FYN, one of the members of the Src family of kinases (SFKs), has been reported to be overexpressed in various types of cancers and correlated with cell motility and proliferation. However, the mechanism is still unclear. In the present study, we found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways. PMID:27349276

  10. 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

  11. Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells.

    PubMed

    Lu, Yan-Jie; Geng, Zhi-Jun; Sun, Xiao-Yan; Li, Yu-Hong; Fu, Xiao-Bing; Zhao, Xiang-Yang; Wei, Bo

    2015-10-01

    The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the β2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that β2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as α-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and β-catenin. Isoprenaline stimulation of β2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting β2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression. PMID:26253173

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

    PubMed

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

    2015-12-01

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

  13. Melanoma and other skin cancers in circumpolar areas.

    PubMed

    Oikarinen, A; Raitio, A

    2000-01-01

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

  14. Skin cancer screening in Okinawa, Japan.

    PubMed

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

    1999-04-01

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

  15. 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.

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

    PubMed

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

    2015-01-01

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

  17. 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

  18. Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin*

    PubMed Central

    Plichta, Jennifer K.; Droho, Steve; Curtis, Brenda J.; Patel, Parita; Gamelli, Richard L.; Radek, Katherine A.

    2014-01-01

    Objectives Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue. Design Experimental mouse scald burn injury. Setting University Research Laboratory. Subjects C57/Bl6 Male mice, 8–12 weeks old. Interventions To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn. Measurements and Main Results Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients. Conclusions These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs

  19. 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

  20. Surgical management of epithelial ovarian cancer.

    PubMed

    Salani, Ritu; Bristow, Robert E

    2012-03-01

    Ovarian cancer affects approximately 21,880 women and accounts for over 13,000 deaths annually in the United States. Although survival rates have improved over the past several decades, directly as a result of advances in chemotherapy and surgery, ovarian cancer continues to have high mortality rates. Understanding the multiple roles of surgery throughout the disease course is the focus of this review. PMID:22343231

  1. 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

    2016-03-31

    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

  2. Epithelial impedance analysis in experimentally induced colon cancer.

    PubMed Central

    Davies, R J; Joseph, R; Kaplan, D; Juncosa, R D; Pempinello, C; Asbun, H; Sedwitz, M M

    1987-01-01

    Epithelial impedance analysis was used to measure the alterations in resistance of the large bowel in a murine model of large bowel cancer. The technique was able to resolve the epithelial resistance from the total resistance of the bowel wall. A progressive decrease in resistance of the bowel epithelium occurs during carcinogenesis induced with dimethyhydrazine. About a 21% decrease in epithelial resistance from 22.0 +/- 1.3 omega.cm-2 to 17.5 +/- 1.1 omega cm-2 (p less than 0.025) was observed after 20 wk of carcinogen administration. The sensitivity of the technique in detecting altered epithelial resistance in premalignant bowel mucosa was improved by examining the impedance profile in a sodium-free Ringer's solution where the epithelium of control colons had a resistance of 24.4 +/- 1.8 omega.cm-2 compared with 19.0 +/- 1.1 omega.cm-2 (p less than 0.02) in colons from animals treated for only 4 wk with the carcinogen. Epithelial impedance analysis would seem to be a sensitive technique capable of identifying changes in the electrical properties or the large bowel early in disease states. PMID:3427187

  3. 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. PMID:25104547

  4. 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

  5. Early events in skin appendage formation: induction of epithelial placodes and condensation of dermal mesenchyme.

    PubMed

    Widelitz, R B; Chuong, C M

    1999-12-01

    The formation of skin appendages represents a morphogenetic process through which a homogeneous system is converted into a patterned system. We have pursued molecules involved in the early placode induction and mesenchymal condensation stages of this process. We found that intracellular and extracellular signaling molecules collaborate to position the location of feather primordia and initiate mesenchymal condensations mediated by adhesion molecules. During the inductive stage, cells interact in a fashion best described by a reaction-diffusion mechanism. Thus in early feather morphogenesis, low level adhesion molecules drive cell interactions. The interactions were modulated by extracellular signaling molecules, which eventually increase the level of signaling molecules at sites of feather initiation and subsequently the level of adhesion molecules (Jiang et al, 1999a). These physico-chemical events lead to the formation of dermal condensations and epithelial placodes at sites of feather primordia, thus achieving the earliest and most fundamental events of skin appendage formation: induction. PMID:10674386

  6. 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

  7. 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 ...

  8. 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: ...

  9. 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

  10. EDAC: Epithelial defence against cancer-cell competition between normal and transformed epithelial cells in mammals.

    PubMed

    Kajita, Mihoko; Fujita, Yasuyuki

    2015-07-01

    During embryonic development or under certain pathological conditions, viable but suboptimal cells are often eliminated from the cellular society through a process termed cell competition. Cell competition was originally identified in Drosophila where cells with different properties compete for survival; 'loser' cells are eliminated from tissues and consequently 'winner' cells become dominant. Recent studies have shown that cell competition also occurs in mammals. While apoptotic cell death is the major fate for losers in Drosophila, outcompeted cells show more variable phenotypes in mammals, such as cell death-independent apical extrusion and cellular senescence. Molecular mechanisms underlying these processes have been recently revealed. Especially, in epithelial tissues, normal cells sense and actively eliminate the neighbouring transformed cells via cytoskeletal proteins by the process named epithelial defence against cancer (EDAC). Here, we introduce this newly emerging research field: cell competition in mammals. PMID:25991731

  11. Lipopolysaccharide O-Antigen Prevents Phagocytosis of Vibrio anguillarum by Rainbow Trout (Oncorhynchus mykiss) Skin Epithelial Cells

    PubMed Central

    Lindell, Kristoffer; Fahlgren, Anna; Hjerde, Erik; Willassen, Nils-Peder; Fällman, Maria; Milton, Debra L.

    2012-01-01

    Colonization of host tissues is a first step taken by many pathogens during the initial stages of infection. Despite the impact of bacterial disease on wild and farmed fish, only a few direct studies have characterized bacterial factors required for colonization of fish tissues. In this study, using live-cell and confocal microscopy, rainbow trout skin epithelial cells, the main structural component of the skin epidermis, were demonstrated to phagocytize bacteria. Mutant analyses showed that the fish pathogen Vibrio anguillarum required the lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide transporter proteins and a methyltransferase. Pretreatment of the epithelial cells with mannose prevented phagocytosis of V. anguillarum suggesting that a mannose receptor is involved in the uptake process. In addition, the O-antigen transport mutants could not colonize the skin but they did colonize the intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary, rainbow trout skin epithelial cells play a role in the fish innate immunity by clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O-antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it to colonize rapidly fish skin tissues. PMID:22662189

  12. Ultraviolet radiation and skin cancer of humans.

    PubMed

    Urbach, F

    1997-08-01

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

  13. 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

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

    PubMed

    Gordon, Louisa G; Rowell, David

    2015-03-01

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

  15. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    PubMed Central

    Baruah, Upasana; Barmon, Debabrata; Kataki, Amal Chandra; Deka, Pankaj; Hazarika, Munlima; Saikia, Bhargab J.

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS) from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m2 ) and carboplatin (5-6 of area under curve). Overall survival (OS) and progression free survival (PFS) were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. PMID:25810573

  16. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Cody, R; Lee, C

    1990-08-01

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

  19. Guidelines for school programs to prevent skin cancer.

    PubMed

    Glanz, Karen; Saraiya, Mona; Wechsler, Howell

    2002-04-26

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

  20. 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.

  1. 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 ...

  2. Enhanced detection of bladder cancer using the epithelial surface marker epithelial membrane antigen: a preliminary report.

    PubMed

    Ring, K S; Karp, F; Benson, M C

    1990-09-01

    The flow cytometry (FCM) technique allows for the rapid quantitative analysis of the DNA content of individual cells. In a variety of genitourinary tumors, DNA ploidy has a significant impact upon prognosis and ultimate patient survival. In patients having transitional cell cancer (TCC) of the bladder, FCM of voided urine and bladder barbotage specimens is highly correlated with cytologic analysis in the detection of malignant cells. One problem with this technique has been decreased sensitivity in samples containing large numbers of inflammatory cells. To improve FCM detection of TCC in bladder wash specimens, we developed a technique using a monoclonal antibody (Mab) specific to human, epithelial membrane antigen (EMA). The EMA cell-surface marker enabled us to differentiate bladder epithelial cells from lymphocytes and cellular debris. In combination with DNA analysis using propidium iodide, the EMA Mab increased the sensitivity and specificity of FCM compared to conventional analysis using propidium iodide alone. We conclude that epithelial cell-surface antigen staining using both EMA Mab and DNA staining can increase the FCM detection of TCC in bladder wash specimens. PMID:2074517

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2010-01-01

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

  7. 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

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

    SciTech Connect

    Reizner, G.T. )

    1993-05-01

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

  9. 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.

  10. 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

  11. Epithelial-mesenchymal transition in gastric cancer (Review).

    PubMed

    Katoh, Masaru

    2005-12-01

    Endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), surgical gastrectomy, and chemotherapy are therapeutic options of gastric cancer; how-ever, prognosis of advanced gastric cancer patients is still poor. Gastric cancer cells with fibroblastoid morphological changes show increased motility and invasiveness due to decreased cell-cell adhesion, which are reminiscent of epithelial-mesenchymal transition (EMT) during embryonic development. Here, EMT signaling networks in gastric cancer were reviewed. E-cadherin at adherens junction is a key molecular target of EMT. CDH1 gene at human chromosome 16q22.1 encodes E-cadherin. Familial diffuse type gastric cancer occurs due to germ-line mutations of the CDH1 gene. Down-regulation of E-cadherin function due to mutation, deletion, CpG hyper-methylation, and SNAIL (SNAI1)- or SIP1-mediated transcriptional repression of the CDH1 gene leads to EMT in gastric cancer. Amplification of ERBB2, MET, FGFR2, PIK3CA, AKT1 genes, up-regulation of WNT2, WNT2B, WNT8B, and down-regulation of SFRP1 lead to EMT in gastric cancer through GSK3beta inhibition and following SNAIL-mediated CDH1 repression. Claudin (CLDN) and PAR3/PAR6/aPKC complex at tight junction are other key molecular targets of EMT. CLDN23 gene is down-regulated in intestinal type gastric cancer. Down-regulation of PAR3/PAR6/aPKC complex also leads to EMT. Single nucleotide polymorphisms (SNPs) and copy number polymorphisms (CNPs) of genes encoding EMT signaling molecules will be identified as novel risk factors of gastric cancer. In addition, antibodies, RNAi compounds, and small molecular inhibitors for EMT signaling molecules will be developed as novel therapeutic agents for gastric cancer. Personalized medicine based on the combination of genetic screening and novel therapeutic agents could dramatically improve the prognosis of gastric cancer patients in the future. PMID:16273224

  12. 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

  13. 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

  14. 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)

  15. 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

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

    PubMed Central

    Katta, Rajani; Brown, Danielle Nicole

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  18. Downregulation of miR-153 contributes to epithelial-mesenchymal transition and tumor metastasis in human epithelial cancer.

    PubMed

    Xu, Qin; Sun, Qiang; Zhang, Jianjun; Yu, Jingshuang; Chen, Wantao; Zhang, Zhiyuan

    2013-03-01

    The epithelial-mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. The aims of this study were to investigate and validate unidentified micro RNAs (miRNAs) that regulate EMT and to reveal their clinical relevance in epithelial cancer patients. By applying miRNA array screening in a natural epithelial-mesenchymal phenotype cell line pair and in a transforming growth factor β-induced EMT cell model, we found miR-153 was markedly downregulated in the cells that underwent an EMT. A close association was confirmed between inhibition of miR-153 and the EMT phenotype, as well as the invasive ability of epithelial cancer cells. Ectopic expression of miR-153 in mesenchymal-like cells resulted in an epithelial morphology change with decreased cellular invasive ability. On the contrary, transfection of a miR-153 inhibitor in epithelial-like cells led to a mesenchymal phenotype change. In vivo ectopic expression of miR-153 significantly inhibited tumor cell metastasis formation. Data from the dual-luciferase reporter gene assay showed, for the first time, that SNAI1 and ZEB2 were direct targets of miR-153. Inverse correlations were also observed between miR-153 and SNA1 and ZEB2 levels in oral cancer patients' samples. Furthermore, low expression level of miR-153 was found to be significantly related to metastasis and poor prognosis in oral cancer patients. These data demonstrate that miR-153 is a novel regulator of EMT by targeting SNAI1 and ZEB2 and indicate its potential therapeutic value for reducing cancer metastasis. PMID:23188671

  19. 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

  20. 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

  1. [Stage III and IV epithelial ovarian cancers. Therapeutic problems].

    PubMed

    Picaud, A; Walter, P; Minko Mi Etoua, D; Faye, A; N'Sounda, C; Nlome Nze, A R; Lunven, B

    1992-01-01

    Between 1986 and 1989 (4 years), 11 epithelial malignant tumours of the ovary were treated in the department of gynecology and obstetrics of the Libreville teaching hospital group. Epithelial tumours accounted for 78 per cent of malignant tumours in the adult. Burkitt's lymphoma predominated in young girls. Cancer of the ovary takes sixth place among female cancers in Gabon, with an incidence identical to that of cancer of the liver. Cases involved stage III and IV malignancies. Four patients died (36 per cent) and seven are still alive (63.6 per cent) with a mean survival of 25 months at the time of the study (the longest living patient having a survival of 5 years). The fullest possible initial surgical excision is essential in ensuring the greater efficacy of polychemotherapy (including Cisplatin), the only guarantee of total second look surgery. Monitoring of residual disease was based upon ultrasonography. Pelvic radiotherapy was used in the presence of a residual pelvic mass measuring less than 3 cm. Future efforts must be direct towards early detection, in particular since more than 45 per cent of our patients were aged under 30. PMID:1565942

  2. Genetic instability in epithelial tissues at risk for cancer.

    PubMed

    Hittelman, W N

    2001-12-01

    Epithelial tumors develop through a multistep process driven by genomic instability frequently associated with etiologic agents such as prolonged tobacco smoke exposure or human papilloma virus (HPV) infection. The purpose of the studies reported here was to examine the nature of genomic instability in epithelial tissues at cancer risk in order to identify tissue genetic biomarkers that might be used to assess an individual's cancer risk and response to chemopreventive intervention. As part of several chemoprevention trials, biopsies were obtained from risk tissues (i.e., bronchial biopsies from chronic smokers, oral or laryngeal biopsies from individuals with premalignancy) and examined for chromosome instability using in situ hybridization. Nearly all biopsy specimens show evidence for chromosome instability throughout the exposed tissue. Increased chromosome instability was observed with histologic progression in the normal to tumor transition of head and neck squamous cell carcinomas. Chromosome instability was also seen in premalignant head and neck lesions, and high levels were associated with subsequent tumor development. In bronchial biopsies of current smokers, the level of ongoing chromosome instability correlated with smoking intensity (e.g., packs/day), whereas the chromosome index (average number of chromosome copies per cell) correlated with cumulative tobacco exposure (i.e., pack-years). Spatial chromosome analyses of the epithelium demonstrated multifocal clonal outgrowths. In former smokers, random chromosome instability was reduced; however, clonal populations appeared to persist for many years, perhaps accounting for continued lung cancer risk following smoking cessation. PMID:11795428

  3. Isolation and culture of adult epithelial stem cells from human skin.

    PubMed

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue. Epithelial stem cells have been identified in the epidermis, hair follicle, and intestine as cells with a high in vitro proliferative potential and as slow-cycling label-retaining cells in vivo (1-3). Adult, tissue-specific stem cells are responsible for the regeneration of the tissues in which they reside during normal physiologic turnover as well as during times of stress (4-5). Moreover, stem cells are generally considered to be multi-potent, possessing the capacity to give rise to multiple cell types within the tissue (6). For example, rodent hair follicle stem cells can generate epidermis, sebaceous glands, and hair follicles (7-9). We have shown that stem cells from the human hair follicle bulge region exhibit multi-potentiality (10). Stem cells have become a valuable tool in biomedical research, due to their utility as an in vitro system for studying developmental biology, differentiation, tumorigenesis and for their possible therapeutic utility. It is likely that adult epithelial stem cells will be useful in the treatment of diseases such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa and alopecias (11-13). Additionally, other skin problems such as burn wounds, chronic wounds and ulcers will benefit from stem cell related therapies (14,15). Given the potential for reprogramming of adult cells into a pluripotent state (iPS cells)(16,17), the readily accessible and expandable adult stem cells in human skin may provide a valuable source of cells for induction and downstream therapy for a wide range of disease including diabetes and

  4. Ozone, skin cancer, and the SST

    SciTech Connect

    Singer, S.F.

    1994-07-01

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

  5. [Epithelial tumor-like changes, precancerous conditions and skin neoplasms (standardization study)].

    PubMed

    Bednár, B; Stanová, M

    1976-05-01

    A retrospective study of bioptic material was used to design the following outline of a histological classification of epithelial skin tumours tentatively compared with handbooks published by the WHO (1) and AFIP (2): I. Tumour-like changes: 1. senile verruca (mixed, acanthotic, melanoacanthotic, hyperkeratonic, reticular, inverted). 2. Virus verrucosities (v. vulgaris, v. plana, c. accuminatum, molluscom contagiosum). 3. Hamartogenic verrucosities (naevus verrucosus, n. comedonicus, fibroepithelial papilloma. 4. Genetically undefined verrucosities (acanthosis nigricans, light cell acanthoma, verrucous dyskeratosis). 5. Cysts (atheroma, epidermoid cyst, dermoid cyst, others). 6. Unclassified. II. Precanceroses: 1. Pseudoepitheliomatous hyperplasis, 2. keratosis senilis, 3. Radiation dermatosis, 4. Unclassified. III. Epithelial tumours A. From surface epithelium 1. Spinocellular carcinoma (basic type, anaplastic, adenoid, sarcomatoid, clear cell carcinoma, intraepidermal). 2. Basocellular carcinoma: a) varieties derived from surface epithelium (intraepithelial, superficial, solid, cystic, invasive), b) varieties with adenoid features (cylindromatous, fibroepithelia), c) varieties with trichoepithelial features (keratinizing, pigment-type, clear cell type), d) naevus varieties (basocellular naevi). 3. Spinobasocellular carcinoma. 4. Unclassifiable. B. Sweat gland tumours: 1. syringocystadenoma papilliferum, 2. hidradenoma papillare, 3. nodular hidradenoma (eccrine spiradenoma, eccrine acrospiroma, myxochondroepithelioma, myoepithelioma, mucinous epithelioma), 4. syringoma, 5. eccrine cylindroma, 6. hidrocystoma, 7. eccrine poroma, 8. carcinomas (so called extramammary Paget carcinoma), 9. unclassifiable. C. Sebaceous gland tumours: 1. adenoma sebaceum, 2. carcinoma sebaceum, 3. quasi tumours (naevus sebaceus, Pringle's hamartoma, steatocystoma multiplex, hyperplasia), 4. unclassifiable. D. Trichoepithelial tumours: 1. trichofolliculoma, 2. follicular poroma, 3

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

    PubMed Central

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

    2011-01-01

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

  7. New Insights of Epithelial-Mesenchymal Transition in Cancer Metastasis

    PubMed Central

    Wu, Yadi; Zhou, Binhua P.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is a key step during embryonic morphogenesis, heart development, chronic degenerative fibrosis, and cancer metastasis. Several distinct traits have been conveyed by EMT, including cell motility, invasiveness, resistance to apoptosis, and some properties of stem cells. Many signal pathways have contributed to the induction of EMT, such as transforming growth factor-β, Wnt, Hedgehog, Notch, and nuclear factor κB. Over the last few years, increasing evidence has shown that EMT plays an essential role in tumor progression and metastasis. Understanding the molecular mechanism of EMT has a great effect in unraveling the metastatic cascade and may lead to novel interventions for metastatic disease. PMID:18604456

  8. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed

    Ley, R D; Reeve, V E

    1997-06-01

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

  9. Chemoprevention of ultraviolet radiation-induced skin cancer.

    PubMed Central

    Ley, R D; Reeve, V E

    1997-01-01

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

  10. 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

  11. Bovine papillomavirus type 9 induces epithelial papillomas on the teat skin of heifers.

    PubMed

    Hatama, Shinichi; Nishida, Tomoko; Kadota, Koichi; Uchida, Ikuo; Kanno, Toru

    2009-05-12

    Experiments were carried out to investigate whether papillomas could be induced on the teat skin of heifers by intradermal injection with bovine papillomavirus type 9 (BPV-9). Three heifers (#1 and 2, two 0.5-year-old Holsteins; #3, a 1.5-year-old Japanese Black) were injected with BPV-9 and one heifer (#4, a 0.5-year-old Holstein) was mock-infected. Viral DNA load in the inocula was quantified by real-time polymerase chain reaction assay and adjusted to 1.56x10(12) copies per injection. Papillomas appeared at the injection sites in the BPV-9-injected heifers #1, 2 and 3 and grew over the 8 (#1 and 2) and 4 (#3)mo observation period, respectively. However, no papillomas were found in the mock-infected heifer #4. The experimentally induced papillomas were excised and examined. Histologically, the lesions were characterized by hyperplasia of the epidermis with hyperkeratosis and marked acanthosis and were morphologically similar to naturally occurring lesions. BPV-9 DNA and bovine papillomavirus capsid antigen were abundant in the lesions. Therefore, we conclude that BPV-9 is an etiological agent causing epithelial papillomas on the teat skin of heifers. PMID:19095383

  12. Loss of epithelial hypoxia-inducible factor prolyl hydroxylase 2 accelerates skin wound healing in mice.

    PubMed

    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; Wielockx, Ben

    2013-09-01

    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

  13. 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

  14. 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

  15. Sef Regulates Epithelial-Mesenchymal Transition in Breast Cancer Cells.

    PubMed

    He, Qing; Gong, Yan; Gower, Lindsey; Yang, Xuehui; Friesel, Robert E

    2016-10-01

    Sef (similar expression to fgf), also know as IL17RD, is a transmembrane protein shown to inhibit fibroblast growth factor signaling in developmental and cancer contexts; however, its role as a tumor suppressor remains to be fully elucidated. Here, we show that Sef regulates epithelial-mesenchymal transition (EMT) in breast cancer cell lines. Sef expression was highest in the normal breast epithelial cell line MCF10A, intermediate expression in MCF-7 cells and lowest in MDA-MB-231 cells. Knockdown of Sef increased the expression of genes associated with EMT, and promoted cell migration, invasion, and a fibroblastic morphology of MCF-7 cells. Overexpression of Sef inhibited the expression of EMT marker genes and inhibited cell migration and invasion in MCF-7 cells. Induction of EMT in MCF10A cells by TGF-β and TNF-α resulted in downregulation of Sef expression concomitant with upregulation of EMT gene expression and loss of epithelial morphology. Overexpression of Sef in MCF10A cells partially blocked cytokine-induced EMT. Sef was shown to block β-catenin mediated luciferase reporter activity and to cause a decrease in the nuclear localization of active β-catenin. Furthermore, Sef was shown to co-immunoprecipitate with β-catenin. In a mouse orthotopic xenograft model, Sef overexpression in MDA-MB-231 cells slowed tumor growth and reduced expression of EMT marker genes. Together, these data indicate that Sef plays a role in the negative regulation of EMT in a β-catenin dependent manner and that reduced expression of Sef in breast tumor cells may be permissive for EMT and the acquisition of a more metastatic phenotype. J. Cell. Biochem. 117: 2346-2356, 2016. © 2016 Wiley Periodicals, Inc. PMID:26950413

  16. 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

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

    PubMed

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

    2015-02-01

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

  18. Sprouty 1 predicts prognosis in human epithelial ovarian cancer

    PubMed Central

    Masoumi-Moghaddam, Samar; Amini, Afshin; Wei, Ai-Qun; Robertson, Gregory; Morris, David L

    2015-01-01

    Sprouty proteins are evolutionary-conserved modulators of receptor tyrosine kinase (RTK) signaling. We have previously reported inverse correlation of the Sprouty 1 (Spry1) protein expression with ovarian cancer cell proliferation, migration, invasion and survival. In the present study, the expression status of Spry1 protein and its clinical relevance in patients with epithelial ovarian cancer were explored. Matched tumor and normal tissue samples from 100 patients with epithelial ovarian cancer were immunohistochemically stained for Spry1. Expression of ERK, p-ERK, Ki67, FGF-2, VEGF and IL-6 and their correlation with Spry1 were also evaluated. In addition, correlation between Spry1 and clinicopathological characteristics and predictive significance of Spry1 for overall survival (OS) and disease-free survival (DFS) were analysed. Our data indicated that Spry1 was significantly downregulated in tumor tissues (p=0.004). Spry1 showed significant inverse correlation with p-ERK/ERK (p=0.045), Ki67 (p=0.010), disease stage (p=0.029), tumor grade (p=0.037), recurrence (p=0.001) and lymphovascular invasion (p=0.042). It was revealed that Spry1 low-expressing patients had significantly poorer OS (p=0.010) and DFS (p=0.012) than those with high expression of Spry1. Multivariate analysis showed that high Spry1 (p=0.030), low stage (p=0.048) and no residual tumor (p=0.007) were independent prognostic factors for a better OS, among which high Spry1 (p=0.035) and low stage (p=0.035) remained as independent predictors of DFS, too. We also found that the expression of Spry1 significantly correlates with the expression of Spry2 (p<0.001), but not that of Spry4. In conclusion, we report for the first time to our knowledge that Spry1 protein is downregulated in human epithelial ovarian cancer. Spry1 expression significantly impacts tumor behavior and shows predictive value as an independent prognostic factor for survival and recurrence. PMID:26101716

  19. Effects of subepithelial fibroblasts on epithelial differentiation in human skin and oral mucosa: heterotypically recombined organotypic culture model.

    PubMed

    Okazaki, Mutsumi; Yoshimura, Kotaro; Suzuki, Yasutoshi; Harii, Kiyonori

    2003-09-01

    The stratified squamous epithelia differ regionally in their patterns of morphogenesis and differentiation. Although some reports suggested that the adult epithelial phenotype is an intrinsic property of the epithelium, there is increasing evidence that subepithelial connective tissue can modify the phenotypic expression of the epithelium. The aim of this study was to elucidate whether the differentiation of cutaneous and oral epithelia is influenced by underlying mesenchymal tissues. Three normal skin samples and three normal buccal mucosa samples were used for the experiments. Skin equivalents were constructed in four ways, depending on the combinations of keratinocytes (cutaneous or mucosal keratinocytes) and fibroblasts (dermal or mucosal fibroblasts), and the effects of subepithelial fibroblasts on the differentiation of oral and cutaneous keratinocytes were studied with histological examinations and immunohistochemical analyses with anti-cytokeratin (keratins 10 and 13) antibodies. For each experiment, three paired skin equivalents were constructed by using single parent keratinocyte and fibroblast sources for each group; consequently, nine (3 x 3) organotypic cultures per group were constructed and studied. The oral and cutaneous epithelial cells maintained their intrinsic keratin expression. The keratin expression patterns in oral and cutaneous epithelia of skin equivalents were generally similar to their original patterns but were partly modified exogenously by the topologically different fibroblasts. The mucosal keratinocytes were more differentiated and expressed keratin 10 when cocultured with dermal fibroblasts, and the expression patterns of keratin 13 in cutaneous keratinocytes cocultured with mucosal fibroblasts were different from those in keratinocytes cocultured with cutaneous fibroblasts. The results suggested that the epithelial phenotype and keratin expression could be extrinsically modified by mesenchymal fibroblasts. In epithelial

  20. 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

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

    PubMed

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

    2013-01-01

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

  2. 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

  3. Science Signaling Podcast for 21 June 2016: MET and skin cancer.

    PubMed

    Yuspa, Stuart H; VanHook, Annalisa M

    2016-01-01

    This Podcast features an interview with Stuart Yuspa, senior author of a Research Article that appears in the 21 June 2016 issue of Science Signaling, about how activation of the receptor tyrosine kinase MET stimulates the formation of squamous cell carcinoma in the skin. Hepatocyte growth factor (HGF) is produced by mesenchymal cells and stimulates MET, which is present on the surface of epithelial cells. HGF-MET signaling directs the proliferation and migration of epithelial cells during the development of various organs and is important during wound healing. Aberrant MET activation has been implicated in several types of cancer, including squamous cell carcinoma. Using a model in which mice overexpressing HGF develop spontaneous squamous cell carcinomas in the skin, Cataisson et al found that MET promoted the development of squamous tumors by stimulating the synthesis and release of ligands that activate the epidermal growth factor receptor (EGFR). This mechanism was similar to that through which oncogenic RAS promotes skin tumors. Blocking EGFR signaling caused HGF-induced squamous tumors to regress, suggesting that EGFR inhibitors might be useful for treating squamous cell carcinomas.Listen to Podcast. PMID:27330186

  4. YY1 modulates taxane response in epithelial ovarian cancer

    PubMed Central

    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, Joe W.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2009-01-01

    Purpose 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. Experimental design 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. Results 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 knockdown in ovarian cancer cell lines results in inhibition of anchorage-independent growth, motility and proliferation, but also increases resistance to taxanes, with no effect on cisplatin sensitivity. Conclusions These results, together with the prior demonstration of augmentation of microtubule-related genes by E2F3, suggest that enhanced taxane sensitivity in tumors with high YY1/E2F activity may be mediated by modulation of putative target genes with microtubule function. PMID:19208743

  5. 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.

  6. 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 ...

  7. 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

  8. 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

  9. 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. PMID:1544753

  10. Alteration of cell-cycle regulation in epithelial ovarian cancer.

    PubMed

    Nam, E J; Kim, Y T

    2008-01-01

    In spite of the clinical importance of epithelial ovarian cancer (EOC), little is known about the pathobiology of its precursor lesions and progression. Regulatory mechanisms of the cell cycle are mainly composed of cyclins, cyclin-dependent kinases (CDK), and CDK inhibitors. Alteration of these mechanisms results in uncontrolled cell proliferation, which is a distinctive feature of human cancers. This review describes the current state of knowledge about the alterations of cell-cycle regulations in the context of p16-cyclin D1-CDK4/6-pRb pathway, p21-p27-cyclin E-CDK2 pathway, p14-MDM2-p53 pathway, and ATM-Chk2-CDC25 pathway, respectively. Recent evidence suggests that ovarian cancer is a heterogenous group of neoplasms with several different histologic types, each with its own underlying molecular genetic mechanism. Therefore, expression of cell cycle regulatory proteins should be tested separately according to each histologic type. In serous ovarian carcinoma, high expression of p16, p53, and p27 and low expression of p21 and cyclin E were shown. In addition, this review focuses on the prognostic significance of cell cycle-regulating proteins in EOC. However, it is difficult to compare the results from different groups due to diverse methodologies and interpretations. Accordingly, researchers should establish standardized criteria for the interpretation of immunohistochemical results. PMID:18298566

  11. [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). PMID:26853278

  12. 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

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

    PubMed

    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. Fertility sparing surgery in early stage epithelial ovarian cancer

    PubMed Central

    Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

    2014-01-01

    Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

  15. Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing.

    PubMed

    Wang, Lin-Lin; Zhao, Rui; Li, Jiao-Yong; Li, Shan-Shan; Liu, Min; Wang, Meng; Zhang, Meng-Zhou; Dong, Wen-Wen; Jiang, Shu-Kun; Zhang, Miao; Tian, Zhi-Ling; Liu, Chang-Sheng; Guan, Da-Wei

    2016-09-01

    Previous studies showed that cannabinoid 2 (CB2) receptor is expressed in multiple effector cells during skin wound healing. Meanwhile, its functional involvement in inflammation, fibrosis, and cell proliferation in other organs and skin diseases implied CB2 receptor might also regulate skin wound healing. To verify this hypothesis, mice excisional wounds were created and treated with highly selective CB2 receptor agonist GP1a (1-(2,4-dichlorophenyl)-6-methyl- N-piperidin-1-yl-4H-indeno[1,2-c]pyrazole-3-carboxamide) and antagonist AM630 ([6-iodo-2- methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone) respectively. The inflammatory infiltration, cytokine expression, fibrogenesis, and wound re-epithelialization were analyzed. After CB2 receptor activation, neutrophil and macrophage infiltrations were reduced, and expressions of monocyte chemotactic protein (MCP)-1, stromal cell-derived factor (SDF)-1, Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)-A were decreased. Keratinocyte proliferation and migration were enhanced. Wound re-epithelialization was accelerated. Fibroblast accumulation and fibroblast-to-myofibroblast transformation were attenuated, and expression of pro-collagen I was decreased. Furthermore, HaCaT cells in vitro were treated with GP1a or AM630, which revealed that CB2 receptor activation promoted keratinocyte migration by inducing the epithelial to mesenchymal transition. These results, taken together, indicate that activating CB2 receptor could ameliorate wound healing by reducing inflammation, accelerating re-epithelialization, and attenuating scar formation. Thus, CB2 receptor agonist might be a novel perspective for skin wound therapy. PMID:27268717

  16. Continuous-wave terahertz imaging of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Joseph, Cecil Sudhir

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

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

    PubMed

    Kibarian, M A; Hruza, G J

    1995-12-01

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

  18. Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

    PubMed Central

    Micalizzi, Douglas S.; Farabaugh, Susan M.

    2010-01-01

    From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer. PMID:20490631

  19. 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.

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

    PubMed Central

    Montagner, Alexandra; Delgado, Maria B; Tallichet-Blanc, Corinne; Chan, Jeremy S K; Sng, Ming K; Mottaz, Hélène; Degueurce, Gwendoline; Lippi, Yannick; Moret, Catherine; Baruchet, Michael; Antsiferova, Maria; Werner, Sabine; Hohl, Daniel; Al Saati, Talal; 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

  1. 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

  2. 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

  3. Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells.

    PubMed

    Li, Rui; Pavuluri, Sivapriya; Bruggeman, Kiara; Long, Benjamin M; Parnell, Andrew J; Martel, Anne; Parnell, Steven R; Pfeffer, Frederick M; Dennison, Andrew J C; Nicholas, Kevin R; Barrow, Colin J; Nisbet, David R; Williams, Richard J

    2016-07-01

    The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides; these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery. PMID:26961467

  4. 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. PMID:26763429

  5. 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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1993-03-01

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

  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. 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

  10. Multimodal nonlinear optical microscopy used to discriminate epithelial ovarian cancer

    NASA Astrophysics Data System (ADS)

    Adur, J.; Pelegati, V. B.; de Thomaz, A. A.; Almeida, D. B.; Bottcher-Luiz, F.; Andrade, L. A. L. A.; Cesar, C. L.

    2011-07-01

    We used human specimens of epithelial ovarian cancer (serous type) to test the feasibility of nonlinear imaging as complementary tools for ovarian cancer diagnosis. Classical hematoxylin-and-eosin stained sections were applied to combining two-photon excitation fluorescence (TPEF), second (SHG), and third (THG) harmonic microscopy within the same imaging platform. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with Hematoxylin & Eosin (H&E) stored for a very long time and that H&E staining enhanced the THG signal. We demonstrate using anisotropy and morphological measurements, that SHG and THG of stained optical sections allow reproducible identification of neoplastic features such as architectural alterations of collagen fibrils at different stages of the neoplastic transformation and cellular atypia. Taken together, these results suggest that, with our viable imaging system, we can qualitatively and quantitatively assess endogenous optical biomarkers of the ovarian tissue with SHG and THG microscopy. This imaging capability may prove to be highly valuable in aiding to determine structural changes at the cellular and tissue levels, which may contribute to the development of new diagnostic techniques.

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

    PubMed

    Varki, Nissi M; Varki, Ajit

    2015-07-19

    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

  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. Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells.

    PubMed

    Singh, Nisha; Chakraborty, Raja; Bhullar, Rajinder Pal; Chelikani, Prashen

    2014-04-01

    The human bitter taste receptors (T2Rs) are chemosensory receptors that belong to the G protein-coupled receptor superfamily. T2Rs are present on the surface of oral and many extra-oral cells. In humans 25 T2Rs are present, and these are activated by hundreds of chemical molecules of diverse structure. Previous studies have shown that many bitter compounds including chloroquine, quinidine, bitter melon extract and cucurbitacins B and E inhibit tumor growth and induce apoptosis in cancer cells. However, the existence of T2Rs in cancer cell is not yet elucidated. In this report using quantitative (q)-PCR and flow cytometry, we characterized the expression of T2R1, T2R4, T2R10, T2R38 and T2R49 in the highly metastatic breast cancer cell line MDA-MB-231, poorly metastatic cell line MCF-7, and non-cancerous mammary epithelial cell line MCF-10A. Among the 5 T2Rs analyzed by qPCR and flow cytometry, T2R4 is expressed at 40-70% in mammary epithelial cells in comparison to commonly used breast cancer marker proteins, estrogen receptor and E-cadherin. Interestingly, the expression of T2R4 was downregulated in breast cancer cells. An increase in intracellular calcium mobilization was observed after the application of bitter agonists, quinine, dextromethorphan, and phenylthiocarbamide that are specific for some of the 5 T2Rs. This suggests that the endogenous T2Rs expressed in these cells are functional. Taken together, our novel findings suggest that T2Rs are differentially expressed in mammary epithelial cells, with some T2Rs downregulated in breast cancer cells. PMID:24613843

  14. 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

  15. 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

  16. 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

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

    MedlinePlus

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

  18. 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 ...

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

    MedlinePlus

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

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

    MedlinePlus

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

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

    MedlinePlus

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

  2. 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

  3. Beta Genus Papillomaviruses and Skin Cancer

    PubMed Central

    Howley, Peter M.; Pfister, Herbert J.

    2015-01-01

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

  4. 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.

  5. Epithelial ovarian cancer following cure of cervical carcinoma (a case report).

    PubMed

    Charak, B S; Parikh, P M; Advani, S H

    1989-07-01

    A case of patient developing epithelial ovarian cancer 15 years after carcinoma of cervix treated successfully with radiotherapy, is reported. The patient has shown good initial response to chemotherapy and surgery. PMID:2634759

  6. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.

    PubMed

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Blake Gilks, C; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Webb, Penelope M; Chenevix-Trench, Georgia; Risch, Harvey A; MacGregor, Stuart

    2016-07-01

    Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach. PMID:27075448

  7. 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.

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

    PubMed

    Marks, R

    1995-01-15

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

  9. 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…

  10. 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…

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

    PubMed Central

    Zurbenko, Igor

    2014-01-01

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

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

    PubMed

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

    2012-11-01

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

  13. Preventing Skin Cancer Through Reduction of Indoor Tanning

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. 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.

  16. Case report and review of literature: leptomeningeal relapse in epithelial ovarian cancer.

    PubMed

    Khalil, A M; Yamout, B I; Tabbal, S D; Salem, Z M; Mroueh, A M

    1994-08-01

    The diagnosis of leptomeningeal relapse in a patient with epithelial ovarian cancer was confirmed by the presence of malignant ovarian cells in the cerebrospinal fluid. There was no clinical evidence of tumor spread elsewhere. Therapy, including intrathecal methotrexate and whole-brain irradiation led to transient clinical improvement. International literature review revealed only 13 other cases of leptomeningeal carcinomatosis in epithelial ovarian cancer; all died within 15 months following the diagnosis of leptomeningeal spread. PMID:8063252

  17. 78 FR 47320 - Preventing Skin Cancer Through Reduction of UV Exposure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

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

  18. 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

  19. 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

  20. 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

  1. Exo70 Isoform Switching upon Epithelial-Mesenchymal Transition Mediates Cancer Cell Invasion

    PubMed Central

    Lu, Hezhe; Liu, Jianglan; Liu, Shujing; Zeng, Jingwen; Ding, Deqiang; Carstens, Russ P.; Cong, Yusheng; Xu, Xiaowei; Guo, Wei

    2014-01-01

    Summary Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2, and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoforms expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal but not the epithelial isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion. PMID:24331928

  2. Loss of CLCA4 Promotes Epithelial-to-Mesenchymal Transition in Breast Cancer Cells

    PubMed Central

    Yu, Yang; Walia, Vijay; Elble, Randolph C.

    2013-01-01

    The epithelial to mesenchymal transition (EMT) is a developmental program in which epithelial cells downregulate their cell-cell junctions, acquire spindle cell morphology and exhibit cellular motility. In breast cancer, EMT facilitates invasion of surrounding tissues and correlates closely with cancer metastasis and relapse. We found previously that the candidate tumor suppressor CLCA2 is expressed in differentiated, growth-arrested mammary epithelial cells but is downregulated during tumor progression and EMT. We further demonstrated that CLCA2 is a p53-inducible proliferation-inhibitor whose loss indicates an increased risk of metastasis. We show here that another member of the CLCA gene family, CLCA4, is expressed in mammary epithelial cells and is similarly downregulated in breast tumors and in breast cancer cell lines. Like CLCA2, the gene is stress-inducible, and ectopic expression inhibits colony formation. Transcriptional profiling studies revealed that CLCA4 and CLCA2 together are markers for mammary epithelial differentiation, and both are downregulated by TGF beta. Moreover, knockdown of CLCA4 in immortalized cells by shRNAs caused downregulation of epithelial marker E-cadherin and CLCA2, while mesenchymal markers N-cadherin, vimentin, and fibronectin were upregulated. Double knockdown of CLCA2 and CLCA4 enhanced the mesenchymal profile. These findings suggest that CLCA4 and CLCA2 play complementary but distinct roles in epithelial differentiation. Clinically, low expression of CLCA4 signaled lower relapse-free survival in basal and luminal B breast cancers. PMID:24386311

  3. 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,…

  4. [Prognostic and predictive factors in epithelial ovarian cancer].

    PubMed

    Boudou-Rouquette, P; Pautier, P; Morice, P; Lhommé, C

    2009-04-01

    Even if prognosis of epithelial ovarian cancer remains very bad, survival and response to treatment are variable according to the patients. Determination of new prognostic markers helps us to adapt therapeutics for each patient and is necessary for the elaboration and the interpretation of clinical research studies. Many prognostic factors related to the tumor, the patient or the treatment, have been evaluated. The goal of this work is to review these parameters. So far, the most powerful variables are volume of residual disease after cytoreductive surgery, FIGO tumor stage, histologic type and grade of differentiation. The progress and accessibility to novel technologies applied to biology will make possible in the future the assessment of new prognostic profiles-based on genetic and/or proteomic tumor characteristics. The future also relies on the identification of predictive factors of response to treatment, but force is to note that on the last hundred publications testing predictive factors (p53, HER2, Topo-2-alpha, BRCA...), none have modified today our clinical practices. PMID:19357017

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

    PubMed

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

    2011-08-01

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

  6. 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

  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. Partially Evoked Epithelial-Mesenchymal Transition (EMT) Is Associated with Increased TGFβ Signaling within Lesional Scleroderma Skin.

    PubMed

    Nikitorowicz-Buniak, Joanna; Denton, Christopher P; Abraham, David; Stratton, Richard

    2015-01-01

    The origin of myofibroblasts in fibrotic conditions remains unknown and in systemic sclerosis (SSc) it has been proposed that activation of local fibroblasts, trans-differentiation of perivascular or vascular cells, recruitment of fibrocyte progenitors, or epithelial to mesenchymal transition (EMT) could be contributing. Data from our laboratory indicate that the epidermis in scleroderma is activated with the keratinocytes exhibiting a phenotype normally associated with tissue repair, including phosphorylation profiles indicative of TGFβ signaling. Since TGFβ is a known inducer of EMT, we investigated if there is evidence of this process in the SSc epidermis. In order to validate antibodies and primers, EMT was modeled in HaCaT cells cultured in the presence of TGFβ1. Skin sections were stained with phosho-SMAD2/3, as well as with epithelial and mesenchymal markers. Moreover, mRNA levels of transcription factors associated with EMT were studied in epidermal blister sheets. We observed critical changes in the scleroderma epidermis; showing significantly increased nuclear translocation of phosphorylated Smad2/3, consistent with active TGFβ signaling in SSc keratinocytes. While profound EMT could be induced in keratinocytes in vitro with the appearance of SNAI1/2 and FSP-1, and an accompanying loss of E-cadherin, in the scleroderma skin active TGFβ signaling was accompanied by only partial EMT-like changes characterised by induction of SNAI1 alone and with no loss of E-cadherin. Together, our findings support a model of altered differentiation and TGFβ dependent activation of scleroderma epithelial cells leading to a partially evoked EMT like process in the fibrotic skin. PMID:26217927

  9. The Role of Optical Radiations in Skin Cancer

    PubMed Central

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

    2013-01-01

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

  10. Identification of biomechanical force as a novel inducer of epithelial-mesenchymal transition features in mechanical stretched skin

    PubMed Central

    Zhou, Jia; Wang, Jing; Zhang, Ning; Zhang, Yifan; Li, Qingfeng

    2015-01-01

    Biomechanical cues of the microenvironment are recognized as potent regulators of cell behaviors. Skin regeneration induced by tissue expansion has been confirmed by results of experimental and clinical studies. However, it is still unknown whether skin regeneration induced by mechanical factor is the same biological process as skin morphogenesis during embryonic development. In order to explore the potential role of biomechanical force (BioF) in skin regeneration and whether epithelial-mesenchymal transition (EMT) is induced by BioF, continuous mechanical tension (CMT) at 10% elongation was applied to human keratinocytes in vitro for 12, 24, 48 and 72 hours. Cell proliferation and differentiation were analyzed, including the expression of markers of EMT: vimentin, FSP1, E-cadherin and N-cadherin. Normal and mechanical stretched skin specimens collected from mice were examined by immunofluorescence analysis and RT-PCR. We found that BioF promoted the proliferation and inhibited differentiation of keratinocytes in vitro. The expression of markers of EMT vimentin, FSP1, E-cadherin and N-cadherin were transiently up-regulated by BioF. Keratinocytes activation, epidermal thickening and EMT features were also observed in the stretched epidermis of mice, compared to normal mice. Furthermore, the mechanism of BioF induced EMT was found to be the enhanced autocrine effect of TNF-α, in part, and direct activation of the NF-κB pathway. Collectively, BioF promoted the proliferation of keratinocytes by transiently inducing some EMT features. BioF, as a vital biomechanical cue of the microenvironment of skin, was identified to be a novel inducer of EMT, regulating keratinocytes’ proliferation, differentiation and homeostasis of skin tissue. PMID:26807167

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Active solute transport across frog skin and epithelial cell systems according to the association-induction hypothesis.

    PubMed

    Ling, G N

    1981-01-01

    The phenomenon of transport of ions, sugars, amino acids, etc. across frog skin and other epithelial systems has been commonly interpreted on the basis of the membrane-pump theory, according to which asymmetry in solute distribution as well as transport into and out of all living cells results from the permeability properties and "pump" activities of the membrane. In the present review, certain findings in the field of transepithelial transport of solutes are given new interpretation on the basis of molecular mechanisms introduced in the association-induction hypothesis, according to which "active transport" of solutes occurs only across bifacial cell systems like frog skin and intestinal epithelium but not in the maintenance of steady levels of solutes in unifacial cell systems such as muscle, nerve, and red blood cells. PMID:7330099

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

    PubMed

    Sánchez C, Francisca

    2006-09-01

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

  17. 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

  18. Human papillomavirus status in extragenital nonmelanoma skin cancers.

    PubMed

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

    2014-01-01

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

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

    PubMed

    Masso, Malcolm

    2006-01-01

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

  20. 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

  1. Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.

    PubMed

    Mackenzie, Robertson; Talhouk, Aline; Eshragh, Sima; Lau, Sherman; Cheung, Daphne; Chow, Christine; Le, Nhu; Cook, Linda S; Wilkinson, Nafisa; McDermott, Jacqueline; Singh, Naveena; Kommoss, Friedrich; Pfisterer, Jacobus; Huntsman, David G; Köbel, Martin; Kommoss, Stefan; Gilks, C Blake; Anglesio, Michael S

    2015-11-01

    Epithelial ovarian cancer (EOC) consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin-stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs. PMID:26099008

  2. 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

  3. 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

  4. 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%.

  5. 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

  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. PMID:10709358

  7. 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

  8. Neuromodulators for Aging Skin

    MedlinePlus

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

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

    PubMed

    Maduray, K; Odhav, B; Nyokong, T

    2012-03-01

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

  10. YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

    PubMed Central

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie

    2015-01-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. PMID:25691658

  11. 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

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

    PubMed

    Dobes, W L

    1995-01-15

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

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Inhibition of epithelial ovarian cancer by Minnelide, a water-soluble pro-drug☆

    PubMed Central

    Rivard, Colleen; Geller, Melissa; Schnettler, Erica; Saluja, Manju; Vogel, Rachel Isaksson; Saluja, Ashok; Ramakrishnan, Sundaram

    2015-01-01

    Objective Minnelide is a water-soluble pro-drug of triptolide, a natural product. The goal of this study was to evaluate the effectiveness of Minnelide on ovarian cancer growth in vitro and in vivo. Methods The effect of Minnelide on ovarian cancer cell proliferation was determined by real time electrical impedance measurements. Multiple mouse models with C200 and A2780 epithelial ovarian cancer cell lines were used to assess the efficacy of Minnelide in inhibiting ovarian cancer growth. Results Minnelide decreased cell viability of both platinum sensitive and resistant epithelial ovarian cancer cells in vitro. Minnelide with carboplatin showed additive effects in vitro. Minnelide monotherapy increased the survival of mice bearing established ovarian tumors. Minnelide, in combination with carboplatin and paclitaxel, improved overall survival of mice. Conclusions Minnelide is a promising pro-drug for the treatment of ovarian cancer, especially when combined with standard chemotherapy. PMID:25172764

  17. Expression of SDF-1 and CXCR4 transcript variants and CXCR7 in epithelial ovarian cancer

    PubMed Central

    JASZCZYNSKA-NOWINKA, KAROLINA; RUCINSKI, MARCIN; ZIOLKOWSKA, AGNIESZKA; MARKOWSKA, ANNA; MALENDOWICZ, LUDWIK K.

    2014-01-01

    Chemokine stromal cell-derived factor-1 (SDF-1) and its receptors, CXCR4 and CXCR7, have been implicated in epithelial ovarian cancer progression and metastasis. However, limited data are available on the expression levels of SDF-1 and CXCR4 variants and CXCR7 in human epithelial ovarian cancer. The present study aimed to characterize the expression pattern and levels of SDF-1, CXCR4 and CXCR7 in normal human ovaries and epithelial ovarian cancer. The expression of SDF-1 and CXCR4 transcript variants and CXCR7 was determined by quantitative polymerase chain reaction (qPCR). Plasma SDF-1α levels were determined by commercially available EIA kits and cancer antigen 125 (CA 125) levels were quantified by automated microparticle enzyme immunosorbent assay. High expression levels of SDF-1 transcript variant 1 were identified in ovarian cancer and control ovaries. By contrast, in both groups the expression levels of SDF-1 transcript variants 3 and 4 were extremely low. Furthermore, SDF-1 variant 1 levels were notably higher in epithelial ovarian cancer than in control ovaries, while data for the remaining transcripts were similar in both groups. CXCR4 transcript variant 2 and CXCR7 expression levels in normal and neoplastic ovaries were similar. In both groups, CXCR4 transcript variant 2 was not detected. Plasma SDF-1α levels were notably higher in females with epithelial ovarian cancer than in the control ovaries. Elevated levels of blood SDF-1α were found prior to surgery, 6 days after surgery and following completion of the first chemotherapy course. These increases were independent of the type of epithelial ovarian cancer. Our results suggest that the expression of SDF-1 and the genes controlling alternative splicing are elevated in epithelial ovarian cancer, leading to an increased formation of SDF-1 variant 1. Elevated plasma SDF-1α levels in epithelial ovarian cancer patients are not associated with the presence of tumors and/or metastases, however reflect a

  18. Expression of SDF-1 and CXCR4 transcript variants and CXCR7 in epithelial ovarian cancer.

    PubMed

    Jaszczynska-Nowinka, Karolina; Rucinski, Marcin; Ziolkowska, Agnieszka; Markowska, Anna; Malendowicz, Ludwik K

    2014-05-01

    Chemokine stromal cell-derived factor-1 (SDF-1) and its receptors, CXCR4 and CXCR7, have been implicated in epithelial ovarian cancer progression and metastasis. However, limited data are available on the expression levels of SDF-1 and CXCR4 variants and CXCR7 in human epithelial ovarian cancer. The present study aimed to characterize the expression pattern and levels of SDF-1, CXCR4 and CXCR7 in normal human ovaries and epithelial ovarian cancer. The expression of SDF-1 and CXCR4 transcript variants and CXCR7 was determined by quantitative polymerase chain reaction (qPCR). Plasma SDF-1α levels were determined by commercially available EIA kits and cancer antigen 125 (CA 125) levels were quantified by automated microparticle enzyme immunosorbent assay. High expression levels of SDF-1 transcript variant 1 were identified in ovarian cancer and control ovaries. By contrast, in both groups the expression levels of SDF-1 transcript variants 3 and 4 were extremely low. Furthermore, SDF-1 variant 1 levels were notably higher in epithelial ovarian cancer than in control ovaries, while data for the remaining transcripts were similar in both groups. CXCR4 transcript variant 2 and CXCR7 expression levels in normal and neoplastic ovaries were similar. In both groups, CXCR4 transcript variant 2 was not detected. Plasma SDF-1α levels were notably higher in females with epithelial ovarian cancer than in the control ovaries. Elevated levels of blood SDF-1α were found prior to surgery, 6 days after surgery and following completion of the first chemotherapy course. These increases were independent of the type of epithelial ovarian cancer. Our results suggest that the expression of SDF-1 and the genes controlling alternative splicing are elevated in epithelial ovarian cancer, leading to an increased formation of SDF-1 variant 1. Elevated plasma SDF-1α levels in epithelial ovarian cancer patients are not associated with the presence of tumors and/or metastases, however reflect a

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

    PubMed

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

    2016-07-01

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

  20. 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

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

    PubMed

    Sordo, Carlos; Gutiérrez, César

    2013-03-01

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

  2. 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

  3. Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression

    PubMed Central

    Xie, Dacheng; Cui, Jiujie; Xia, Tian; Jia, Zhiliang; Wang, Liang; Wei, Wenfei; Zhu, Anna; Gao, Yong; Xie, Keping; Quan, Ming

    2015-01-01

    Transcriptional co-activator with PDZ binding motif (TAZ) is a transducer of the Hippo pathway and promotes cancer development and progression. In the present study, we sought to determine the roles and underlying mechanisms of elevated expression and activation of TAZ in pancreatic cancer development and progression. The mechanistic role of TAZ and Hippo signaling in promotion of pancreatic cancer development and progression was examined using cell culture, molecular biology, and mouse models. The relevance of our experimental and mechanistic findings was validated using human pancreatic tumor specimens. We found that TAZ expression was markedly higher in pancreatic tumors than in normal pancreatic tissue. Further analysis of the correlation of TAZ expression with tissue microarray clinicopathologic parameters revealed that this expression was positively associated with tumor differentiation. Also, TAZ expression was higher in pancreatic cancer cell lines than in pancreatic ductal epithelial cells. TAZ activation in pancreatic cancer cells promoted their proliferation, migration, invasion, and epithelial-mesenchymal transition. Further mechanistic studies demonstrated that aberrant expression and activation of TAZ in pancreatic cancer cells resulted from suppression of the expression of Merlin, a positive regulator upstream of the Hippo pathway, and that the oncogenic function of TAZ in pancreatic cancer cells was mediated by TEA/ATTS domain transcription factors. Therefore, TAZ functioned as an oncogene and promoted pancreatic cancer epithelial-mesenchymal transition and progression. TAZ thus may be a target for effective therapeutic strategies for pancreatic cancer. PMID:26416426

  4. 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

  5. Patient Satisfaction after Treatment of Nonmelanoma Skin Cancer

    PubMed Central

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

    2009-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Mowlawi, Ali Asghar; Yazdani, Majed

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

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

    PubMed

    Putnam, G L; Yanagisako, K L

    1982-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    1995-09-01

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

  10. Inhibition of prostate cancer growth by muscadine grape skin extract and resveratrol through distinct mechanisms.

    PubMed

    Hudson, Tamaro S; Hartle, Diane K; Hursting, Stephen D; Nunez, Nomeli P; Wang, Thomas T Y; Young, Heather A; Arany, Praveen; Green, Jeffrey E

    2007-09-01

    The phytochemical resveratrol contained in red grapes has been shown to inhibit prostate cancer cell growth, in part, through its antioxidant activity. Muscadine grapes contain unique phytochemical constituents compared with other grapes and are potentially a source for novel compounds with antitumor activities. We compared the antitumor activities of muscadine grape skin extract (MSKE), which we show contains no resveratrol, with that of resveratrol using primary cultures of normal prostate epithelial cells (PrEC) and the prostate cancer cell lines RWPE-1, WPE1-NA22, WPE1-NB14, and WPE1-NB26, representing different stages of prostate cancer progression. MSKE significantly inhibited tumor cell growth in all transformed prostate cancer cell lines but not PrEC cells. Prostate tumor cell lines, but not PrEC cells, exhibited high rates of apoptosis in response to MSKE through targeting of the phosphatidylinositol 3-kinase-Akt and mitogen-activated protein kinase survival pathways. The reduction in Akt activity by MSKE is mediated through a reduction in Akt transcription, enhanced proteosome degradation of Akt, and altered levels of DJ-1, a known regulator of PTEN. In contrast to MSKE, resveratrol did not induce apoptosis in this model but arrested cells at the G(1)-S phase transition of the cell cycle associated with increased expression of p21 and decreased expression of cyclin D1 and cyclin-dependent kinase 4 proteins. These results show that MSKE and resveratrol target distinct pathways to inhibit prostate cancer cell growth in this system and that the unique properties of MSKE suggest that it may be an important source for further development of chemopreventive or therapeutic agents against prostate cancer. PMID:17804756

  11. 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.

  12. Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity

    PubMed Central

    2011-01-01

    The epithelial-to-mesenchymal transition (EMT) is a critical developmental process that has recently come to the forefront of cancer biology. In breast carcinomas, acquisition of a mesenchymal-like phenotype that is reminiscent of an EMT, termed oncogenic EMT, is associated with pro-metastatic properties, including increased motility, invasion, anoikis resistance, immunosuppression and cancer stem cell characteristics. This oncogenic EMT is a consequence of cellular plasticity, which allows for interconversion between epithelial and mesenchymal-like states, and is thought to enable tumor cells not only to escape from the primary tumor, but also to colonize a secondary site. Indeed, the plasticity of cancer cells may explain the range of pro-metastatic traits conferred by oncogenic EMT, such as the recently described link between EMT and cancer stem cells and/or therapeutic resistance. Continued research into this relationship will be critical in developing drugs that block mechanisms of breast cancer progression, ultimately improving patient outcomes. PMID:22078097

  13. Voriconazole-associated phototoxic dermatoses and skin cancer.

    PubMed

    Goyal, Rakesh K

    2015-01-01

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

  14. 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 %.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Grainyhead-like 2 regulates epithelial plasticity and stemness in oral cancer cells.

    PubMed

    Chen, Wei; Yi, Jin Kyu; Shimane, Tetsu; Mehrazarin, Shebli; Lin, Yi-Ling; Shin, Ki-Hyuk; Kim, Reuben H; Park, No-Hee; Kang, Mo K

    2016-05-01

    Grainyhead-like 2 (GRHL2) is one of the three mammalian homologues of Drosophila Grainyhead involved in epithelial morphogenesis. We recently showed that GRHL2 also controls normal epithelial cell proliferation and differentiation. In this study, we investigated the role of GRHL2 in oral carcinogenesis and the underlying mechanism. GRHL2 expression was elevated in cells and tissues of oral squamous cell carcinomas (OSCCs) compared with normal counterparts. Knockdown of GRHL2 resulted in the loss of in vivo tumorigenicity, cancer stemness and epithelial phenotype of oral cancer cells. GRHL2 loss also inhibited oral cancer cell proliferation and colony formation. GRHL2 regulated the expression of miR-200 family and Octamer-binding transcription factor 4 (Oct-4) genes through direct promoter DNA binding. Overexpression of miR-200 genes in the oral cancer cells depleted of GRHL2 partially restored the epithelial phenotype, proliferative rate and cancer stemness, indicating that miR-200 genes in part mediate the functional effects of GRHL2. Taken together, this study demonstrates a novel connection between GRHL2 and miR-200, and supports protumorigenic effect of GRHL2 on OSCCs. PMID:26933170

  1. Use of Tanning Beds and Incidence of Skin Cancer

    PubMed Central

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

    2012-01-01

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

  2. Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.

    PubMed

    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

  3. 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

  4. 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

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

    PubMed

    Slaten, D; Parrott, R; Steiner, C

    1999-06-01

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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Stem cell state and the epithelial-to-mesenchymal transition: Implications for cancer therapy.

    PubMed

    Donnenberg, Vera S; Donnenberg, Albert D

    2015-06-01

    The cancer stem cell paradigm, the epithelial-to-mesenchymal transition and its converse, the mesenchymal-to-epithelial transition, have reached convergence. Implicit in this understanding is the notion that cancer cells can change state, and with such change come bidirectional alterations in motility, proliferative activity, and drug resistance. As such, tumors present a moving target for antineoplastic therapy. This article will review the evolving adult stem cell paradigm and how changes in our understanding of the bidirectional nature of cancer cell differentiation may affect the selection and timing of antineoplastic therapy. The goal is to determine how to best administer therapies potentially targeted against the cancer stem cell state in the context of established treatment regimens, and to evaluate long-term effects beyond tumor regression. PMID:25708160

  14. Epithelial-mesenchymal transition and drug resistance in breast cancer (Review).

    PubMed

    Huang, Jing; Li, Hongzhong; Ren, Guosheng

    2015-09-01

    Breast cancer is the leading cause of cancer death in women worldwide. Insensitivity of tumor cells to drug therapies is an essential reason arousing such high mortality. Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. It is well known that EMT plays an important role in breast cancer progression. Recently, mounting evidence has demonstrated involvement of EMT in antagonizing chemotherapy in breast cancer. Here, we discuss the biological significance and clinical implications of these findings, with an emphasis on novel approaches that effectively target EMT to increase the efficacy of anticancer therapies. PMID:26202679

  15. 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

  16. 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

  17. Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Sukhbaatar, Nyamdelger; Reiner, Agnes Teresa; Grimm, Christoph; Horvat, Reinhard; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome.. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use. PMID:25991672

  18. 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

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

    PubMed

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

    2015-02-01

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

  20. 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

  1. 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. PMID:26984362

  2. Circular polarization terahertz iolarization of nonmelanoma skin cancers

    NASA Astrophysics Data System (ADS)

    Martin, Jillian P.

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

  3. 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

  4. 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

  5. Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

    PubMed Central

    Santibanez, Juan F.

    2013-01-01

    Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer. PMID:23984088

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  7. Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

    SciTech Connect

    Kaur, Manjinder; Agarwal, Rajesh

    2007-11-01

    Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin and its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance-associated proteins and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models.

  8. Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development.

    PubMed

    Jeon, So-Ye; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-04-01

    As the primary female sex steroid hormones, estrogens and progesterone play important roles to regulate growth, differentiation, and function of a broad range of target tissues in the human body and maintain the function of female reproductive tissues. Ovarian cancer is the most cause of cancer death in gynecological malignancy. Despite enormous outcomes in the understanding of ovarian cancer pathology, this disease has resulted in poor survival rates since most patients are asymptomatic until the disease has been metastasized. The exact molecular events leading to metastasis of ovarian tumor cells have not yet been well elucidated, although it is recognized that the acquisition of capacity for migration and invasiveness would be a necessary prerequisite. During metastasis, epithelial-mesenchymal transition (EMT) is an important process, in which epithelial cells lose their intracellular adhesion and cell polarity and acquire increased motility and invasive properties to become mesenchymal like cells. The process of cancer cells to undergo EMT is regulated through the up- and down- regulation of a multiple cellular markers and signaling proteins. In this review, we focused the roles of women sex steroid hormones, estrogen and progesterone, in ovarian cancer, especially the ovarian cancer undergoing EMT and metastatic process. All things considered, we may suggest that progesterone is a potent hormone which inhibits the growth of human ovarian cancer cells and development to metastasis whereas estrogen may act as a risk factor of ovarian cancer progression and that progesterone therapy may be an alternative clinically effective tool for the treatment of human ovarian cancer. PMID:26873134

  9. 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

  10. Fibrosis and Cancer: Do Myofibroblasts Come Also From Epithelial Cells Via EMT?

    PubMed Central

    Radisky, Derek C.; Kenny, Paraic A.; Bissell, Mina J.

    2010-01-01

    Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and pro-inflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosis and malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments. PMID:17211838

  11. 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

  12. The Clinicopathologic Characteristics and 5-year Survival Rate of Epithelial Ovarian Cancer in Yazd, Iran

    PubMed Central

    Karimi-Zarchi, Mojgan; Mortazavizadeh, Seyed Mohammad Reza; Bashardust, Nasrollah; Zakerian, Neda; Zaidabadi, Mahbube; Yazdian-Anari, Pouria; Teimoori, Soraya

    2015-01-01

    Introduction Ovarian cancer is the second most common malignancy in women, the most common cause of gynecologic cancer deaths, and most patients have advanced stage disease at the time of diagnosis. The purpose of this study was to estimate the 5-year survival of patients with epithelial ovarian cancer based on age, tumor histology, stage of disease, and type of treatment. Methods This study was conducted on 120 patients with epithelial ovarian cancer referred to Shahid Sadoughi hospital and Shah Vali oncology clinic of Yazd from 2006 to 2012. Demographic data and patient records were studied to evaluate the treatment outcome, pathology of the tumor, and stage of disease. Finally, the overall survival rate and tumor-free survival of patients was assessed. Results The mean patient age was 53.87± 14.11 years. Most participants had stage I (36.7%) or stage II (35%) disease. Serous adenocarcinoma (57.6%) was the most common pathology found in patients with epithelial ovarian cancer. The overall survival of patients in this study was significantly associated with the histological tumor type (p = 0.000) and disease stage (p = 0.0377). Stage I (84.18%) and serous adenocarcinoma (72.81%) demonstrated the best survival. The tumor-free survival rates were not associated with histology types (p = 0.079), surgical procedure (p = 0.18), or chemotherapy (p = 0.18). Conclusion The survival of patients with epithelial ovarian cancer was significantly associated with disease stage. Serous adenocarcinoma also had the best prognosis among the pathologies studied. Therefore, early detection of ovarian cancer can substantially increase the survival rate. PMID:26516450

  13. Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer

    PubMed Central

    Galaal, Khadra; Naik, Raj; Bristow, Robert E; Patel, Amit; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. Objectives To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. Selection criteria We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alone in women with recurrent epithelial ovarian cancer. Data collection and analysis Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. Main results The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. Authors’ conclusions We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities. The results of the ongoing RCT AGO

  14. How do epidermal matrix metalloproteinases support re-epithelialization during skin healing?

    PubMed

    Michopoulou, Anna; Rousselle, Patricia

    2015-04-01

    Epithelialization of normal wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore the epidermal barrier function. Keratinocyte migration is one of the earliest and crucial events determining the efficiency of the overall wound repair process. In response to various stimuli including that of growth factors, cytokines and the extracellular matrix, activated keratinocytes at the edges of the wound undergo dramatic morphological changes according to their migratory behaviour through development of protrusive adhesion contacts and cytoskeleton rearrangements. These phenotypic changes are accompanied by the upregulated expression of a new set of genes, among which are adhesion receptors and specific matrix degrading enzymes named matrix metalloproteinases (MMPs). The tightly regulated spatial and temporal MMP expression is crucial for proper re-epithelialization. These multi-domain zinc-containing endopeptidases are necessary for the proper completion of multiple features of epidermal regeneration. They play a key role in the migration process by controlling the repeated cycles of keratinocyte attachment and retraction. In the meantime, they process, degrade or remodel the extracellular matrix often producing cleavages in a gain-of-function manner. PMID:26083673

  15. Immunohistological insight into the correlation between neuropilin-1 and epithelial-mesenchymal transition markers in epithelial ovarian cancer.

    PubMed

    Adham, Sirin A I; Al Harrasi, Ibtisam; Al Haddabi, Ibrahim; Al Rashdi, Afrah; Al Sinawi, Shadia; Al Maniri, Abdullah; Ba-Omar, Taher; Coomber, Brenda L

    2014-09-01

    The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E-cadherin and Slug. We used tissue microarrays containing the three main subtypes of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid adenocarcinoma and representative cases retrieved from our pathology archives. Immunohistochemistry was performed to detect the expression levels and location of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on cancer cells but not in normal ovarian surface epithelium (OSE). The Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug and E-cadherin in the malignant subtypes of ovarian tissues was significantly higher (5.18 ± 0.64, 4.84 ± 0.7, 4.98 ± 0.68, respectively) than their expression in the normal and benign tissues (1.04 ± 0.29, 0.84 ± 0.68, 1.71 ± 0.66, respectively), with no significant differences among the studied subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors and it was exclusively localized in the stroma of all mucinous tumors. The Spearman's rho value indicated that NRP-1 is positively related to the EMT markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner in the EMT process in EOC tumors. PMID:24850663

  16. 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

  17. Regulation of Epithelial-Mesenchymal Transition in Breast Cancer Cells by Cell Contact and Adhesion

    PubMed Central

    Cichon, Magdalena A; Nelson, Celeste M; Radisky, Derek C

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell–cell interactions is a key step in the earliest stages of cancer development. PMID:25698877

  18. Sorcin silencing inhibits epithelial-to-mesenchymal transition and suppresses breast cancer metastasis in vivo.

    PubMed

    Hu, Yunhui; Li, Shuangjing; Yang, Ming; Yan, Cihui; Fan, Dongmei; Zhou, Yuan; Zhang, Yanjun; Yagüe, Ernesto; Xiong, Dongsheng

    2014-01-01

    Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance. As there is a clear association between drug resistance and an aggressive phenotype, we asked whether sorcin affects also the motility, invasion, and stem cell characteristics of cancer cells. We have used both RNA interference (transient and stable expression of hairpins) and a lentiviral expression vector to experimentally modulate sorcin expression in a variety of cells. We demonstrate that sorcin depletion in MDA-MB-231 breast cancer cells reduces the pool of CD44(+)/CD24(-) and ALDH1(high) cancer stem cells (CSCs) as well as mammosphere-forming capacity. We also observe that sorcin regulates epithelial-mesenchymal transition and CSCs partly through E-cadherin and vascular endothelial growth factor expression. This leads to the acquisition of an epithelial-like phenotype, attenuating epithelial-mesenchymal transition and suppression of metastases in nude mice. The sorcin-depleted phenotype can also be reproduced in lung adenocarcinoma A549 cells and lung fibrosarcoma HT1080 cells. In addition, overexpression of sorcin in MCF7 cells, which have low endogenous sorcin expression levels, increases their migration and invasion in vitro. This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer. PMID:24337682

  19. Oral epithelial stem cells – implications in normal development and cancer metastasis

    PubMed Central

    Papagerakis, Silvana; Pannone, Giuseppe; Zheng, Li; About, Imad; Taqi, Nawar; Nguyen, Nghia P.T.; Matossian, Margarite; McAlpin, Blake; Santoro, Angela; McHugh, Jonathan; Prince, Mark E.; Papagerakis, Petros

    2014-01-01

    Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination. PMID:24803391

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed

    de Gruijl, F R; Forbes, P D

    1995-07-01

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

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

    PubMed

    Cumberland, Lara; Dana, Ali; Liegeois, Nanette

    2009-08-01

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

  8. 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

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

    PubMed

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

    1991-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Dogan, Nurcan

    2013-03-01

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

  11. 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.

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

    PubMed Central

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

    2015-01-01

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

  13. 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

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

    PubMed

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

    2003-01-01

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

  15. Epithelial-mesenchymal transition in human cancer: comprehensive reprogramming of metabolism, epigenetics, and differentiation.

    PubMed

    Li, Linna; Li, Wenliang

    2015-06-01

    The epithelial-mesenchymal transition (EMT) is a developmental process that is important for embryogenesis, wound healing, organ fibrosis, and cancer metastasis. Cancer-associated EMT is not a simple process to acquire migration and invasion ability, but a complicated and comprehensive reprogramming, involved in metabolism, epigenetics and differentiation, through which differentiated epithelial cancer cells reverse to an undifferentiated state, not only expressing stem cell markers, but also acquiring stem cell-like functions. Here we review recent ideas and discoveries that illustrate the links among metabolism, epigenetics, and dedifferentiation during EMT, with special emphasis on the primary driving force and ultimate goal of cancer-associated EMT - of the energy and for the energy. Furthermore, we highlight on the specificity of epigenetic modification during EMT, with an aim to explain how the repression of epithelial genes and activation of mesenchymal genes are coordinated simultaneously through EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on epigenetic and metabolic levels, and discuss its potential for clinical application. PMID:25595324

  16. 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

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

    PubMed

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

    2015-12-15

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

  18. 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

  19. A systematic approach identifies FOXA1 as a key factor in the loss of epithelial traits during the epithelial-to-mesenchymal transition in lung cancer

    PubMed Central

    2013-01-01

    Background The epithelial-to-mesenchymal transition is an important mechanism in cancer metastasis. Although transcription factors including SNAIL, SLUG, and TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown transcription factors could also be involved. Identification of the full complement of transcription factors is essential for a more complete understanding of gene regulation in this process. Chromatin immunoprecipitation-sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding of transcription factors; here, we developed a systematic approach to integrate existing ChIP-Seq and transcriptome data. We scanned multiple transcription factors to investigate their functional impact on the epithelial-to-mesenchymal transition in the human A549 lung adenocarcinoma cell line. Results Among the transcription factors tested, impact scores identified the forkhead box protein A1 (FOXA1) as the most significant transcription factor in the epithelial-to-mesenchymal transition. FOXA1 physically associates with the promoters of its predicted target genes. Several critical epithelial-to-mesenchymal transition effectors involved in cellular adhesion and cellular communication were identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG, and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition via its regulatory network indicates that FOXA1 may play an important role in the initiation of lung cancer metastasis. Conclusions We identified FOXA1 as a potentially important transcription factor and negative regulator in the initial stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to-mesenchymal transition via its transcriptional regulatory network. Further, this study demonstrates how ChIP-Seq and expression data could be integrated to delineate the impact of transcription factors on a specific biological process. PMID:24093963

  20. DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

    PubMed Central

    REITER, MAXIMILIAN; BAUMEISTER, PHILIPP; JAISER, SONJA; REISS, ANDREAS; SCHWENK-ZIEGER, SABINA; KLEINSASSER, NORBERT; HARRÉUS, ULRICH

    2012-01-01

    Tobacco-associated nitrosamines are known carcinogens causing DNA damage in epithelial cells of the head and neck. A matched case-control study was performed to evaluate the sensitivity of patients with squamous cell cancer (SCC) of the oropharynx, and controls to tobacco-associated nitrosamines. Quantitative DNA repair was evaluated following a period of 15 and 30 min. Fresh biopsies from 100 male donors of macroscopically healthy oropharyngeal cells and lymphocytes (50 SCC patients and 50 controls) were incubated with N-nitrosodiethylamine (NDEA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosonornicotine (NNN). DNA damage in epithelial cells and lymphocytes was assessed using the comet assay. Following incubation with NDEA, cells underwent a period of DNA repair. All of the nitrosamines caused equivalent genotoxic damage in mucosal cells and lymphocytes of the two groups. Lymphocyte DNA repair capacity in the control group (26.8 and 37.1% after 15 and 30 min) was comparable to the tumor group (23.6 and 40.6%). However, epithelial cell DNA repair capacity of carcinoma patients was significantly reduced to 17.1% (15 min) and 23% (30 min) compared to the DNA repair of the control group (36.2%, 15 min and 46.0%, 30 min). Mutagen sensitivity was comparable in patients and controls. Thus, reduced epithelial cell DNA repair capacity of tumor patients is a possible endogenous risk factor for the development of head and neck squamous cell cancer. PMID:22740863

  1. Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition

    PubMed Central

    Piao, Junjie; Sun, Jie; Han, Longzhe; Chen, Liyan; Yan, Guanghai; Lin, Zhenhua

    2016-01-01

    Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer. PMID:26933912

  2. Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women

    PubMed Central

    Palmieri, Rachel T.; Wilson, Melanie A.; Iversen, Edwin S.; Clyde, Merlise A.; Calingaert, Brian; Moorman, Patricia G.; Poole, Charles; Anderson, A. Rebecca; Anderson, Stephanie; Anton-Culver, Hoda; Beesley, Jonathan; Hogdall, Estrid; Brewster, Wendy; Carney, Michael E.; Chen, Xiaoqing; Chenevix-Trench, Georgia; Chang-Claude, Jenny; Cunningham, Julie M.; DiCioccio, Richard A.; Doherty, Jennifer A.; Easton, Douglas F.; Edlund, Christopher K.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Goode, Ellen L.; Goodman, Marc T.; Kjaer, Susanne Kruger; Hogdall, Claus K; Hopkins, Michael P.; Jenison, Eric L.; Blaakaer, Jan; Lurie, Galina; McGuire, Valerie; Menon, Usha; Moysich, Kirsten B.; Ness, Roberta B.; Pearce, Celeste Leigh; Pharoah, Paul D.P.; Pike, Malcolm C.; Ramus, Susan J.; Rossing, Mary Anne; Song, Honglin; Terada, Keith Y.; Van Den Berg, David; Vierkant, Robert A.; Wang-Gohrke, Shan; Webb, Penelope M.; Whittemore, Alice S.; Wu, Anna H.; Ziogas, Argyrios; Berchuck, Andrew; Schildkraut, Joellen M.

    2009-01-01

    Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNPs) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (p=0.002) with a <25% chance of being a false positive finding (q-value=0.240). Using a multivariate model search algorithm over eleven IL18 tagging SNPs, we found the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (OR=1.24, 95% CI: 1.06, 1.45). In a replication stage, twelve independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (OR=0.99, 95% CI: 0.94, 1.05) when data from the twelve OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial NCO data. This analysis demonstrates the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. PMID:19064572

  3. Surgical treatment pattern and outcomes in epithelial ovarian cancer patients from a cancer institute in Kerala, India

    PubMed Central

    Georgeena, P; Rajanbabu, Anupama; Vijaykumar, DK; Pavithran, K; Sundaram, KR; Deepak, KS; Sanal, MR

    2016-01-01

    Objective To evaluate the treatment and survival pattern of patients with advanced epithelial ovarian cancer. Methods and results Retrospective study of all advanced epithelial ovarian cancer patients treated in the department of gynaecologic oncology from an academic centre, in a four year period from 1 January 2008–31 December 2011. Selection criteria All patients with advanced epithelial ovarian cancer (stage III and IV) who underwent surgery from 2008–2011and had a follow-up of at least three months after completion of treatment were included. The decision on whether primary surgery or neoadjuvant chemotherapy (NACT) in advanced ovarian cancer was based on age, performance status, clinical and imaging findings. Results A total of 178 cases of epithelial ovarian cancer were operated on during this four year period. Among them 28 patients were recurrent cases, 22 had early stages of ovarian cancer, and the rest 128 had stage III and IV ovarian cancer. In these 128 patients, 50(39.1%) underwent primary surgery and 78(60.9%) had NACT followed by surgery. In the primary surgery group 36(72.0%) patients had optimal debulking while in the NACT group 59(75.6%) patient had optimal debulking. With a median follow-up of 34 months, the median overall survival (OS) and progression free survival (PFS) was 53 and 49 months respectively. Patients who underwent primary surgery had better median PFS than patients who had NACT (56 months versus 39 months, p = 0.002). In stage III C the difference median PFS was significant for those treated with primary surgery when compared with NACT (55 months versus 39 months, p = 0.012). In patients who had optimal debulking to no residual disease (n = 90), primary surgery gave a significant improved PFS (59 months versus 38 months, p = 0.001) when compared with NACT. In univariate analysis, NACT was associated with increased risk of death (HR: 0.350; CI: 0.177–0.693). Conclusion In advanced epithelial ovarian cancer, primary surgery

  4. 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

  5. Influence of stromal-epithelial interactions on breast cancer in vitro and in vivo.

    PubMed

    Potter, Shirley M; Dwyer, Roisin M; Hartmann, Marion C; Khan, Sonja; Boyle, Marie P; Curran, Catherine E; Kerin, Michael J

    2012-01-01

    Stromal cell-secreted chemokines including CCL2 have been implicated in the primary tumor microenvironment, as mediators of tumor cell migration, proliferation, and angiogenesis. Expression of CCL2 and its principal receptor CCR2 was analyzed by RQ-PCR in primary tumor cells and breast cancer cell lines. Breast cancer cell lines (MDA-MB-231, T47D) were co-cultured directly on a monolayer of primary breast tumor and normal stromal cells, retrieved using EpCAM+ magnetic beads, and changes in expression of CCL2, CCR2, MMP11, ELK1, VIL2, and Ki67 detected by RQ-PCR. Epithelial cell migration and proliferation in response to stromal cell-secreted factors was also analyzed. In vivo, tumor xenografts were formed by co-injecting T47D cells with primary tumor stromal cells. Following establishment, tumors were harvested and digested, epithelial cells retrieved and analyzed by RQ-PCR. Whole tumor tissue was also analyzed by immunohistochemistry for CD31 and the VIL2 encoded protein Ezrin. Tumor stromal cells expressed significantly higher levels of CCL2 than normal cells, with no CCR2 expression detected. Primary epithelial cells and breast cancer cell lines expressed elevated CCL2, with relative expression of CCR2 found to be higher than the ligand. Interaction of breast cancer epithelial cells with primary tumor, but not normal stromal cells, stimulated increased expression of CCL2 (8-fold), ELK1 (6-fold), VIL2 (6-fold), and MMP11 (17-fold). Factors secreted by stromal cells, including CCL2, stimulated a significant increase in epithelial cell migration, with no effect on cell proliferation in vitro observed. In vivo, the presence of stromal cells resulted in tumors of increased volume, mediated at least in part through neoangiogenesis demonstrated by immunohistochemistry (CD31). Admixed tumor xenografts exhibited increased expression of Ki67, MMP11, VIL2, and ELK1. Elevated Ezrin protein was also detected, with increased cytoplasmic localization. The results presented

  6. 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

  7. 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

  8. The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

    PubMed Central

    Demirkan, Binnaz

    2013-01-01

    Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK), receptor activator of nuclear kappa ligand (RANKL), vitamin D, bone sialoprotein (BSP), osteopontin (OPN), and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ), insulin-like growth factor I & II (IGF I & II), platelet-derived growth factor (PDGF), parathyroid hormone-related protein (PTH(rP)), vascular endothelial growth factor (VEGF), epithelial growth factors II/I (ErbB/EGF), interleukin 6 (IL-6), IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs), catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP), and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention. PMID:26237148

  9. Role of Glycans in Cancer Cells Undergoing Epithelial-Mesenchymal Transition.

    PubMed

    Li, Xiang; Wang, Xin; Tan, Zengqi; Chen, Si; Guan, Feng

    2016-01-01

    The term "cancer" refers to a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Epithelial-mesenchymal transition (EMT), a process whereby epithelial cells lose their cell polarity and cell-cell adhesion ability, and acquire migratory and invasive properties to gain mesenchymal phenotype, is an important step leading to tumor metastasis. Glycans, such as N-glycans, O-glycans, and glycosphingolipids, are involved in numerous biological processes, including inflammation, virus/bacteria-host interactions, cell-cell interactions, morphogenesis, and cancer development and progression. Aberrant expression of glycans has been observed in several EMT models, and the functional roles of such glycans in cancer development and progression has been investigated. We summarize here recent research progress regarding the functions of glycans in cancer cells undergoing EMT. Better understanding of the mechanisms underlying aberrant glycan patterns in EMT and cancer will facilitate the development of such glycans as cancer biomarkers or as targets in design and synthesis of anti-tumor drugs. PMID:26925388

  10. SIX1 coordinates with TGFβ signals to induce epithelial-mesenchymal transition in cervical cancer

    PubMed Central

    Sun, Shu-Hua; Liu, Dan; Deng, Yun-Te; Zhang, Xiao-Xue; Wan, Dong-Yi; Xi, Bi-Xin; Huang, Wei; Chen, Qian; Li, Meng-Chen; Wang, Ming-Wei; Yang, Fei; Shu, Ping; Wu, Ke-Zhi; Gao, Qing-Lei

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a critical role in promoting tumor invasion and metastasis. However, the key cofactors that modulate the signal transduction to induce EMT have note been fully explored to date. The present study reports that sine oculis homeobox homolog 1 (SIX1) is able to promote EMT of cervical cancer by coordinating with transforming growth factor (TGF)β-SMAD signals. The expression of SIX1 was negatively correlated with the expression of the epithelial marker E-cadherin in two independent groups of cervical cancer specimens. SIX1 could promote the transition of mesenchymal phenotype in the presence of active TGFβ signals in vitro and in vivo. TGFβ-SMAD signals were required for the SIX1-mediated promotion of EMT and metastatic capacity of cervical cancer cells. Together, SIX1 and TGFβ cooperated to induce more remarkable changes in the transition of phenotype than each of them alone, and coordinated to promote cell motility and tumor metastasis in cervical cancer. These results suggest that the coordination of SIX1 and TGFβ signals may be crucial in the EMT program, and that SIX1/TGFβ may be considered a valuable marker for evaluating the metastatic potential of cervical cancer cells, or a therapeutic target in the treatment of cervical cancer. PMID:27446426

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

    PubMed Central

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

    2006-01-01

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

  12. Dose-survival relationship for epithelial cells of human skin after multifraction irradiation: evaluation by a quantitative method in vivo

    SciTech Connect

    Arcangeli, G.; Mauro, F.; Nervi, C.; Withers, H.R.

    1980-07-01

    The dose-survival relationship for normal epithelial cells after single and fractionated radiation exposures has been established by Withers for the mouse, but it is not available for humans according to a strict criterion for survival of single cell reproductive integrity. In an attempt to obtain such a quantitative estimation, 2 patients requiring radical radiation therapy to the chest wall were treated according to particular Multiple Daily Fractionation (MDF) protocols: i) 250 + 150 + 150 rad/day, 4 hr interval, 5 days/week; and ii) 150 + 150 + 150 + 150 rad/day, 3.5 hr interval, 5 days/week. In both cases, different strips of skin received different total doses: 6300, 6850, and 7150 rad, and 6300, 6750, and 7200 rad, respectively. In case (i), moist desquamation appeared and thereafter repopulating colonies of epithelium could be recognized and counted. Using these counts a survival curve having a D/sub o/ value of 490 +- 150 rad was estimated according to the formula proposed by Withers. In case (ii), no moist desquamation was reached at the doses delivered. The difference observed may imply that the initial region of the survival curve deviates appreciably from exponential between doses of 150 and 250 rad. If such is the case, a /sub 1/D/sub o/ value of 490 rad may represent an underestimate. These results are discussed from the point of view of both the shape of the survival curve and the effectiveness of nonconventional fractionation courses.

  13. 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

  14. 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

  15. Intake of specific carotenoids and the risk of epithelial ovarian cancer.

    PubMed

    Zhang, Min; Holman, C D'Arcy J; Binns, Colin W

    2007-07-01

    There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, few studies have examined the association between intake of specific carotenoids and the risk of epithelial ovarian cancer and the results for carotenoids have been inconclusive. To investigate whether the intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and lycopene is inversely associated with ovarian cancer risk, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer and 652 age-matched controls were randomly recruited during the same period. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable FFQ. The US Department of Agriculture nutrient composition database was used to calculate the intake of specific carotenoids. Unconditional logistic regression analyses were used to estimate OR and 95 % CI, accounting for age, locality, education, BMI, smoking, tea drinking, parity, oral contraceptive use, hormone replacement therapy, menopausal status, family history of ovarian cancer, physical activity and energy intake. Compared with the highest v. the lowest quartile of intake, the adjusted OR were 0.39 (95 % CI 0.23, 0.66) for alpha-carotene, 0.51 (95 % CI 0.31, 0.84) for beta-carotene, 0.51 (95 % CI 0.31, 0.83) for beta-cryptoxanthin, 0.45 (0.27, 0.76) for lutein and zeaxanthin, and 0.33 (95 % CI 0.20, 0.56) for total carotenoids, with statistically significant tests for trend. It is concluded that a higher intake of carotenoids can reduce the risk of epithelial ovarian cancer. PMID:17367574

  16. 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

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

    PubMed

    Gonzaga, Evelyn R

    2009-01-01

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

  18. Flotillin-1 protein is upregulated in human endometrial cancer and localization shifts from epithelial to stromal with increasing tumor grade.

    PubMed

    Winship, Amy Louise; Rainczuk, Kate; Dimitriadis, Evdokia

    2016-01-01

    Endometrial cancer is the most common invasive gynecological malignancy. Flotillin-1 is an integral membrane protein and estrogen responsive gene. Flotillin-1 expression and localization in human endometrial cancers grades 1-3 was investigated using real-time RT-PCR and immunohistochemistry. Flotillin-1 mRNA levels were unchanged in endometrial cancer versus benign endometrium. Flotillin-1 protein was significantly reduced in the epithelial compartment with increasing tumor grade, although levels increased in the tumor stroma across grades. We have identified a novel factor in human endometrial cancer and observed a shift in epithelial to stromal localization with increasing tumor grade in women. PMID:26682635

  19. 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

  20. Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor.

    PubMed

    Meyer-Hoffert, Ulf; Wu, Zhihong; Schröder, Jens-Michael

    2009-01-01

    Kallikreins-related peptidases (KLKs) are serine proteases and have been implicated in the desquamation process of the skin. Their activity is tightly controlled by epidermal protease inhibitors like the lympho-epithelial Kazal-type inhibitor (LEKTI). Defects of the LEKTI-encoding gene serine protease inhibitor Kazal type (Spink)5 lead to the absence of LEKTI and result in the genodermatose Netherton syndrome, which mimics the common skin disease atopic dermatitis. Since many KLKs are expressed in human skin with KLK5 being considered as one of the most important KLKs in skin desquamation, we proposed that more inhibitors are present in human skin. Herein, we purified from human stratum corneum by HPLC techniques a new KLK5-inhibiting peptide encoded by a member of the Spink family, designated as Spink9 located on chromosome 5p33.1. This peptide is highly homologous to LEKTI and was termed LEKTI-2. Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin. Spink9 mRNA expression was detected in human skin samples and in cultured keratinocytes. LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5. At sites of plantar hyperkeratosis, LEKTI-2 expression was increased. We suggest that LEKTI-2 contributes to the regulation of the desquamation process in human skin by specifically inhibiting KLK5. PMID:19190773

  1. 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

  2. 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

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

    PubMed Central

    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. PMID:27119108

  4. Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial-mesenchymal transition.

    PubMed

    Zhang, Q; Wei, T; Shim, K; Wright, K; Xu, K; Palka-Hamblin, H L; Jurkevich, A; Khare, S

    2016-06-16

    Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241-5253). We investigated the mechanisms by which SPRY regulates epithelial-mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3' untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1(-/-) and Spry2(-/-) double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis. PMID:26434583

  5. 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

  6. Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer. A Continuing Debate.

    PubMed

    Piver

    1996-01-01

    If instead of the title "Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," the title were "Drug X Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," there would be great media and medical attention worldwide to such a report. Correctly so. Regrettably, there probably is no new Drug X in the foreseeable future that will significantly reduce the death rate from ovarian cancer, be it Taxol®, taxotere, topotecan, gemcitabine, or liposomal doxorubicin-although each may result in significant responses and some prolongation of median survival. Epithelial ovarian cancer is a much more complex disease than anyone envisioned, when it was believed that extensive debulking surgery and the newest cytotoxic chemotherapy would radically reduce the death rate from ovarian cancer in the United States. Over 20 years after the first patient was treated with cisplatin for epithelial ovarian cancer, the annual death rate from ovarian cancer continued to increase. Just in the past decade, the number of women in the United States dying from ovarian cancer has increased 18% (Fig. 1) [1]. Although ovarian cancer is estimated to account for 26,700 cases and 14,800 deaths in 1996, it is a low-prevalence disease in comparison with breast cancer, which in 1996 is estimated to account for 185,700 cases and 44,560 deaths. Inexplicably, similar to breast cancer, the lifetime risk for ovarian cancer in the United States continues to increase. The most recent Surveillance, Epidemiology and End Results (SEER) calculations of lifetime risk for ovarian cancer are that 1 in 55 women will develop ovarian cancer over their lifetime, or 1.8%, up from the 1970 figures of 1 in 70, or 1.4% [2]. The 1.8% baseline lifetime risk for the general population is used to estimate the lifetime risk of known ovarian cancer risk factors (Table 1). Even utilizing what are now believed to be two of the most effective cytotoxic drugs against stage III and IV epithelial

  7. Aquaporin 3 promotes epithelial-mesenchymal transition in gastric cancer

    PubMed Central

    2014-01-01

    Background Gastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC. Methods AQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines. Results AQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC. Conclusions AQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment. PMID:24887009

  8. 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

  9. 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

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

    PubMed

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

    2013-01-01

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

  11. 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

  12. CD133 initiates tumors, induces epithelial-mesenchymal transition and increases metastasis in pancreatic cancer

    PubMed Central

    Nomura, Alice; Banerjee, Sulagna; Chugh, Rohit; Dudeja, Vikas; Yamamoto, Masato; Vickers, Selwyn M.; Saluja, Ashok K.

    2015-01-01

    CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer. However, the functional role of this surface glycoprotein in the cancer stem cell remains elusive. In this study, we determined that CD133 overexpression induced “stemness” properties in MIA-PaCa2 cells along with increased tumorigenicity, tumor progression, and metastasis in vivo. Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion. EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects. This study showed that CD133 expression contributes to pancreatic cancer “stemness,” tumorigenicity, EMT induction, invasion, and metastasis. PMID:25829252

  13. Role of the stem cell niche in the pathogenesis of epithelial ovarian cancers

    PubMed Central

    Flesken-Nikitin, Andrea; Odai-Afotey, Ashley A; Nikitin, Alexander Yu

    2014-01-01

    Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Recent extensive genomic analyses of epithelial ovarian cancer (EOC), particularly the most common and deadly form of high-grade serous ovarian carcinoma, have provided important insights into the repertoire of molecular aberrations that are characteristic for this malignancy. However, interpretation of the discovered aberrations is complicated because the origin and mechanisms of progression of EOC remain uncertain. Here, we summarize current views on the cell of origin of EOC and discuss recent findings of a cancer-prone stem cell niche for ovarian surface epithelium, one of the major likely sources of EOC. We also outline future directions and challenges in studying the role of stem cell niches in EOC pathogenesis. PMID:27308341

  14. 4.1N suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer cells.

    PubMed

    Zhang, Letian; Hu, Ajin; Li, Mengrui; Zhang, Hongquan; Ren, Caixia; An, Xiuli; Liu, Congrong

    2016-01-01

    Protein 4.1N (4.1N) is a member of the protein 4.1 family and is essential for the regulation of cell adhesion, motility and signaling. Previous studies have suggested that 4.1N may serve a tumor suppressor role. However, the molecular mechanisms remain unclear. In the current study, the role of 4.1N in the downregulation of hypoxia‑induced factor 1α (HIF‑1α) under hypoxic conditions and therefore the suppression of hypoxia induced epithelial‑mesenchymal transition (EMT) was investigated. The data were obtained from overexpressed and knockdown 4.1N epithelial ovarian cancer (EOC) cell lines. It was identified that 4.1N was capable of regulating the sub‑cellular localization and expression levels of HIF‑1α, by which 4.1N served a dominant role in the suppression of hypoxia‑induced EMT and associated genes. Collectively, the data of the current study identified 4.1N as an inhibitor of hypoxia‑induced tumor progression in EOC cells and highlighted its potential role in EOC therapy. PMID:26648170

  15. 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.

  16. Association between ambient ultraviolet radiation and risk of epithelial ovarian cancer.

    PubMed

    Tran, Bich; Jordan, Susan J; Lucas, Robyn; Webb, Penelope M; Neale, Rachel

    2012-11-01

    Evidence is accumulating to suggest that higher exposure to solar ultraviolet radiation (UVR) is associated with decreased risk of internal cancers, but data for ovarian cancer are unclear. We aimed to examine the association between lifetime ambient UVR and ovarian cancer in a population-based-case-control study. The study included women aged 18 to 79 years with a new diagnosis of invasive (n = 1,215) or borderline (n = 285) epithelial ovarian cancer identified through a network of clinics and state cancer registries throughout Australia. Controls (n = 1,459), frequency matched to cases by age (5-year groups) and state of residence, were randomly selected from the National Electoral Roll. We asked participants to report where they had lived at different periods of their life and assigned an estimate of UVR using data from NASA's Total Ozone Mapping Spectrometer database (1997-2003). We estimated the association between ambient UVR and risk of ovarian cancer using conditional logistic regression adjusted for potential confounders. Women in the highest third of average daily ambient UVR over their lifetime were at significantly lower risk of all epithelial ovarian cancers than those in the lowest third [OR, 0.70; 95% confidence interval (CI), 0.56-0.88]. The inverse association was stronger for borderline tumors (0.47, 0.31-0.71) than invasive tumors (0.78, 0.61-1.00). The effect sizes for overall and borderline tumors were unchanged after adjusting for confounders, whereas the inverse association for invasive tumors was attenuated. These data suggest that exposure to ambient UVR may reduce the risk of ovarian cancer. PMID:23034146

  17. 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

  18. The immunomodulating roles of glycoproteins in epithelial ovarian cancer

    PubMed Central

    Patankar, Manish S.; Gubbels, Jennifer A.A.; Felder, Mildred; Connor, Joseph P.

    2015-01-01

    The complexity of the immune system demands an intricate defense mechanism by tumors. Ovarian and other tumors employ specific glycoproteins and the associated glycan sequences to modulate immune responses. Glycoproteins enable tumor cells that express or secrete these molecules to evade immune cell attack and induce the immune system to promote tumor growth. This review focuses first on the immune environment in ovarian cancer, and the mechanisms of activation and inhibition that immune cells undergo in order to either attack or ignore a target cell. Next we illustrate the immunomodulatory roles of ovarian cancer-associated glycans and glycoproteins in 1. preventing immune synapse formation, 2. serving as ligands of immune cell receptors, 3. scavenging cytokines and chemokines, and 4. participating in the formation of autoantibodies against the tumor. The importance of these immunomodulating strategies from the view points of understanding the tumor immunology of ovarian tumors, potential origin of such mechanisms, and specific strategies to circumvent the glycoconjugate-mediated suppression of immune responses is discussed in this review. PMID:22201900

  19. 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

  20. 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

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

    MedlinePlus

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

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

    PubMed

    Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué

    2015-10-01

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

  3. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Aust, Stefanie; Knogler, Thomas; Pils, Dietmar; Obermayr, Eva; Reinthaller, Alexander; Zahn, Lisa; Radlgruber, Ilja; Mayerhoefer, Marius Erik; Grimm, Christoph; Polterauer, Stephan

    2015-01-01

    Objective Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients. Methods We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis. Results Muscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively). Conclusion MA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA. PMID:26457674

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

    PubMed Central

    Katiyar, Santosh K.

    2010-01-01

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

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

    MedlinePlus

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

  6. 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

  7. PEBP4 silencing inhibits hypoxia-induced epithelial-to-mesenchymal transition in prostate cancer cells.

    PubMed

    Li, Weiping; Dong, Yongchao; Zhang, Bin; Kang, Yindong; Yang, Xukai; Wang, He

    2016-07-01

    Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family and has been reported to be upregulated in various cancer types. The definite function of PEBP4 in regulating the EMT of prostate cancer, however, is still unclear. Here, we examined the functional role of PEBP4 and the underlying molecular mechanisms in hypoxia-induced EMT in prostate cancer cells. Our results showed that PEBP4 mRNA and protein expression was markedly increased in the human prostate cancer tissues and cell lines. Knockdown of PEBP4 significantly inhibited hypoxia-induced migration/invasion and EMT program. Furthermore, knockdown of PEBP4 prevented hypoxia-induced the expression of p-Akt and p-mTOR in prostate cancer cells. Taken together, this study reported here provided evidence that knockdown of PEBP4 inhibited hypoxia-induced EMT in prostate cancer cells. Our study uncovered a novel role for PEBP4 in prostate cancer progression, which might support the potential for PEBP4 targeting in prostate cancer therapy. PMID:27261570

  8. The mechanism between epithelial mesenchymal transition in breast cancer and hypoxia microenvironment.

    PubMed

    Gao, Tong; Li, Jia-Zhi; Lu, Ying; Zhang, Chun-Ying; Li, Qing; Mao, Jun; Li, Lian-Hong

    2016-05-01

    Hypoxia microenvironment widely exists in solid tumor tissues, which is mainly due to the rapid growth of cells within the tumor more than the speed of capillary in neoplasm, resulting in tumor tissue hypoxia. In hypoxia, hypoxia inducible factor 1 (HIF-1) is activated and regulate the expression of a series of hypoxia inducible genes, resulting in a series of hypoxia adaptation reaction. Researchs proved that, HIF-1 is closely related to the invasion, metastasis, prognosis of the tumor, and the expression of HIF-1 is higher in metastatic tissues compared with primary cancer tissues. In the evolution process of breast cancer, epithelial mesenchymal transition (EMT) define the characteristics of migration and invasion of breast cancer cells, which can also allow cancer cells to acquire the ability of self-renewing and stemness, so as to promote the generation of breast cancer stem cells. The incidence of EMT cancer stem cells are higher within the resistant to conventional treatment. This review focuses on breast cancer (stem cells), targeting the mechanism between hypoxia and EMT in tumor (stem cells), with the purpose of finding the new therapy to breast cancer. PMID:27133080

  9. 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

  10. CPEB1 mediates epithelial-to-mesenchyme transition and breast cancer metastasis.

    PubMed

    Nagaoka, K; Fujii, K; Zhang, H; Usuda, K; Watanabe, G; Ivshina, M; Richter, J D

    2016-06-01

    In mouse mammary epithelial cells, cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the apical localization of ZO-1 mRNA, which encodes a critical tight junction component. In mice lacking CPEB1 and in cultured cells from which CPEB has been depleted, randomly distributed ZO-1 mRNA leads to the loss of cell polarity. We have investigated whether this diminution of polarity results in an epithelial-to-mesenchyme (EMT) transition and possible increased metastatic potential. Here, we show that CPEB1-depleted mammary epithelial cells alter their gene expression profile in a manner consistent with an EMT and also become motile, which are made particularly robust when cells are treated with transforming growth factor-β, an enhancer of EMT. CPEB1-depleted mammary cells become metastatic to the lung following injection into mouse fat pads while ectopically expressed CPEB1 prevents metastasis. Surprisingly, CPEB1 depletion causes some EMT/metastasis-related mRNAs to have shorter poly(A) tails while other mRNAs to have longer poly(A) tails. Matrix metalloproteinase 9 (MMP9) mRNA, which encodes a metastasis-promoting factor, undergoes poly(A) lengthening and enhanced translation upon CPEB reduction. Moreover, in human breast cancer cells that become progressively more metastatic, CPEB1 is reduced while MMP9 becomes more abundant. These data suggest that at least in part, CPEB1 regulation of MMP9 mRNA expression mediates metastasis of breast cancer cells. PMID:26411364

  11. 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

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

    PubMed

    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

  13. Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression

    PubMed Central

    SUN, BO; FANG, YANTIAN; LI, ZHENYANG; CHEN, ZONGYOU; XIANG, JIANBIN

    2015-01-01

    Currently, cancer metastases remain a major clinical problem that highlights the importance of recognition of the metastatic process in cancer diagnosis and treatment. A critical process associated with the metastasis process is the transformation of epithelial cells toward the motile mesenchymal state, a process called epithelial-mesenchymal transition (EMT). Increasing evidence suggests the crucial role of the cytoskeleton in the EMT process. The cytoskeleton is composed of the actin cytoskeleton, the microtubule network and the intermediate filaments that provide structural design and mechanical strength that is necessary for the EMT. The dynamic reorganization of the actin cytoskeleton is a prerequisite for the morphology, migration and invasion of cancer cells. The microtubule network is the cytoskeleton that provides the driving force during cell migration. Intermediate filaments are significantly rearranged, typically switching from cytokeratin-rich to vimentin-rich networks during the EMT process, accompanied by a greatly enhanced cell motility capacity. In the present review, the recent novel insights into the different cytoskeleton underlying EMT are summarized. There are numerous advances in our understanding of the fundamental role of the cytoskeleton in cancer cell invasion and migration. PMID:26405532

  14. Medical treatment of early stage and rare histological variants of epithelial ovarian cancer.

    PubMed

    Cont, Nicoletta Tomasi; Ferrero, Annamaria; Peccatori, Fedro Alessandro; D'Alonzo, Marta; Codacci-Pisanelli, Giovanni; Colombo, Nicoletta; Biglia, Nicoletta

    2015-01-01

    Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient's performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients' quality of life. PMID:26557882

  15. 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

  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. Medical treatment of early stage and rare histological variants of epithelial ovarian cancer

    PubMed Central

    Cont, Nicoletta Tomasi; Ferrero, Annamaria; Peccatori, Fedro Alessandro; D’Alonzo, Marta; Codacci-Pisanelli, Giovanni; Colombo, Nicoletta; Biglia, Nicoletta

    2015-01-01

    Epithelial ovarian cancer is often considered a single pathological entity, but increasing evidence suggests that it is rather a group of different neoplasms, each with unique pathological characteristics, molecular features, and clinical behaviours. This heterogeneity accounts for the different sensitivity to antineoplastic drugs and makes the treatment of ovarian tumours a challenge. For early-stage disease, as well as for heavily pre-treated patients with recurrent ovarian cancer, the benefit of chemotherapy remains uncertain. Clear-cell, mucinous, low-grade serous, and endometrioid carcinomas show different molecular characteristics, which require different therapeutic approaches. In the era of personalised cancer medicine, understanding the pathogenesis and the genetic background of each subtype of epithelial ovarian tumour may lead to a tailored therapy, maximising the benefits of specific treatments and possibly reducing the side effects. Furthermore, personal factors, such as the patient’s performance status, should be taken into account in the management of ovarian cancer, with the aim of safeguarding the patients’ quality of life. PMID:26557882

  18. Epithelial-mesenchymal interaction mechanisms leading to the over-expression of neprilysin are involved in the UVB-induced formation of wrinkles in the skin.

    PubMed

    Imokawa, Genji

    2016-08-01

    In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive UVB irradiation of animal skin at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. That also elicits a marked alteration in the three-dimensional structure of elastic fibres, which is closely associated with a subsequent reduction in the elastic properties of the skin. While UVB irradiation stimulates the activity of skin fibroblast-derived elastase in the dermis, a synthetic inhibitor specific for skin fibroblast-derived elastase as well as an extract of Zingiber officinale (L.) Rose capable of inhibiting skin fibroblast-derived elastase, but not neutrophil elastase, prevented wrinkle formation in our studies of animal and human facial skin, respectively. The close interrelationship among wrinkle formation, elastic properties and elastic fibre linearity is revealed by the effects of different concentrations of the elastase inhibitor, which indicates that enhanced elastase activity by dermal fibroblasts plays a pivotal role in the UVB wrinkling mechanism. Fortunately, we were able to identify human skin fibroblast-derived elastase as the previously known enzyme neprilysin/neutral endopeptidase. Using both a UVB-conditioned medium assay and a co-culture system, we characterized the epithelial-mesenchymal interaction between keratinocytes and fibroblasts which leads to increased expression of neprilysin at the transcriptional, translational and enzymatic levels. Our results demonstrate that interleukin-1α and granulocyte-macrophage colony-stimulating factor are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by skin fibroblasts. PMID:27539896

  19. 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

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

    PubMed

    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. Lithium chloride induces mesenchymal‑to‑epithelial reverting transition in primary colon cancer cell cultures.

    PubMed

    Costabile, Valeria; Duraturo, Francesca; Delrio, Paolo; Rega, Daniela; Pace, Ugo; Liccardo, Raffaella; Rossi, Giovanni Battista; Genesio, Rita; Nitsch, Lucio; Izzo, Paola; De Rosa, Marina

    2015-05-01

    Epithelial‑to‑mesenchymal transition (EMT) confers stem cell‑like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E‑cadherin decreases, resulting in loss of cell‑cell adhesion and increased migration. Expression of Twist1 and other pleiotropic transcription factors, such as Snail, is known to activate EMT. We established primary colon cancer cell cultures from samples of operated patients and validated cultures by cytogenetic and molecular biology approaches. Western blot assay, quantitative real‑time PCR and immunofluorescence were performed to investigate the expression of E‑cadherin, vimentin, β‑catenin, cytokeratin‑20 and ‑18, Twist1, Snail, CD44, cyclooxygenase‑2 (COX2), Sox2, Oct4 and Nanog. Moreover, cell differentiation was induced by incubation with LiCl‑containing medium for 10 days. We observed that these primary colorectal cancer (CRC) cells lost expression of the E‑cadherin epithelial marker, which was instead expressed in cancer and normal colon mucosa of the same patient, while overexpressed vimentin (mesenchymal marker), Twist1, Snail (EMT markers) and COX2. Cytokeratin‑18 was expressed both in tissues and cell cultures. Expression of stem cell markers, such as CD44, Oct4 and Nanog, were also observed. Following differentiation with the glycogen synthase kinase 3β (GSK3β) inhibitor LiCl, the cells began to express E‑cadherin and, at once, Twist1 and Snail expression was strongly downregulated, suggesting a MET‑reverting process. In conclusion, we established primary colon mesenchymal cancer cell cultures expressing mesenchymal and epithelial biomarkers together with high level of EMT transcription factors. We propose that they could represent a good model for studying EMT and its reverting mechanism, the mesenchymal‑to‑epithelial transition (MET). Our observation indicates that LiCl, a GSK3β inhibitor, induces MET in vitro, suggesting that LiCl and GSK3β could represent

  3. 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

  4. Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression.

    PubMed

    Greening, David W; Gopal, Shashi K; Mathias, Rommel A; Liu, Lin; Sheng, Jingyi; Zhu, Hong-Jian; Simpson, Richard J

    2015-04-01

    Epithelial-mesenchymal transition (EMT) is a highly conserved process defined by the loss of epithelial characteristics, and acquisition of the mesenchymal phenotype. In addition to its central role in development, EMT has been implicated as a cellular process during tumourigenesis which facilitates tumour cell invasion and metastasis. The EMT process has been largely defined by signal transduction networks and transcriptional factors that activate mesenchymal-associated gene expression. Knowledge of secretome components that influence EMT including secreted proteins/peptides and membrane-derived extracellular vesicles (EVs) (i.e., exosomes) has emerged. Here we review EV cargo associated with inducing the hallmarks of EMT and cancer progression, modulators of cell transformation, invasion/migration, angiogenesis, and components involved in establishing the metastatic niche. PMID:25721809

  5. 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

  6. HDAC inhibition impedes epithelial-mesenchymal plasticity and suppresses metastatic, castration-resistant prostate cancer.

    PubMed

    Ruscetti, M; Dadashian, E L; Guo, W; Quach, B; Mulholland, D J; Park, J W; Tran, L M; Kobayashi, N; Bianchi-Frias, D; Xing, Y; Nelson, P S; Wu, H

    2016-07-21

    PI3K (phosphoinositide 3-kinase)/AKT and RAS/MAPK (mitogen-activated protein kinase) pathway coactivation 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 inhibitor LBH589, inhibits epithelial-mesenchymal plasticity and stemness activities in vitro and markedly 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 androgen receptor acetylation and in turn sensitizing castration-resistant mesenchymal-like tumor cells to androgen deprivation therapy. 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

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

    PubMed

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

    2009-11-01

    Metastasis is a complex multistep process, which requires the concerted action of many genes and is the primary cause of cancer death. Both pathways that regulate metastasis enhancement and those that regulate its suppression contribute to the tumour dissemination process. To identify new metastasis suppressors, we set up a forward genetic screen in a mouse model. We transduced a genome-wide RNA interference (RNAi) library into the non-metastatic 168FARN breast cancer cell line and orthotopically transplanted the cells into mouse mammary fat pads. We then selected cells that could metastasize to the lung and identified an RNAi for the KLF17 gene. Conversely, we demonstrate that ectopic expression of KLF17 in a highly metastatic 4T1 breast cancer cell line inhibits the ability of cells 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 protein functions by directly binding to the promoter region of Id1 (which encodes a key metastasis regulator in breast cancer) to inhibit its transcription. Finally, we demonstrate that KLF17 expression is significantly downregulated in primary human breast cancer samples and that the combined expression pattern of KLF17 and Id1 can serve as a potential biomarker for lymph node metastasis in breast cancer. PMID:19801974

  8. 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

  9. Bioinformatic approaches to augment study of epithelial-to-mesenchymal transition in lung cancer.

    PubMed

    Beck, Tim N; Chikwem, Adaeze J; Solanki, Nehal R; Golemis, Erica A

    2014-10-01

    Bioinformatic approaches are intended to provide systems level insight into the complex biological processes that underlie serious diseases such as cancer. In this review we describe current bioinformatic resources, and illustrate how they have been used to study a clinically important example: epithelial-to-mesenchymal transition (EMT) in lung cancer. Lung cancer is the leading cause of cancer-related deaths and is often diagnosed at advanced stages, leading to limited therapeutic success. While EMT is essential during development and wound healing, pathological reactivation of this program by cancer cells contributes to metastasis and drug resistance, both major causes of death from lung cancer. Challenges of studying EMT include its transient nature, its molecular and phenotypic heterogeneity, and the complicated networks of rewired signaling cascades. Given the biology of lung cancer and the role of EMT, it is critical to better align the two in order to advance the impact of precision oncology. This task relies heavily on the application of bioinformatic resources. Besides summarizing recent work in this area, we use four EMT-associated genes, TGF-β (TGFB1), NEDD9/HEF1, β-catenin (CTNNB1) and E-cadherin (CDH1), as exemplars to demonstrate the current capacities and limitations of probing bioinformatic resources to inform hypothesis-driven studies with therapeutic goals. PMID:25096367

  10. 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.

  11. 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. PMID:26644004

  12. 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

  13. A pilot study of an exercise & cognitive behavioral therapy intervention for epithelial ovarian cancer patients

    PubMed Central

    2013-01-01

    Background Ovarian cancer has the highest mortality rate of all gynaecologic cancers. Faced with poor prognoses, stressful treatment effects and a high likelihood of recurrence, survivors must confront significant physical and psychological morbidities that negatively impact health-related quality of life. Frequently reported side effects include cancer-related fatigue, peripheral neuropathy, and psychological distress. Exercise and cognitive behavioral therapy interventions have counteracted such adverse effects in other cancer populations. Objective To investigate the feasibility and benefits of a 24-week home-based exercise intervention, coordinated with 12 weeks of cognitive behavioral therapy (two sessions per month), developed for two types of patients diagnosed with epithelial ovarian cancer: 1) those undergoing primary treatment with adjuvant chemotherapy after primary surgery; 2) those on surveillance after completing treatment within the last 2 years. Methods Participants were recruited from the Gynaecologic Oncology Clinic. Eligible participants completed baseline assessments and were provided with home-based exercise equipment. Cognitive behavioral therapy was provided every other week for patients via telephone. Assessments were completed at baseline (T1), 3 months (T2) and 6 months (T3). Results 19 of the 46 eligible patients approached were enrolled, with 7 patients in the treatment group and 12 in the surveillance group. There was a significant within group increase in peak VO2 from baseline to 6 months: F(2,16) = 5.531, p = 0.015, partial η2 = 0.409. Conclusion The combined 6-month exercise-cognitive behavioral therapy intervention was associated with significant increases in aerobic fitness in epithelial ovarian cancer patients assessed. These improvements were similar regardless of whether the patient was receiving chemotherapy or under surveillance. PMID:23557323

  14. 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

  15. 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

  16. 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

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

    PubMed Central

    Bulman, Amanda; Neagu, Monica; Constantin, Carolina

    2013-01-01

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

  18. 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

  19. IL1{beta}-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

    SciTech Connect

    Zhu, Yingting; Zhu, Min; Lance, Peter

    2012-11-15

    COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1{beta} in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1{beta}, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1{beta}. Further analysis indicated that the major COX-2 product, prostaglandin E{sub 2}, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1{beta}. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1{beta} in the fibroblasts.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. The role of KLF4 in UVB-induced murine skin tumor development and its correlation with cyclin D1, p53, and p21(Waf1/Cip1) in epithelial tumors of the human skin.

    PubMed

    Choi, Woo Jin; Youn, Sung Hwan; Back, Jung Ho; Park, Saebomi; Park, Eun Joo; Kim, Kwang Joong; Park, Hye Rim; Kim, Arianna L; Kim, Kwang Ho

    2011-04-01

    The zinc-finger-type transcriptional factor KLF4 is expressed in a variety of tissues including skin. KLF4 can function as either a tumor suppressor or an oncogene, depending on the type of tissue in which it is expressed, by modulating the expression of various factors. To understand the role of KLF4 in human skin cancer and also to evaluate the expression of cyclin D1, p53, and p21(Waf1/Cip1) in relation to the expression of KLF4, we evaluated the pattern of KLF4 expression during UVB-induced skin tumor development in SKH-1 hairless mice and in human skin cancer. We also determined whether there are correlations between the expression of KLF4, cyclin D1, p53, and p21 and non-melanoma skin tumors. KLF4 expression was found in the basal layer of non-irradiated control murine skin. Chronic UVB irradiation caused a progressive decrease in KLF4 expression, which was substantially decreased in UVB-induced murine skin tumors. In human precancerous lesions, KLF4 expression was maintained in 64.3% of Bowen's disease samples and 90.0% of AK samples. In contrast, KLF4 expression was significantly reduced in human cancer lesions (p = 0.004). A positive correlation was found between the expression of KLF4 and p21(Waf1/Cip1) in AK, whereas there was a negative correlation between the expression of cyclin D1 and p21(Waf1/Cip1) in Bowen's disease. Thus, our results suggest that KLF4 may function as a tumor suppressor in the skin and that the deregulated expression of KLF4 in the context of p21(Waf1/Cip1) and cyclin D1 expression may be involved in skin tumorigenesis. PMID:21132436

  5. Use of Plasma Metabolomics to Identify Diagnostic Biomarkers for Early Stage Epithelial Ovarian Cancer

    PubMed Central

    Fan, Lijun; Yin, Mingzhu; Ke, Chaofu; Ge, Tingting; Zhang, Guangming; Zhang, Wang; Zhou, Xiaohua; Lou, Ge; Li, Kang

    2016-01-01

    The early detection of ovarian carcinoma is difficult due to the absence of recognizable physical symptoms and a lack of sensitive screening methods. The currently available biomarkers (such as CA125 and HE4) are insufficiently reliable to distinguish early stage (I/II) epithelial ovarian cancer (EOC) patients from normal individuals because they possess a relatively poor sensitivity and specificity. To evaluate the application of metabolomics to biomarker discovery in the early stages of epithelial ovarian cancer (EOC), plasma samples from 21 early stage EOC patients and 31 healthy controls were analyzed with ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-Tof/MS) in conjunction with multivariate statistical analysis. Eighteen metabolites, including lysophospholipids, 2-piperidone and MG (18:2), were found to be disturbed in early stage EOC with satisfactory diagnostic accuracy (AUC=0.920). These biomarkers were specifically validated in the EOC nude mouse model, and five of the biomarkers (lysophospholipids, adrenoyl ethanolamide et al.) were highly suspected of being associated with EOC because they were differentially expressed with the same tendency in the EOC nude mice versus normal controls. In conclusion, the selected metabolic biomarkers have considerable utility and significant potential for diagnosing early ovarian cancer and investigating its underlying mechanisms. PMID:27390602

  6. 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.

  7. MUC1 extracellular domain confers resistance of epithelial cancer cells to anoikis

    PubMed Central

    Zhao, Q; Piyush, T; Chen, C; Hollingsworth, M A; Hilkens, J; Rhodes, J M; Yu, L-G

    2014-01-01

    Anoikis, a special apoptotic process occurring in response to loss of cell adhesion to the extracellular matrix, is a fundamental surveillance process for maintaining tissue homeostasis. Resistance to anoikis characterises cancer cells and is a pre-requisite for metastasis. This study shows that overexpression of the transmembrane mucin protein MUC1 prevents initiation of anoikis in epithelial cancer cells in response to loss of adhesion. We show that this effect is largely attributed to the elongated and heavily glycosylated extracellular domain of MUC1 that protrudes high above the cell membrane and hence prevents activation of the cell surface anoikis-initiating molecules such as integrins and death receptors by providing them a mechanically ‘homing' microenvironment. As overexpression of MUC1 is a common feature of epithelial cancers and as resistance to anoikis is a hallmark of both oncogenic epithelial–mesenchymal transition and metastasis, MUC1-mediated cell resistance to anoikis may represent one of the fundamental regulatory mechanisms in tumourigenesis and metastasis. PMID:25275599

  8. 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

  9. IKK inhibitor suppresses epithelial-mesenchymal transition and induces cell death in prostate cancer.

    PubMed

    Ping, Hao; Yang, Feiya; Wang, Mingshuai; Niu, Yinong; Xing, Nianzeng

    2016-09-01

    IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway activation is a key event in the acquisition of invasive and metastatic capacities in prostate cancer. A potent small-molecule compound, BMS-345541, was identified as a highly selective IKKα and IKKβ inhibitor to inhibit kinase activity. This study explored the effect of IKK inhibitor on epithelial-mesenchymal transition (EMT), apoptosis and metastasis in prostate cancer. Here, we demonstrate the role of IKK inhibitor reducing proliferation and inducing apoptosis in PC-3 cells. Furthermore, BMS345541 inhibited IκBα phosphorylation and nuclear level of NF-κB/p65 in PC-3 cells. We also observed downregulation of the N-cadherin, Snail, Slug and Twist protein in a dose-dependent manner. BMS‑345541 induced upregulation of the epithelial marker E-cadherin and phosphorylated NDRG1 at protein level. Moreover, BMS‑345541 reduced invasion and metastasis of PC-3 cells in vitro. In conclusion, IKK has a key role in both EMT and apoptosis of prostate cancer. IKK inhibitor can reverse EMT and induce cell death in PCa cells. IKK was identified as a potential target structure for future therapeutic intervention in PCa. PMID:27432067

  10. Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

    PubMed Central

    Carriere, Patrick P.; Llopis, Shawn D.; Naiki, Anna C.; Nguyen, Gina; Phan, Tina; Nguyen, Mary M.; Preyan, Lynez C.; Yearby, Letitia; Pratt, Jamal; Burks, Hope; Davenport, Ian R.; Nguyen, Thu A.; Parker-Lemieux, KiTani; Payton-Stewart, Florastina; Williams, Christopher C.; Boué, Stephen M.; Burow, Matthew E.; Collins-Burow, Bridgette; Hilliard, Aaron; Davidson, A. Michael; Tilghman, Syreeta L.

    2015-01-01

    Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer. PMID:26703648

  11. Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm.

    PubMed

    Garson, Kenneth; Vanderhyden, Barbara C

    2015-02-01

    The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer. PMID:25301968

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

    PubMed Central

    Greaves, Mel

    2014-01-01

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

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

    PubMed

    Glanz, Karen; Mayer, Joni A

    2005-08-01

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

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

    PubMed

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

    2015-02-01

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

  15. Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Yoon, Ji-Young; Koo, Yu-Jin; Kim, Mi-Jung; Kim, Tae-Jin; Lim, Kyung-Taek

    2014-01-01

    Objective To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. Methods Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. Results Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. Conclusion IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study. PMID:25469337

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

    PubMed Central

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

    2016-01-01

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

  17. Biological role and clinical implications of homeobox genes in serous epithelial ovarian cancer.

    PubMed

    Miller, Katherine R; Patel, Jai N; Ganapathi, Mahrukh K; Tait, David L; Ganapathi, Ram N

    2016-06-01

    Homeobox (HOX) genes are a family of transcription factors that are essential regulators of development. HOX genes play important roles in normal reproductive physiology, as well as in the development and progression of serous carcinomas, the predominant and most aggressive subtype of epithelial ovarian cancer (EOC). This review discusses aberrant HOX gene expression in serous EOC and its impact on tumor development and progression. Further identification of HOX target genes may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of patients with serous EOC. PMID:26957480

  18. The miR-200 Family: Versatile Players in Epithelial Ovarian Cancer.

    PubMed

    Muralidhar, Goda G; Barbolina, Maria V

    2015-01-01

    The role of microRNAs (miRNAs or miRs) in the pathology of epithelial ovarian cancer (EOC) has been extensively studied. Many miRNAs differentially expressed in EOC as compared to normal controls have been identified, prompting further inquiry into their role in the disease. miRNAs belonging to the miR-200 family have repeatedly surfaced over multiple profiling studies. In this review, we attempt to consolidate the data from different studies and highlight mechanisms by which these miRNAs influence progression of metastasis and chemo-resistance in EOC. PMID:26213923

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

    PubMed Central

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

    2015-01-01

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

  20. 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

  1. 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

  2. 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

  3. 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. PMID:27188428

  4. Black tea polyphenols reverse epithelial-to-mesenchymal transition and suppress cancer invasion and proteases in human oral cancer cells.

    PubMed

    Chang, Yu-Chao; Chen, Pei-Ni; Chu, Shu-Chen; Lin, Chin-Yin; Kuo, Wu-Hsien; Hsieh, Yih-Shou

    2012-08-29

    Epithelial-to-mesenchymal transition (EMT) in cancer cells is considered to be a prerequisite for acquiring invasive/migratory phenotype and subsequent metastasis. This study provides molecular evidence associated with the antimetastatic effect of black tea polyphenol extracts (BTE), which contain polyphenols including gallic acid, gallocatechin, catechin, epigallocatechin-3-gallate, epicatechin-3-gallate, and theaflavin 3,3'-digallate, in an an oral squamous cell culture system by showing a nearly complete inhibition on the invasion (p < 0.001) of SCC-4 cells via reduced activities of MMP-2 (p < 0.001) and u-PA (p < 0.001). Immunoblot was performed to find that BTE could induce up-regulation of epithelial markers such as E-cadherin and inhibit mesenchymal markers such as snail-1 and vimentin. BTE inhibited p-FAK and p-paxillin, indicating the anti-EMT effect of BTE in oral squamous cell carcinoma. BTE was evidenced by its inhibition of the tumor growth of SCC-4 cells via cancer cell xenografted nude mice mode. These results suggested that BTE could reduce invasion by reversing EMT in human oral cancer cells. PMID:22827697

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

    PubMed

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  7. 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

  8. Dual Infection and Superinfection Inhibition of Epithelial Skin Cells by Two Alphaherpesviruses Co-Occur in the Natural Host

    PubMed Central

    Jarosinski, Keith W.

    2012-01-01

    Hosts can be infected with multiple herpesviruses, known as superinfection; however, superinfection of cells is rare due to the phenomenon known as superinfection inhibition. It is believed that dual infection of cells occurs in nature, based on studies examining genetic exchange between homologous alphaherpesviruses in the host, but to date, this has not been directly shown in a natural model. In this report, gallid herpesvirus 2 (GaHV-2), better known as Marek’s disease virus (MDV), was used in its natural host, the chicken, to determine whether two homologous alphaherpesviruses can infect the same cells in vivo. MDV shares close similarities with the human alphaherpesvirus, varicella zoster virus (VZV), with respect to replication in the skin and exit from the host. Recombinant MDVs were generated that express either the enhanced GFP (eGFP) or monomeric RFP (mRFP) fused to the UL47 (VP13/14) herpesvirus tegument protein. These viruses exhibited no alteration in pathogenic potential and expressed abundant UL47-eGFP or -mRFP in feather follicle epithelial cells in vivo. Using laser scanning confocal microscopy, it was evident that these two similar, but distinguishable, viruses were able to replicate within the same cells of their natural host. Evidence of superinfection inhibition was also observed. These results have important implications for two reasons. First, these results show that during natural infection, both dual infection of cells and superinfection inhibition can co-occur at the cellular level. Secondly, vaccination against MDV with homologous alphaherpesvirus like attenuated GaHV-2, or non-oncogenic GaHV-3 or meleagrid herpesvirus (MeHV-1) has driven the virus to greater virulence and these results implicate the potential for genetic exchange between homologous avian alphaherpesviruses that could drive increased virulence. Because the live attenuated varicella vaccine is currently being administered to children, who in turn could be superinfected

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

    PubMed

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

    2009-10-01

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

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

    PubMed

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

    2004-04-01

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

  11. 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 expos