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Sample records for human basal cell

  1. The human airway epithelial basal cell transcriptome.

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    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  2. Expression of basal cell keratins in human prostate cancer metastases and cell lines.

    NARCIS (Netherlands)

    Leenders, G.J.L.H. van; Aalders, M.W.; Hulsbergen-van de Kaa, C.A.; Ruiter, D.J.; Schalken, J.A.

    2001-01-01

    Within normal human prostate epithelium, basal and luminal cells can be discriminated by their expression of keratins (K). While basal cells express K5/14, luminal cells show expression of K8/18 and an intermediate cell population can be identified by co-expression of K5/18. Prostate cancer is predo

  3. Basal HIF-1a expression levels are not predictive for radiosensitivity of human cancer cell lines

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    Schilling, D.; Multhoff, G. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Helmholtz Center Munich, CCG - Innate Immunity in Tumor Biology, Munich (Germany). German Research Center for Environmental Health - Inst. of Pathology; Bayer, C.; Emmerich, K.; Molls, M.; Vaupel, P. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Dept. of Radiation Oncology; Huber, R.M. [Klinikum der Univ. Muenchen (Germany). Dept. of Pneumology

    2012-04-15

    High levels of hypoxia inducible factor (HIF)-1a in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1a on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1a levels. HIF-1a levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1a, HIF-2a, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1a siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. According to their basal HIF-1a status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1a expressors. The functionality of the high basal HIF-1a expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1a. Linear regression analysis revealed no correlation between basal HIF-1a levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. Our data suggest that basal HIF-1a levels in human tumor cell lines do not predict their radiosensitivity under normoxia. (orig.)

  4. Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates

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    Mohammad Moad

    2017-08-01

    Full Text Available Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1 enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.

  5. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise...... by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total...

  6. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J;

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise......, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused...... dermal area (expressed as mast cells per square millimeter). This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations...

  7. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

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    Huang, Li-Wen [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hsieh, Bau-Shan; Cheng, Hsiao-Ling [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hu, Yu-Chen [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chang, Wen-Tsan [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan (China); Chang, Kee-Lung, E-mail: Chang.KeeLung@msa.hinet.net [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  8. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells.

    Science.gov (United States)

    Huang, Li-Wen; Hsieh, Bau-Shan; Cheng, Hsiao-Ling; Hu, Yu-Chen; Chang, Wen-Tsan; Chang, Kee-Lung

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  9. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.

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    Salvador-Membreve, Daile Meek C; Jacinto, Sonia D; Rivera, Windell L

    2014-12-01

    Trichomonas vaginalis, the causative agent of trichomoniasis is generally known to inhabit the genitourinary tract. However, several case reports with supporting molecular and immunological identifications have documented its occurrence in the respiratory tract of neonates and adults. In addition, the reports have documented that its occurrence is associated with respiratory failures. The medical significance or consequence of this association is unclear. Thus, to establish the possible outcome from the interaction of T. vaginalis with lung cells, the cytopathic effects of the parasites were evaluated using monolayer cultures of the human lung alveolar basal carcinoma epithelial cell line A549. The possible effect of association of T. vaginalis with A549 epithelial cells was analyzed using phase-contrast, scanning electron microscopy and fluorescence microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal-violet and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assays were conducted for cytotoxicity testing. The results demonstrate that T. vaginalis: (1) adheres to A549 epithelial cells, suggesting a density-dependent parasite-cell association; (2) adherence on A549 is through flagella, membrane and axostyle; (3) causes cell detachment and cytotoxicity (50-72.4%) to A549 and this effect is a function of parasite density; and (4) induces apoptosis in A549 about 20% after 6 h of incubation. These observations indicate that T. vaginalis causes cytopathic effects on A549 cell. To date, this is the first report showing a possible interaction of T. vaginalis with the lung cells using A549 monolayer cultures. Further studies are recommended to completely elucidate this association.

  10. Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes.

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    Gunnarsson, Anders Patrik; Christensen, Rikke; Praetorius, Jeppe; Jensen, Uffe Birk

    2017-01-15

    Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization. Although CSPG4-positive basal cells express higher levels of Itgβ1 the colony-forming efficiency is slightly lower than CSPG4-negative basal cells. Sorting the directly isolated keratinocytes based on Itgβ1 did not reveal differences in colony-forming efficiency between keratinocytes expressing high or low levels of Itgβ1. However, after the first passage Itgβ1 could be used to predict colony-forming efficiency whether the culture was established from CSPG4-positive or CSPG4-negative basal cell keratinocytes. Although we were unable to detect differences in the colony-forming assay, global gene expression profiling showed that CSPG4-positive basal cell keratinocytes are distinct from CSPG4-negative basal cell keratinocytes. Our study demonstrates that it is possible to generate antibodies against trypsin-resistant epitopes of CSPG4. Our study also documents a marked change in behaviour upon cell culturing and challenges the way we assess for stemness within the human epidermal basal layer.

  11. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

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    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (ppolarimetry together with PLS statistics hold promise for automated pathology classification. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Vismodegib in basal cell carcinoma.

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    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  13. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

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    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  14. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

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    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  15. Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes

    DEFF Research Database (Denmark)

    Gunnarsson, Anders Patrik Alexander; Christensen, Rikke; Prætorius, Jeppe

    2016-01-01

    unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization. Although CSPG4-positive......Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been...... that CSPG4-positive basal cell keratinocytes are distinct from CSPG4-negative basal cell keratinocytes. Our study demonstrates that it is possible to generate antibodies against trypsin-resistant epitopes of CSPG4. Our study also documents a marked change in behaviour upon cell culturing and challenges...

  16. Natural killer cells and HLA-G expression in the basal decidua of human placenta adhesiva.

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    van Beekhuizen, H J; Joosten, I; Lotgering, F K; Bulten, J; van Kempen, L C

    2010-12-01

    Retained placenta is caused by abnormal adherence of the placenta to the uterine wall, leading to delayed expulsion of the placenta and causing postpartum haemorrhage. The mildest form of retained placenta is the placenta adhesiva (PA), of which the cause is unknown. The aim of our study was to explore possible differences in immune response in the basal decidua between PA and control placentas (CP). We performed a descriptive analysis of immunohistochemical differences in 17 PA and 10 CP. Our results show that in PA the amount of uterine natural killer (uNK) cells is significantly reduced (0.2 uNK cell/standardised area) as compared to CP (9.8 uNK cell/standardised area, p placenta.

  17. Sunlight exposure and cutaneous human papillomavirus seroreactivity in basal cell and squamous cell carcinomas of the skin.

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    Iannacone, Michelle R; Wang, Wei; Stockwell, Heather G; O'Rourke, Kathleen; Giuliano, Anna R; Sondak, Vernon K; Messina, Jane L; Roetzheim, Richard G; Cherpelis, Basil S; Fenske, Neil A; Michael, Kristina M; Waterboer, Tim; Pawlita, Michael; Rollison, Dana E

    2012-08-01

    Ultraviolet radiation exposure may interact synergistically with cutaneous human papillomavirus (HPV) infection in the development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin. To investigate differences in the risk of sunlight-associated BCC and SCC by cutaneous genus-specific HPV serostatus, a case-control study was conducted among 204 BCC and 156 SCC cases who were recruited from a university dermatology clinic and 297 controls who had no history of cancer and screened negative for current skin cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between measures of sunlight exposure and BCC/SCC, stratified by genus-specific HPV serostatus, with adjustment for age and sex. Sunburn due to cutaneous sensitivity to sunlight exposure (P = .006) and poor tanning ability (P = .003) were associated with a higher seroprevalence for genus beta HPV types. Poor or no tanning ability was more strongly associated with SCC among individuals who were seropositive for antibodies to cutaneous HPV types in genera alpha (OR, 15.60; 95% CI, 5.40-45.1; P = .01 for interaction) and beta (OR, 6.86; 95% CI, 3.68-12.80; P = .001 for interaction), compared with individuals who were seronegative for these HPV types. Seropositivity for HPV types in genera alpha or beta increased the risk of SCC associated with poor tanning ability.

  18. Nevoid basal cell carcinoma syndrome

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    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  19. Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma

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    Paolini Francesca

    2011-11-01

    Full Text Available Abstract Background The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC, is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC. The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. Methods The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. Results No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%, HPV100 (11,5% and HPV15 (11,5% all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3% with the highest percentages (> 30% of positive cells detected in 8 cases. A statistically significant (p = 0,012 increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%; in particular in HPV positive samples over-expressing p16INK4a. Conclusions Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15. The association of these viruses with the up

  20. Cryotherapy in basal cell carcinoma

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    Sandra A

    1999-01-01

    Full Text Available Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  1. Cadmium Malignantly Transforms Normal Human Breast Epithelial Cells into a Basal-like Phenotype

    OpenAIRE

    2009-01-01

    Background Breast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation. Methods Cells were continuously exposed to low-level cadmium (2.5 μM) and checked in vi...

  2. Knockdown of GSK3β increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells

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    Weikel, Karen A.; Cacicedo, José M.; Ruderman, Neil B.; Ido, Yasuo

    2016-01-01

    High concentrations of glucose and palmitate increase endothelial cell inflammation and apoptosis, events that often precede atherogenesis. They may do so by decreasing basal autophagy and AMP-activated protein kinase (AMPK) activity, although the mechanisms by which this occurs are not clear. Decreased function of the lysosome, an organelle required for autophagy and AMPK, have been associated with hyperactivity of glycogen synthase kinase 3β (GSK3β). To determine whether GSK3β affects nutrient-induced changes in autophagy and AMPK activity, we used a primary human aortic endothelial cell (HAEC) model of type 2 diabetes that we had previously characterized with impaired AMPK activity and autophagy [Weikel et al. (2015) Am. J. Phys. Cell Physiol. 308, C249–C263]. Presently, we found that incubation of HAECs with excess nutrients (25 mM glucose and 0.4 mM palmitate) increased GSK3β activity and impaired lysosome acidification. Suppression of GSK3β in these cells by treatment with a chemical inhibitor or overexpression of kinase-dead GSK3β attenuated these lysosomal changes. Under control and excess nutrient conditions, knockdown of GSK3β increased autophagosome formation, forkhead box protein O1 (FOXO1) activity and AMPK signalling and decreased Akt signalling. Similar changes in autophagy, AMPK and Akt signalling were observed in aortas from mice treated with the GSK3β inhibitor CHIR 99021. Thus, increasing basal autophagy and AMPK activity by inhibiting GSK3β may be an effective strategy in the setting of hyperglycaemia and dyslipidaemia for restoring endothelial cell health and reducing atherogenesis. PMID:27534430

  3. Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels.

    Science.gov (United States)

    Vinoth, Kumar Jayaseelan; Manikandan, Jayapal; Sethu, Swaminathan; Balakrishnan, Lakshmidevi; Heng, Alexis; Lu, Kai; Poonepalli, Anuradha; Hande, Manoor Prakash; Cao, Tong

    2015-01-01

    Previously, we demonstrated that undifferentiated human embryonic stem cells (hESC) displayed higher resistance to oxidative and genotoxic stress compared to somatic cells, but did not further probe the underlying mechanisms. Using H₂O₂-induced genotoxicity as a model, this study investigated whether higher resistance of hESC to oxidative and genotoxic stress could be due to lower innate basal intracellular levels of reactive oxygen species (ROS), as compared to their differentiated fibroblastic progenies (H1F) and two other somatic cell types - human embryonic palatal mesenchymal (HEPM) cells and peripheral blood lymphocytes (PBL). Comet assay demonstrated that undifferentiated hESC consistently sustained lower levels of DNA damage upon acute exposure to H₂O₂ for 30 min, compared to somatic cells. DCFDA and HE staining with flow cytometry showed that undifferentiated hESC had lower innate basal intracellular levels of reactive oxygen species compared to somatic cells, which could lead to their higher resistance to genotoxic stress upon acute exposure to H₂O₂.

  4. PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas.

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    Zaphiropoulos, P G; Undén, A B; Rahnama, F; Hollingsworth, R E; Toftgård, R

    1999-02-15

    By a combination of cDNA library screening, rapid amplification of cDNA ends analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 with 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to chromosome 1p33-34, a region often lost in a variety of tumors. Several alternatively spliced mRNA forms of PTCH2 were identified, including transcripts lacking segments thought to be involved in sonic hedgehog binding and mRNAs with differentially defined 3' terminal exons. In situ hybridization revealed high expression of PTCH2 transcripts in both familial and sporadic basal cell carcinomas in similarity to what has been observed for PTCH1, suggesting a negative regulation of PTCH2 by PTCH1. This finding tightly links PTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 has related, but yet distinct, functions than PTCH1.

  5. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  6. Screening of urocanic acid isomers in human basal and squamous cell carcinoma tumors compared with tumor periphery and healthy skin.

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    Decara, Juan Manuel; Aguilera, José; Abdala, Roberto; Sánchez, Purificación; Figueroa, Félix L; Herrera, Enrique

    2008-10-01

    Trans-urocanic acid is a major chromophore for ultraviolet (UV) radiation in human epidermis. The UV induces photoisomerization of trans-urocanic acid (tUCA) form to cis-urocanic acid (cUCA) and has been reported as an important mediator in the immunosuppression induced by UV. This immunomodulation has been recognized as an important factor related to skin cancer development. This is the first time that UCA isomers have been measured in epidermis of skin biopsies from patients with squamous cell carcinoma (SCC) and with basal cell carcinoma (BCC) and compared with the tumor periphery and biopsies of healthy photoexposed and non-photoexposed skin as controls. The UCA isomers were separated and quantified by high performance liquid chromatography. Analysis of UCA in healthy skin showed significant increase in total UCA content in non-photoexposed body sites compared with highly exposed skins. In contrast, the percentage of cUCA was higher in photoexposed body sites. Maximal levels of cUCA were found in cheek, forehead and forearm and lower levels in abdomen and thigh. No differences were found in total UCA concentration between the tumor samples and healthy photoexposed skin. However, differences were found in relation between isomers. Higher levels of cUCA were detected in SCC biopsies (44% of total UCA) compared with samples of BCC and that of healthy photoexposed skin (30%). These results suggest that the UV radiation exposure, a main factor in development of SCC can be mediated, apart from direct effect to cells (DNA damage), by immunosuppression pathways mediated by high production of cUCA.

  7. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells.

    Science.gov (United States)

    Pires, Maira M; Hopkins, Benjamin D; Saal, Lao H; Parsons, Ramon E

    2013-03-01

    Breast cancer can be classified into different molecular subtypes with varying clinical and pathological characteristics. The basal-like breast cancer subtype represents one of the most aggressive and lethal types of breast cancer, and due to poor mechanistic understanding, it lacks targeted therapy. Many basal-like breast cancer patient samples display alterations of established drivers of cancer development, including elevated expression of EGFR, p53 inactivating mutations and loss of expression of the tumor suppressor PTEN; however, their contribution to human basal-like breast cancer pathogenesis remains ill-defined. Using non-transformed human mammary epithelial cells, we set out to determine whether altering EGFR, p53 and PTEN in different combinations could contribute to basal-like breast cancer progression through transformation of cells. Altering PTEN in combination with either p53 or EGFR in contrast to any of the single alterations caused increased growth of transformed colonies in soft agar. Concomitantly modifying all three genes led to the highest rate of cellular proliferation and the greatest degree of anchorage-independent colony formation. Results from our effort to engineer a model of BBC expressing alterations of EGFR, p53 and PTEN suggest that these changes are cooperative and likely play a causal role in basal-like breast cancer pathogenesis. Consideration should be given to targeting EGFR and restoring p53 and PTEN signaling simultaneously as a strategy for treatment of this subtype of breast cancer.

  8. Determination of the relationship between basal cell carcinoma and human papilloma virus, based on immunohistochemistry staining method

    Directory of Open Access Journals (Sweden)

    Mokhtari M

    2009-01-01

    Full Text Available Background: Basal cell carcinoma (BCC is the most common skin cancer among Caucasians, and in most cases, occurs in the sun-exposed areas. In recent years, in addition to many other etiologies such as exposure to UV radiation, and occasionally xeroderma pigmentosa, burns, tattoos, and pox scars, human papillomavirus (HPV is also considered to have an etiologic role. Different studies were conducted with varied results in this regard. Aims: We evaluate this plausible relationship between HPV and BCC by means of immunohistochemistry (IHC staining method. Methods: This is an analytic cross-sectional study in which 160 samples were selected randomly consisting of 80 BCC lesions and 80 safe margins. Sampling was done among paraffin-embedded blocks in pathology ward of Kashani and Alzahra hospitals, Isfahan-Iran, from 2004-2007. A section of each block was IHC stained for HPV immunoreactivity (DAKO, Denmark. This was followed by microscopic evaluation in terms of being positive or negative. Results: Fifty seven point five percent of the samples belonged to men and the others to women. In 10%, HPV marker was positive, both in lesion and margin. In 83.8% neither the lesions nor the margins were immunoreactive for HPV. Only in 5 cases (6.3% the lesion was positive and the margin was negative for this marker. There was no case of immunoreactivity for HPV marker in margins, while it was negative in lesions. Our study results followed by McNemar analysis did not show a significant relationship between BCC incidence and HPV existence. This was consistent in both genders ( P > 0.05, power > 90%. Conclusion: In this study we did not find a significant relationship between BCC and HPV, but based on review of articles it appears that large multicentric studies are to be conducted in this regard.

  9. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  10. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  11. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  12. High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B cells contributes to influenza A virus resistance.

    Directory of Open Access Journals (Sweden)

    Lai-Giea Seng

    Full Text Available Respiratory epithelial cells play a key role in influenza A virus (IAV pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77 IAVs in normal primary human bronchial epithelial (NHBE and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN regulatory factor-7 (IRF-7, stimulator of IFN genes (STING and IFN stimulated genes (ISGs. Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.

  13. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  14. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  15. Protein degradation rate is the dominant mechanism accounting for the differences in protein abundance of basal p53 in a human breast and colorectal cancer cell line.

    Science.gov (United States)

    Lakatos, Eszter; Salehi-Reyhani, Ali; Barclay, Michael; Stumpf, Michael P H; Klug, David R

    2017-01-01

    We determine p53 protein abundances and cell to cell variation in two human cancer cell lines with single cell resolution, and show that the fractional width of the distributions is the same in both cases despite a large difference in average protein copy number. We developed a computational framework to identify dominant mechanisms controlling the variation of protein abundance in a simple model of gene expression from the summary statistics of single cell steady state protein expression distributions. Our results, based on single cell data analysed in a Bayesian framework, lends strong support to a model in which variation in the basal p53 protein abundance may be best explained by variations in the rate of p53 protein degradation. This is supported by measurements of the relative average levels of mRNA which are very similar despite large variation in the level of protein.

  16. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R;

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed...

  17. Human mesenchymal stromal cells could deliver erythropoietin and migrate to the basal layer of hair shaft when subcutaneously implanted in a murine model.

    Science.gov (United States)

    Mok, P L; Cheong, S K; Leong, C F; Chua, K H; Ainoon, O

    2012-08-01

    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.

  18. Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells.

    Science.gov (United States)

    Lovelace, Erica S; Maurice, Nicholas J; Miller, Hannah W; Slichter, Chloe K; Harrington, Robert; Magaret, Amalia; Prlic, Martin; De Rosa, Stephen; Polyak, Stephen J

    2017-01-01

    Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects. In the HIV-negative setting, SM treatment showed trends towards suppressing pro-inflammatory cytokines from non-activated and pathogen-associated molecular pattern (PAMP)-activated primary human monocytes, and non-activated and cytokine- and T cell receptor (TCR)-activated mucosal-associated invariant T (MAIT) cells. The data suggest that SM elicits broad anti-inflammatory and immunoregulatory activity in primary human immune cells. By using novel compounds to alter cellular inflammatory status, it may be possible to regulate inflammation in both non-disease and disease states.

  19. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  20. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1988-11-15

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  1. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  2. Classification of basal cell carcinoma in human skin using machine learning and quantitative features captured by polarization sensitive optical coherence tomography.

    Science.gov (United States)

    Marvdashti, Tahereh; Duan, Lian; Aasi, Sumaira Z; Tang, Jean Y; Ellerbee Bowden, Audrey K

    2016-09-01

    We report the first fully automated detection of basal cell carcinoma (BCC), the most commonly occurring type of skin cancer, in human skin using polarization-sensitive optical coherence tomography (PS-OCT). Our proposed automated procedure entails building a machine-learning based classifier by extracting image features from the two complementary image contrasts offered by PS-OCT, intensity and phase retardation (PR), and selecting a subset of features that yields a classifier with the highest accuracy. Our classifier achieved 95.4% sensitivity and specificity, validated by leave-one-patient-out cross validation (LOPOCV), in detecting BCC in human skin samples collected from 42 patients. Moreover, we show the superiority of our classifier over the best possible classifier based on features extracted from intensity-only data, which demonstrates the significance of PR data in detecting BCC.

  3. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiulong, E-mail: songxiulong@hotmail.com; Wei, Zhengxi; Shaikh, Zahir A., E-mail: zshaikh@uri.edu

    2015-08-15

    Cadmium (Cd) is a common environmental toxicant and an established carcinogen. Epidemiological studies implicate Cd with human breast cancer. Low micromolar concentrations of Cd promote proliferation of human breast cancer cells in vitro. The growth promotion of breast cancer cells is associated with the activation of MAPK/ERK pathway. This study explores the mechanism of Cd-induced activation of MAPK/ERK pathway. Specifically, the role of cell surface receptors ERα, EGFR, and Src kinase was evaluated in human breast cancer MCF-7 cells treated with 1–3 μM Cd. The activation of ERK was studied using a serum response element (SRE) luciferase reporter assay. Receptor phosphorylation was detected by Western blot analyses. Cd treatment increased both the SRE reporter activity and ERK1/2 phosphorylation in a concentration-dependent manner. Cd treatment had no effect on reactive oxygen species (ROS) generation. Also, blocking the entry of Cd into the cells with manganese did not diminish Cd-induced activation of MAPK/ERK. These results suggest that the effect of Cd was likely not caused by intracellular ROS generation, but through interaction with the membrane receptors. While Cd did not appear to activate either EGFR or Src kinase, their inhibition completely blocked the Cd-induced activation of ERK as well as cell proliferation. Similarly, silencing ERα with siRNA or use of ERα antagonist blocked the effects of Cd. Based on these results, it is concluded that not only ERα, but also basal activities of EGFR and Src kinase are essential for Cd-induced signal transduction and activation of MAPK/ERK pathway for breast cancer cell proliferation. - Highlights: • Low micromolar concentrations of Cd rapidly activate ERK1/2 in MCF-7 cells. • Signal transduction and resulting cell proliferation require EGFR, ERα, and Src. • These findings implicate Cd in promotion of breast cancer.

  4. Requirement of ERα and basal activities of EGFR and Src kinase in Cd-induced activation of MAPK/ERK pathway in human breast cancer MCF-7 cells.

    Science.gov (United States)

    Song, Xiulong; Wei, Zhengxi; Shaikh, Zahir A

    2015-08-15

    Cadmium (Cd) is a common environmental toxicant and an established carcinogen. Epidemiological studies implicate Cd with human breast cancer. Low micromolar concentrations of Cd promote proliferation of human breast cancer cells in vitro. The growth promotion of breast cancer cells is associated with the activation of MAPK/ERK pathway. This study explores the mechanism of Cd-induced activation of MAPK/ERK pathway. Specifically, the role of cell surface receptors ERα, EGFR, and Src kinase was evaluated in human breast cancer MCF-7 cells treated with 1-3μM Cd. The activation of ERK was studied using a serum response element (SRE) luciferase reporter assay. Receptor phosphorylation was detected by Western blot analyses. Cd treatment increased both the SRE reporter activity and ERK1/2 phosphorylation in a concentration-dependent manner. Cd treatment had no effect on reactive oxygen species (ROS) generation. Also, blocking the entry of Cd into the cells with manganese did not diminish Cd-induced activation of MAPK/ERK. These results suggest that the effect of Cd was likely not caused by intracellular ROS generation, but through interaction with the membrane receptors. While Cd did not appear to activate either EGFR or Src kinase, their inhibition completely blocked the Cd-induced activation of ERK as well as cell proliferation. Similarly, silencing ERα with siRNA or use of ERα antagonist blocked the effects of Cd. Based on these results, it is concluded that not only ERα, but also basal activities of EGFR and Src kinase are essential for Cd-induced signal transduction and activation of MAPK/ERK pathway for breast cancer cell proliferation.

  5. Use of Drawing Lithography-Fabricated Polyglycolic Acid Microneedles for Transdermal Delivery of Itraconazole to a Human Basal Cell Carcinoma Model Regenerated on Mice

    Science.gov (United States)

    Zhang, Jennifer; Wang, Yan; Jin, Jane Y.; Degan, Simone; Hall, Russell P.; Boehm, Ryan D.; Jaipan, Panupong; Narayan, Roger J.

    2016-04-01

    Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedgehog (SHH) signaling pathway. In this study, polyglycolic acid microneedle arrays and stainless steel microneedle arrays were used for transdermal delivery of itraconazole to a human BCC model which was regenerated on mice. One-by-four arrays of 642- μm-long polyglycolic acid microneedles with sharp tips were prepared using injection molding and drawing lithography. Arrays of 85 stainless steel 800- μm-tall microneedles attached to syringes were obtained for comparison purposes. Skin grafts containing devitalized split-thickness human dermis that had been seeded with human keratinocytes transduced to express human SHH protein were sutured to the skin of immunodeficient mice. Mice with this human BCC model were treated daily for 2 weeks with itraconazole dissolved in 60% dimethylsulfoxane and 40% polyethylene glycol-400 solution; transdermal administration of the itraconazole solution was facilitated by either four 1 × 4 polyglycolic acid microneedle arrays or stainless steel microneedle arrays. The epidermal tissues treated with polyglycolic acid microneedles or stainless steel microneedles were markedly thinner than that of the control (untreated) graft tissue. These preliminary results indicate that microneedles may be used to facilitate transdermal delivery of itraconazole for localized treatment of BCC.

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

    Science.gov (United States)

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

    2016-02-29

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

  7. Molecular characterization of Italian nevoid basal cell carcinoma syndrome patients.

    Science.gov (United States)

    Pastorino, L; Cusano, R; Nasti, S; Faravelli, F; Forzano, F; Baldo, C; Barile, M; Gliori, S; Muggianu, M; Ghigliotti, G; Lacaita, M G; Lo Muzio, L; Bianchi-Scarra, G

    2005-03-01

    Mutations in the PTCH gene, the human homolog of the Drosophila patched gene, have been found to lead to the autosomal dominant disorder termed Nevoid Basal Cell Carcinoma Syndrome (NBCCS, also called Gorlin Syndrome). Patients display an array of developmental anomalies and are prone to develop a variety of tumors, with multiple Basal Cell Carcinomas occurring frequently. We provide here the results of molecular testing of a set of Italian Nevoid Basal Cell Carcinoma Syndrome patients. Twelve familial patients belonging to 7 kindreds and 5 unaffected family members, 6 non-familial patients and an additional set of 7 patients with multiple Basal Cell Carcinoma but no other criteria for the disease were examined for mutations in the PTCH gene. All of the Nevoid Basal Cell Carcinoma Syndrome patients were found to carry variants of the PTCH gene. We detected nine novel mutations (1 of which occurring twice): 1 missense mutation (c.1436T>G [p.L479R]), 1 nonsense mutation (c.1138G>T [p.E380X]), 6 frameshift mutations (c.323_324ins2, c.2011_2012dup, c.2535_2536dup, c.2577_2583del, c.3000_3005del, c.3050_3051del), 1 novel splicing variant (c.6552A>T) and 3 mutations that have been previously reported (c.3168+5G>A, c.1526G>T [p.G509V], and c.3499G>A [p.G1167R]). None of the patients with multiple Basal Cell Carcinoma but no other criteria for the syndrome, carried germline coding region mutations.

  8. Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

    Science.gov (United States)

    Xiong, S. Y.; Yang, J. G.; Zhuang, J.

    2011-10-01

    In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

  9. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  10. Adenoid basal cell carcinoma and its mimics

    Directory of Open Access Journals (Sweden)

    Sujata Jetley

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common malignant tumor of skin. The most common site (80% is head and neck. BCC exhibits a varied morphology such as adenoid, keratotic, sebaceous, basosquamous, apocrine, eccrine or fibroepithelial. Tumors with a similar histopathological picture are cutaneous adenoid cystic carcinoma and primary cutaneous cribriform apocrine carcinoma. Immunohistochemistry, along with clinical findings, acts as an adjunct in reaching an accurate diagnosis. Here, we present an interesting case of adenoid BCC in a 55-year-old man.

  11. Basal Cell Carcinoma in Young Patients

    Directory of Open Access Journals (Sweden)

    Uğur Horoz

    2017-03-01

    Full Text Available Basal cell carcinoma (BCC is the most common type of skin cancer and has a direct relationship with chronic sun exposure. Other risk factors include fair skin and eyes, freckling, family history, genetic disorders, immunosuppression, ionizing radiation, arsenic, and polyaromatic hydrocarbons. BCC usually progresses slowly. Lesions are usually seen over sun-exposed areas, which are most commonly on the face and neck. Local invasion may occur, but it rarely metastasizes. The incidence of BCC peaks in the seventh decade of life. BCC is an uncommon lesion during childhood, youth, and pregnancy. It has rarely been reported during childhood. BCC seen during childhood can be inherited with diseases such as xeroderma pigmentosum, albinism, Bazex syndrome, and basal cell nevus syndrome or after high-dose radiotherapy. In this study, we present the cases of a 14-year-old girl with BCC on the right popliteal region and a 23-year-old pregnant woman with BCC on the nasal tip. Both patients underwent total excision, and there were neither recurrence nor any complication during the follow-up

  12. Basal cell nevus syndrome or Gorlin syndrome.

    Science.gov (United States)

    Thalakoti, Srikanth; Geller, Thomas

    2015-01-01

    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  13. DMBT1 promotes basal and meconium-induced nitric oxide production in human lung epithelial cells in vitro

    DEFF Research Database (Denmark)

    Müller, Hanna; Weiss, Christel; Renner, Marcus

    2017-01-01

    Meconium aspiration syndrome (MAS) is characterized by surfactant inactivation and inflammation. As lung epithelial cells up-regulate nitric oxide (NO) in response to inflammation, the NO production following meconium exposition was examined in relation to expression of Deleted in Malignant Brain...

  14. High fat diet promotes prostatic basal-to-luminal differentiation and accelerates initiation of prostate epithelial hyperplasia originated from basal cells

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    Oh-Joon Kwon

    2016-05-01

    Full Text Available Recent lineage tracing studies showed that the prostate basal and luminal cells in adult mice are two independent lineages under the physiological condition, but basal cells are capable of generating luminal progenies during bacterial infection-induced prostatitis. Because acute bacterial infection in human prostate tissues is relatively rare, the disease relevance of the bacterial infection-induced basal-to-luminal differentiation is uncertain. Herein we employ a high fat diet-induced sterile prostate inflammation model to determine whether basal-to-luminal differentiation can be induced by inflammation irrespective of the underlying etiologies. A K14-CreER model and a fluorescent report line are utilized to specifically label basal cells with the green fluorescent protein. We show that high fat diet promotes immune cell infiltration into the prostate tissues and basal-to-luminal differentiation. Increased cell proliferation accompanies basal-to-luminal differentiation, suggesting a concurrent regulation of basal cell proliferation and differentiation. This study demonstrates that basal-to-luminal differentiation can be induced by different types of prostate inflammation evolved with distinct etiologies. Finally, high fat diet also accelerates initiation and progression of prostatic intraepithelial neoplasia that are originated from basal cells with loss-of-function of the tumor suppressor Pten. Because prostate cancer originated from basal cells tends to be invasive, our study also provides an alternative explanation for the association between obesity and aggressive prostate cancer.

  15. Toxic Effects of the Major Components of Diesel Exhaust in Human Alveolar Basal Epithelial Cells (A549

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    Pavel Rossner

    2016-08-01

    Full Text Available We investigated the toxicity of benzo[a]pyrene (B[a]P, 1-nitropyrene (1-NP and 3-nitrobenzanthrone (3-NBA in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM, 1-NP (1 and 10 μM and 3-NBA (0.5 and 5 μM. Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression of CYP1A1, CYP1B1, NQO1, POR, AKR1C2 and COX2 were analyzed. Bulky DNA adducts were induced after both treatment periods; the effect of 1-NP was weak. 3-NBA induced high levels of bulky DNA adducts even after 4-h treatment, suggesting rapid metabolic activation. Oxidative DNA damage was not affected. 1-NP caused protein oxidation and weak induction of lipid peroxidation after 4-h incubation. 3-NBA induced lipid peroxidation after 24-h treatment. Unlike B[a]P, induction of the aryl hydrocarbon receptor, measured as mRNA expression levels of CYP1A1 and CYP1B1, was low after treatment with polycyclic aromatic hydrocarbon (PAH nitro-derivatives. All test compounds induced mRNA expression of NQO1, POR, and AKR1C2 after 24-h treatment. AKR1C2 expression indicates involvement of processes associated with reactive oxygen species generation. This was supported further by COX2 expression induced by 24-h treatment with 1-NP. In summary, 3-NBA was the most potent genotoxicant, whereas 1-NP exhibited the strongest oxidative properties.

  16. Basal Cell Nevus Syndrome. A Case Presentation

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    Ángel Luis Cruz Leiva

    2007-12-01

    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  17. Basal cell carcinoma in oculo-cutaneous albinism

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    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  18. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment. PMID:27828631

  19. Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms.

    Science.gov (United States)

    Lacour, J P

    2002-04-01

    Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.

  20. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

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    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  1. The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.

    LENUS (Irish Health Repository)

    Flanagan, Annabelle M

    2007-04-01

    Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies

  2. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    Science.gov (United States)

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  3. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    Science.gov (United States)

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  4. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    Science.gov (United States)

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  5. Immunohistochemical study of basal cell adenoma in the parotid gland.

    Science.gov (United States)

    Hamano, H; Abiko, Y; Hashimoto, S; Inoue, T; Shimono, M; Takagi, T; Noma, H

    1990-02-01

    Basal cell adenoma of the parotid gland was studied with immunohistochemical methods. We observed cells in the tumor with positive reaction to polyclonal keratin, prekeratin, monoclonal PKK-1, polyclonal S-100 protein, monoclonal S-100 protein (alpha), secretory component, actin and laminin. However, no cells which stained positively with monoclonal KL-1, amylase, carcinoembryonic antigen, or epithelial membrane antigen were recognized. From these immunohistochemical results and our ultrastructural observations reported previously, we conclude that the cells constituting the basal cell adenoma are ductal, myoepithelial, and squamous cells but not secretory ones. It is also suggested that the origins of basal cell ademona as well as those of pleomorphic and clear cell adenoma are undifferentiated cells of intercalated duct.

  6. Multiplexed coding in the human basal ganglia

    Science.gov (United States)

    Andres, D. S.; Cerquetti, D.; Merello, M.

    2016-04-01

    A classic controversy in neuroscience is whether information carried by spike trains is encoded by a time averaged measure (e.g. a rate code), or by complex time patterns (i.e. a time code). Here we apply a tool to quantitatively analyze the neural code. We make use of an algorithm based on the calculation of the temporal structure function, which permits to distinguish what scales of a signal are dominated by a complex temporal organization or a randomly generated process. In terms of the neural code, this kind of analysis makes it possible to detect temporal scales at which a time patterns coding scheme or alternatively a rate code are present. Additionally, finding the temporal scale at which the correlation between interspike intervals fades, the length of the basic information unit of the code can be established, and hence the word length of the code can be found. We apply this algorithm to neuronal recordings obtained from the Globus Pallidus pars interna from a human patient with Parkinson’s disease, and show that a time pattern coding and a rate coding scheme co-exist at different temporal scales, offering a new example of multiplexed neuronal coding.

  7. Clinical variants, stages, and management of basal cell carcinoma

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    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  8. Multiple superficial basal cell carcinomas (basalomatosis) following cobalt irradiation

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    Wollenberg, A.; Przybilla, B. [Muenchen Univ. (Germany). Dermatologische Klinik und Poliklinik; Peter, R.U. [Federal Armed Forces Medical Academy, Munich (Germany). Inst. of Radiobiology

    1995-10-01

    Basalomatosis is an uncommon skin condition characterized by the occurrence of multiple basal cell carcinomas. Many cases reported in the literature have been attributed to arsenic treatment in psoriasis patients. We report a patient with basalomatosis caused by cobalt-60 ({sup 60}Co) irradiation. A 55-year-old farmer developed 43 basal cell carcinomas 20 years after treatment of an immuno-blastoma with {sup 60}Co irradiation. All the tumours were located within the radiation fields. Other possible causes of basalomatosis, such as arsenic intoxication and basal cell naevus syndrome, were excluded. The patient`s multiple superficial basal cell carcinomas probably represent a late adverse effect of the {sup 60}Co irradiation. (Author).

  9. BASAL CELL CARCINOMA IN AN UNUSUAL SITE - VULVA

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    Sumangala G

    2016-06-01

    Full Text Available Basal cell carcinoma (BCC is the most common malignancy of the skin, but BCC of the vulva is a rare entity. BCC of vulva accounts for less than 5% of all vulvar neoplasms and less than 1% of all basal cell carcinomas. Vulvar basal cell carcinoma has a low propensity for metastatic spread but has a high chance of local recurrence after simple excision. We report a 50- year-old woman presenting with pruritus vulva. Physical examination revealed a 2.5 x 1.5 cm hyperpigmented plaque on the left labium majus. The histopathology was consistent with superficially invasive basal cell carcinoma. The patient underwent radical local excision including the clitoris and remained disease free at postsurgical follow-up after eight months.

  10. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion.

    Science.gov (United States)

    Florio, Marta; Albert, Mareike; Taverna, Elena; Namba, Takashi; Brandl, Holger; Lewitus, Eric; Haffner, Christiane; Sykes, Alex; Wong, Fong Kuan; Peters, Jula; Guhr, Elaine; Klemroth, Sylvia; Prüfer, Kay; Kelso, Janet; Naumann, Ronald; Nüsslein, Ina; Dahl, Andreas; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B

    2015-03-27

    Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

  11. TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Griewank, Klaus G; Murali, Rajmohan; Schilling, Bastian; Schimming, Tobias; Möller, Inga; Moll, Iris; Schwamborn, Marion; Sucker, Antje; Zimmer, Lisa; Schadendorf, Dirk; Hillen, Uwe

    2013-01-01

    Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors.

  12. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    Science.gov (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  13. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma

    OpenAIRE

    Torres, T.; I. Fernandes; Costa, V.; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  14. The relation between dermoscopy and histopathology of basal cell carcinoma*

    Science.gov (United States)

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Kemeriz, Funda

    2015-01-01

    BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. PMID:26131865

  15. Basal cell carcinomas in elderly patients treated by cryotherapy.

    Science.gov (United States)

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases.

  16. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    Science.gov (United States)

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  17. Clinicopathological evaluation of radiation induced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meibodi Naser

    2008-01-01

    Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

  18. Basal cell carcinomas in elderly patients treated by cryotherapy

    Directory of Open Access Journals (Sweden)

    Chiriac A

    2013-03-01

    Full Text Available Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain can be applied and resolve such cases. Keywords: basal cell carcinoma, cryotherapy

  19. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

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    Birgül Tepe

    2012-06-01

    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  20. Multiple jaw cysts not associated with basal cell nevus syndrome

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    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-09-15

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  1. GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

    Science.gov (United States)

    Abdou, Asmaa Gaber; Eldien, Marwa Mohammad Serag; Elsakka, Daliah

    2015-09-01

    Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

  2. Nevoid Basal Cell Carcinoma Syndrome : A Case Report

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    K Rajanikanth

    2004-01-01

    Full Text Available The nevoid basal cell carcinoma syndrome (NBCCS or Gorlin - Goltz syndrome is an autosomal disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The major organ systems involved are skin, bones, central nervous system, eyes, gonads and endocrine. This particular syndrome is extensively described in the literature under different names. However, there are only few cases reported in the Indian literature. An unusual case of a 33-year old male with large odontogenic keratocyst involving impacted canine in the mandible, along with multiple cysts and impacted teeth in the maxilla; bifid rib and vertebral anomalies has been described.

  3. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  4. Internalization and localization of basal insulin peglispro in cells.

    Science.gov (United States)

    Moyers, Julie S; Volk, Catherine B; Cao, Julia X C; Zhang, Chen; Ding, Liyun; Kiselyov, Vladislav V; Michael, M Dodson

    2017-10-15

    Basal insulin peglispro (BIL) is a novel, PEGylated insulin lispro that has a large hydrodynamic size compared with insulin lispro. It has a prolonged duration of action, which is related to a delay in insulin absorption and a reduction in clearance. Given the different physical properties of BIL compared with native insulin and insulin lispro, it is important to assess the cellular internalization characteristics of the molecule. Using immunofluorescent confocal imaging, we compared the cellular internalization and localization patterns of BIL, biosynthetic human insulin, and insulin lispro. We assessed the effects of BIL on internalization of the insulin receptor (IR) and studied cellular clearance of BIL. Co-localization studies using antibodies to either insulin or PEG, and the early endosomal marker EEA1 showed that the overall internalization and subcellular localization pattern of BIL was similar to that of human insulin and insulin lispro; all were rapidly internalized and co-localized with EEA1. During ligand washout for 4 h, concomitant loss of insulin, PEG methoxy group, and PEG backbone immunostaining was observed for BIL, similar to the loss of insulin immunostaining observed for insulin lispro and human insulin. Co-localization studies using an antibody to the lysosomal marker LAMP1 did not reveal evidence of lysosomal localization for insulin lispro, human insulin, BIL, or PEG using either insulin or PEG immunostaining reagents. BIL and human insulin both induced rapid phosphorylation and internalization of human IR. Our findings show that treatment of cells with BIL stimulates internalization and localization of IR to early endosomes. Both the insulin and PEG moieties of BIL undergo a dynamic cellular process of rapid internalization and transport to early endosomes followed by loss of cellular immunostaining in a manner similar to that of insulin lispro and human insulin. The rate of clearance for the insulin lispro portion of BIL was slower than

  5. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  6. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    Science.gov (United States)

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  7. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review

    Science.gov (United States)

    Cohen, Philip R

    2016-01-01

    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  8. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing ...

  9. [Successful therapy of metastatic basal cell carcinoma with vismodegib].

    Science.gov (United States)

    Zutt, M; Mazur, F; Bergmann, M; Lemke, A J; Kaune, K M

    2014-11-01

    A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

  10. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

    Full Text Available O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor

  11. Basal Secretion of Lysozyme from Human Airways in Vitro

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    Patricia Roger

    1999-01-01

    Full Text Available The aim of this study was to examine the basal release of lysozyme from isolated human lung tissues. Measurements of lysozyme in the fluids derived from lung preparations were performed using a rate-of-lysis assay subsequent to acidification of the biological samples. Lysozyme released from bronchial preparations into fluids was greater than that observed for parenchymal tissues. The lysozyme quantities detected in bronchial fluids were not modified by removal of the surface epithelium. Furthermore, the quantities of lysozyme in bronchial fluids was correlated with the size of the bronchial preparations. These results suggest that the lysozyme was principally secreted by the human bronchi (submucosal layer rather than by parenchyma tissues and that a greater release was observed in the proximal airways.

  12. A Case of Basal Cell Adenoma of the Upper Lip

    Directory of Open Access Journals (Sweden)

    Masanori Kudoh

    2014-01-01

    Full Text Available Basal cell adenoma is a rare type of benign salivary gland tumor found most commonly in the parotid gland. We present a rare case of basal cell adenoma arising in the minor salivary gland of the upper lip. The patient was a 59-year-old Japanese man who visited our department in December 2012 with a chief complaint of a mass in the upper lip, which had increased in size over several years. A mobile, elastic, and relatively soft mass without tenderness was palpable in the upper lip region. The mucosa of the upper lip covering the mass was normal. Tumor extirpation was performed under local anesthesia. Histologically, the tumor had a capsule and was composed of islands of relatively uniform, monotonous cells. Immunohistochemically, the inner tumor comprised tubuloductal structures that showed strong staining for CK7, while the outer tumor showed weak staining for CK7. The outer tumor cells also stained positively for CD10 and p63. The MIB-1 (Ki-67 labeling index was extremely low. Basal cell adenoma was diagnosed based on these results. The postoperative course was uneventful 12 months after surgery and there has been no recurrence.

  13. Immunohistochemical characterization of basal cell adenomas of the salivary gland.

    Science.gov (United States)

    Takahashi, H; Fujita, S; Okabe, H; Tsuda, N; Tezuka, F

    1991-03-01

    Seven cases of basal cell adenomas of the salivary gland were analyzed by immunohistochemical methods with a broad panel of routinely used antibodies. Histologically the epithelial elements were classified as tubuloglandular, trabecular and solid patterns. The authors' results indicated the following: 1) The duct lining cells of tubuloglandular and trabecular patterns have distinct epithelial features with cytokeratins (KL 1, PKK 1, *PKK 2 and PKK 3), alpha-one-antichymotrypsin (alpha 1-ACT), carcinoembryonic antigen (CEA) and S-100 alpha subunit positivity. 2) The basaloid cells in the trabecular and solid patterns expressed two immunophenotypes: one had actin, neuron-specific enolase (NSE), S-100 protein and S-100 beta subunit patterns typical of myoepithelial cells in normal glands. The other basaloid cells had vimentin and S-100 protein patterns. The former cell type could be found in 4 of 7 cases and the latter was found in 7 cases. This represents a minor participation of the myoepithelial cells in the basal cell adenoma. 3) The basement membrane and stromal connective tissue around the neoplastic cells were positive for alpha-one-antitrypsin (alpha 1-AT). This antibody is a good marker in identifying the basement membrane-like material.

  14. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran

    2012-01-01

    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  15. Expression of stromelysin 3 in basal cell carcinomas.

    Science.gov (United States)

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  16. Pigmented basal cell carcinoma of the eyelid in Hispanics

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    Lily Koo Lin

    2008-10-01

    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  17. Photodynamic therapy for basal cell skin cancer ENT-organs

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    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  18. Abberent expression of oncogenic and tumor-suppressive microRNAs and their target genes in human adenocarcinoma alveolar basal epithelial cells

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    Elham Tafsiri

    2016-01-01

    Conclusion: The significant differential expression level of these miRNAs made them as candidate biomarkers in NSCLC tumor tissues of patients. Perhaps Bcl-2 down-regulation and Akt-3 up-regulation can be linked with survival signals in A549 cell line. We can conclude that Bcl-2 and Akt-3 might be therapeutic targets to inhibit cell proliferation in NSCLC.

  19. Basal lamina structural alterations in human asymmetric aneurismatic aorta

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    M Cotrufo

    2009-06-01

    Full Text Available Basal lamina (BL is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation.We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens.We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study.We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RTPCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin a2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type

  20. Inverting adherent cells for visualizing ECM interactions at the basal cell side

    Energy Technology Data Exchange (ETDEWEB)

    Gudzenko, Tetyana [DFG-Center for Functional Nanostructures, Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe (Germany); Franz, Clemens M., E-mail: clemens.franz@kit.edu [DFG-Center for Functional Nanostructures, Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe (Germany)

    2013-05-15

    Interactions with the extracellular matrix (ECM) govern a wide range of cellular functions, including survival, migration and invasion. However, in adherent cells these interactions occur primarily on the basal cell side, making them inaccessible to high-resolution, surface-scanning imaging techniques such as atomic force microscopy (AFM) or scanning electron microscopy (SEM). Here we describe a fast and reliable method for inverting adherent cells, exposing the basal cell membrane for direct analysis by AFM or SEM in combination with fluorescence microscopy. Cells including their matrix adhesion sites remain intact during the inversion process and are transferred together with the complete array of basally associated ECM proteins. Molecular features of ECM proteins, such as the characteristic 67 nm collagen D-periodicity, are well preserved after inversion. To demonstrate the versatility of the method, we compared basal interactions of fibroblasts with fibrillar collagen I and fibronectin matrices. While fibroblasts remodel the fibronectin layer exclusively from above, they actively invade even thin collagen layers by contacting individual collagen nanofibrils both basally and apically through a network of cellular extensions. Cell–matrix entanglement coincides with enhanced cell spreading and flattening, indicating that nanoscale ECM interactions govern macroscopic changes in cell morphology. The presented cell inversion technique can thus provide novel insight into nanoscale cell–matrix interactions at the basal cell side. - Highlights: ► We present a novel method for inverting adherent cells to expose the basal cell side. ► Basal cell sides can be imaged at high resolution by AFM and SEM. ► Cells can be inverted together with the underlying extracellular matrix. ► AFM images of inverted cells provide a nanoscale look at basal cell–ECM interactions.

  1. Effects of aging on nitrergic system in human basal nuclei

    Directory of Open Access Journals (Sweden)

    Bruno Lopes dos Santos

    2014-10-01

    Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

  2. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... defects than standard excisions with 4 or 6 mm margins. Closure of skin defects was achieved by side-to-side closure in 49% and by local flaps in 40%. There were no relapses during the observation time. The safety, cosmetic and functional outcome were excellent. CONCLUSIONS: We recommend that MMS...

  3. Optical coherence tomography in the diagnosis of basal cell carcinoma

    DEFF Research Database (Denmark)

    Hussain, Alia Arif; Themstrup, Lotte; Jemec, Gregor Borut Ernst

    2015-01-01

    Since its introduction in dermatology in the late 1990s optical coherence tomography (OCT) has been used to study many skin diseases, in particular non-melanoma skin cancer and it s precursors. Special attention has been paid to superficial basal cell carcinoma (BCC), and a number of smaller...... observational studies have been published. The diagnostic criteria for BCC of these studies are systematically reviewed. A systemic review of English language studies was performed using PubMed, Google Scholar and Royal Danish Library, to search for primary papers on OCT and BCC. The references of retrieved...

  4. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

    Directory of Open Access Journals (Sweden)

    Didem Didar Balcı,

    2008-07-01

    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  5. Basal cell carcinomas in elderly patients treated by cryotherapy

    OpenAIRE

    Chiriac A.; Mihaila D.; Foia L; Solovan C

    2013-01-01

    Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in ...

  6. Treatment of nevoid basal cell carcinoma syndrome: a case report

    Science.gov (United States)

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by various embryological deformities and carcinoma formation. It is caused by PTCHI gene mutations and is autosomal dominantly inherited. Some of the main symptoms of NBCCS are multiple basal cell carcinomas, multiple keratocystic odontogenic tumors (KCOTs) of the mandible, hyperkeratosis of the palmar and plantar, skeletal deformity, calcification of the falx cerebri, and facial defomity. Recurrent KCOT is the main symptom of NBCCS and is present in approximately 90% of patients. In NBCCS, KCOTs typically occur in multiples. KCOTs can be detected in patients under the age of 10, and new and recurring cysts develop until approximately the age of 30. The postoperation recurrence rate is approximately 60%. This case report presents a 14-year-old female patient with a chief complaint of a cyst found in the maxilla and mandible. The patient was diagnosed with NBCCS, and following treatment of marsupialization and enucleation, the clinical results were satisfactory. PMID:27847737

  7. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis.

    Science.gov (United States)

    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; Min, Kyueng-Whan; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu

    2015-07-10

    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.

  8. The co-factor of LIM domains (CLIM/LDB/NLI) maintains basal mammary epithelial stem cells and promotes breast tumorigenesis.

    Science.gov (United States)

    Salmans, Michael L; Yu, Zhengquan; Watanabe, Kazuhide; Cam, Eric; Sun, Peng; Smyth, Padhraic; Dai, Xing; Andersen, Bogi

    2014-07-01

    Mammary gland branching morphogenesis and ductal homeostasis relies on mammary stem cell function for the maintenance of basal and luminal cell compartments. The mechanisms of transcriptional regulation of the basal cell compartment are currently unknown. We explored these mechanisms in the basal cell compartment and identified the Co-factor of LIM domains (CLIM/LDB/NLI) as a transcriptional regulator that maintains these cells. Clims act within the basal cell compartment to promote branching morphogenesis by maintaining the number and proliferative potential of basal mammary epithelial stem cells. Clim2, in a complex with LMO4, supports mammary stem cells by directly targeting the Fgfr2 promoter in basal cells to increase its expression. Strikingly, Clims also coordinate basal-specific transcriptional programs to preserve luminal cell identity. These basal-derived cues inhibit epidermis-like differentiation of the luminal cell compartment and enhance the expression of luminal cell-specific oncogenes ErbB2 and ErbB3. Consistently, basal-expressed Clims promote the initiation and progression of breast cancer in the MMTV-PyMT tumor model, and the Clim-regulated branching morphogenesis gene network is a prognostic indicator of poor breast cancer outcome in humans.

  9. Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.

    Science.gov (United States)

    Sharpe, Hayley J; Pau, Gregoire; Dijkgraaf, Gerrit J; Basset-Seguin, Nicole; Modrusan, Zora; Januario, Thomas; Tsui, Vickie; Durham, Alison B; Dlugosz, Andrzej A; Haverty, Peter M; Bourgon, Richard; Tang, Jean Y; Sarin, Kavita Y; Dirix, Luc; Fisher, David C; Rudin, Charles M; Sofen, Howard; Migden, Michael R; Yauch, Robert L; de Sauvage, Frederic J

    2015-03-09

    Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

  10. Filaggrin Gene Mutations and Risk of Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Kaae, Jesper Rabølle; Thyssen, J P; Johansen, J D

    2013-01-01

    Basal cell carcinoma (BCC) is prevalent in lightly-pigmented Europeans. While ultraviolet (UV) radiation is an important risk factor, genetic predispositions to BCC have also been identified (1) . Atopic dermatitis (AD), a condition with a heritability that reaches 71-84%, might increase the risk...... of BCC (2) . Loss-of-function mutations in the filaggrin gene (FLG) are observed in approximately 10% of Northern Europeans and are strongly associated with AD (3) . FLG mutations lead to reduced epidermal filaggrin protein and metabolite levels, including the chromophore trans-urocanic acid (UCA) (4......) . Mice with knockdown of filaggrin, or lack of functional histidase, show decreased epidermal trans-UCA levels and increased UVB-induced skin damage (5) . FLG mutation carriers also have 10% increased serum vitamin D levels suggesting increased penetration of UVB (6) . We evaluated the prevalence of FLG...

  11. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  12. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia

    2015-01-01

    was 66.1 years. The most common localisations were the forehead (31.3%), the nose (31.0%) and the cheek (14.7%). Primary BCC comprised 54.0%; the remaining cases were relapses, most frequently after curettage (36.9%), radiotherapy (18.9%) and photodynamic therapy (11.7%). MMS leads to 40% smaller skin......INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... of the surrounding healthy skin, and it also offers higher cure rates than standard tumour excision with a predefined margin of healthy skin. The superiority of MMS relies on the fact that the entire (100%) margin of the excised tissue is examined microscopically for residual tumour in contrast to the traditional...

  13. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells.

    Science.gov (United States)

    Gao, Xia; Bali, Aman S; Randell, Scott H; Hogan, Brigid L M

    2015-11-09

    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.

  14. Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review.

    Science.gov (United States)

    Fujii, Katsunori; Miyashita, Toshiyuki

    2014-10-01

    Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant neurocutaneous disease characterized by developmental anomalies such as palmar pits and rib anomaly, and tumorigenesis such as medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a mutation of PTCH1, a human homologue of Drosophila patched, including frameshift, missense, or nonsense mutations. Genotype-phenotype correlation has not been established. PTCH1 is a member of hedgehog signaling, which is a highly conserved pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as PTCH1. Given that hedgehog signaling regulates cell growth and development, disorder of this pathway gives rise to not only developmental anomalies but also diverse tumors such as those seen in Gorlin syndrome. We recently reported, for the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the frequency was 1/235,800 in the Japanese population, and that the frequency of basal cell carcinomas was significantly lower in Japan than in the USA and Europe, suggesting that ethnicity and genetic background contribute to these differences. Given that many clinical trials using newly discovered molecular inhibitors are still ongoing, these agents should become the new therapeutic options for hedgehog pathway-dependent tumors in patients with or without Gorlin syndrome.

  15. Normal sexual dimorphism in the human basal ganglia.

    NARCIS (Netherlands)

    Rijpkema, M.J.P.; Everaerd, D.S.; Pol, C.; Franke, B.; Tendolkar, I.; Fernandez, G.S.E.

    2012-01-01

    Male and female brains differ in both structure and function. Investigating this sexual dimorphism in healthy subjects is an important first step to ultimately gain insight into sex-specific differences in behavior and risk for neuropsychiatric disorders. The basal ganglia are among the main regions

  16. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

    2008-01-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2......)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P...... = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44...

  17. Research resource: Comparative nuclear receptor atlas: basal and activated peritoneal B-1 and B-2 cells.

    Science.gov (United States)

    Diehl, Cody J; Barish, Grant D; Downes, Michael; Chou, Meng-Yun; Heinz, Sven; Glass, Christopher K; Evans, Ronald M; Witztum, Joseph L

    2011-03-01

    Naïve murine B cells are typically divided into three subsets based on functional and phenotypic characteristics: innate-like B-1 and marginal zone B cells vs. adaptive B-2 cells, also known as follicular or conventional B cells. B-1 cells, the innate-immune-like component of the B cell lineage are the primary source of natural antibodies and have been shown to modulate autoimmune diseases, human B-cell leukemias, and inflammatory disorders such as atherosclerosis. On the other hand, B-2 cells are the principal mediators of the adaptive humoral immune response and represent an important pharmacological target for various conditions including rheumatoid arthritis, lupus erythematosus, and lymphomas. Using the resources of the Nuclear Receptor Signaling Atlas program, we used quantitative real-time PCR to assess the complement of the 49 murine nuclear receptor superfamily expressed in quiescent and toll-like receptor (TLR)-stimulated peritoneal B-1 and B-2 cells. We report the expression of 24 nuclear receptors in basal B-1 cells and 25 nuclear receptors in basal B-2 cells, with, in some cases, dramatic changes in response to TLR 4 or TLR 2/1 stimulation. Comparative nuclear receptor profiling between B-1 and peritoneal B-2 cells reveals a highly concordant expression pattern, albeit at quantitatively dissimilar levels. We also found that splenic B cells express 23 nuclear receptors. This catalog of nuclear receptor expression in B-1 and B-2 cells provides data to be used to better understand the specific roles of nuclear receptors in B cell function, chronic inflammation, and autoimmune disease.

  18. The nevoid basal-cell carcinoma syndrome. Simultaneous extirpation of numerous basal-cell carcinomas on the face by curettage and electrodesiccation under general anesthesia.

    Science.gov (United States)

    Camisa, C

    1981-11-01

    The case of a young, mentally retarded woman with the nevoid basal-cell carcinoma syndrome is presented in whom about 150 basal-cell carcinomas on the face were treated simultaneously be curettage and electrodesiccation with the patient under general anesthesia. Such a method is excellent for eradicating numerous carcinomas rapidly, effectively, and at once, especially when cooperation of the patient is not optimal.

  19. Are the basal cells of the mammalian epididymis still an enigma?

    Science.gov (United States)

    Arrighi, S

    2014-10-01

    Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced.

  20. Neglected Basal Cell Carcinomas in the 21st Century

    Directory of Open Access Journals (Sweden)

    Erika Varga

    2011-01-01

    Full Text Available Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC, the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the “ideal candidates” for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect.

  1. Ameloblastoma vs basal cell carcinoma: an immunohistochemical comparison.

    Science.gov (United States)

    Jawad, Salam N; Abdullah, Bashar H

    2016-12-01

    Despite behavioral mimicry of ameloblastoma (AB) and basal cell carcinoma (BCC), they are classified at 2 extremes within pertinent WHO classifications with respect to benign and malignant designation. This study aims to appraise the current allocation of AB in the classification through an immunohistochemical comparison of some aspects of behavior with BCC. Sections from retrospectively retrieved formalin-fixed, paraffin-embedded tissue blocks of AB (n = 37) and BCC (n = 34) were comparatively examined for the immunohistochemical expression for Ki-67, Bcl-2, MMP-2, MMP-9, CD31, and D2-40 monoclonal antibodies. No statistically significant differences between the tumors were found regarding the immunoexpressions of Bcl-2 (P = .252), CD31 microvessel density (P = .895), lymphatic vessel density (P = .642), and MMP-9 stromal expression (P = .083). MMP-2 expression was significantly higher in epithelial and stromal regions of AB (P = .009 and P = .001, respectively), whereas Ki-67 and MMP-9 epithelial expressions were significantly higher in BCC (P < .000 and P = .026, respectively). Within the studied immunohistochemical attributes for tumor behavior, the study accentuated the overall behavioral mimicry of the tumors and indicated that BCCs surmount ABs by the proliferative rate only. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Everolimus for Compassionate Use in Multiple Basal Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Laura Eibenschutz

    2013-01-01

    Full Text Available Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR and has been shown to have antineoplastic activity in addition to its use as an immunosuppressive agent for the prevention of organ transplant rejection. We report the use of everolimus for the compassionate treatment of four elderly, nontransplant patients presenting with multiple basal cell carcinomas (BCC. All patients had a long history of BCC, had refused surgery as a current treatment option, and did not respond to alternative treatments (including topical 5-fluorouracil and imiquimod. Patients were treated with oral everolimus (1.5–3.0 mg daily for 12 months or longer: a complete and sustained response was seen in one case, and partial responses were seen in two other cases. Everolimus was well tolerated in these elderly patients. These promising preliminary data suggest that further dose-finding, controlled clinical studies are warranted to evaluate the antineoplastic effects of everolimus in patients affected by BCC who cannot or will not undergo surgery.

  3. Vismodegib: in locally advanced or metastatic basal cell carcinoma.

    Science.gov (United States)

    Keating, Gillian M

    2012-07-30

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  4. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    DEFF Research Database (Denmark)

    Su, Ying; Subedee, Ashim; Bloushtain-Qimron, Noga;

    2015-01-01

    genetic and epigenetic (DNA methylation and chromatin) profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree......Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated...... of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required...

  5. High discordance between punch biopsy and excision in establishing basal cell carcinoma subtype: analysis of 500 cases

    NARCIS (Netherlands)

    Wolberink, E.A.W.; Pasch, M.C.; Zeiler, M.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2013-01-01

    Background Basal cell carcinoma (BCC) is the most frequently occurring cancer in humans. Worldwide incidences rise about 10% each year, increasing the burden on dermatologists, general practitioners and pathologists as well as increasing costs for the health care system. Increasingly non-surgical tr

  6. Dramatic Response of a Case ofRecurrent Basal Cell Carcinoma toSystemic Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohammad Mohammadianpanah

    2010-10-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer among humans, and the standard treatment is surgery. Other modalities are reserved as a second line of treatment. Topical chemotherapy may be used in primary BCC. Systemic chemotherapy has no role in the primary treatment of BCC, although it may be efficacious in metastatic cases. We report the case of a patient with persistent recurrent BCC following multiple surgeries and radiotherapy, who achieved a dramatic response with a cisplatinand 5-flourouracil chemotherapy regimen.

  7. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Science.gov (United States)

    Wu, You Kure; Fujishima, Kazuto; Kengaku, Mineko

    2015-01-01

    Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s) from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  8. 分泌性蛋白hk10在眼睑基底细胞癌中的表达%The study of human kallikrein 10 expession in eyelid basal cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王大庆; 罗清礼

    2012-01-01

    目的:研究在眼睑基底细胞癌(basal cell carcinoma,BCC)中NES1基因的分泌蛋白(human kallikrein 10,hk10)的表达情况,并分析其表达与表型之间的关系,从蛋白水平上研究NES1在BCC的发生发展过程中的作用.方法:采用免疫组化的方法检测hk10在31例眼睑BCC中表达情况,并分析其表达与表型之间的关系,采用Image-Pro Plus5.0图像分析系统对免疫组化结果进行扫描,定量分析hk10在不同组眼睑BCC中的表达.结果:免疫组化结果显示hk10主要表达在细胞浆中,呈棕黄色.在正常眼睑上皮组织中,hk10主要分布在上皮各层的鳞状上皮细胞胞浆中,靠近基底细胞层表达稍强;BCC原发组与BCC复发组在平均光密度上无显著性差异(P>0.05),在累积光密度(IOD)上,二者的差异具有统计学意义,BCC原发组具有较强的表达.结论:hk10在正常眼睑上皮组织中高表达,在眼睑基底细胞癌(BCC)中,hk10明显表达下调;NES1阳性表达细胞的减少,可能在眼睑BCC的复发中起一定作用;NES1作为一种新的抑癌基因,其可以作为眼睑BCC的肿瘤分子标记.

  9. Two years results of electronic brachytherapy for basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Rosa Ballester-Sánchez

    2017-06-01

    Full Text Available Purpose: The use of radiation therapy (RT for non-melanoma skin cancer (NMSC has been changing throughout the last century. Over the last decades, the use of radiotherapy has surged with the development of new techniques, applicators, and devices. In recent years, electronic brachytherapy (eBT devices that use small x-ray sources have been introduced as alternative to radionuclide dependence. Nowadays, several devices have been incorporated, with a few series reported, and with a short follow-up, due to the recent introduction of these systems. The purpose of this work is to describe the clinical results of our series after two years follow-up with a specific eBT system. Material and methods: This is a prospective single-center, non-randomized pilot study, to assess clinical results of electronic brachytherapy in basal cell carcinoma using the Esteya® system. In 2014, 40 patients with 60 lesions were treated. Patient follow-up on a regular basis was performed for a period of two years. Results: Twenty-six patients with 44 lesions achieved two years follow-up. A complete response was documented in 95.5% of cases. Toxicity was mild (G1 or G2 in all cases, caused by erythema, erosion, or alopecia. Cosmesis was excellent in 88.6% of cases, and good in the rest. Change in pigmentation was the most frequent cosmetic alteration. Conclusions : This work is special, since the equipment’s treatment voltage was 69.5 kV, and this is the first prospective study with long term follow-up with Esteya®. These preliminary report show excellent results with less toxicity and excellent cosmesis. While surgery has been the treatment of choice, certain patients might benefit from eBT treatment. These are elderly patients with comorbidities or undergoing anticoagulant treatment as well as those who simply refuse surgery or might have other contraindications.

  10. Basal cell carcinoma characteristics as predictors of depth of invasion.

    Science.gov (United States)

    Welsch, Michael Jude; Troiani, Blake M; Hale, Lauren; DelTondo, Joe; Helm, Klaus F; Clarke, Loren E

    2012-07-01

    Pretreatment risk stratification of basal cell carcinoma (BCC) is largely based on histologic subtype reported from biopsy specimens. We sought to determine the degree of concordance between characteristics identified on biopsy specimen and excision and to determine if histologic characteristics other than subtype correlated with depth of invasion. Histologic specimens of 100 BCC biopsy specimens and corresponding excisions were reviewed. Anatomic site, histologic subtype, maximum depth of extension, contour of the lobules at the leading edge, elastosis characteristics, presence of necrosis, calcification, and ulceration were recorded. Concordance between biopsy specimens and their excisions with relation to depth of tumor lobules was analyzed. The concordance between the subtype of biopsy specimen and excision was 62%. Micronodular tumors had the greatest mean depth, followed by infiltrative, nodular, and superficial subtypes. Subtype reported from biopsy specimen (P = .0002) and excision (P < .0001) correlated to depth and was superior to age, contours of excision specimens, the presence of necrosis, and the extent of excisional solar elastosis. Gender, anatomic site, contours of biopsy specimens, elastosis color, elastosis type, the presence of ulceration, and calcification did not correlate with depth. Selection bias is present as only standard excisions were included; BCCs treated by other methods were not examined. BCC subtype identified on biopsy specimen may not correlate with subtype identified on excision. Morphologic subtype has the highest correlation with depth and reporting should reflect the highest risk growth pattern if a biopsy specimen contains more than one pattern. Consideration should be given to reporting necrosis and degree of solar elastosis. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. Laser ablation of basal cell carcinomas guided by confocal microscopy

    Science.gov (United States)

    Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2016-02-01

    Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

  12. Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

    Directory of Open Access Journals (Sweden)

    Zou Yongxin

    2010-02-01

    Full Text Available Abstract Background LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear. Results In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs. Conclusions Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.

  13. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.

    Science.gov (United States)

    Enard, Wolfgang; Gehre, Sabine; Hammerschmidt, Kurt; Hölter, Sabine M; Blass, Torsten; Somel, Mehmet; Brückner, Martina K; Schreiweis, Christiane; Winter, Christine; Sohr, Reinhard; Becker, Lore; Wiebe, Victor; Nickel, Birgit; Giger, Thomas; Müller, Uwe; Groszer, Matthias; Adler, Thure; Aguilar, Antonio; Bolle, Ines; Calzada-Wack, Julia; Dalke, Claudia; Ehrhardt, Nicole; Favor, Jack; Fuchs, Helmut; Gailus-Durner, Valérie; Hans, Wolfgang; Hölzlwimmer, Gabriele; Javaheri, Anahita; Kalaydjiev, Svetoslav; Kallnik, Magdalena; Kling, Eva; Kunder, Sandra; Mossbrugger, Ilona; Naton, Beatrix; Racz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Busch, Dirk H; Graw, Jochen; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Quintanilla-Martinez, Leticia; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fisher, Simon E; Morgenstern, Rudolf; Arendt, Thomas; de Angelis, Martin Hrabé; Fischer, Julia; Schwarz, Johannes; Pääbo, Svante

    2009-05-29

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.

  14. Basket and basal-duct cells in domestic animals: different cytokeratin expression and shape.

    Science.gov (United States)

    Zedda, M; Farina, V

    1996-12-01

    Cytokeratins (CKs) are a multigenic family of proteins constituting intermediate filaments in epithelia, indicated in humans by the numbers 1-20. Different cell-types can be immunocytochemically identified on the grounds of their CK expression. This investigation was designed to study CK expression of basket cells (BCs) and basal-duct cells (BDCs) in some domestic animals. Frozen sections of mammary and major salivary glands from cows, sheep, pigs and rabbits were treated using the immunofluorescent method, using as monoclonal antibodies clones CK-E3, CKB1, KS-1A3, and LDS-68, respectively, revealing the human CKs 17, 14, 13, 7. BCs surrounding acini and BDCs were stained by CK 17 antibody only in the rabbit. CK 14 was detectable in both cell types in cows, sheep and pigs, except in the case of bovine salivary BCs. CK 13 was revealed in BCs and BDCs of all mammary glands and also rabbit salivary glands. In the salivary glands of the other species, only BDCs were stained. CK 7 gave unreliable results in all the species and cell types examined. Interestingly, in the rabbit, also BDCs are basket-like in shape. The antibodies employed showed different staining depending on species and gland. On the grounds of immunoreactivity and shape, BCs and BDCs can be considered the same cell type in the rabbit. In the other species, they appear to be different, since BDCs may express additional CKs and are triangular-shaped, whereas BCs are truly basket-like. It is worth noting that clone KS-1A3 in the rabbit and CKB1 in the sheep and pig can be considered markers of the basket/ basal system.

  15. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ying Su

    2015-06-01

    Full Text Available Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

  16. [Basal cell carcinoma of prostate: a report of three cases].

    Science.gov (United States)

    Liu, Z; Ma, L L; Zhang, S D; Lu, M; Tian, Y; He, Q; Jin, J

    2016-02-18

    To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was

  17. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Directory of Open Access Journals (Sweden)

    Fecher LA

    2015-11-01

    Full Text Available Leslie A Fecher,1,3 William H Sharfman2 1Department of Internal Medicine and Dermatology, Indiana University Health Simon Cancer Center, Indianapolis, IN, USA; 2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3Department of Internal Medicine and Dermatology, University of Michigan, MI, USA Abstract: Cutaneous basal cell carcinoma (BCC is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449, a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. Keywords: basal cell carcinoma, hedgehog, smoothened, vismodegib, Gorlin, basal cell nevus syndrome

  18. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kimonis, V.E.; Yang, M.L.; Bale, S.J. [National Institute of Arthritis and Musculoskeletal and Skin Disease, Bethesda, MD (United States)] [and others

    1997-03-31

    Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include {open_quotes}coarse face{close_quotes} in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. 48 refs., 3 figs., 5 tabs.

  19. Giant cell temporal arteritis associated with overlying basal cell carcinoma: co-incidence or connection?

    Directory of Open Access Journals (Sweden)

    Salem Alowami

    2012-06-01

    Full Text Available Giant cell arteritis is a granulomatous vasculitis of large and medium sized arteries manifesting as temporal arteritis and/or polymyalgia rheumatica. The histological assessment of temporal artery biopsies is frequently encountered in anatomical pathology and has important diagnostic consequences in patients clinically suspected of having giant cell arteritis. We present an intriguing case of giant cell arteritis associated with a Basal cell carcinoma and discuss the ongoing controversy pertaining to the association of giant cell arteritis/polymyalgia rheumatica with malignancy.

  20. Successful imiquimod treatment of multiple basal cell carcinomas after radiation therapy for Hodgkin's disease.

    Science.gov (United States)

    Beyeler, Mirjam; Urosevic, Mirjana; Pestalozzi, Bernhard; Dummer, Reinhard

    2005-01-01

    We present a case of a 55-year-old male patient who developed five basal cell carcinomas 23 years after radiation therapy of Hodgkin's disease. In 1980 he received radiation therapy twice. Due to relapses, he was treated with aggressive polychemotherapy and underwent autologous stem cell transplantation, which then led to complete remission. Until now he is in complete remission. However, multiple superficial basal cell carcinomas have developed on irradiation fields that have been successfully treated by imiquimod.

  1. Basal cell carcinoma arising on a verrucous epidermal nevus: a case report.

    Science.gov (United States)

    Viana, Analia; Aguinaga, Felipe; Marinho, Flauberto; Rodrigues, Rosangela; Cuzzi, Tullia; Ramos-E-Silva, Marcia

    2015-01-01

    We report a case of basal cell carcinoma that appeared from an epidermal verrucous nevus in a 61-year-old patient. The onset of basal cell carcinoma in sebaceous nevi, basal cell nevi and dysplastic nevi is relatively common, but it is rarely associated with epidermal verrucous nevi. There is no consensus on whether the two lesions have a common cellular origin or whether they merely represent a collision of two distinct tumors. Since this association - as with other malignant tumors - is rare, there is no need for prophylactic removal of epidermal verrucous nevi.

  2. Mechanisms and efficacy of vismodegib in the treatment of basal cell carcinoma.

    Science.gov (United States)

    Amin, Shivan H; Motamedi, Kevin K; Ochsner, Matthew C; Song, Tara E; Hybarger, C Patrick

    2013-11-01

    Historically patients with advanced basal cell carcinoma have been subjected to large surgical resections for the treatment of their disease. However, with the development of vismodegib, a first in class molecule that acts to inhibit the hedgehog pathway, patients with advanced and metastatic basal cell carcinoma may have renewed hope in limiting the morbidity involved with surgery. Preliminary data shows a relatively good safety profile and promising results, although further research remains to be conducted. Current progress on utilization of vismodegib for the treatment of advanced basal cell carcinoma is reviewed in this article. Only literature with objective clinical evidence was included in this review.

  3. Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

    Directory of Open Access Journals (Sweden)

    Zänker Kurt S

    2011-05-01

    Full Text Available Abstract Background Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines. Methods Migration was assessed in luminal (MCF-7, post-EMT (MDA-MB-231, MDA-MB-435S, and basal-like (MDA-MB-468 human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG was tested. Results Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration. Conclusions Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients.

  4. Basaloid Squamous Cell Carcinoma of the Head and Neck: Subclassification into Basal, Ductal, and Mixed Subtypes Based on Comparison of Clinico-pathologic Features and Expression of p53, Cyclin D1, Epidermal Growth Factor Receptor, p16, and Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Kyung-Ja Cho

    2017-07-01

    Full Text Available Background Basaloid squamous cell carcinoma (BSCC is a rare variant of squamous cell carcinoma with distinct pathologic characteristics. The histogenesis of BSCC is not fully understood, and the cancer has been suggested to originate from a totipotent primitive cell in the basal cell layer of the surface epithelium or in the proximal duct of secretory glands. Methods Twenty-six cases of head and neck BSCC from Asan Medical Center, Seoul, Korea, reported during a 14-year-period were subclassified into basal, ductal, and mixed subtypes according to the expression of basal (cytokeratin [CK] 5/6, p63 or ductal markers (CK7, CK8/18. The cases were also subject to immunohistochemical study for CK19, p53, cyclin D1, epidermal growth factor receptor (EGFR, and p16 and to in situ hybridization for human papillomavirus (HPV, and the results were clinico-pathologically compared. Results Mixed subtype (12 cases was the most common, and these cases showed hypopharyngeal predilection, older age, and higher expression of CK19, p53, and EGFR than other subtypes. The basal subtype (nine cases showed frequent comedo-necrosis and high expression of cyclin D1. The ductal subtype (five cases showed the lowest expression of p53, cyclin D1, and EGFR. A small number of p16- and/or HPV-positive cases were not restricted to one subtype. BSCC was the cause of death in 19 patients, and the average follow-up period for all patients was 79.5 months. Overall survival among the three subtypes was not significantly different. Conclusions The results of this study suggest a heterogeneous pathogenesis of head and neck BSCC. Each subtype showed variable histology and immunoprofiles, although the clinical implication of heterogeneity was not determined in this study.

  5. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    Science.gov (United States)

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.

  6. Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype

    Science.gov (United States)

    Johanning, Gary L.; Malouf, Gabriel G.; Zheng, Xiaofeng; Esteva, Francisco J.; Weinstein, John N.; Wang-Johanning, Feng; Su, Xiaoping

    2017-01-01

    Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus. Expression of the HERV-K envelope gene (env) was highly significantly increased in basal tumors in comparison with the also-upregulated expression of other HERV-K genes. Analysis of reverse-phase protein array data indicated that increased expression of HERV-K is associated with decreased mutation of H-Ras (wild-type). Our results show elevation of HERV-K expression exclusively in the basal subtype of IDC breast cancer (as opposed to the other subtypes) and suggest HERV-K as a possible target for cancer vaccines or immunotherapy against this highly aggressive form of breast cancer. PMID:28165048

  7. Differentiation of apical and basal dendrites in pyramidal cells and granule cells in dissociated hippocampal cultures.

    Directory of Open Access Journals (Sweden)

    You Kure Wu

    Full Text Available Hippocampal pyramidal cells and dentate granule cells develop morphologically distinct dendritic arbors, yet also share some common features. Both cell types form a long apical dendrite which extends from the apex of the cell soma, while short basal dendrites are developed only in pyramidal cells. Using quantitative morphometric analyses of mouse hippocampal cultures, we evaluated the differences in dendritic arborization patterns between pyramidal and granule cells. Furthermore, we observed and described the final apical dendrite determination during dendritic polarization by time-lapse imaging. Pyramidal and granule cells in culture exhibited similar dendritic patterns with a single principal dendrite and several minor dendrites so that the cell types were not readily distinguished by appearance. While basal dendrites in granule cells are normally degraded by adulthood in vivo, cultured granule cells retained their minor dendrites. Asymmetric growth of a single principal dendrite harboring the Golgi was observed in both cell types soon after the onset of dendritic growth. Time-lapse imaging revealed that up until the second week in culture, final principal dendrite designation was not stabilized, but was frequently replaced by other minor dendrites. Before dendritic polarity was stabilized, the Golgi moved dynamically within the soma and was repeatedly repositioned at newly emerging principal dendrites. Our results suggest that polarized growth of the apical dendrite is regulated by cell intrinsic programs, while regression of basal dendrites requires cue(s from the extracellular environment in the dentate gyrus. The apical dendrite designation is determined from among multiple growing dendrites of young developing neurons.

  8. Studies on the radiosensitivity of cells from patients with basal cell naevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Featherstone, T.; Taylor, A.M.; Harnden, D.G.

    1983-01-01

    No difference in survival was observed between cultured cells from basal cell naevus syndrome (BCNS) patients and normal controls following exposure of fibroblasts to ionizing radiation. Potential lethal damage repair in BCNS cells, measured by holding experiments, was also no different from normal. G0-irradiated lymphocytes from BCNS patients were found to have a significantly higher level of X-ray-induced chromosome aberrations compared with normals. This increase is, however, small, and, taken together with the survival data, suggests that increased cell killing as a measure of the unusual clinical radiosensitivity is not the major effect of the BCNS gene.

  9. Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Macha MA

    2013-07-01

    Full Text Available Muzafar A Macha,1 Surinder K Batra,1,2 Apar Kishor Ganti3,41Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, 2Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, 3Department of Internal Medicine, VA Nebraska-Western Iowa Health Care System, Omaha, 4Division of Oncology-Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Basal cell carcinoma (BCC is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC.Keywords: basal cell carcinoma, vismodegib, hedgehog pathway

  10. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Jones

    2011-01-01

    Full Text Available Gorlin syndrome (Naevoid Basal Cell Carcinoma Syndrome is a rare autosomal dominant syndrome caused by mutations in the PTCH gene with a birth incidence of approximately 1 in 19,000. Patients develop multiple basal cell carcinomas of the skin frequently in early life and also have a predisposition to additional malignancies such as medulloblastoma. Gorlin Syndrome patients also have developmental defects such as bifid ribs and other complications such as jaw keratocysts. We studied the incidence and frequency of basal cell carcinomas in 202 Gorlin syndrome patients from 62 families and compared this to their gender and mutation type. Our data suggests that the incidence of basal cell carcinomas is equal between males and females and the mutation type cannot be used to predict disease burden.

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

    Science.gov (United States)

    ... basal cell nevus syndrome. For example, the drug vismodegib (Erivedge) has been shown to lower the number ... do, these cancers can be hard to treat. Vismodegib and sonidegib, drugs that target the hedgehog signaling ...

  12. Bax/bcl-2: cellular modulator of apoptosis in feline skin and basal cell tumours.

    Science.gov (United States)

    Madewell, B R; Gandour-Edwards, R; Edwards, B F; Matthews, K R; Griffey, S M

    2001-01-01

    Bcl-2 and bax are two members of the BCL-2 gene family that play a prominent role in the regulation of apoptosis. Bax and bcl-2 expression were examined immunohistochemically in normal (healthy) feline skin and in 24 benign feline cutaneous basal cell tumours. The tumours were also examined for cellular proliferation by measurement of reactivity for the proliferation marker Ki-67, and for apoptosis by in-situ labelling for fragmented DNA. Bcl-2 was detected in normal basal epithelium and in 23 of 24 basal cell tumours. Bax was detected in both basal and suprabasal epithelium, but in only seven of 24 tumours. For tumours that expressed both bax and bcl-2, the bax:bcl-2 ratio was low. Neither bax nor bcl-2 expression was detected in 14 feline cutaneous squamous cell carcinomas. Basal cell tumours showed modest cellular proliferation (median, 17.5% Ki-67- reactive cells), but few (less than 1%) apoptotic cells. The slow, indolent growth of feline cutaneous basal cells in these benign skin tumours may be a response, at least in part, to opposing regulatory expressions of bcl-2 and bax.

  13. Urticaria after methyl aminolevulinate photodynamic therapy in a patient with nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Wolfe, Christopher M; Green, W Harris; Hatfield, H Keith; Cognetta, Armand B

    2012-11-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized in several countries for the treatment of basal cell carcinoma, but allergic sensitization has been reported by the manufacturer. To the best of our knowledge, we report the first case of urticaria following MAL-PDT in a patient with nevoid basal cell carcinoma syndrome. Prophylactic use of antihistamines may allow continued use of MAL-PDT in this setting.

  14. A functional and structural investigation of the human fronto-basal volitional saccade network

    NARCIS (Netherlands)

    Neggers, S.F.W.; Diepen, R.M. van; Zandbelt, B.B.; Vink, M.; Mandl, R.C.W.; Gutteling, T.P.

    2012-01-01

    Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diff

  15. Organic Anion Transporter 4-Mediated Transport of Olmesartan at Basal Plasma Membrane of Human Placental Barrier.

    Science.gov (United States)

    Noguchi, Saki; Nishimura, Tomohiro; Fujibayashi, Ayasa; Maruyama, Tetsuo; Tomi, Masatoshi; Nakashima, Emi

    2015-09-01

    Mechanisms regulating fetal transfer of olmesartan, an angiotensin-II receptor type 1 antagonist, are important as potential determinants of life-threatening adverse fetal effects. The purpose of this study was to examine the olmesartan transport mechanism through the basal plasma membrane (BM) of human syncytiotrophoblasts forming the placental barrier. Uptake of olmesartan by human placental BM vesicles was potently inhibited by dehydroepiandrosterone sulfate (DHEAS), estrone 3-sulfate, and bromosulfophthalein, which are all typical substrates of organic anion transporter (OAT) 4 localized at the BM of syncytiotrophoblasts, and was increased in the absence of chloride. In tetracycline-inducible OAT4-expressing cells, [(3) H]olmesartan uptake was increased by tetracycline treatment. Olmesartan uptake via OAT4 was concentration dependent with a Km of 20 μM, and was increased in the absence of chloride. [(3) H]Olmesartan efflux via OAT4 was also observed and was trans-stimulated by extracellular chloride and DHEAS. Thus, OAT4 mediates bidirectional transport of olmesartan and appears to regulate fetal transfer of olmesartan at the BM of syncytiotrophoblasts. Efflux transport of olmesartan via OAT4 from syncytiotrophoblasts to the fetal circulation might be facilitated in the presence of an inwardly directed physiological chloride gradient and extracellular DHEAS. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Primary cilia in the basal cells of equine epididymis: a serendipitous finding.

    Science.gov (United States)

    Arrighi, Silvana

    2013-04-01

    Occurrence of a solitary cilium was an unexpected discovery while studying the ultrastructure of epididymal epithelium in equidae. Primary cilia were detected in epididymal basal cells of all individuals of the equines studied - horses, donkey and mules - independently from age and tract of the duct, emerging from the basal cell surface and insinuating into the intercellular spaces. More rarely solitary cilia occurred also at the luminal surface of the principal cells. The ciliary apparatus was constituted by a structurally typical basal body continuous with the finger-like ciliary shaft extending from the cell surface, and an adjacent centriole oriented at right angles to the basal body. The cilium was structured as the typical primary, non-motile cilia found in many mammalian cells, having a 9+0 microtubular pattern. The basal diplosome was randomly associated with other cellular organelles including the Golgi complex, the endoplasmic reticulum, the microfilament network, the plasma membrane, vesicles and pits. Primary ciliogenesis is a new and unexpected finding in the epididymal epithelium. A monitoring role of luminal factors and extracellular liquids might be attributed to this organelle, likely acting as chemical receptor of the luminal environment, thus modulating the epithelial function by a cell-to-cell crosstalk involving the entire epithelium.

  17. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than...

  18. Basal level of autophagy is increased in aging human skin fibroblasts in vitro, but not in old skin.

    Science.gov (United States)

    Demirovic, Dino; Nizard, Carine; Rattan, Suresh I S

    2015-01-01

    Intracellular autophagy (AP) is a stress response that is enhanced under conditions of limitation of amino acids, growth factors and other nutrients, and also when macromolecules become damaged, aggregated and fibrillated. Aging is generally accompanied by an increase in intracellular stress due to all the above factors. Therefore, we have compared the basal levels of AP in serially passaged human facial skin fibroblasts undergoing aging and replicative senescence in vitro, and ex vivo in the skin biopsies from the photo-protected and photo-exposed area of the arms of 20 healthy persons of young and old ages. Immunofluorescence microscopy, employing antibodies against a specific intracellular microtubule-associated protein-1 light chain-3 (LC3) as a well established marker of AP, showed a 5-fold increase in the basal level of LC3 in near senescent human skin fibroblasts. However, no such age-related increase in LC3 fluorescence and AP could be detected in full thickness skin sections from the biopsies obtained from 10 healthy young (age 25 to 30 yr) and 10 old (age 60 to 65 yr) donors. Furthermore, there was no difference in the basal level of LC3 in the skin sections from photo-protected and photo-exposed areas of the arm. Thus, in normal conditions, the aging phenotype of the skin cells in culture and in the body appears to be different in the case of AP.

  19. An Interesting Case of Basal Cell Carcinoma with Raynaud's Phenomenon Following Chronic Arsenic Exposure.

    Science.gov (United States)

    Gulshan, S; Rahman, M J; Sarkar, R; Ghosh, S; Hazra, R

    2016-01-01

    Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma. On further enquiry, he was found to reside in an arsenic endemic zone and was investigated for blood arsenic level which was elevated. Punch biopsy from different lesions from body confirmed nodular basal cell carcinoma. Presently the patient has stopped drinking water from the local tubewell. On follow-up he shows improvement of Raynaud's phenomenon and skin lesions.

  20. AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion.

    Science.gov (United States)

    Mojallal, Mahdi; Zheng, Yujuan; Hultin, Sara; Audebert, Stéphane; van Harn, Tanja; Johnsson, Per; Lenander, Claes; Fritz, Nicolas; Mieth, Christin; Corcoran, Martin; Lembo, Frédérique; Hallström, Marja; Hartman, Johan; Mazure, Nathalie M; Weide, Thomas; Grandér, Dan; Borg, Jean-Paul; Uhlén, Per; Holmgren, Lars

    2014-08-01

    The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

  1. Expression of basal cell marker revealed by RAM11 antibody during epithelial regeneration in rabbits.

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    Tadeusz Cichocki

    2010-06-01

    Full Text Available RAM11 is a mouse monoclonal anti-rabbit macrophage antibody recognizing connective tissue and vascular macrophages. Our previous report showed that RAM11 reacted with basal cells of stratified squamous epithelia of rabbit skin, oral mucosa and esophagus. The aim of the present study was to follow the appearance of RAM11 immunoreactivity in basal cells of regenerating oral epithelium in rabbits. No RAM11 immunostaining was observed in the regenerating epithelium examined on days 1 and 3 of wound healing. A weak immunofluorescence first appeared on day 7 in single basal cells and 32% of RAM11- positive basal cells were observed on day 14. These findings indicate that expression of the antigen recognized by RAM11 antibody is a transient event in the differentiation of oral keratinocytes which not always occurs during epithelial repair, although it is a constant feature of epithelial turnover in mature epithelium. Therefore this antigen can be regarded as basal cell marker only in mature stratified squamous epithelia.

  2. A rare occurrence of basal cell adenoma of palate: A case report with comprehensive immunohistochemical analysis

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    Surinder Pal Singh Sodhi

    2015-01-01

    Full Text Available Basal cell adenoma (BCA of the salivary glands is an uncommon type of monomorphic adenoma which constitutes 1% of all salivary gland tumors. It most commonly involves parotid gland, while it rarely occurs in minor salivary glands. Upper lip, buccal mucosa, and lower lip are the common intraoral sites; whereas, palate being the rarest one. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma (AdCC is mandatory. Considering the rarity of this lesion and histologic paradox regarding its diagnosis, we report a case of BCA of palate with emphasis on need of comprehensive immunohistochemical (IHC analysis.

  3. Transdifferentiation between Luminal- and Basal-Type Cancer Cells

    Science.gov (United States)

    2013-12-01

    growth factor receptor 3; EREG, epiregulin (a member of EGF family); ITGA6; Integrin alpha 6; ITGB4, Integrin beta 4; Cox2, Cyclooxygenase 2; IL 1B...targets E-cadherin in LNCaP, an E-cadherin positive prostate cancer cell line, can reduce PKD1 activation as judged by S910 autophosphorylation (Fig 1C...purchased from Open Biosystems/Thermo Scientific. Cell culture and immunofluorescence staining. Prostate LNCaP and lung cancer cell lines were

  4. Ezh2 represses the basal cell lineage during lung endoderm development.

    Science.gov (United States)

    Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

    2015-01-01

    The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation.

  5. Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.

    Science.gov (United States)

    Dicker, Anthony J; Serewko, Magdalena M; Russell, Terry; Rothnagel, Joseph A; Strutton, Geoff M; Dahler, Alison L; Saunders, Nicholas A

    2002-05-01

    In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

  6. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

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    Ülker KARAGECE YALÇIN

    2012-05-01

    Full Text Available Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin blocks.Results: p53 expression was observed in 98% of basal cell carcinoma, 88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression was also noted in non-dysplastic appearing epithelium in actinic keratosis cases. COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma, squamous cell carcinoma and actinic keratosis groups, respectively. Skin appendages, inflammatory cells and vascular structures were also stained by COX-2 besides tumor tissue. COX-2 expression increased by the p53 expression increase in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions were not related in terms of tumor type in the BCC and were not related in terms of differentiation in SCC.Conclusion: The existence of p53 expression in actinic keratosis cases has supported the idea that p53 plays a role in the early steps of carcinogenesis in skin cancers. The fact that the expression of COX-2 increases in line with the increase of p53 expression in basal cell carcinoma and squamous cell carcinoma cases indicates that COX-2 expression may be affected by p53

  7. Repair of tracheal epithelium by basal cells after chlorine-induced injury

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    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  8. Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis.

    Science.gov (United States)

    Felix, Martina; Chayengia, Mrinal; Ghosh, Ritabrata; Sharma, Aditi; Prasad, Mohit

    2015-11-01

    Group cell migration is a highly coordinated process that is involved in a number of physiological events such as morphogenesis, wound healing and tumor metastasis. Unlike single cells, collectively moving cells are physically attached to each other and retain some degree of apical-basal polarity during the migratory phase. Although much is known about direction sensing, how polarity is regulated in multicellular movement remains unclear. Here we report the role of the protein kinase Pak3 in maintaining apical-basal polarity in migrating border cell clusters during Drosophila oogenesis. Pak3 is enriched in border cells and downregulation of its function impedes border cell movement. Time-lapse imaging suggests that Pak3 affects protrusive behavior of the border cell cluster, specifically regulating the stability and directionality of protrusions. Pak3 functions downstream of guidance receptor signaling to regulate the level and distribution of F-actin in migrating border cells. We also provide evidence that Pak3 genetically interacts with the lateral polarity marker Scribble and that it regulates JNK signaling in the moving border cells. Since Pak3 depletion results in mislocalization of several apical-basal polarity markers and overexpression of Jra rescues the polarity of the Pak3-depleted cluster, we propose that Pak3 functions through JNK signaling to modulate apical-basal polarity of the migrating border cell cluster. We also observe loss of apical-basal polarity in Rac1-depleted border cell clusters, suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary.

  9. Basal Cell Carcinoma in Gorlin's Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

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    Yannick Gache

    Full Text Available Basal cell carcinoma (BCC is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH. PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS, a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis

  10. Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging

    Science.gov (United States)

    Fan, Shunping; Peng, Xiao; Liu, Lixin; Liu, Shaoxiong; Lu, Yuan; Qu, Junle

    2014-02-01

    Basal cell carcinoma (BCC) is the most common type of human skin cancer. The traditional diagnostic procedure of BCC is histological examination with haematoxylin and eosin staining of the tissue biopsy. In order to reduce complexity of the diagnosis procedure, a number of noninvasive optical methods have been applied in skin examination, for example, multiphoton tomography (MPT) and fluorescence lifetime imaging microscopy (FLIM). In this study, we explored two-photon optical tomography of human skin specimens using two-photon excited autofluorescence imaging and FLIM. There are a number of naturally endogenous fluorophores in skin sample, such as keratin, melanin, collagen, elastin, flavin and porphyrin. Confocal microscopy was used to obtain structures of the sample. Properties of epidermic and cancer cells were characterized by fluorescence emission spectra, as well as fluorescence lifetime imaging. Our results show that two-photon autofluorescence lifetime imaging can provide accurate optical biopsies with subcellular resolution and is potentially a quantitative optical diagnostic method in skin cancer diagnosis.

  11. Basal cell adenoma in the parotid: a bizarre myoepithelial-derived stroma rich variant.

    Science.gov (United States)

    Huang, Yong

    2014-01-01

    Basal cell adenoma (BCA) is a specific entity that lacks the myxochondroid stromal component of a pleomorphic adenoma. There are six histopathological types of BCA: solid, tubular, trabecular, membranous, cribriform, and myoepithelial-derived stroma rich. Myoepithelial-derived stroma rich variant is so rare, especially with cellular atypia. Herin we describe a rare case of BCA arising in the parotid on a 25-year-old man. A well-demarcated nodule arising in the parotid that was composed of basaloid cells, forming small duct-like or tubular structures containing basement membrane-like material, as well as highly cellular elongated cells with hyperchromatic, enlarged, pleomorphic, and bizarre nuclei. Immunohistochemically, S100 protein and p63 highlighted the basal aspect of the peripheral epithelial cells and peripheral spindle and bizarre cells, while CK7 expressed on the luminal cells. We made a diagnosis of "basal cell adenoma, myoepithelial-derived stroma rich variant, with bizarre myoepithelial proliferation". The differential diagnosis includes cellular pleomorphic adenoma, basal cell adenocarcinoma, and carcinoma ex pleomorphic adenoma. After follow-up for 3 years, there was no evidence of recurrence. Further pathological characteristics of this disease are discussed.

  12. A Case Report of Syringocystadenoma Papilliferum Mimicking Basal Cell Carcinoma on the Face

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    Engin Sezer

    2012-03-01

    Full Text Available Syringocystadenoma papilliferum is clinically characterized by verrucous nodules or plaques, mainly observed on the scalp during childhood. Histopathologically, epidermal invagination showing luminal epithelial cells with decapitation secretion is diagnostic. Herein, we describe an unusual late-onset case of syringocystadenoma papilliferum mimicking basal cell carcinoma on the face.

  13. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

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    Marica B Ericson

    2008-03-01

    Full Text Available Marica B Ericson1,2, Ann-Marie Wennberg1, Olle Larkö11Department of Dermatology; 2Department of Physics, Göteborg University, Göteborg, SwedenAbstract: The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field.Keywords: photodynamic therapy, actinic keratosis, basal cell carcinoma

  14. Nevoid Basal-Cell Syndrome: literature review and case report in a family

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    Alfio José Tincani

    Full Text Available The Nevoid Basal-Cell Carcinoma Syndrome (NBCC, or as it is also referred to, basal-cell nevus syndrome or Gorlin-Goltz syndrome, is characterized by multiple early-appearing basal cell carcinomas, keratocytosis of the mandible, and anomalies of the ocular, skeletal reproductive system. We describe four patients in the same family, all of them possessing a large number of skin tumors associated with other typical clinical and X-Ray anomalies of NBCC. The definitive treatment of NBCC has yet to be established, however, early diagnosis is very important as well as the periodical follow-up examination of ten patients, mainly due to the transformations in the skin lesions that may occur.

  15. Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell naevus syndrome.

    Science.gov (United States)

    Drummond, Alessandra; Pichler, Janine; Argenziano, Giuseppe; Zalaudek, Iris; Longo, Caterina; Lallas, Aimilios; Piana, Simonetta; Moscarella, Elvira

    2015-11-01

    Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and opthalmological abnormalities. The treatment of choice of the often multiple and large BCC consists of a combined approach including surgery, liquid nitrogen and other topical treatment modalities. Imiquimod 5% cream is an immune-response-modifying drug with antiviral and anti-tumour activity. Recent reports have associated the immune-stimulant properties of imiquimod with the exacerbation of several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome who developed a lichen planopilaris on the same site of the scalp, which had been previously treated with two cycles of imiquimod for multiple BCC.

  16. Sonic hedgehog-expressing basal cells are general post-mitotic precursors of functional taste receptor cells

    Science.gov (United States)

    Miura, Hirohito; Scott, Jennifer K.; Harada, Shuitsu; Barlow, Linda A.

    2014-01-01

    Background Taste buds contain ~60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I - glial cells, II - bitter/sweet/umami receptor cells, and III - sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turnover rapidly suggesting that Shh+ cells are precursors of some or all taste cell types. Results To fate map Shh-expressing cells, mice carrying ShhCreERT2 and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. PMID:24590958

  17. Hedgehog signaling pathway: A novel target for cancer therapy: Vismodegib, a promising therapeutic option in treatment of basal cell carcinomas

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    Afroz Abidi

    2014-01-01

    Full Text Available The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449, an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib.

  18. Hedgehog signaling pathway: a novel target for cancer therapy: vismodegib, a promising therapeutic option in treatment of basal cell carcinomas.

    Science.gov (United States)

    Abidi, Afroz

    2014-01-01

    The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC) and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449), an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib.

  19. Benign Pigmented Dermal Basal Cell Tumor in a Namibian Cheetah (Acinonyx jubatus

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    Sonja K. Heinrich

    2016-01-01

    Full Text Available A 3.5-year-old wild born cheetah (Acinonyx jubatus, living in a large enclosure on a private Namibian farm, developed a large exophytic nodular neoplasm in its skin at the height of the left shoulder blade. We describe the clinical appearance, the surgical removal, and histological examination of the tumor, which was diagnosed as a moderately pigmented benign basal cell tumor. A three-year follow-up showed no evidence of recurrence after the surgery. Although neoplasia is reported in nondomestic felids, only very few concern cheetahs. So far, no case of basal cell tumor was described in this species.

  20. A child with xeroderma pigmentosum for excision of basal cell carcinoma

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    Sridevi M Mulimani

    2013-01-01

    Full Text Available Xeroderma pigmentosum (XP is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we are reporting a 9-year-old child with XP scheduled for excision of basal cell carcinoma under general anaesthesia.

  1. Jaw cyst-Basal cell nevus-Bifid rib syndrome: a case report.

    Science.gov (United States)

    Rai, S; Gauba, K

    2007-01-01

    Jaw cyst-Basal cell nevus-Bifid rib syndrome or Gorlin-Goltz syndrome involves multiple organ system. The most common findings include multiple odontogenic keratocysts in the jaws and basal cell nevus on the skin that have an early age onset. These multiple odontogenic keratocysts warrant aggressive treatment at the earliest because of the damage and possible complications associated with them. Recurrence in these lesions is the most characteristic feature that has to be taken in consideration while explaining the prognosis to the patient. A case report of a child affected with Gorlin-Goltz syndrome diagnosed, treated and followed at this hospital is presented here.

  2. Jaw cyst-Basal cell nevus-Bifid rib syndrome: A case report

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    Rai S

    2007-09-01

    Full Text Available Jaw cyst-Basal cell nevus-Bifid rib syndrome or Gorlin-Goltz syndrome involves multiple organ system. The most common findings include multiple odontogenic keratocysts in the jaws and basal cell nevus on the skin that have an early age onset. These multiple odontogenic keratocysts warrant aggressive treatment at the earliest because of the damage and possible complications associated with them. Recurrence in these lesions is the most characteristic feature that has to be taken in consideration while explaining the prognosis to the patient. A case report of a child affected with Gorlin-Goltz syndrome diagnosed, treated and followed at this hospital is presented here.

  3. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    Science.gov (United States)

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  4. Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome

    OpenAIRE

    Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

    2015-01-01

    Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma ...

  5. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

    1999-06-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

  6. Case of radiation cancer associated with spinocellular carcinoma and basal cell epithelial tumor

    Energy Technology Data Exchange (ETDEWEB)

    Oohara, K.; Ootsuka, F. (Tokyo Univ. (Japan). Faculty of Medicine); Mizoguchi, M.

    1980-12-01

    The patient was a 66 year-old male who had received radiotherapy for psoriasis vulgaris in frontal plane for 10 years since the age of 19. This radiotherapy was carried out once a week for 5 to 6 weeks and stopped for following 5 to 6 weeks. The source and the dose were unknown. Multiple superficial basal cell epithelial tumor occurred 32 to 33 years after that in the region over which radiation had been given. Moreover, 37 years after that, spinocellular carcinoma occurred in the same region. Spinocellular carcinoma in this case increased rapidly and reached the depth of frontal plane. Atypic of cancer cells was marked, and various findings were observed. Characteristics of these tumor cells were mixture of spindle cells and cells with vacuoles. Partially, findings common to basal cell epithelial tumor were coexisted, and senile keratosis was also discovered.

  7. Cyclin D2 in the basal process of neural progenitors is linked to non-equivalent cell fates

    Science.gov (United States)

    Tsunekawa, Yuji; Britto, Joanne M; Takahashi, Masanori; Polleux, Franck; Tan, Seong-Seng; Osumi, Noriko

    2012-01-01

    Asymmetric cell division plays an indispensable role during corticogenesis for producing new neurons while maintaining a self-renewing pool of apical progenitors. The cellular and molecular determinants favouring asymmetric division are not completely understood. Here, we identify a novel mechanism for generating cellular asymmetry through the active transportation and local translation of Cyclin D2 mRNA in the basal process. This process is regulated by a unique cis-regulatory sequence found in the 3′ untranslated region (3′UTR) of the mRNA. Unequal inheritance of Cyclin D2 protein to the basally positioned daughter cell with the basal process confers renewal of the apical progenitor after asymmetric division. Conversely, depletion of Cyclin D2 in the apically positioned daughter cell results in terminal neuronal differentiation. We demonstrate that Cyclin D2 is also expressed in the developing human cortex within similar domains, thus indicating that its role as a fate determinant is ancient and conserved. PMID:22395070

  8. Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis

    OpenAIRE

    Shin, Dong-Hui; Park, Ji-Hye; Lee, Jeong-Yeon; Won, Hee-Young; Jang, Ki-Seok; MIN, KYUENG-WHAN; Jang, Si-Hyong; Woo, Jong-Kyu; Oh, Seung Hyun; Kong, Gu

    2015-01-01

    Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in th...

  9. Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma.

    Science.gov (United States)

    Aditya, Suruchi; Rattan, Aditya

    2013-10-01

    Incidence of basal cell carcinoma (BCC), the most common skin cancer in humans, is rising. Surgery is the mainstay of treatment but there is no standard of care for locally advanced or metastatic disease. Hedgehog signaling proteins are critical for cell growth and differentiation during embryogenesis; Hh pathway is silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of smoothened inhibitors such as vismodegib. Food and drug administration approved this oral, once-daily medication in 2012 to treat adults with metastatic BCC or locally advanced, recurrent BCC after surgery and also for patients with locally advanced BCC who are not candidates for surgery or radiation treatment. Clinical studies have shown it to be highly efficacious and the most common adverse effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic modifiers, exemplified by Hh directed therapeutics offer a new hope to patients with high-surgical morbidity or inoperable tumors.

  10. Vismodegib: A smoothened inhibitor for the treatment of advanced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Suruchi Aditya

    2013-01-01

    Full Text Available Incidence of basal cell carcinoma (BCC, the most common skin cancer in humans, is rising. Surgery is the mainstay of treatment but there is no standard of care for locally advanced or metastatic disease. Hedgehog signaling proteins are critical for cell growth and differentiation during embryogenesis; Hh pathway is silenced in adults. Dysregulated or aberrant Hh signaling has been implicated in the pathogenesis of BCC. This hyperactive pathway can be inhibited by use of smoothened inhibitors such as vismodegib. Food and drug administration approved this oral, once-daily medication in 2012 to treat adults with metastatic BCC or locally advanced, recurrent BCC after surgery and also for patients with locally advanced BCC who are not candidates for surgery or radiation treatment. Clinical studies have shown it to be highly efficacious and the most common adverse effects include, muscle spasms, alopecia and dysgeusia. Use of targeted biologic modifiers, exemplified by Hh directed therapeutics offer a new hope to patients with high-surgical morbidity or inoperable tumors.

  11. Cobalt uptake and binding in human red blood cells

    DEFF Research Database (Denmark)

    Simonsen, Lars Ole; Brown, Anthony M; Harbak, Henrik

    2011-01-01

    The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 µmol (l cells)(-1) h(-1) at 100 µM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore...

  12. Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma.

    Science.gov (United States)

    Leav, I; Schelling, K H; Adams, J Y; Merk, F B; Alroy, J

    2001-08-01

    The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and

  13. Magnetic Resonance Imaging Findings of Basal Cell Adenoma in Curschmann-Steinert Myotonic Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Rudolph, J.; Berl, J.; Hamm, B.; Klingebiel, R. [Univ. Medicine Berlin, Campus Charite Mitte (Germany). Dept. of Radiology

    2006-03-15

    Myotonic dystrophy Curschmann Steinert is a common hereditary disorder that in some cases can be combined with cutaneous tumors, which is an association that is rarely described in the literature. We present the magnetic resonance imaging in the unusual combination of a patient with known myotonic dystrophy and recurrent basal cell tumor.

  14. ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.

    NARCIS (Netherlands)

    Gudbjartsson, D.F.; Sulem, P.; Stacey, S.N.; Goldstein, A.M.; Rafnar, T.; Sigurgeirsson, B.; Benediktsdottir, K.R.; Thorisdottir, K.; Ragnarsson, R.; Sveinsdottir, S.G.; Magnusson, V.; Lindblom, A.; Kostulas, K.; Botella-Estrada, R.; Soriano, V.; Juberias, P.; Grasa, M.; Saez, B.; Andres, R.; Scherer, D.; Rudnai, P.; Gurzau, E.; Koppova, K.; Kiemeney, L.A.L.M.; Jakobsdottir, M.; Steinberg, S.; Helgason, A.; Gretarsdottir, S.; Tucker, M.A.; Mayordomo, J.I.; Nagore, E.; Kumar, R.; Hansson, J.; Olafsson, J.H.; Gulcher, J.; Kong, A.; Thorsteinsdottir, U.; Stefansson, K.

    2008-01-01

    Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations

  15. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion

    NARCIS (Netherlands)

    Mendenhall, W.M.; Ferlito, A.; Takes, R.P.; Bradford, C.R.; Corry, J.; Fagan, J.J.; Rinaldo, A.; Strojan, P.; Rodrigo, J.P.

    2012-01-01

    Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination

  16. Soft X-ray therapy of basal cell carcinomas of the eye lids

    Energy Technology Data Exchange (ETDEWEB)

    Landthaler, M.; Hendel, B.; Schiele-Luftmann, K.; Braun-Falco, O.

    1983-03-01

    Reported are the results of soft X-ray therapy of 237 patients with 245 basal cell carcinomas of the eye lids. The medial angle of the eye and the lower eye lid were mostly affected. Histologically in 62% solid basal cell carcinomas and in 14% sclerodermiform basal cell carcinomas could be diagnostized. By soft X-ray therapy 92% of all basal cell carcinomas could be healed. All recurrences were observed in the first 2 years following radiotherapy. They were relatively more frequent at the lateral angle of the eye. Recurrences occured in 4.9% of female patients, and in 13.0% of male patients. In two thirds they may be due to elected conditions of radiotherapy; in one third the cause of recurrences are not known. The cosmetic result was good or excellent in 95% of patients during the first 2 years following radiotherapy. After more than 5 years this rate declined to 65%. A good functional result could be obtained in 88% of the patients.

  17. Basal-cell carcinoma resulting from radiation therapy for hypertrophic tonsils

    Energy Technology Data Exchange (ETDEWEB)

    Hanke, C.W.; O' Brian, J.J.; Shidnia, H.; Becker, J.M.

    1985-02-01

    Benign dermatologic conditions are no longer treated with therapeutic radiation because of the late complications that can result. One of the most serious complications that may occur is the development of skin cancer of various types. In this report, a patient received radiation for hypertrophic tonsils and later developed basal-cell carcinomas in the irradiated areas.

  18. Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients

    NARCIS (Netherlands)

    Waalboer-Spuij, Rick; Holterhues, Cynthia; van Hattem, Simone; Schuttelaar, Marie Louise A.; Gaastra, Menno T. W.; Kuijpers, Danielle I. M.; Hollestein, Loes M.; Nijsten, Tamar E. C.

    2015-01-01

    Objective: To document the impact on patient-reported outcomes and health-related quality of life (HRQoL) of treatment with imiquimod cream in patients with actinic keratosis (AK) and superficial basal cell carcinoma (sBCC). Methods: This open-label, multicenter study included AK and sBCC patients

  19. Patient Perception of Imiquimod Treatment for Actinic Keratosis and Superficial Basal Cell Carcinoma in 202 Patients

    NARCIS (Netherlands)

    Waalboer-Spuij, Rick; Holterhues, Cynthia; van Hattem, Simone; Schuttelaar, Marie Louise A.; Gaastra, Menno T. W.; Kuijpers, Danielle I. M.; Hollestein, Loes M.; Nijsten, Tamar E. C.

    2015-01-01

    Objective: To document the impact on patient-reported outcomes and health-related quality of life (HRQoL) of treatment with imiquimod cream in patients with actinic keratosis (AK) and superficial basal cell carcinoma (sBCC). Methods: This open-label, multicenter study included AK and sBCC patients e

  20. Basal Cell Carcinoma Of The Lower Extremities - A Report Of Two Cases

    Directory of Open Access Journals (Sweden)

    Nada Ritambhra

    2001-01-01

    Full Text Available The most common malignancy of the skin is basal cell carcinoma (BCC, usually occurring in the head and neck. It can occur elsewhere as also in the lower extremity. We describe two patients with BCC in the lower extremities, which were nodular type and without any predisposing factors.

  1. Which histological characteristics of basal cell carcinomas influence the quality of optical coherence tomography imaging?

    DEFF Research Database (Denmark)

    Mogensen, M.; Thrane, Lars; Jørgensen, Thomas Martini;

    2009-01-01

    We explore how histopathology parameters influence OCT imaging of basal cell carcinomas (BCC) and address whether such parameters correlate with the quality of the recorded OCT images. Our results indicate that inflammation impairs OCT imaging and that sun-damaged skin can sometimes provide more...

  2. Incidence of cancer in first-degree relatives of basal cell carcinoma patients

    NARCIS (Netherlands)

    M.M. van Rossum; D. Wopereis; T. Hoyer; I. Soerjomataram (Isabelle); J. Schalkwijk; P.C.M. van de Kerkhof; L.A.L.M. Kiemeney (Bart); N. Hoogerbrugge (Nicoline)

    2009-01-01

    textabstractThere is evidence to suggest that genetic factors play an important role in the development of basal cell carcinomas (BCCs), and that skin neoplasms might be a sign for a genetic predisposition to cancer. We investigated whether the incidence of visceral and skin malignancies among first

  3. Analysis of effectiveness of a surgical treatment algorithm for basal cell carcinoma*

    Science.gov (United States)

    Luz, Flávio Barbosa; Ferron, Camila; Cardoso, Gilberto Perez

    2016-01-01

    BACKGROUND Surgical excision is the treatment of choice for basal cell carcinoma and micrographic surgery considered the gold standard, however not yet used routinely worldwide available, as in Brazil. Considering this, a previously developed treatment guideline, which the majority of tumors were treated by conventional technique (not micrographic) was tested. OBJECTIVE To establish the recurrence rate of basal cell carcinomas treated according to this guideline. METHOD Between May 2001 and July 2012, 919 basal cell carcinoma lesions in 410 patients were treated according to the proposed guideline. Patients were followed-up and reviewed between September 2013 and February 2014 for clinical, dermatoscopic and histopathologic detection of possible recurrences. RESULTS After application of exclusion criteria, 520 lesions were studied, with 88.3% primary and 11.7% recurrent tumors. Histological pattern was indolent in 85.5%, 48.6% were located in high risk areas and 70% small tumors. Only 7.3% were treated by Mohs micrographic surgery. The recurrence rate, in an average follow-up period of 4.37 years, was 1.3% for primary and 1.63% for recurrent tumors. Study limitations: unicenter study, with all patients operated on by the same surgeon. CONCLUSION The treatment guideline utilized seems a helpful guide for surgical treatment of basal cell carcinoma, especially if micrographic surgery is not available. PMID:28099591

  4. Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas

    DEFF Research Database (Denmark)

    Haak, C S; Togsverd-Bo, K; Thaysen-Petersen, D

    2015-01-01

    BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate...

  5. Daylight-mediated photodynamic therapy of basal cell carcinomas - an explorative study

    DEFF Research Database (Denmark)

    Wiegell, S R; Skødt, V; Wulf, H C

    2014-01-01

    BACKGROUND: Studies have shown that daylight-photodynamic therapy (PDT) is an effective treatment of actinic keratoses, nearly pain free and more convenient for both the clinics and patients. Treatment of basal cell carcinomas (BCCs) is another main indication for PDT. OBJECTIVES: The aim...

  6. Imaging of basal cell carcinoma by high-definition optical coherence tomography

    DEFF Research Database (Denmark)

    Boone, M A L M; Norrenberg, S; Jemec, G B E

    2012-01-01

    With the continued development of noninvasive therapies for basal cell carcinoma (BCC) such as photodynamic therapy and immune therapies, noninvasive diagnosis and monitoring become increasingly relevant. High-definition optical coherence tomography (HD-OCT) is a high-resolution imaging tool...

  7. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion

    NARCIS (Netherlands)

    Mendenhall, W.M.; Ferlito, A.; Takes, R.P.; Bradford, C.R.; Corry, J.; Fagan, J.J.; Rinaldo, A.; Strojan, P.; Rodrigo, J.P.

    2012-01-01

    Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination

  8. Aggrecan-based extracellular matrix is an integral part of the human basal ganglia circuit.

    Science.gov (United States)

    Brückner, G; Morawski, M; Arendt, T

    2008-01-24

    The extracellular matrix is known to be involved in neuronal communication and the regulation of plastic changes, and also considered to protect neurons and synapses against damage. The goal of this study was to investigate how major extracellular matrix components (aggrecan, link protein, hyaluronan) constitute the pathways of the nigral system in the human basal ganglia circuit affected by neurodegeneration in Parkinson's disease. Here we show that aggrecan- and link protein-related components form clear regional distribution patterns, whereas hyaluronan is widely distributed in gray and white matter. Two predominant phenotypes of the aggrecan-based matrix can be discriminated: (1) perineuronal nets (PNs) and (2) axonal coats (ACs) encapsulating preterminal fibers and synaptic boutons. Clearly contoured PNs are associated with GABAergic projection neurons in the external and internal division of the globus pallidus, the lateral and reticular part of the substantia nigra, as well as subpopulations of striatal and thalamic inhibitory interneurons. Dopaminergic nigral neurons are devoid of PNs but are contacted to a different extent by matrix-coated boutons forming subnucleus-specific patterns. A very dense network of ACs is characteristic especially of the posterior lateral cell groups of the compact substantia nigra (nigrosome 1). In the subthalamic nucleus and the lateral thalamic nuclei numerous AC-associated axons were attached to principal neurons devoid of PNs. We conclude from the region-specific patterns that the aggrecan-based extracellular matrix is adapted to the fast processing of sensorimotor activities which are the therapeutic target of surgery and deep brain stimulation in the treatment of advanced stages of Parkinson's disease.

  9. JunB mediates basal- and TGFβ1-induced smooth muscle cell contractility.

    Directory of Open Access Journals (Sweden)

    Aruna Ramachandran

    Full Text Available Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1, a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK and myosin light chain (MLC20. Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton.

  10. Immunohistochemical evaluation of E-cadherin expression in basal cell carcinoma of the skin

    Directory of Open Access Journals (Sweden)

    Vladimír Bartoš

    2015-08-01

    Full Text Available Introduction: E-cadherin is important cell-cell adhesion molecule, that plays a crucial role in the maintenance of tissue microarchitecture. In many human malignancies, reduced or loss of E-cadherin production in neoplastic cells correlates with tumor dedifferentiation and acquisition of the invasive and metastatic potential. In contrast to most other cancers, basal cell carcinoma (BCC of the skin possess some unique features, such as slow local growth, strong stroma-dependency, and virtual absence of metastases. Aim: In the present study, we immunohistochemically evaluated expression of E-cadherin in a set of cutaneous BCCs. Material and methods: Study group consisted of 41 primary BCCs cathegorized into non-infiltrative subroup (superfical and nodular subtypes and infiltrative subroup (nodular-infiltrative and infiltrative subtypes. Results: E-cadherin was expressed in all tumor specimens with variable quantitative range and intensity. There were 19 cases (46.3 % with preserved and 22 cases (53.7 % with reduced E-cadherin expression. In superficial, nodular, nodular-infiltrative and infiltrative BCC subtypes, reduced E-cadherin immunoreactivity was found in 40 % (2/5, 56.2 % (9/16, 54.5 % (6/11 and 55.5 % (5/9, respectively. We did not confirm a significant correlation between expression of E-cadherin and both given, non-infiltrative and infiltrative BCC subgroup. None of the tumors examined showed apparent decreasing immunostaining intensity in tumor tissue with increasing depth of invasion. There were not convincing differences either between the central and peripheral parts of tumor mass, or in the vertical dimension. Conclusions: Reduction of E-cadherin expression per se does not seem to directly contribute to the acqusition of more aggressive phenotype in cutaneous BCC. This may represent another peculiarity, by which BCC differs from the most other epithelial malignancies and reflect a distinct tumor biology.

  11. Replacing the Promoter of the Murine Gene Encoding P-selectin with the Human Promoter Confers Human-like Basal and Inducible Expression in Mice.

    Science.gov (United States)

    Liu, Zhenghui; Zhang, Nan; Shao, Bojing; Panicker, Sumith R; Fu, Jianxin; McEver, Rodger P

    2016-01-15

    In humans and mice, megakaryocytes/platelets and endothelial cells constitutively synthesize P-selectin and mobilize it to the plasma membrane to mediate leukocyte rolling during inflammation. TNF-α, interleukin 1β, and LPS markedly increase P-selectin mRNA in mice but decrease P-selectin mRNA in humans. Transgenic mice bearing the entire human SELP gene recapitulate basal and inducible expression of human P-selectin and reveal human-specific differences in P-selectin function. Differences in the human SELP and murine Selp promoters account for divergent expression in vitro, but their significance in vivo is not known. Here we generated knockin mice that replace the 1.4-kb proximal Selp promoter with the corresponding SELP sequence (Selp(KI)). Selp(KI) (/) (KI) mice constitutively expressed more P-selectin on platelets and more P-selectin mRNA in tissues but only slightly increased P-selectin mRNA after injection of TNF-α or LPS. Consistent with higher basal expression, leukocytes rolled more slowly on P-selectin in trauma-stimulated venules of Selp(KI) (/) (KI) mice. However, TNF-α did not further reduce P-selectin-dependent rolling velocities. Blunted up-regulation of P-selectin mRNA during contact hypersensitivity reduced P-selectin-dependent inflammation in Selp(KI) (/-) mice. Higher basal P-selectin in Selp(KI) (/) (KI) mice compensated for this defect. Therefore, divergent sequences in a short promoter mediate most of the functionally significant differences in expression of human and murine P-selectin in vivo.

  12. Lactoferrin at basal side of mouse mammary epithelium derives in part from stroma cells.

    Science.gov (United States)

    Pecorini, Chiara; Delpal, Serge; Truchet, Sandrine; Le Provost, Fabienne; Baldi, Antonella; Ollivier-Bousquet, Michèle

    2009-11-01

    Lactoferrin is synthesized by glandular epithelial cells and neutrophils and is also present on both sides of the mammary epithelium. We have studied the origin of lactoferrin detected in the various compartments of mouse mammary tissue. As revealed by immunogold electron microscopy, lactoferrin is present in mammary epithelial cells and in the basal region of the epithelium, associated with connective tissue and stroma cells at all physiological stages studied. A perturbation of protein synthesis or transport after in vitro treatment with cycloheximide or brefeldin A does not abrogate lactoferrin labelling in the basal region of the epithelium. The expression of lactoferrin has also been observed in the fat pads of mammary glands from mice surgically depleted of epithelial cells. The sealing of one teat for 24 h is accompanied by an increase in both the number of stroma cells and the labelling of myoepithelial cells. Thus, the lactoferrin present in the interstitial space of the mouse mammary epithelium originates in part from stroma cells. Possible roles of lactoferrin at the basal side of the mammary epithelium are discussed.

  13. A functional and structural investigation of the human fronto-basal volitional saccade network.

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    Sebastiaan F W Neggers

    Full Text Available Almost all cortical areas are connected to the subcortical basal ganglia (BG through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI to investigate the functional and structural organization of the human (prefrontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF: a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of

  14. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature

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    Achla Bharti Yadav

    2015-09-01

    Full Text Available Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature.

  15. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    Energy Technology Data Exchange (ETDEWEB)

    Kerner, S.A.; Scott, R.A.; Pike, J.W. (Baylor College of Medicine, Houston, TX (USA))

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  16. Creation of computerized 3D MRI-integrated atlases of the human basal ganglia and thalamus

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    Abbas F. Sadikot

    2011-09-01

    Full Text Available Functional brain imaging and neurosurgery in subcortical areas often requires visualization of brain nuclei beyond the resolution of current Magnetic Resonance Imaging (MRI methods. We present techniques used to create: 1 a lower resolution 3D atlas, based on the Schaltenbrand and Wahren print atlas, which was integrated into a stereotactic neurosurgery planning and visualization platform (VIPER; and 2 a higher resolution 3D atlas derived from a single set of manually segmented histological slices containing nuclei of the basal ganglia, thalamus, basal forebrain and medial temporal lobe. Both atlases were integrated to a canonical MRI (Colin27 from a young male participant by manually identifying homologous landmarks. The lower resolution atlas was then warped to fit the MRI based on the identified landmarks. A pseudo-MRI representation of the high-resolution atlas was created, and a nonlinear transformation was calculated in order to match the atlas to the template MRI. The atlas can then be warped to match the anatomy of Parkinson’s disease surgical candidates by using 3D automated nonlinear deformation methods. By way of functional validation of the atlas, the location of the sensory thalamus was correlated with stereotactic intraoperative physiological data. The position of subthalamic electrode positions in patients with Parkinson’s disease was also evaluated in the atlas-integrated MRI space. Finally, probabilistic maps of subthalamic stimulation electrodes were developed, in order to allow group analysis of the location of contacts associated with the best motor outcomes. We have therefore developed, and are continuing to validate, a high-resolution computerized MRI-integrated 3D histological atlas, which is useful in functional neurosurgery, and for functional and anatomical studies of the human basal ganglia, thalamus and basal forebrain.

  17. Clinical Success With Imiquimod Alone and In Combination With Intralesional Interferon In Basal Cell Carcinoma

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    Hayriye Sarıcaoğlu

    2013-12-01

    Full Text Available Background: Basal cell carcinoma (BCC is the most common type of skin cancer in humans. Surgery is still the gold standart for treatment of BCCs. However, there are also less-invasive, nonsurgical therapies such as imiquimod cream and intralesional interferon (IFN alpha-2b for the patients who are poor candidates for surgery and who care cosmetic outcomes. Objective: We report 11 BCC cases with various subtypes successfully treated with either imiquimod alone or in combination with interferon alfa-2b. Methods: Patients with various subtypes of histopathologically proven BCCs who were treated with imiquimod or combination of imiquimod and IFN alpha-2b between 2005-2010 years at our outpatient clinic are included in this report. Results: Of 11 patients we reported, only 4 patients (3 infiltrative, 1 solid types recieved intralesional interferon alpha-2b 3 million IU, 3 times a week combined with topical imiquimod. The rest 7 patients recieved only imiquimod 5% cream. All patients were cured with these regimens. Conclusion: Imiquimod is found to be effective not only in superficial, but also infiltrative, solid, and nodular types. Intralesional interferon alpha-2b is also known to be effective in BCCs and it has a synergistic effect when combined with imiquimod.

  18. Basal Cell Carcinoma Surgery: Simple Undermining Approach in Two Patients with Different Tumour Locations

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    Georgi Tchernev

    2017-07-01

    Full Text Available Basal cell carcinoma (BCC is the most common human malignancy, accounting for the majority of all non-melanoma skin cancers (NMSC. In the past several decades the worldwide incidence of BCC has constantly been increasing. Even though it is a slow growing tumour that, left untreated, rarely metastasizes, it has a distinctive invasive growth pattern, posing a considerable risk for local invasion and destruction of underlying tissues, such as muscle, cartilage, bone or vital structures. Advanced BCCs include such locally invasive or metastatic tumours. Complete surgical excision is the standard therapy for most uncomplicated BCC cases with good prognosis and cure rates. Treatment of advanced forms of BCCs poses significant therapeutic challenges, most often requiring complicated surgery, radiotherapy, and/or targeted therapies directed towards the sonic hedgehog signalling pathway (SHH. We present two cases of large BCCs located on the scalp and posterior thorax, which underwent surgical excision with clear margins, followed by reconstruction of the defect after extensive undermining of the skin.

  19. Mid-face location of primary basal cell carcinoma related to cancer aggressivity

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    Prasetyadi Mawardi

    2016-08-01

    Full Text Available Objective: To study the aggressiveness of basal cell carcinoma (BCC on the mid-face location. Methods: A total of 30 patients were diagnosed using specimen biopsy with hematoxylineosin stain at Moewardi Public Hospital in Surakarta, Central Java, Indonesia. The age, gender distribution, site of the lesion, as well as clinic-pathological appearance were analyzed. Results: There were 30 patients consisting of 46.7% males and 53.3% females with ages ranging from 33 to 91 years old and with the most common occupation, such as farmers (53.6% and housewives (26.7%. Morpheaform subtypes BCC were more frequent than other types. Based on the predilection, most of the BCC were found to be in the mid-face (76.7% and using determined criteria of histopathological examination, the aggressive appearance was 77% and non-aggressive BCC was 23%. The BCC on the mid-face location was more aggressive than the other sites (P < 0.05. Conclusions: BCC is the most common skin tumor in humans with rare metastases, which might cause significant damage due to its local recurrences and aggressiveness. BCC on the mid-face is significantly more aggressive than that on the other predilection sites.

  20. Basal cell adenoma of the parotid gland: Cytological diagnosis of an uncommon tumor

    Directory of Open Access Journals (Sweden)

    Amoolya Bhat

    2015-01-01

    Full Text Available Basal cell adenoma (BCA is a rare benign epithelial tumor of the salivary gland, displaying monomorphic basaloid cells without a myxochondroid component, representing 1-3% of all salivary gland neoplasms seen predominantly in women over 50 years of age. It is uncommon in young adults. Cytodiagnosis of basaloid tumors chiefly basal cell adenoma of the salivary gland, is extremely challenging. The cytological differential diagnoses range from benign to malignant, neoplastic to non- neoplastic lesions. Histopathological examination is a must for definitive diagnosis, as these entities differ in prognosis and therapeutic aspects. We present a 22-years-old male with this uncommon diagnosis with a discussion on the role of cytological diagnosis. Fine needle aspiration cytology is a simple, minimally invasive method for the preoperative diagnosis of various types of neoplastic and non-neoplastic lesions. The knowledge of its pitfalls and limitations contributes to a more effective approach to treatment.

  1. BASAL TISSUE FACTOR EXPRESSION IN ENDOTHELIAL-CELL CULTURES IS CAUSED BY CONTAMINATING SMOOTH-MUSCLE CELLS - REDUCTION BY USING CHYMOTRYPSIN INSTEAD OF COLLAGENASE

    NARCIS (Netherlands)

    MULDER, AB; BLOM, NR; SMIT, JW; RUITERS, MHJ; VANDERMEER, J; HALIE, MR; BOM, VJJ

    1995-01-01

    A discrepancy exists between basal tissue factor (TF) expression found in endothelial cell cultures and the failure to detect TF in unpertubated endothelial cells in vivo. We demonstrated that basal TF expression in endothelial cell cultures originated from contaminating cells. These cells were ultr

  2. Long-term safety, tolerability, and efficacy of vismodegib in two patients with metastatic basal cell carcinoma and basal cell nevus syndrome

    Directory of Open Access Journals (Sweden)

    Glen J. Weiss

    2011-12-01

    Full Text Available Tumor responses in advanced basal cell carcinoma (BCC have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with advanced BCC participating. These two patients have had no new BCCs develop for at least 2.25 years. Both patients have been receiving ongoing daily treatment with vismodegib for greater than 2.75 years without experiencing any significant side effects. After prolonged continuous daily dosing with a SMO antagonist, we have not observed a significant alteration in hematologic parameters or physical abnormalities of the pectoral regions of two patients with advanced BCC.

  3. RNA Helicase DDX5 Regulates MicroRNA Expression and Contributes to Cytoskeletal Reorganization in Basal Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Huang, Jing; Hu, Zhi

    2011-11-15

    RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was upregulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR-182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by upregulation of tumor suppressor PDCD4 (a known miR-21 target); as well as upregulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 downregulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5→miR-182→actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer.

  4. An unusual case report of basal cell adenoma: A Diagnostic Enchanter

    Science.gov (United States)

    Rehani, Shweta; Mehendiratta, Monica; Kumra, Madhumani; Gupta, Ramakant; Jain, Kanu

    2014-01-01

    Oral lesions show a wide range of biologic behaviours. There are various lesions which may mimic others and present in such an unusual manner thus making them very difficult to diagnose clinico-pathologically. An accurate diagnosis is not only important for correct treatment planning but also for determination of prognosis. Thus, it is very important for a surgical pathologist to be aware of the various atypical presentations of the lesions. The present unusual case report of basal cell adenoma occurring on upper lip with frank areas of calcifications and abundant inspissated mucoid secretions is an example of one such case. BCA is an uncommon benign epithelial salivary gland neoplasm. It is one of the nine subcategories of salivary gland epithelial tumours according to WHO 2005 classification of salivary gland tumors. It is composed of basaloid cells organized with a prominent basal cell layer and distinct basement membrane-like structure and no myxochondroid stromal component as seen in pleomorphic adenomas. To our best knowledge, no case in English literature has been reported BCA with exuberant inspissated mucoid secretions and frank areas of calcifications to such a large extent and this is the first case to report the same. Key words: Basal cell adenoma, calcifications, diagnosis, inspissated mucoid secretions, surgical pathologist. PMID:25674334

  5. Dynamic behaviour of human neuroepithelial cells in the developing forebrain

    Science.gov (United States)

    Subramanian, Lakshmi; Bershteyn, Marina; Paredes, Mercedes F.; Kriegstein, Arnold R.

    2017-01-01

    To understand how diverse progenitor cells contribute to human neocortex development, we examined forebrain progenitor behaviour using timelapse imaging. Here we find that cell cycle dynamics of human neuroepithelial (NE) cells differ from radial glial (RG) cells in both primary tissue and in stem cell-derived organoids. NE cells undergoing proliferative, symmetric divisions retract their basal processes, and both daughter cells regrow a new process following cytokinesis. The mitotic retraction of the basal process is recapitulated by NE cells in cerebral organoids generated from human-induced pluripotent stem cells. In contrast, RG cells undergoing vertical cleavage retain their basal fibres throughout mitosis, both in primary tissue and in older organoids. Our findings highlight developmentally regulated changes in mitotic behaviour that may relate to the role of RG cells to provide a stable scaffold for neuronal migration, and suggest that the transition in mitotic dynamics can be studied in organoid models. PMID:28139695

  6. Review of ocular manifestations of nevoid basal cell carcinoma syndrome: What an ophthalmologist needs to know

    Directory of Open Access Journals (Sweden)

    Judy J Chen

    2015-01-01

    Full Text Available Nevoid basal cell carcinoma syndrome (NBCCS is a rare, autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs, odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. Myriad ophthalmologic findings are associated with NBCCS, including periocular BCCs, hypertelorism, strabismus, myelinated nerve fibers, and disorders of the retina and retinal pigment epithelium. We performed a literature search in PubMed for articles on the ophthalmologic manifestations of Gorlin syndrome, published between 1984 and 2014. Of 33 papers, 31 were included. Although Gorlin syndrome is due to mutations in a single gene, it displays variable phenotypic expressivity. Therefore, familiarity with this disorder across clinical specialties is necessary to avoid misdiagnosis. The ophthalmologist should be included in the multidisciplinary team for the management of Gorlin syndrome in order to prevent visual loss and improve the quality of life of these patients.

  7. Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wicking, C.; Berkman, J.; Wainwright, B. [Univ. of Queensland, Brisbane (Australia)] [and others

    1994-08-01

    Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM. 27 refs., 4 figs., 1 tab.

  8. Systemic treatments for basal cell carcinoma (BCC): the advent of dermato-oncology in BCC.

    Science.gov (United States)

    Ali, F R; Lear, J T

    2013-07-01

    Basal cell carcinoma (BCC) is the most common cancer in the U.K. and its incidence is increasing. Vismodegib, a hedgehog pathway inhibitor, has recently been licensed by the U.S. Food and Drug Administration for treatment of advanced BCC. Phase 2 trials have demonstrated efficacy in cases of locally advanced and metastatic BCC, as well as cases of hereditary basal cell naevus (Gorlin) syndrome. Side-effects are frequent and considerable and include myalgia, taste disturbance, alopecia, weight loss and fatigue. Further research is needed to investigate means of circumventing these side-effects, and longitudinal data are required to assess the long-term benefits of, and the nature of resistance to, this novel class of agents. Alternative hedgehog inhibitors are currently in clinical development. We review the current data pertaining to this novel treatment modality and discuss its likely future role in the management of BCC.

  9. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    Science.gov (United States)

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  10. Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma.

    Science.gov (United States)

    Fife, Kate; Herd, Robert; Lalondrelle, Susan; Plummer, Ruth; Strong, Amy; Jones, Sarah; Lear, John T

    2017-01-01

    Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies. Quinine was useful to alleviate muscle cramps. For taste disturbances, food swaps alongside dietician referral were suggested. The experts concluded that these common adverse events can be successfully managed to allow optimum treatment duration of vismodegib.

  11. Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

    OpenAIRE

    Doan HQ; Silapunt S; Migden MR

    2016-01-01

    Hung Q Doan,1 Sirunya Silapunt,1 Michael R Migden2,3 1Department of Dermatology, University of Texas, McGovern Medical School, 2Mohs Surgery Unit, Department of Dermatology, 3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destr...

  12. Thorium X treatment: multiple basal cell carcinomas within a port-wine stain.

    Science.gov (United States)

    Natkunarajah, J; Cliff, S

    2009-07-01

    Thorium X is an ionizing radiation treatment that was commonly used by dermatologists in the 1930 s to 1950 s to treat a variety of benign dermatoses and vascular lesions including port-wine stains. By the 1960 s, thorium X was discontinued due to poor clinical results and the carcinogenic potential. We report a 64-year-old man with a history of multiple basal cell carcinomas in a facial port wine stain, which had previously been treated with thorium X.

  13. Recurrence rate of basal cell carcinoma with positive histopathological margins and related risk factors*

    Science.gov (United States)

    Lara, Fernanda; Santamaría, Jesus Rodriguez; Garbers, Luiz Eduardo Fabricio de Melo

    2017-01-01

    BACKGROUND The best way to approach surgically removed basal cell carcinoma with positive histopathological margins is a controversial issue. Some authors believe that the more appropriate treatment is an immediate reoperation while others prefer a periodic follow up. The rates of recurrence are variable in literature, between 10% and 67%. OBJECTIVE To define the recurrence rate of basal cell carcinoma with positive margins after surgery. Secondarily, identify morphological aspects that can suggest a more frequent tumoral recurrence. METHODS This was a retrospective and observational study made by analysis of medical records of 487 patients between January 2003 and December 2009 in Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR). From 402 basal cell carcinomas surgically treated, 41 fulfilled inclusion criteria and were evaluated for five years or more. Recurrence rate of these tumors was analyzed in all patients and clinical characteristics such as sex, age, tumor size, tumor site, ulceration, and histological type were evaluated in order to find if they were related to more common tumoral recurrence. RESULTS The rate of positive margins after surgery was 12.18%. There were five cases of tumoral recurrence in the observation group and three cases in the re-excision group. Tumor size, site, histological type, ulceration and type of positive margin did not differ statistically between groups. It was not possible to consider if these factors were important in recurrence rates. STUDY LIMITATIONS Ideally, a prospective study with a larger sample would be more accurate. CONCLUSION The treatment of choice in basal cell carcinoma with positive margins must be individualized to reduce recurrence rates. PMID:28225958

  14. Cerebral gigantism associated with jaw cyst basal cell naevoid syndrome in two families.

    Science.gov (United States)

    Cramer, H; Niederdellmann, H

    1983-01-01

    We report 9 subjects from 2 families with the syndrome of cerebral gigantism, seven of the patients also had jaw cyst basal cell naevoid syndrome. Neurological, radiological, somatic and biochemical features of this hitherto unreported association are described. Neurological symptoms included mild hydrocephalus, ventricular malformation, cerebellar syndrome, intracranial calcification, oculomotor disturbances, EEG abnormalities and rarely, mild peripheral nervous disorders. A disturbance of calcium metabolism appears to be a prominent feature of the genetically determined nonprogressive syndrome.

  15. Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.

  16. Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway.

    Science.gov (United States)

    Weeden, Clare E; Chen, Yunshun; Ma, Stephen B; Hu, Yifang; Ramm, Georg; Sutherland, Kate D; Smyth, Gordon K; Asselin-Labat, Marie-Liesse

    2017-01-01

    Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC.

  17. Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Guangping Tai

    Full Text Available The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15, an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63 has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas

  18. Basal cell carcinoma and breast carcinoma following repeated fluoroscopic examinations of the chest.

    Science.gov (United States)

    Myskowski, P L; Gumpertz, E; Safai, B

    1985-03-01

    A 69-year-old white Italian woman was first seen at Memorial Sloan-Kettering Cancer Center in 1981 concerning several skin growths on her back. The patient had had several basal cell carcinomas surgically removed from her back during the preceding 5 years. There was no history of arsenic ingestion or prolonged sun exposure and her family history was negative for skin cancer. The patient had developed pulmonary tuberculosis in 1938 and was treated with pneumothorax therapy. She had had more than 50 fluoroscopic examinations of the chest following this therapy, as well as multiple diagnostic x-ray films since that time. She recalled that she had faced the fluoroscopy beam during the procedure. In 1959, she had a transabdominal hysterectomy for fibroid tumors. In 1980 she underwent a right modified radical mastectomy for adenoid cystic carcinoma of the breast; biopsies of lymph nodes were negative. Physical examination revealed a thin, white woman with a right mastectomy scar. On the back, clustered in the interscapular region, were multiple scars and nine erythematous nodules with pearly borders, telangiectasia, and translucent surfaces. Within several nodules there were areas of light and dark brown pigmentation. There were no other suspicious lesions on the head, chest, or extremities, nor did the patient show any evidence of the basal cell nevus syndrome. Biopsy of all lesions revealed basal cell carcinoma, some of which were pigmented, without evidence of chronic radiodermatitis. All lesions were treated with curettage and electrodesiccation three times with good cosmetic results (Fig. 1).

  19. Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

    Science.gov (United States)

    Husein-ElAhmed, Husein; Fernandez-Pugnaire, Maria Antonia

    2016-01-01

    BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. PMID:28099598

  20. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  1. Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors.

    Science.gov (United States)

    Tell, Robert W; Horvath, Curt M

    2014-09-02

    Signal transducer and activator of transcription 3 (STAT3), a latent transcription factor associated with inflammatory signaling and innate and adaptive immune responses, is known to be aberrantly activated in a wide variety of cancers. In vitro analysis of STAT3 in human cancer cell lines has elucidated a number of specific targets associated with poor prognosis in breast cancer. However, to date, no comparison of cancer subtype and gene expression associated with STAT3 signaling in human patients has been reported. In silico analysis of human breast cancer microarray and reverse-phase protein array data was performed to identify expression patterns associated with STAT3 in basal-like and luminal breast cancers. Results indicate clearly identifiable STAT3-regulated signatures common to basal-like breast cancers but not to luminal A or luminal B cancers. Furthermore, these differentially expressed genes are associated with immune signaling and inflammation, a known phenotype of basal-like cancers. These findings demonstrate a distinct role for STAT3 signaling in basal breast cancers, and underscore the importance of considering subtype-specific molecular pathways that contribute to tissue-specific cancers.

  2. Mevalonate metabolism regulates Basal breast cancer stem cells and is a potential therapeutic target.

    Science.gov (United States)

    Ginestier, Christophe; Monville, Florence; Wicinski, Julien; Cabaud, Olivier; Cervera, Nathalie; Josselin, Emmanuelle; Finetti, Pascal; Guille, Arnaud; Larderet, Gaelle; Viens, Patrice; Sebti, Said; Bertucci, François; Birnbaum, Daniel; Charafe-Jauffret, Emmanuelle

    2012-07-01

    There is increasing evidence that breast tumors are organized in a hierarchy, with a subpopulation of tumorigenic cancer cells, the cancer stem cells (CSCs), which sustain tumor growth. The characterization of protein networks that govern CSC behavior is paramount to design new therapeutic strategies targeting this subpopulation of cells. We have sought to identify specific molecular pathways of CSCs isolated from 13 different breast cancer cell lines of luminal or basal/mesenchymal subtypes. We compared the gene expression profiling of cancer cells grown in adherent conditions to those of matched tumorsphere cultures. No specific pathway was identified to be commonly regulated in luminal tumorspheres, resulting from a minor CSC enrichment in tumorsphere passages from luminal cell lines. However, in basal/mesenchymal tumorspheres, the enzymes of the mevalonate metabolic pathway were overexpressed compared to those in cognate adherent cells. Inhibition of this pathway with hydroxy-3-methylglutaryl CoA reductase blockers resulted in a reduction of breast CSC independent of inhibition of cholesterol biosynthesis and of protein farnesylation. Further modulation of this metabolic pathway demonstrated that protein geranylgeranylation (GG) is critical to breast CSC maintenance. A small molecule inhibitor of the geranylgeranyl transferase I (GGTI) enzyme reduced the breast CSC subpopulation both in vitro and in primary breast cancer xenografts. We found that the GGTI effect on the CSC subpopulation is mediated by inactivation of Ras homolog family member A (RHOA) and increased accumulation of P27(kip1) in the nucleus. The identification of protein GG as a major contributor to CSC maintenance opens promising perspectives for CSC targeted therapy in basal breast cancer.

  3. Apico-basal forces exerted by apoptotic cells drive epithelium folding.

    Science.gov (United States)

    Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

    2015-02-12

    Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

  4. Multiple basal cell carcinomas arising in a port-wine stain with a remote history of therapeutic irradiation.

    Science.gov (United States)

    Kim, Byung-Soo; Lee, Jae-Bong; Jang, Ho-Sun; Kwon, Yoo-Wook; Kwon, Kyung-Sool; Oh, Chang-Keun

    2004-10-01

    The coexistence of a basal cell carcinoma and a port-wine stain is a very rare condition that may be associated with previous treatments. We present a case of multiple basal cell carcinomas developing within the boundaries of a port-wine stain, which had been treated with a tholium X and argon laser. Our case suggests that port-wine stains which were previously treated with irradiation or argon laser should be examined carefully and regularly by both physician and patient, because they may hide basal cell carcinomas.

  5. Basal Cell Adenoma with Perplexity in Diagnosis – A Case Report

    Science.gov (United States)

    Rehani, Shweta; Mathias, Yulia; Wadhwa, Manish

    2016-01-01

    Every salivary gland tumour irrespective of its benign or malignant nature or occurrence, exhibits certain unique and overlapping histopathologic features. Basal Cell Adenoma (BCA) is a rare salivary gland tumour and hence it becomes our responsibility to report every case with unique histopathologic features so that it can add to our present knowledge of this lesion. Often, the pathologists experience difficulty while diagnosing lesions like BCA which contain basaloid cells due to its similarity with other lesions of similar histological appearance. Hence, this paper discusses a case of BCA with rare histopathologic features along with the possible differential diagnosis. PMID:27135016

  6. Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

    Directory of Open Access Journals (Sweden)

    Demetrio eMilardi

    2016-03-01

    Full Text Available The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders.

  7. TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli

    Science.gov (United States)

    Munne, Pauliina M.; Gu, Yuexi; Tumiati, Manuela; Gao, Ping; Koopal, Sonja; Uusivirta, Sanna; Sawicki, Janet; Wei, Gong-Hong; Kuznetsov, Sergey G.

    2014-04-01

    Multiple observations suggest a cell type-specific role for TP53 in mammary epithelia. We developed an in vitro assay, in which primary mouse mammary epithelial cells (mMECs) progressed from lumenal to basal-like phenotypes based on expression of Krt18 or ΔNp63, respectively. Such transition was markedly delayed in Trp53-/- mMECs suggesting that Trp53 is required for specification of the basal, but not lumenal cells. Evidence from human basal-like cell lines suggests that TP53 may support the activity of ΔNp63 by preventing its translocation from nucleoplasm into nucleoli. In human lumenal cells, activation of TP53 by inhibiting MDM2 or BRCA1 restored the nucleoplasmic expression of ΔNp63. Trp53-/- mMECs eventually lost epithelial features resulting in upregulation of MDM2 and translocation of ΔNp63 into nucleoli. We propose that TP63 may contribute to TP53-mediated oncogenic transformation of epithelial cells and shed light on tissue- and cell type-specific biases observed for TP53-related cancers.

  8. γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe.

    Science.gov (United States)

    Donahue, Manus J; Rane, Swati; Hussey, Erin; Mason, Emily; Pradhan, Subechhya; Waddell, Kevin W; Ally, Brandon A

    2014-03-01

    Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA(+)]/[NAA-NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA(+)]/[NAA-NAAG] and perfusion (R=-0.46; P=0.037), yet no relationship between AAT and [GABA(+)]/[NAA-NAAG] (R=-0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA(+)]/[NAA-NAAG] and perfusion (R=-0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.

  9. In vivo thickness measurement of basal cell carcinoma and actinic keratosis with optical coherence tomography and 20-MHz ultrasound

    DEFF Research Database (Denmark)

    Mogensen, Mette; Nürnberg, B.M.; Forman, J.L.

    2009-01-01

    and 34 lesions [23 basal cell carcinoma (BCC) and 11 actinic keratosis (AK) lesions] biopsies. The influence of skin pigmentation and infiltration analgesia on OCT image quality was studied. Skin colour...

  10. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S

    2017-03-01

    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  11. Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal cortical function, and sympathetic tone.

    Science.gov (United States)

    Irwin, M; Hauger, R; Patterson, T L; Semple, S; Ziegler, M; Grant, I

    1997-01-01

    The association between Alzheimer caregiving and natural killer (NK) cell activity and basal plasma levels of adrenocorticotropic hormone (ACTH), cortisol, beta-endorphin, prolactin, epinephrine, norepinephrine, and neuropeptide Y was determined in 100 spousal Alzheimer caregivers and 33 age- and gender-comparable control volunteers upon intake into a study of the psychological and physiologic impact of caregiving. The relationship between these physiologic measures and individual characteristics such as age, gender, medical status, severity of stress, severity of depressive symptoms, and caregiver burden was tested. In addition, the association between NK activity and alterations of the neuroendocrine measures was investigated. As compared to controls, the Alzheimer caregivers had similar levels of NK activity and of basal plasma neuroendocrine hormones and sympathetic measures. While older age and male gender status were associated with increased levels of ACTH, neither medical caseness, severity of life stress, nor severity of depressive symptoms was associated with alterations in any of the multiple physiologic domains. Classification of Alzheimer caregiver burden identified caregivers who were mismatched in terms of the amount of care they were required to provide and the amount of respite time received. The mismatched caregivers had significantly higher basal plasma ACTH but no change in other physiological measures, as compared to non-mismatched caregivers. NK activity was negatively correlated with plasma levels of neuropeptide Y but not with any of the other neuroendocrine measures. Based on this cross-sectional evaluation of NK activity and neuroendocrine and sympathetic measures, we conclude that most Alzheimer caregivers do not show evidence of altered basal physiology.

  12. Pattern of HPV infection in basal cell carcinoma and in perilesional skin biopsies from immunocompetent patients

    Directory of Open Access Journals (Sweden)

    Zakrzewska Krystyna

    2012-12-01

    Full Text Available Abstract Background The association between human papillomavirus (HPV infection and non-melanoma skin cancers (NMSCs such as squamous cell carcinoma (SCC and basal cell carcinoma (BCC is not yet fully understood. We analysed the prevalence and spectrum of cutaneous beta-HPV types and mucosal/genital HPV types in paired biopsies (tumour and corresponding perilesional skin obtained from 50 BCC immunocompetent patients. A small group of SCC patients (n=9 was also included. We also evaluated some previously postulated risk factors for HPV infection in NMSC patients. Results All biopsies were negative for mucosal/genital HPV types. Overall, beta-HPV DNA was detected more often in SCC compared to BCC patients (78% vs 55% of total samples. The frequency of infection increased with the patient’s age [OR=4.88 (95% CI 1.29-18.39]. There was no significant correlation between beta-HPV positivity and sex, skin type and UV exposure. The prevalence of beta-HPV species 1 types was significantly higher than those belonging to other beta-HPV species in biopsies from BCC (p=0.022 but not from SCC subjects (p=0.091. There was no significant difference in the overall prevalence of beta-HPV infection and the number of viral types between tumour lesions and perilesional skin. BCC samples were significantly more likely to be infected with beta-HPV species 1 types compared to perilesional skin (p=0.036 and showed a higher frequency of mixed infections (p=0.028. Conclusions These findings demonstrate that beta-HPV types belonging to species 1 are the most common HPV types detected in the skin of BCC patients. Moreover beta-1-HPV types and mixed infections are significantly more frequent in tumour samples than in healthy perilesional skin. Our results suggest that beta-1-HPVs as well as co-infection with more than one viral type could be important in NMSC and in particular in BCC. Further studies aimed to compare the biological activity of viral types in tumours and in

  13. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    Science.gov (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  14. Risk and outcome analysis of 1832 consecutively excised basal cell carcinomas in a tertiary referral plastic surgery unit.

    LENUS (Irish Health Repository)

    Malik, Vinod

    2012-02-01

    BACKGROUND: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form the majority of the surgical workload for most modern cutaneous malignancy centres. Primary surgical removal of basal cell carcinomas remains the gold standard of treatment but, despite almost two centuries of surgical experience, rates of incomplete surgical excision of up to 50% are still reported. The aim of this study was to assess, quantify and perform comparative analysis of the outcomes and predictive factors of consecutive primarily-excised basal cell carcinomas in a tertiary centre over a six-year period. METHODS: Retrospective audit was conducted on all patients who underwent surgical excision of basal cell carcinomas from January 2000 to December 2005. Assessment parameters included patient biographics, tumour management differences and detailed histopathological analysis of tumour margins and subtypes. RESULTS: One thousand eight hundred and thirty two basal cell carcinomas were excised from 1329 patients over the designated time period. Two hundred and fifty one (14%) lesions were incompletely excised with 135 (7.4%) involving the peripheral margin only, 48 (2.6%) the deep margin only and 41 (2.2%) involving both. Nasal location was the most common predictor of incomplete excision. CONCLUSIONS: Overall basal cell carcinomas excision rates compared favourably with international reported standards but attention to a variety of surgical and histological risk factors may improve this further.

  15. Naevi as a risk factor for basal cell carcinoma in Caucasians: a Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun. To in...... higher number of naevi on the arms and the legs than did female controls, but also had more naevi on the trunk. For females, the risk for basal cell carcinoma increased with increasing number of naevi. Naevi were not a risk factor for basal cell carcinoma in males.......The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun....... To investigate whether the number of common naevi is a risk factor for basal cell carcinoma in Caucasians we performed whole-body counting of naevi > or =2 mm in a Danish case-control study with 145 cases of primary basal cell carcinoma and 119 controls matched on age, gender and place of residence. Naevi were...

  16. Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

    Science.gov (United States)

    Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

    2015-01-01

    Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

  17. Primary Sjogren%u2019s Syndrome Associated with Basal Cell Carcinoma: Case Report

    Directory of Open Access Journals (Sweden)

    Tugba Kosker

    2013-04-01

    Full Text Available Sjogren%u2019s syndrome is a chronic autoimmune disease characterized by xerostomia and xerophthalmia, known as the %u2018sicca symptoms%u2019. Patients with Sjogren%u2019s syndrome, characteristically have positive nuclear and cytoplasmic antigens, typically Anti-Ro/SSA and Anti-La/SSB because of lymphocytic infiltration of the exocrine glands. Patients with primary Sjogren%u2019s syndrome, develop systemic complications, non-Hodgkin lymphoma being the most feared of these. We describe here a case of Sjogren%u2019s syndrome with basal cell carcinoma, which presented with an ulcerated lesion on nasal dorsum.

  18. Surgical treatment and dilemmas in the treatment of basal cell carcinomas with intracranial propagation

    Directory of Open Access Journals (Sweden)

    Rasulić Lukas G.

    2014-01-01

    Full Text Available Background/Aim. Basal cell carcinoma (BCC is one of the most common malignant skin tumors on the head in 90% of cases and is characterized by a high local infiltrating potential and destructive growth. The aim of this study was to show the characteristics of a correlation between pathohistological types of basal cell carcinoma and the size of this lesion, aggressiveness and infiltration of basal cell carcinoma, and its effect on the course of the therapy. Methods. We analyzed 27 patients operated on for BCC that affected the scalp and the bone. We described and considered the clinical characteristics (size, depth of invasion, duration and speed of intracranial propagation and then made comparison with the type of BCC. We described the extent of surgical treatment and the width of excision to determine the best course of the treatment. The patients went through examinations during the next three years. Results. According to the histopathological type the most common tumors were: infiltrative (60.2%, noduloinfiltrative (37.2%, and morpheaform (2.6%. Tumors were clinically manifested as ulcerative lesions, ulcus rodens and ulcus terebrans. Tumor diameters ranged from 2 to 25 cm. The depth of intracranial propagation depended on the histological type and tumor size. Most relapses (35% occurred with morpheaform type of BCC. In 17 of the cases, BCC affected the bone without intracranial propagation. In 10 of the cases, basalioma infiltrated intracranial space - in 8 of the cases it infiltrated the dura and in 6 of the cases the brain parenchyma, of which in two of them, the superior sagittal sinus was affected and had to be surgically tied off. Conclusion. The aggressiveness and infiltration of basal cell carcinoma into the brain parenchyma is directly linked to the histological type and the size of the tumor. The larger the basalioma or if histopathological findings confirm morpheaform type of basalioma the larger surrounding healthy tissue

  19. Synchronous unilateral basal cell adenoma of the parotid gland: A case report.

    Science.gov (United States)

    Kuang, Jin; Rao, Qian; Zhang, Hao; Cheng, Zhigang

    2014-10-01

    The current study reports the case of a 68-year-old male who presented with a 4-month history of a painless slow-growing mass in the left parotid region. Magnetic resonance imaging revealed two independent, round lesions in the superficial and deep lobes of the parotid gland on the left side, respectively. A total parotidectomy was performed and basal cell adenomas (BCAs) were identified by histopathological examination. At the 6-month follow-up examination, no sign of recurrence was found. This study describes the clinical features of a rare case of synchronous unilateral BCA in the parotid gland and also provides a review of the literature.

  20. Basal Cell Carcinoma is as Common as the Sum of all Other Cancers

    DEFF Research Database (Denmark)

    Holm, Ann-Sofie; Nissen, Christoffer V; Wulf, Hans Christian

    2016-01-01

    Reliable estimates of disease incidence are fundamental to planning future healthcare services. However, in many countries registration of basal cell carcinoma (BCC) is often non-existent. This study examines how many BCC treatments were carried out in Denmark in 2013. The Danish Cancer Registry...... records are inadequate in relation to BCC registration, as BCCs treated are 3 times the number of individuals in the Danish Cancer Registry, and there are nearly as many BCCs as the sum of all other cancers. The increasing BCC incidence will result in difficulties in ensuring treatment capacity....

  1. Giant Anterior Chest Wall Basal Cell Carcinoma: An Approach to Palliative Reconstruction

    Directory of Open Access Journals (Sweden)

    Pauline Joy F. Santos

    2016-01-01

    Full Text Available Anterior chest wall giant basal cell carcinoma (GBCC is a rare skin malignancy that requires a multidisciplinary treatment approach. This case report demonstrates the challenges of anterior chest wall GBCC reconstruction for the purpose of palliative therapy in a 72-year-old female. Surgical resection of the lesion included the manubrium and upper four ribs. The defect was closed with bilateral pectoral advancement flaps, FlexHD, and pedicled VRAM. The palliative nature of this case made hybrid reconstruction more appropriate than rigid sternal reconstruction. In advanced metastatic cancers, the ultimate goals should be to avoid risk for infection and provide adequate coverage for the defect.

  2. Confocal and dermoscopic features of basal cell carcinoma in Gorlin-Goltz syndrome: A case report.

    Science.gov (United States)

    Casari, Alice; Argenziano, Giuseppe; Moscarella, Elvira; Lallas, Aimilios; Longo, Caterina

    2016-01-14

    Gorlin-Goltz (GS) syndrome is an autosomal dominant disease linked to a mutation in the PTCH gene. Major criteria include the onset of multiple basal cell carcinoma (BCC), keratocystic odontogenic tumours in the jaws and bifid ribs. Dermoscopy and reflectance confocal microscopy represent imaging tools that are able to increase the diagnostic accuracy of skin cancer in a totally noninvasive manner, without performing punch biopsies. Here we present a case of a young woman in whom the combined approach of dermoscopy and RCM led to the identification of multiple small inconspicuous lesions as BCC and thus to the diagnosis of GS syndrome.

  3. Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction

    DEFF Research Database (Denmark)

    Mogensen, Mette; Jørgensen, Thomas Martini; Thrane, Lars

    2010-01-01

    BACKGROUND: Optical coherence tomography (OCT) is a possible imaging method for delineation of non-melanoma skin cancer. Speckle noise is the dominant noise contribution in OCT images; it limits the ability to identify cellular structures especially skin cancer. QUESTIONS ADDRESSED: This report...... suggests a method for improving OCT image quality for skin cancer imaging. EXPERIMENTAL DESIGN: OCT is an optical imaging method analogous to ultrasound. Two basal cell carcinomas (BCC) were imaged using an OCT speckle reduction technique (SR-OCT) based on repeated scanning by altering the distance between...... to a clinically relevant level when imaging BCC lesions....

  4. Vismodegib: a promising drug in the treatment of basal cell carcinomas.

    Science.gov (United States)

    Dirix, Luc; Rutten, Annemie

    2012-08-01

    Hedgehog pathway signaling is important for embryonic development; however, inappropriate reactivation of this pathway in adults has been linked to several forms of cancer. Vismodegib (Erivedge™), a first-in-class hedgehog pathway inhibitor, blocks the pathway by inhibiting the activity of the signaling protein SMO. Preclinical studies have provided promising indications of potential tumor-reducing activity in several cancers. Thus far, clinical pharmacology and Phase I studies have demonstrated the unique pharmacokinetic profile of vismodegib, its efficacy in certain types of tumors and a generally tolerable adverse-event profile. A pivotal Phase II clinical trial confirmed the favorable benefit:risk profile of vismodegib in advanced basal cell carcinoma.

  5. A massive neglected giant basal cell carcinoma in a schizophrenic patient treated successfully with vismodegib.

    Science.gov (United States)

    Andersen, Rosa Marie; Lei, Ulrikke

    2015-01-01

    The small molecule vismodegib is a great treatment alternative to patients challenged, e.g. psychiatric disorders, suffering from severe basal cell carcinoma of the skin in which surgery or other treatment modalities is not possible because of patient's wish or condition. We present a case of a 73-year-old schizophrenic patient with a 15-year history of a neglected tumour located at the forehead and scalp, admitted to hospital in a state of inanition because of tumour expansion to the meninges and severe anaemia caused by bleeding, treated successfully with vismodegib.

  6. The potential impact of 4-octylphenol on the basal and stimulated testosterone formation by isolated mice Leydig cells

    Directory of Open Access Journals (Sweden)

    Tomáš JAMBOR

    2016-12-01

    Full Text Available Octylphenol is biodegradation product of alkylphenolethoxylates frequently used in detergents, paints and other industrial applications. This compound is classified as an endocrine disruptor. Recent studies have hypothesized that occupational exposure to octylphenol poses adverse effects on reproductive system of humans and wildlife species. Enzymes involved in the steroid biosynthesis pathway are really sensitive targets for the action of various endocrine-disrupting chemicals. Aim of in vitro study was determined the effect of 4-octylphenol on basal and human chorionic gonadotropin stimulated testosterone formation of ICR mice Leydig cells. On the other hand, was classified potential impact of mentioned endocrine disruptor on Leydig cell viability after 44 h of cultivation. Cell suspension was cultured with addition of 0.04; 0.2; 1.0; 2.5 and 5.0 μg*mL-1 of 4-octylphenol and compared to the control. Hormone quantification from the medium was performed by enzyme-linked immunosorbent assay. Viability of cell suspension was determined by the metabolic activity assay. Unstimulated testosterone production significantly (P˂0.001 increased with 2.5 and 5.0 μg*mL-1 4-octylphenol. Cell viability was also significantly (P˂0.001; P˂0.05 stimulated by 4-octylphenol. Although human chorionic gonadotropin stimulated testosterone secretion was significantly (P˂0.05 affected by the lowest concentration (0.04 μg*mL-1 in the cell viability was recorded significantly (P˂0.001; P˂0.05 higher mitochondrial activity (1.0; 2.5 and 5.0 μg*mL-1. Considerably more detailed and systematic research in this area is required for a better understanding of potential risk to humans or animals.

  7. Basal lamina inhibition suppresses synthesis of calcium-dependent proteins associated with mammary epithelial cell spreading.

    Science.gov (United States)

    Rocha, V; Hom, Y K; Marinkovich, M P

    1986-08-01

    Spreading of mouse mammary epithelial cells on collagen gels is closely correlated with the synthesis of a group of putative calcium-binding proteins (CBP) (Braslau et al., Exp cell res 155 (1984) 213). Collagen synthesis was shown to occur during cell spreading, while omission of serum prevented cell spreading and the synthesis of collagen. The proline analogues cis-hydroxyproline and L-azetidine-2-carboxylic acid were shown to inhibit epithelial cell spreading and to suppress the collagen synthesis that occurs during serum-supported cell spreading. Inhibition of collagen synthesis resulted in the inhibition of CBP synthesis associated with cell spreading. In contrast, the collagen cross-linking inhibitor B-aminopropionitrile did not inhibit cell spreading nor did it suppress collagen synthesis; CBP synthesis was also normal during treatment with this inhibitor. Thus, mammary epithelial cell spreading on collagen gels and CBP synthesis can both be suppressed by inhibition of collagen synthesis indicating that they may be integrated in some manner. It is suggested that inhibition of cell spreading during inhibition of collagen synthesis results from failure to assemble a normal basal lamina; this may in turn signal suppression of CBP synthesis.

  8. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  9. Functional properties of granule cells with hilar basal dendrites in the epileptic dentate gyrus.

    Science.gov (United States)

    Kelly, Tony; Beck, Heinz

    2017-01-01

    The maturation of adult-born granule cells and their functional integration into the network is thought to play a key role in the proper functioning of the dentate gyrus. In temporal lobe epilepsy, adult-born granule cells in the dentate gyrus develop abnormally and possess a hilar basal dendrite (HBD). Although morphological studies have shown that these HBDs have synapses, little is known about the functional properties of these HBDs or the intrinsic and network properties of the granule cells that possess these aberrant dendrites. We performed patch-clamp recordings of granule cells within the granule cell layer "normotopic" from sham-control and status epilepticus (SE) animals. Normotopic granule cells from SE animals possessed an HBD (SE(+) HBD(+) cells) or not (SE(+) HBD(-) cells). Apical and basal dendrites were stimulated using multiphoton uncaging of glutamate. Two-photon Ca(2+) imaging was used to measure Ca(2+) transients associated with back-propagating action potentials (bAPs). Near-synchronous synaptic input integrated linearly in apical dendrites from sham-control animals and was not significantly different in apical dendrites of SE(+) HBD(-) cells. The majority of HBDs integrated input linearly, similar to apical dendrites. However, 2 of 11 HBDs were capable of supralinear integration mediated by a dendritic spike. Furthermore, the bAP-evoked Ca(2+) transients were relatively well maintained along HBDs, compared with apical dendrites. This further suggests an enhanced electrogenesis in HBDs. In addition, the output of granule cells from epileptic tissue was enhanced, with both SE(+) HBD(-) and SE(+) HBD(+) cells displaying increased high-frequency (>100 Hz) burst-firing. Finally, both SE(+) HBD(-) and SE(+) HBD(+) cells received recurrent excitatory input that was capable of generating APs, especially in the absence of feedback inhibition. Taken together, these data suggest that the enhanced excitability of HBDs combined with the altered intrinsic

  10. Ovarian fibromas in pediatric patients with basal cell nevus (Gorlin) syndrome.

    Science.gov (United States)

    Ball, Allison; Wenning, Joan; Van Eyk, Nancy

    2011-02-01

    Gorlin syndrome is a rare genetic condition consisting of multiple basal cell nevi associated with other entities such as medulloblastoma, skeletal abnormalities, and ovarian fibromas. A 15-year-old girl presented with abdominal discomfort. Magnetic resonance imaging showed multiple bilateral solid adnexal masses, the largest measuring 5.5 cm × 6.1 cm × 5.6 cm. At laparoscopy, 10 ovarian fibromas, ranging from 3 mm to 7 cm in size, were removed from each ovary. Concurrent with her gynecologic course, she was found to have maxillary sinus cysts and multiple basal cell nevi. The patient's history was also significant for a medulloblastoma as an infant. Given this constellation of findings, a diagnosis of Gorlin syndrome was made. The development of ovarian fibromas in the pediatric population is rare. When diagnosed, the possibility of Gorlin syndrome must be considered. Furthermore, females with Gorlin syndrome would benefit from regular gynecologic surveillance. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  11. A Case of Orbital Myiasis in Recurrent Eyelid Basal Cell Carcinoma Invasive into the Orbit

    Directory of Open Access Journals (Sweden)

    Triptesh Raj Pandey

    2016-01-01

    Full Text Available Introduction. Orbital myiasis is the infestation of the orbital tissues by fly larvae or maggots. Compromise of periorbital tissues by malignant disease, surgery, ischemia, or infection may predispose the patient to orbital myiasis. Case Report. A 73-year-old male patient with neglected recurrent basal cell carcinoma of the eyelid invasive into the orbit presented with complaints of intense itching and crawling sensation with maggots wriggling and falling from the wound of left orbit. The patient improved following manual removal of the maggots along with oral Ivermectin treatment. Recurrence of the basal cell carcinoma was confirmed by punch biopsy from the wound and extended exenteration of the orbit followed by reconstructive surgery was done. Conclusion. Orbital myiasis is a rare and preventable ocular morbidity that can complicate the malignancies resulting in widespread tissue destruction. The broad spectrum antiparasitic agent, Ivermectin, can be used as noninvasive means to treat orbital myiasis. In massive orbital myiasis and those associated with malignancies, exenteration of the orbit must be seriously considered.

  12. A candidate region for Nevoid Basal Cell Carcinoma Syndrome defined by genetic and physical mapping

    Energy Technology Data Exchange (ETDEWEB)

    Wainwright, B.; Negus, K.; Berkman, J. [Univ. of Queensland, Brisbane (Australia)] [and others

    1994-09-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS, or Gorlin`s syndrome) is a cancer predisposition syndrome charcterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12 cM interval between the microsatellite marker loci D9S12 and D9S109. Combined multipoint and haplotype analyses of Australian pedigrees has further refined the localization to a 2 cM interval between markers D9S196 and D9S180. Our loss of heterozygosity (LOH) studies from sporadic (n= 58) and familial (n=41) BCCs indicate that 50% have deletions within the NBCCS candidate region. All LOH is consistent with the genetic mapping of the NBCCS locus. Additionally, one sporadic tumor indicates that the smallest region of overlap in the deletions is within the interval D9S287 (proximal) and D9S180 (distal). A series of YAC clones from within this region has been mapped by FISH to examine chimerism. These clones, which have been mapped with respect to one another, form a contig which encompasses the candidate region from D9S196 to D9S180.

  13. Reconstruction of the Upper Eyelid with Flaps and Free Grafts after Excision of Basal Cell Carcinoma

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    Alessandro Guido Actis

    2011-11-01

    Full Text Available Purpose: To describe a reconstructive technique of the superior eyelid with flaps and free grafts after excision of a basal cell carcinoma. Methods: Single case report of a 79-year-old woman who presented to our hospital with a basal cell carcinoma of the upper eyelid margin with initial erosion. Results: A large and full-thickness excision of the carcinoma was performed. The reconstruction technique should be customized to the individual patient. In this case, the use of a full-thickness tarsal graft from the contralateral upper eyelid, followed by an ipsilateral bipedicled flap and finally by a skin graft, was an effective surgical procedure, performed in one stage, without complications, and with good functional and esthetic results. Conclusions: Malignant neoplasms represent the leading cause of plastic reconstruction in the orbital region. Surgical techniques must be individualized for each patient and for each type of carcinoma. Reconstructive techniques with free grafts and flaps yield excellent results in the orbital region, particularly when some advice and a few fundamental rules are followed, namely accurate hemostasis of the receiving graft bed by moderate use of diathermy, careful suturing of the edges, and application of a compressive dressing for at least 4 days. Postoperative complications are very rare.

  14. The SINS trial: A randomised controlled trial of excisional surgery versus imiquimod 5% cream for nodular and superficial basal cell carcinoma

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    Armstrong Sarah J

    2010-04-01

    Full Text Available Abstract Background Basal cell carcinoma is the commonest human cancer. Despite increasing incidence it remains poorly researched. While not life threatening it can cause significant cosmetic disfigurement. Imiquimod, a cream which enhances the body's immune response, may help deal with the number of cases that occur in low-risk sites, especially when good cosmetic results and home use without surgery are needed. This study aims 1. To compare excisional surgery with imiquimod cream for nodular or superficial basal cell carcinoma in low risk sites, with respect to 3 year clinical clearance, cost-effectiveness and cosmetic results. 2. To ascertain if certain phenotypic features and gene polymorphisms predict tumour responsiveness to treatment. Methods/Design Five hundred participants with low risk nodular or superficial basal cell carcinoma will be recruited from hospitals to this multi-centre, randomised, parallel group, controlled phase III trial. Treatment in the imiquimod group is for 6 weeks for superficial basal cell carcinoma and 12 weeks for nodular basal cell carcinoma. Both treatment groups are followed up in clinic for 3 years. Primary outcome variable: the proportion of participants with clinical evidence of success (no recurrence at 3 years. The primary outcome will be compared between the two treatment groups. Secondary outcomes include: i clinical success at 1, 2 and 5 years, ii time to first recurrence, iii cosmetic appearance of lesion site after treatment, iv level of pain, and v cost-effectiveness. Safety and tolerability data will also be reported. Discussion This study protocol describes a pragmatic randomised controlled trial which it is hoped will address the above uncertainties. Three-year results will be available towards the end of 2010. Trial registration Meta-register: NCT00066872, Eudract No. 2004-004506-24, ISRCTN48755084.

  15. CD10 expression helps to differentiate basal cell carcinoma from trichoepithelioma

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    Mitra Heidarpour

    2011-01-01

    Full Text Available Background: The distinction between basal cell carcinoma (BCC and trichoepithelioma (TE may be very difficult in some cases because of the close similarities of these two lesions clinically and histopathologically. The purpose of this study is to investigate the usefulness of CD10 in distinguishing BCC and TE. Methods: The immunohistochemical expression of CD10 was evaluated in an archived group of 30 BCCs and 12 TEs in a retrospective cross sectional study. The localization of anti-CD10 to the tumoral and/or stromal cells was determined in each case and was compared between these two tumors using Fisher′s Exact Test. Results: In BCC cases, the expression of CD10 was noted in tumoral cells in 26 cases (83.2%. Of these, 3 cases showed positivity of the stromal and basaloid cells, two cases demonstrated stromal expression alone and two BCCs were not immunoreactive. On the other hand, 10 out of 12 (83.3% TEs showed positive stromal immunoreactivity. Of these, one case also showed positivity of the basaloid cells. One TE demonstrated epithelial expression alone and one TE was not immunoreactive. The pattern of staining of basaloid cells and stromal cells in BCC and trichoepithelioma was statistically different (p < 0.001. Conclusions: We conclude that CD10 is a useful marker in the differential diagnosis of BCC versus TE.

  16. Accumulation of multipotent progenitors with a basal differentiation bias during aging of human mammary epithelia

    DEFF Research Database (Denmark)

    Garbe, James C; Pepin, Francois; Pelissier, Fanny A

    2012-01-01

    of the cellular and molecular mechanisms that underlies these observations is lacking. In this study, we generated a large collection of normal human mammary epithelial cell strains from women ages 16 to 91 years, derived from primary tissues, to investigate the molecular changes that occur in aging breast cells......Women older than 50 years account for 75% of new breast cancer diagnoses, and the majority of these tumors are of a luminal subtype. Although age-associated changes, including endocrine profiles and alterations within the breast microenvironment, increase cancer risk, an understanding....... We found that in finite lifespan cultured and uncultured epithelial cells, aging is associated with a reduction of myoepithelial cells and an increase in luminal cells that express keratin 14 and integrin-a6, a phenotype that is usually expressed exclusively in myoepithelial cells in women younger...

  17. How histological features of basal cell carcinomas influence image quality in optical coherence tomography

    DEFF Research Database (Denmark)

    Mogensen, Mette; Nürnberg, Birgit M.; Thrane, Lars

    2011-01-01

    Optical coherence tomography (OCT) has the potential to diagnose and measure the depth of nonmelanoma skin cancer (NMSC) in skin, but some lesions appear blurred in OCT images. The aim of this study is to identify histological characteristics of basal cell carcinomas (BCC) that correlate with good...... quality OCT images of the same lesions. A total of 34 patients with BCC were OCT scanned. The influence of histology parameters (e.g. inflammation, sun damage of skin, carcinoma cell size) on OCT image quality was studied by comparing 15 BCC lesions easily identified compared to 19 BCC lesions...... that produced only blurred in OCT images. Inflammation was more pronounced in blurred OCT images, whereas solar elastosis dominated in easily identified lesions. Hyperkeratosis did not impair imaging significantly. OCT image quality of BCC may depend on specific histology parameters....

  18. Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

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    Julian Arista-Nasr

    2016-04-01

    Full Text Available ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12 and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

  19. Optimization of the basal medium for improving production and secretion of taxanes from suspension cell culture of Taxus baccata L

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    Kajani Abolghasem

    2012-10-01

    Full Text Available Abstract Background and purpose of the study Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale. Methods We investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing. Results The yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1 and 10-deacetyl baccatin III (4.2 mgl-1 were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1 in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1, Baccatin III (5.0 mgl-1, and 10-deacetyl baccatin III (1.45 mgl-1 were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media.

  20. Optimization of the basal medium for improving production and secretion of taxanes from suspension cell culture of Taxus baccata L

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    Abolghasem Abbasi Kajani

    2012-10-01

    Full Text Available Background and purpose of the study Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale.MethodsWe investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing.ResultsThe yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1 and 10-deacetyl baccatin III (4.2 mgl-1 were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1 in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1, Baccatin III (5.0 mgl-1, and 10-deacetyl baccatin III (1.45 mgl-1 were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media.

  1. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules.

    Science.gov (United States)

    Yang, Chih-Chao; Graves, Hillary K; Moya, Ivan M; Tao, Chunyao; Hamaratoglu, Fisun; Gladden, Andrew B; Halder, Georg

    2015-02-10

    Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical-basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non-cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non-cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation.

  2. Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.

    Science.gov (United States)

    Lesiak, Aleksandra; Sobolewska-Sztychny, Dorota; Majak, Paweł; Sobjanek, Michał; Wodz, Karolina; Sygut, Karolina Przybyłowska-; Majsterek, Ireneusz; Wozniacka, Anna; Narbutt, Joanna

    2016-01-01

    In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

  3. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

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    Wahid M

    2017-01-01

    Full Text Available Mohd Wahid, Arshad Jawed, Sajad Ahmad Dar, Raju K Mandal, Shafiul Haque Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia Abstract: Patients suffering from advanced basal cell carcinoma (BCC have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee that corresponds to 43% (95% confidence interval [CI]: 28–59 and 38% (95% CI: 28–48 in their respective categories. Disease control was found in 93% (39 patients and 80% (74 patients of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance, nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. Keywords: locally advanced basal cell carcinoma, metastatic basal

  4. Comparative histochemical study of Bowen’s disease and actinic keratosis: preserved normal basal cells in Bowen’s disease

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    H Ishida

    2009-12-01

    Full Text Available The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen’s disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen’s disease were completely negative. Compatible with this result, the basal cells in Bowen’s disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 ß E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14, which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen’s disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen’s disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 ß B4 (monoclonal antibody against cytokeratin 1, which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen’s disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen’s disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly

  5. Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

    Science.gov (United States)

    Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

    2011-05-01

    Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

  6. The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.

    Science.gov (United States)

    Rasotto, R; Goldschmidt, M H; Castagnaro, M; Carnier, P; Caliari, D; Zappulli, V

    2014-01-01

    Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of

  7. MUSTARDE’S FLAP FOR POST BASAL CELL CARCINOMA EXCISION LOWER EYELID RECONSTRUCTION: OUR EXPERIENCE

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    Amit

    2015-06-01

    Full Text Available PURPOSE: To review the role of Mustarde’s flap for post basal cell carcinoma excision lower eyelid reconstruction , its clinical outcomes and complications. METHODS: The Mustarde’s rotational cheek flap has been used to reconstruct the lower eyelids of 16 patients from 2008 to 2015 in proven cases of bcc. RESULT S: Mustarde’s flaps have very high functionally as well as cosmetic acceptability with minimum patient morbidity. The most frequent complications were downward contraction and sagging of the flap and ectropion of the lid margin. To prevent them, the zygomatico - cheek flap must be carefully designed, rotated, and sutured as high as possible so that immediately postoperatively, t he palpebral fissure is only a narrow slit.

  8. Superficial basal cell carcinoma treated with 70% trichloroacetic acid applied topically: a case study

    Science.gov (United States)

    Chiriac, Anca; Brzezinski, Piotr; Moldovan, Cosmin; Podoleanu, Cristian; Coros, Marius Florin; Stolnicu, Simona

    2017-01-01

    Background Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting millions of people worldwide. The treatment concept for BCCs is the surgical one, but it is costly, as such, searching for alternative medical therapeutics is justified. Aim To highlight the efficacy of high concentration (70%) trichloroacetic acid (TCA) as a choice therapy for low-risk BCC. Method and patient Authors present, for the first time, the use of a high concentration TCA applied once a week for 2 consecutive weeks with a toothpick, on a patient with BCC on the right preauricular area. Results On examination 4 weeks later, the lesion was not clinically and dermatoscopically evidenced. Conclusion High concentration TCA could be an effective and safe, non-invasive choice of therapy for low-risk BCC, easy to perform, not expensive, with good cosmetic results, especially for patients who are not likely to undergo invasive or expensive treatments. PMID:28260938

  9. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

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    Akiko Hirofuji

    2011-01-01

    Full Text Available We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs. These multiple lesions (occurring in the chest, neck, and back showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology.

  10. Photodynamic therapy of nodular basal cell carcinoma with multifiber contact light delivery.

    Science.gov (United States)

    Thompson, Marcelo Soto; Andersson-Engels, Stefan; Svanberg, Sune; Johansson, T; Palsson, Sara; Bendsoe, Niels; Derjabo, A; Kapostins, J; Stenram, Unne; Spigulis, J; Svanberg, Katarina

    2006-01-01

    To overcome the limited treatment depth of superficial photodynamic therapy we investigate interstitial light delivery. In the present work the treatment light was delivered using a system in which three or six clear-cut fibers were placed in direct contact with the tumor area. This placement was thought to represent a step toward general purpose interstitial PDT. Twelve nodular basal cell carcinomas were treated employing delta-aminolevulinic acid and 635 nm laser irradiation. Fluorescence measurements were performed monitoring the buildup and subsequent bleaching of the produced sensitizer protoporphyrin IX. The treatment efficacy, judged at a 28-month follow-up, showed a 100% complete response. Two punch excisions at 7 months converted two partial responses to complete responses. One patient failed to appear at all follow-up sessions. The outcome of the treatments was comparable to superficial photodynamic therapy in terms of histological, clinical, and cosmetic results.

  11. Basal Cell Carcinoma: From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease

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    Daniela Göppner

    2011-01-01

    Full Text Available Due to intensified research over the past decade, the Hedgehog (HH pathway has been identified as a pivotal defect implicated in roughly 25% of all cancers. As one of the most frequent cancer worldwide, the development of Basal cell carcinoma (BCC due to activation of the HH pathway has been convincingly demonstrated. Thus the discovery of this central tumor-promoting signalling pathway has not only revolutionized the understanding of BCC carcinogenesis but has also enabled the development of a completely novel therapeutic approach. Targeting just a few of several potential mutations, HH inhibitors such as GDC-0449 achieved already the first promising results in metastatic or locally advanced BCC. This paper summarizes the current understanding of BCC carcinogenesis and describes the current “mechanism-based” therapeutic strategies.

  12. AN UNUSUAL LOCATION OF BASAL CELL CARCINOMA: THE CLITORIS AND THE VULVA

    Science.gov (United States)

    Asuman, Cömert; Özlem, Akin; Burçak, Tümerdem; Önder, Peker

    2008-01-01

    Vulvar basal cell carcinoma (BCC) is rare, accounting for less than 5% of all vulvar neoplasms and less than 1% of all BCCs. Vulvar BCCs are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They may be invasive and destructive if neglected or improperly treated. Nevertheless, they have a very low propensity for metastatic spread, but frequently recur after simple excision. We report a 78 year-old woman presenting with the complaint of painful vulvar ulceration and vaginal bleeding. The physical examination revealed a 3 × 2 cm indurated nodulo-ulcerative lesion involving the clitoris, both labia minora and left labium majus. The histopathology was consistent with the “solid type BCC” that invaded the subcutaneous tissue without lymph node metastasis. The patient underwent wide local excision with clitoral amputation and remained disease free at post-surgical follow-up after 18 months. PMID:19882033

  13. An unusual location of basal cell carcinoma: The clitoris and the vulva

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    Asuman Comert

    2008-01-01

    Full Text Available Vulvar basal cell carcinoma (BCC is rare, accounting for less than 5% of all vulvar neoplasms and less than 1% of all BCCs. Vulvar BCCs are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They may be invasive and destructive if neglected or improperly treated. Nevertheless, they have a very low propensity for metastatic spread, but frequently recur after simple excision. We report a 78 year-old woman presenting with the complaint of painful vulvar ulceration and vaginal bleeding. The physical examination revealed a 3 x 2 cm indurated nodulo-ulcerative lesion involving the clitoris, both labia minora and left labium majus. The histopathology was consistent with the "solid type BCC" that invaded the subcutaneous tissue without lymph node metastasis. The patient underwent wide local excision with clitoral amputation and remained disease free at post-surgical follow-up after 18 months.

  14. Biodegradable Nanofiber for Delivery of Immunomodulating Agent in the Treatment of Basal Cell Carcinoma

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    Richard Garrett

    2015-11-01

    Full Text Available In this paper we investigate a potential new treatment option for basal cell carcinoma using electrospun polymer nanofibers. Poly(ε-caprolactone fibers incorporated with the anti-cancer drug imiquimod were successfully produced for the first time. These fibers were characterized and their diffusion release profile tested in vitro. A range of different electrospinning parameters were investigated in order to determine the most effective approach in optimizing the fibers for future in vivo testing. Characterization showed stable and homogeneous distribution of imiquimod. Although the drug was released faster than what would be needed to replicate the current treatment model, this system would ideally allow for a treatment option which reduces side effects and is more convenient for the patient than the current topical treatment.

  15. Recurrence of keratocyst in nevoid basal cell carcinoma syndrome: A major diagnostic dilemma for clinicians

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    Anurag Gupta

    2013-01-01

    Full Text Available The odontogenic keratocysts (OKC usually represent a particular entity that has been of interest primarily due to biological aggressiveness and to its frequent recurrence. Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome is a hereditary condition characterized by a wide-range of developmental abnormalities and a predisposition to neoplasms. There are several possible reasons why OKC recur so frequently and require meticulous surgical planning and execution. This article has attempted to show that there is a lack of published evidence regarding the cause of frequent recurrent of OKC that presented in NBCCS. However, the findings of the study revealed differences in opinion regarding the treatment modalities, which necessitates further long term clinical studies that could precisely document certain reliable guidelines in this point of view.

  16. Automated identification of basal cell carcinoma by polarization-sensitive optical coherence tomography

    Science.gov (United States)

    Duan, Lian; Marvdashti, Tahereh; Lee, Alex; Tang, Jean Y.; Ellerbee, Audrey K.

    2014-01-01

    We report an automated classifier to detect the presence of basal cell carcinoma in images of mouse skin tissue samples acquired by polarization-sensitive optical coherence tomography (PS-OCT). The sensitivity and specificity of the classifier based on combined information of the scattering intensity and birefringence properties of the samples are significantly higher than when intensity or birefringence information are used alone. The combined information offers a sensitivity of 94.4% and specificity of 92.5%, compared to 78.2% and 82.2% for intensity-only information and 85.5% and 87.9% for birefringence-only information. These results demonstrate that analysis of the combination of complementary optical information obtained by PS-OCT has great potential for accurate skin cancer diagnosis. PMID:25360384

  17. Basal cell carcinoma with halo phenomenon in a young female: Significance of dermatoscopy in early diagnosis

    Directory of Open Access Journals (Sweden)

    Pinar Yuksel Basak

    2015-01-01

    Full Text Available Halo phenomenon of nevus may be observed as a circular reaction, although it is unusual around tumors. A 29-year-old woman presented with a pigmented lesion on the cheek since three years. She noted whitening of the skin around the lesion almost after a year following its appearance. Dermatologic examination revealed a pigmented nodular lesion with a hypopigmented halo on the left infraorbital region. The clinical impression was halo nevus, whereas basal cell carcinoma (BCC was considered in dermatoscopic differential diagnosis. The diagnosis was infiltrative-type BCC histopathologically. The persistence of a perilesional halo around an enlarging pigmented lesion should be carefully examined with accompanying dermatoscopic findings even in young patients for early diagnosis of tumoral lesions.

  18. Nodulocystic basal cell carcinoma arising directly from a seborrheic keratosis: A rare case report

    Directory of Open Access Journals (Sweden)

    Kana Shibao

    2016-01-01

    Full Text Available Seborrheic keratoses (SKs are common epidermal tumors composed of benign keratinocytes. Malignant skin tumors including basal cell carcinoma (BCC rarely arise within SKs. We report a rare case of an 82-year-old man with nodulocystic BCC that appeared at the center of a scaly hyperpigmented SK that had been presented for more than 10 years. It was histologically confirmed that CK19-positive BCC arose directly from the wall of the pseudohorn cyst, a part of the SK. Nodular and/or cystic BCC also rarely arise within SKs while the most common histologic type of BCC within SKs is the superficial type. Careful observation of SKs is important even though it is rarely a background condition for malignant transformation.

  19. Vismodegib: The first drug approved for advanced and metastatic basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    A K Dubey

    2013-01-01

    Full Text Available Treatment of basal cell carcinoma (BCC usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA. The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  20. Vismodegib in the treatment of basal cell carcinoma: indications for clinical practice.

    Science.gov (United States)

    Calzavara Pinton, Piergiacomo; Licitra, Lisa; Peris, Katia; Santoro, Armando; Ascierto, Paolo Antonio

    2015-01-01

    Basal cell carcinoma (BCC) is a frequent skin cancer which can cause substantial morbidity due to its location on the face, its frequency of relapse and its capacity to invade local tissues. The primary treatment of BCC usually involves surgery or radiotherapy. In patients who have exhausted surgical and radiotherapy options or with metastatic BCC, guidelines recommend the use of the Hedgehog pathway inhibitor vismodegib. This molecule is indicated for the treatment of adults with metastatic BCC, or with locally advanced BCC which has recurred following surgery or who are not eligible to surgery or radiation. This paper aims to provide suggestions on the optimal management of BCC patients treated with vismodegib in clinical practice, according to the large experience gained by a group of Italian dermatologists and oncologists. In particular, the focus of this paper will be on the monitoring of patients and the management of adverse events.

  1. Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus.

    Science.gov (United States)

    Peris, Ketty; Licitra, Lisa; Ascierto, Paolo A; Corvò, Renzo; Simonacci, Marco; Picciotto, Franco; Gualdi, Giulio; Pellacani, Giovanni; Santoro, Armando

    2015-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

  2. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    Science.gov (United States)

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  3. Investigation of basal cell carcinoma using dynamic focus optical coherence tomography.

    Science.gov (United States)

    Avanaki, Mohammad R N; Hojjatoleslami, Ali; Sira, Mano; Schofield, John B; Jones, Carole; Podoleanu, Adrian Gh

    2013-04-01

    Optical coherence tomography (OCT) is becoming a popular modality for skin tumor diagnosis and assessment of tumor size and margin status. We conducted a number of imaging experiments on periocular basal cell carcinoma (BCC) specimens using an OCT configuration. This configuration employs a dynamic focus (DF) procedure where the coherence gate moves synchronously with the peak of the confocal gate, which ensures better signal strength and preservation of transversal resolution from all depths. A DF-OCT configuration is used to illustrate morphological differences between the BCC and its surrounding healthy skin in OCT images. The OCT images are correlated with the corresponding histology images. To the best of our knowledge, this is the first paper to look at DF-OCT imaging in examining periocular BCC.

  4. Cell size and basal metabolic rate in hummingbirds Tamaño celular y tasa metabólica basal en picaflores

    Directory of Open Access Journals (Sweden)

    Juan C. Opazo

    2005-06-01

    Full Text Available Nucleotypic theory suggests that genome size play indirect roles in determining organismal fitness. Among endotherms this theory has been demonstrated by an inverse correlation between basal metabolic rate (BMR and genome size. Nonetheless, accumulation of variables, especially for some key groups of endotherms, involved in C-value enigma (e.g., cell size will fortify this theory. In this sense, hummingbird species are of particular interest because they are an energetic extreme in avian and endotherm evolution. Knowing that cell size is proportional to C-value, in this study we tested for a relationship between mean corpuscular volume of red blood cells and BMR in four species of hummingbirds ranging from 4 to 20 g. In comparison with other birds, our hummingbird data show higher BMR and the smallest mean corpuscular volumes, thereby providing further support for the nucleotypic theoryLa teoría nucleotípica sugiere que el tamaño del genoma juega un rol indirecto en la adecuación biológica, a través de las variables con las que se relaciona. En endotermos esta teoría ha sido demostrada por la relación inversa entre la tasa metabólica basal y el tamaño del genoma. La acumulación de variables, en grupos claves de endotermos, relacionadas con esta problemática (e.g., tamaño celular son ideales para poner a prueba esta teoría. En este sentido, los picaflores son de particular interés ya que son el extremo energético dentro de los endotermos. Sabiendo que el tamaño celular es proporcional al tamaño del genoma, en este trabajo ponemos a prueba la relación del volumen corpuscular medio y la tasa metabólica basal, e indirectamente el tamaño del genoma, en cuatro especies de picaflores con masas corporales que van desde 4 a 20 g. Los datos de metabolismo mostraron estar dentro de los mayores descritos para aves, asimismo, los tamaños de los eritrocitos fueron los más pequeños dentro de los valores reportados en la literatura

  5. Anthropometric measures in relation to Basal Cell Carcinoma: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Pandeya Nirmala

    2006-03-01

    Full Text Available Abstract Background The relationship between anthropometric indices and risk of basal cell carcinoma (BCC is largely unknown. We aimed to examine the association between anthropometric measures and development of BCC and to demonstrate whether adherence to World Health Organisation guidelines for body mass index, waist circumference, and waist/hip ratio was associated with risk of BCC, independent of sun exposure. Methods Study participants were participants in a community-based skin cancer prevention trial in Nambour, a town in southeast Queensland (latitude 26°S. In 1992, height, weight, and waist and hip circumferences were measured for all 1621 participants and weight was remeasured at the end of the trial in 1996. Prevalence proportion ratios were calculated using a log-binomial model to estimate the risk of BCC prior to or prevalent in 1992, while Poisson regression with robust error variances was used to estimate the relative risk of BCC during the follow-up period. Results At baseline, 94 participants had a current BCC, and 202 had a history of BCC. During the 5-year follow-up period, 179 participants developed one or more new BCCs. We found no significant association between any of the anthropometric measures or indices and risk of BCC after controlling for potential confounding factors including sun exposure. There was a suggestion that short-term weight gain may increase the risk of developing BCC for women only. Conclusion Adherence to World Health Organisation guidelines for body mass index, waist circumference and waist/hip ratio is not significantly associated with occurrence of basal cell carcinomas of the skin.

  6. Supraestructure maxillectomy and orbital exenteration for treatment of basal cell carcinoma of inferior eyelid: Case report and review.

    Directory of Open Access Journals (Sweden)

    Sebastian Villalon-Lopez

    2005-01-01

    Full Text Available Basal cell carcinoma (BCC is the most frequent type of skin cancer in humans, with cumulative exposure to ultraviolet radiation (UVR as important risk factor for development of the illness as such as severe solar burns during childhood or adolescence. BCC is mainly located on sun exposed sites, being head and neck the areas of more incidence; although nose, eyelids and periorbitary tissue are unfavorable due to cosmetic results that BCC involves. Tumors can be classified as: nodular, superficial, micronodular, morphea variety, infiltrating, pigmented, metatypic and fibroepithelioma of Pinkus. Several treatment options as surgical and non-surgical are available. The goal of treatment is complete excision of the tumor with preservation of surrounding structures in a way aesthetically acceptable. Mohs′ micrographic surgery is the standard treatment for all non-melanoma skin cancer. Orbital exenteration is also used for treatment of malignancies of ocular tissues, mainly squamous cell carcinoma, sebaceous cell carcinoma and BCC. The tissue beneath the surgical site can be left for second-intention granulation or covered with a cutaneous implant of partial thickness. The case of a 77 year-old patient is presented with BCC of inferior eyelid of 14 years duration, formerly managed with radiotherapy and, due to recurrent illness and invasion to the maxillary antrum; he needed supraestructure maxillectomy with left orbital exenteration.

  7. Supraestructure maxillectomy and orbital exenteration for treatment of basal cell carcinoma of inferior eyelid: Case report and review

    Directory of Open Access Journals (Sweden)

    Villalon-Lopez J

    2006-01-01

    Full Text Available Basal cell carcinoma (BCC is the most frequent type of skin cancer in humans, with cumulative exposure to ultraviolet radiation as an important risk factor for development of illness such as severe solar burns during childhood or adolescence. BCC is mainly located on sun-exposed sites, head and neck being the areas of more incidences; although nose, eyelids and periorbitary tissue are unfavorable due to cosmetic results that BCC involves. Tumors can be classified as nodular, superficial, micronodular, morphea variety, infiltrating, pigmented, metatypic and fibroepithelioma of Pinkus. Several treatment options such as surgical and nonsurgical are available. The goal of treatment is complete excision of the tumor with preservation of surrounding structures in a way aesthetically acceptable. Mohs′ micrographic surgery is the standard treatment for all nonmelanoma skin cancers. Orbital exenteration is also used for treatment of malignancies of ocular tissues, mainly squamous cell carcinoma, sebaceous cell carcinoma and BCC. The tissue beneath the surgical site can be left for second-intention granulation or covered with a cutaneous implant of partial thickness. The case of a 77-year-old patient is presented with BCC of inferior eyelid of 14 years′ duration, formerly managed with radiotherapy; however, due to recurrent illness and invasion to the maxillary antrum, he needed supraestructure maxillectomy with left orbital exenteration.

  8. The Action of Discoidin Domain Receptor 2 in Basal Tumor Cells and Stromal Cancer-Associated Fibroblasts Is Critical for Breast Cancer Metastasis.

    Science.gov (United States)

    Corsa, Callie A S; Brenot, Audrey; Grither, Whitney R; Van Hove, Samantha; Loza, Andrew J; Zhang, Kun; Ponik, Suzanne M; Liu, Yuming; DeNardo, David G; Eliceiri, Kevin W; Keely, Patricia J; Longmore, Gregory D

    2016-06-14

    High levels of collagen deposition in human and mouse breast tumors are associated with poor outcome due to increased local invasion and distant metastases. Using a genetic approach, we show that, in mice, the action of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2) in both tumor and tumor-stromal cells is critical for breast cancer metastasis yet does not affect primary tumor growth. In tumor cells, DDR2 in basal epithelial cells regulates the collective invasion of tumor organoids. In stromal cancer-associated fibroblasts (CAFs), DDR2 is critical for extracellular matrix production and the organization of collagen fibers. The action of DDR2 in CAFs also enhances tumor cell collective invasion through a pathway distinct from the tumor-cell-intrinsic function of DDR2. This work identifies DDR2 as a potential therapeutic target that controls breast cancer metastases through its action in both tumor cells and tumor-stromal cells at the primary tumor site.

  9. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  10. Influences of Plant Growth Regulators,Basal Media and Carbohydrate Levels on Cell Suspension Culture of Panax ginseng

    Institute of Scientific and Technical Information of China (English)

    TangWei; WuJiongyuan; 等

    1995-01-01

    A cell suspension culture of Panax ginseng which may be continuously subcultured has been established.Embryogenic callus derived from clutured young leaves was used to initiate the culture,Plant growth regulators,basal medium formula and carbohydrate levels were examined to determine their various effects on suspension culture cell growth and development ,The best selection of plant growth regulator,basal medium and carbohydrate level is 2mg/L 2,4-D:0.5mg/L KT,MS and 3% sucrose respectively.

  11. Naevi as a risk factor for basal cell carcinoma in Caucasians: a Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun...... recorded according to size and body region and the skin phototype was assessed. There was no correlation between self-reported skin type and the number of naevi. Females with basal cell carcinoma had more naevi than did female controls (median number of naevi: 65 and 32, respectively) while males...

  12. Distribution and role in regeneration of N-CAM in the basal laminae of muscle and Schwann cells.

    Science.gov (United States)

    Rieger, F; Nicolet, M; Pinçon-Raymond, M; Murawsky, M; Levi, G; Edelman, G M

    1988-08-01

    The neural cell adhesion molecule (N-CAM) is a membrane glycoprotein involved in neuron-neuron and neuron-muscle adhesion. It can be synthesized in various forms by both nerve and muscle and it becomes concentrated at the motor endplate. Biochemical analysis of a frog muscle extract enriched in basal lamina revealed the presence of a polydisperse, polysialylated form of N-CAM with an average Mr of approximately 160,000 as determined by SDS-PAGE, which was converted to a form of 125,000 Mr by treatment with neuraminidase. To define further the role of N-CAM in neuromuscular junction organization, we studied the distribution of N-CAM in an in vivo preparation of frog basal lamina sheaths obtained by inducing the degeneration of both nerve and muscle fibers. Immunoreactive material could be readily detected by anti-N-CAM antibodies in such basal lamina sheaths. Ultrastructural analysis using immunogold techniques revealed N-CAM in close association with the basal lamina sheaths, present in dense accumulation at places that presumably correspond to synaptic regions. N-CAM epitopes were also associated with collagen fibrils in the extracellular matrix. The ability of anti-N-CAM antibodies to perturb nerve regeneration and reinnervation of the remaining basal lamina sheaths was then examined. In control animals, myelinating Schwann cells wrapped around the regenerated axon and reinnervation occurred only at the old synaptic areas; new contacts between nerve and basal lamina had a terminal Schwann cell capping the nerve terminal. In the presence of anti-N-CAM antibodies, three major abnormalities were observed in the regeneration and reinnervation processes: (a) regenerated axons in nerve trunks that had grown back into the old Schwann cell basal lamina were rarely associated with myelinating Schwann cell processes, (b) ectopic synapses were often present, and (c) many of the axon terminals lacked a terminal Schwann cell capping the nerve-basal lamina contact area. These

  13. Basal cytokeratin phenotypes of myoepithelial cells indicates the origin of ductal carcinomas in situ of the breast.

    Science.gov (United States)

    Chen, Ling; Yin, Xiaona; Lu, Shanshan; Chen, Guorong; Dong, Lei

    2015-09-01

    Terminal duct lobular unit (TDLU) is widely accepted as the origin of ductal carcinoma in situ of breast. The differentiation states of myoepithelial cells of breast ductal system hint the development of breast hyperplastic lesions. Basal cytokeratin (CK) phenotypes indicate the differentiation of myoepithelial cells. Using antibodies of CK5/6, CK14, and CK17, this study reports the basal CK phenotypes of myoepithelial cells in 20 foci of normal breast, 20 usual ductal hyperplasias, 36 ductal carcinomas in situ (DCIS), and 28 sclerosing adenosis (SA). The results showed that the positive staining of basal CKs of myoepithelial cells in normal ducts were significantly higher than those in normal lobules. The basal CK expression of myoepithelial cells of DCIS and usual ductal hyperplasia was similar to that of normal duct, whereas that of SA was similar to that of normal lobule. We propose a modified model of TDLU origin of intraductal carcinoma that most of DCIS originate from terminal ducts of TDLU, whereas most SA originate from lobules.

  14. LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway

    Science.gov (United States)

    Xiao, Deshen; Lai, Weiwei; Pan, Yu; Jiang, Yiqun; Chen, Ling; Mao, Chao; Zhou, Jian; Xi, Sichuan; Cao, Ya; Liu, Shuang; Tao, Yongguang

    2016-01-01

    Basal cell carcinomas (BCC) of the skin are the most common of human cancers. The noncanonical NF-κB pathway is dependent on IKKα. However, the role of IKKα in BCC has not been elucidated. We show here that IKKα is expressed in the nucleus in BCC and non-malignant diseases. Nuclear IKKα could directly bind to the promoters of inflammation factors and LGR5, a stem cell marker, in turn, upregulating LGR5 expression through activation of STAT3 signaling pathway during cancer progression. Activation of STAT3 signaling pathway contributes LGR5 expression in dependent of IKKα after the interplay between STAT3 and IKKα. Meanwhile knockdown of IKKα inhibits tumor growth and transition of epithelial stage to mescheme stage. Taken together, we demonstrate that IKKα functions as a bone fide chromatin regulator in BCC, whose promoted expression contributes to oncogenic transformation via promoting expression stemness- and inflammatory- related genes. Our finding reveals a novel viewpoint for how IKKα may involve in BCCs tumor progression in the inflammatory microenvironment. PMID:27049829

  15. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Paola Savoia

    2015-09-01

    Full Text Available Basal cell carcinoma (BCC is the most common cancer in individuals with fair skin type (I–II and steadily increasing in incidence (70% of skin malignancy. It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC.

  16. Preliminary study for non – invasive optical detection of squamous and basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Ali Ahmed Mohammed

    2012-11-01

    Full Text Available Abstract Background The early detection of skin cancer may highly increase the chances of its healing. One of the non-invasive methods of such detection based on the Oblique- Incidence Diffuse Reflectance (OIDR measurements of the reflected diode laser light from the skin. In this research we designed and implemented the OIDR reflectometry measuring system with a 650 nm diode laser source to aid physicians in diagnosing both squamous cell carcinomas (SCC and basal cell carcinomas(BCC. Method The laser is delivered obliquely to the skin surface by an optical fiber fitted through a tube holder of CCD camera. The diffused reflected laser light from the skin is captured by the CCD camera and sent to a computer, which is supplied by a specially prepared Matlab program to analyze these images in order to decide in a time whether the lesion is malignant or benign. Fifty cases were diagnosed under supervision of the consultant section of The Governmental Specialized Marjan Teaching Hospital – MOH – Iraq. Result The fifty diagnosed cases by this technique, the results were 90% accurate. Conclusion The method of laser oblique-incidence diffuse reflectance (OIDR combined with using the developed algorithms that have high classification rates may prove useful in the clinic as the process is fast, noninvasive and accurate.

  17. Molecular classification of basal cell carcinoma of skin by gene expression profiling.

    Science.gov (United States)

    Jee, Byul A; Lim, Hyoseob; Kwon, So Mee; Jo, Yuna; Park, Myong Chul; Lee, Il Jae; Woo, Hyun Goo

    2015-12-01

    Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC.

  18. Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults.

    Science.gov (United States)

    Foote, J A; Harris, R B; Giuliano, A R; Roe, D J; Moon, T E; Cartmel, B; Alberts, D S

    2001-01-20

    Risk factors for non-melanoma skin cancer among populations with evidence of precursor damage are not well described. We examined and compared risk factors associated with the development of cutaneous basal-cell (BCC) or squamous-cell (SCC) carcinoma among a group of 918 adults with significant sun damage (> or = 10 clinically assessable actinic keratoses) but no prior history of skin cancer. These adults were participants in a 5-year skin chemoprevention trial between 1985 and 1992, who had been randomized to the placebo group and followed for occurrence of skin cancer. During the study, a total of 129 first SCC and 164 first BCC lesions were diagnosed. The overall BCC and SCC incidence rates for this group of men and women, mean age 61 years, were 4,106 and 3,198 per 100,000 person-years, respectively. Different constitutional and exposure factors were independently associated with BCC compared to SCC. Only increased age independently predicted BCC occurrence among this population. In contrast, older age along with male gender, natural red hair color and adult residence in Arizona for 10 or more years independently predicted SCC occurrence. The substantial incidence of skin cancer found among this population confirms the need for active dermatological monitoring among individuals with multiple visible actinic lesions.

  19. Mineral composition of and the relationships between them of human basal ganglia in very old age.

    Science.gov (United States)

    Tohno, Yoshiyuki; Tohno, Setsuko; Azuma, Cho; Minami, Takeshi; Ke, Lining; Ongkana, Nutcharin; Sinthubua, Apichat; Mahakkanukrauh, Pasuk

    2013-01-01

    Trace elements and the relationships among them were investigated by direct chemical analysis in three basal ganglia regions in very old age individuals and age- and gender-related differences were assessed. After ordinary dissections at Nara Medical University were finished, the caudate nucleus, putamen, and globus pallidus belonging to the basal ganglia were removed from the identical cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years (average age = 83.3 ± 7.5 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca, P, and Mg contents increased significantly in the putamen with aging and the Mg content increased significantly in the globus pallidus with aging, but no elements increased significantly in the caudate nucleus with aging. Regarding the relationships among elements in the basal ganglia, extremely significant direct correlations were found among the Ca, P, and Mg contents in the putamen. These results suggested that slight calcification occurred in the putamen in very old age. With regard to seven elements of Ca, P, S, Mg, Zn, Fe, and Na, it was examined whether there were significant correlations among the caudate nucleus, putamen, and globus pallidus. It was found that there were extremely significant direct correlations among all of the three basal ganglia in the P content. Likewise, with regard to the Fe content, there were extremely or very significant direct correlations among all of the three basal ganglia. Regarding the gender difference in elements, it was found that the Ca content of the caudate nucleus was significantly higher in women than in men.

  20. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage.

    Directory of Open Access Journals (Sweden)

    Nisha M Badders

    Full Text Available BACKGROUND: Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%. Stem cell activity can be enriched by >200 fold (over 80% of activity, based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42% basal/total epithelial cells to 22% and Lrp5-/- mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16(Ink4a and TA-p63. CONCLUSIONS/SIGNIFICANCE: This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component of normal mammary stem cell function.

  1. Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium.

    Science.gov (United States)

    Krolewski, Richard C; Packard, Adam; Schwob, James E

    2013-03-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion.

  2. Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae.

    Directory of Open Access Journals (Sweden)

    Le Wang

    Full Text Available The digital laminae is a two layer tissue that attaches the distal phalanx to the inner hoof wall, thus suspending the horse's axial skeleton in the hoof capsule. This tissue fails at the epidermal:dermal junction in laminitic horses, causing crippling disease. Basal epithelial cells line the laminar epidermal:dermal junction, undergo physiological change in laminitic horses, and lose versican gene expression. Versican gene expression is purportedly under control of the canonical Wnt signaling pathway and is a trigger for mesenchymal-to-epithelial transition; thus, its repression in laminar epithelial cells of laminitic horses may be associated with suppression of the canonical Wnt signaling pathway and loss of the epithelial cell phenotype. In support of the former contention, we show, using laminae from healthy horses and horses with carbohydrate overload-induced laminitis, quantitative real-time polymerase chain reaction, Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis, and immunofluorescent tissue staining, that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in laminar basal epithelial cells of healthy horses. Furthermore, expression of positive regulators is suppressed and negative regulators elevated in laminae of laminitic compared to healthy horses. We also show that versican gene expression in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, consistent with regulation by the canonical Wnt signaling pathway. In addition, gene and protein expression of β-catenin correlates positively with that of integrin β4 and both are strongly suppressed in laminar basal epithelial cells of laminitic horses, which remain E-cadherin(+/vimentin(-, excluding mesenchymal transition as contributing to loss of the adherens junction and hemidesmosome components. We propose that suppression of the canonical Wnt signaling pathway, and

  3. Naevi as a risk factor for basal cell carcinoma in Caucasians: a Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun...

  4. Cost-effectiveness of Mohs micrographic surgery vs surgical excision for basal cell carcinoma of the face

    NARCIS (Netherlands)

    B.A.B. Essers (Brigitte); C.D. Dirksen (Carmen); F.H. Nieman (Fred); N.W.J. Smeets (Nicole W.); G.A.M. Krekels (Gertruud); M.H. Prins (Martin); H.A.M. Neumann (Martino)

    2006-01-01

    textabstractObjective: To assess the cost-effectiveness of Mohs micrographic surgery (MMS) compared with the surgical excision for both primary and recurrent basal cell carcinoma (BCC). Design: A cost-effectiveness study performed alongside a prospective randomized clinical trial in which MMS was co

  5. Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

    NARCIS (Netherlands)

    Peppelman, M.; Nguyen, K.P.; Alkemade, H.A.; Maessen-Visch, B.; Hendriks, J.C.; van Erp, P.E.; Adang, E.M.; Gerritsen, M.J.

    2016-01-01

    BACKGROUND: Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and

  6. Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer

    OpenAIRE

    Graveel, Carrie R.; DeGroot, Jack D.; Su, Yanli; Koeman, Julie; Dykema, Karl; Leung, Samuel; Snider, Jacqueline; Davies, Sherri R.; Swiatek, Pamela J.; Cottingham, Sandra; Watson, Mark A.; Matthew J Ellis; Sigler, Robert E.; Furge, Kyle A.; Vande Woude, George F

    2009-01-01

    Understanding the signaling pathways that drive aggressive breast cancers is critical to the development of effective therapeutics. The oncogene MET is associated with decreased survival in breast cancer, yet the role that MET plays in the various breast cancer subtypes is unclear. We describe a knockin mouse with mutationally activated Met (Metmut) that develops a high incidence of diverse mammary tumors with basal characteristics, including metaplasia, absence of progesterone receptor and E...

  7. A genome-wide analysis of gene-caffeine consumption interaction on basal cell carcinoma.

    Science.gov (United States)

    Li, Xin; Cornelis, Marilyn C; Liang, Liming; Song, Fengju; De Vivo, Immaculata; Giovannucci, Edward; Tang, Jean Y; Han, Jiali

    2016-12-01

    Animal models have suggested that oral or topical administration of caffeine could inhibit ultraviolet-induced carcinogenesis via the ataxia telangiectasia and rad3 (ATR)-related apoptosis. Previous epidemiological studies have demonstrated that increased caffeine consumption is associated with reduced risk of basal cell carcinoma (BCC). To identify common genetic markers that may modify this association, we tested gene-caffeine intake interaction on BCC risk in a genome-wide analysis. We included 3383 BCC cases and 8528 controls of European ancestry from the Nurses' Health Study and Health Professionals Follow-up Study. Single nucleotide polymorphism (SNP) rs142310826 near the NEIL3 gene showed a genome-wide significant interaction with caffeine consumption (P = 1.78 × 10(-8) for interaction) on BCC risk. There was no gender difference for this interaction (P = 0.64 for heterogeneity). NEIL3, a gene belonging to the base excision DNA repair pathway, encodes a DNA glycosylase that recognizes and removes lesions produced by oxidative stress. In addition, we identified several loci with P value for interaction caffeine consumption-related SNPs reported by previous genome-wide association studies and risk of BCC, both individually and jointly, but found no significant association. In sum, we identified a DNA repair gene that could be involved in caffeine-mediated skin tumor inhibition. Further studies are warranted to confirm these findings. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. [Aproaches to immunotherapy in different immunophenotypes of cutaneous basal cell carcinoma].

    Science.gov (United States)

    Petrunin, D D; Okovityĭ, S V; Kostalevskaia, A V; Suchkov, S V

    2012-01-01

    The combination of two immunomodulating agents (genferon derived from exogenous IFN-alpha2b and cycloferon, endogenous IFN inductor) was added to the complex therapy of 60 patients with different cutaneous basal cell carcinoma (CBCC) immunophenotypes. All patients underwent tumor resection, 1-3 days after surgery the patients received immunotropic therapy by focal cycloferon injections (2 ml of 12.5% solution) on days 1, 2, 4, 6, 8 and 10 post-operation with simultaneous genferon therapy via suppositoria (1 000 000 ME) twice a day for 10 days. The therapy was well-tolerated. Essential parameters of immune homeostasis were evaluated before and 3 months after immunotropic therapy. During further observation (for a mean period of 1.8 years) none of the patients displayed any signs of CBCC relapse. The immunological studies results give evidence for correction of immune disturbances characteristic for CBCC patients. This data confirm the effectiveness of immunotropic therapy for relapse prevention and immune disorders correction and allow recommending it for CBCC patients with high relapse risk.

  9. Nonsurgical treatment options for basal cell carcinoma - focus on advanced disease.

    Science.gov (United States)

    Goldenberg, Gary; Hamid, Omid

    2013-12-01

    Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

  10. Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Fujii, Katsunori; Ohashi, Hirofumi; Suzuki, Maiko; Hatsuse, Hiromi; Shiohama, Tadashi; Uchikawa, Hideki; Miyashita, Toshiyuki

    2013-12-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1, encoding a receptor for the secreted protein, sonic hedgehog. Recently, a Chinese family with NBCCS carrying a missense mutation in PTCH2, a close homolog of PTCH1, was reported. However, the pathological significance of missense mutations should be discussed cautiously. Here, we report a 13-year-old girl diagnosed with NBCCS based on multiple keratocystic odontogenic tumors and rib anomalies carrying a frameshift mutation in the PTCH2 gene (c.1172_1173delCT). Considering the deleterious nature of the frameshift mutation, our study further confirmed a causative role for the PTCH2 mutation in NBCCS. The absence of typical phenotypes in this case such as palmar/plantar pits, macrocephaly, falx calcification, hypertelorism and coarse face, together with previously reported cases, suggested that individuals with NBCCS carrying a PTCH2 mutation may have a milder phenotype than those with a PTCH1 mutation.

  11. [Sclerodermiform basal cell carcinoma. Apropos of a study of 83 cases].

    Science.gov (United States)

    Loddé, J P; Grangier, Y; Le Roux, P; Fabre, E

    1998-08-01

    The authors present a study of 83 cases of sclerodermiform basal cell carcinoma. This series constitutes 2.3% of all skin cancers treated in the authors' unit from 1981 to 1996. The predominant site of these carcinomas is the centrofacial region with 46% of tumours involving the nose. In the majority of cases, treatment consisted of cover by a flap (52.6% of cases). Full-thickness skin grafts were used in 29% of cases and excision-suture was performed in 18.4% of cases. The authors emphasize the need to perform large resection with safety margins determined by the macroscopically visible tumour diameter. As frozen section pathological examination is not contributive, they prefer to defer reconstruction until the final pathology results are obtained. The only exception is the need to cover a vital region, such as the eye. These carcinomas must be followed in the long-term, as 20% of recurrences were detected in this series, comprising many orbitopalpebral sites, associated with difficult staging, and which always have a reserved prognosis. The authors therefore propose the use of epitheses in so-called high-risk sites. The three main guidelines in this disease, one of the most worrying forms of skin cancer, are surgical aggressiveness, modesty in terms of the cosmetic result and alertness in the follow-up.

  12. One-stop-shop treatment for basal cell carcinoma, part of a new disease management strategy.

    Science.gov (United States)

    van der Geer, S; Frunt, M; Romero, H L; Dellaert, N P; Jansen-Vullers, M H; Demeyere, T B J; Neumann, H A M; Krekels, G A M

    2012-09-01

    The number of skin cancer patients, especially patients with basal cell carcinoma (BCC), is rapidly increasing. Resources available at dermato-oncology units have not increased proportionally, which affects the throughput time of patients. To assess the feasibility and safety of implementation of the one-stop-shop concept for the treatment of patients with BCC at a dermato-oncology unit. A pilot study on a one-stop-shop concept for BCC was performed to investigate procedure safety and patient satisfaction. Fresh frozen sections were used to diagnose the tumours, and subsequently treatment with photodynamic therapy or excision was performed on the same day. Time spent in the hospital was measured and questionnaires were used to evaluate patient satisfaction. Sixteen patients, who together had 19 tumours, were included. Diagnoses were made within a mean time of 100 min (range 27-160 min). The mean throughput time was 4 hours and 7 min (range 60-420 min). No complications were observed, and patient satisfaction was high. The one-stop-shop concept for the treatment of skin cancer patients is feasible and efficient for both patients and dermato-oncology units. Further research is necessary to investigate cost-effectiveness when larger patient groups are involved. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  13. Dermoscopic features of basal cell carcinomas: differences in appearance under non-polarized and polarized light.

    Science.gov (United States)

    Liebman, Tracey N; Jaimes-Lopez, Natalia; Balagula, Yevgeniy; Rabinovitz, Harold S; Wang, Steven Q; Dusza, Stephen W; Marghoob, Ashfaq A

    2012-03-01

    Basal cell carcinomas (BCCs) can be diagnosed using different dermoscopic modalities. To evaluate dermoscopic features of BCCs using nonpolarized and polarized dermoscopy to highlight similarities and differences between dermoscopic modalities. Retrospective study of 149 BCCs under nonpolarized dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy (PNCD). Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to histopathologic subtype. The most common dermoscopic structures in BCCs across all modalities included globules (50.3-51.0%), dots (49.7-50.3%), white structureless areas (63.1-74.5%), structureless gray-brown areas (24.2-24.8%), and ulcerations (28.2%). The most frequently observed vasculature included arborizing vessels (18.8-38.3%), short fine telangiectasias (SFTs) (73.8-82.6%), and vascular blush (41.6-83.2%). Structures with higher levels of agreement across modalities included pigmented structures and ulcerations. Lower levels of agreement existed between contact and noncontact modalities for certain vascular features. White shiny structures, which include shiny white lines (chrysalis and crystalline structures) (0-69.1%), shiny white areas (0-25.5%), and rosettes (0-11.4%), exhibited no agreement between NPD and polarized modalities. This study highlights differences in dermoscopic features of BCCs under three dermoscopic modalities. Shiny white lines (chrysalis and crystalline structures) and shiny white areas may be used as additional criteria to diagnose BCCs. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  14. Accuracy and reliability of Tzanck test compared to histopathology for diagnosis of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Dey

    2015-01-01

    Full Text Available Background: Histopathology is considered the gold standard for diagnosis of basal cell carcinoma (BCC but is time consuming and needs expertise to make a correct diagnosis. On the other hand, Tzanck test is a simple, easy, inexpensive and rapid test which uses exfoliative cytology to make a diagnosis. Objective: To compare the results of Tzanck test with histopathology in the diagnosis of BCC and to evaluate the diagnostic reliability and accuracy of Tzanck test in BCC. Materials and Method: Twenty-six patients with clinical suspicion of BCC were recruited. Samples for Tzanck test and histopathology were taken and diagnoses made independently. Results of Tzanck test were compared with histopathology. Results: Twenty-three cases were histopathologically proved to be BCC. Tzanck test correlated in 12 cases of BCC and could exclude all three non-BCC lesions. In 11 cases it failed to diagnose BCC. The sensitivity and specificity of Tzanck test were 52.2% and 100%, respectively, and positive and negative predictive values were 100% and 21.4%. Conclusion: Tzanck test can be recommended for initial, rapid evaluation of a clinically diagnosed case of BCC. Under experienced hands, it reliably confirms BCC. The limitation is low negative predictive value. Since it does not give information about subtypes of BCC which is of great value in therapeutic planning, histopathological confirmation is mandatory.

  15. Secondary Involvement of the Mandible due to Basal Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Pegah Mosannen Mozaffary

    2015-05-01

    Full Text Available Basal cell carcinoma (BCC is the most common cutaneous malignancy among Caucasians. Rare examples of aggressive and neglected BCC have been reported. Here we report a unique case of a neglected BCC with significant jaw involvement. A 50-year-old female, referred by an otorhinologist, presented with a large ulcer on her chin, which was extended to her mandibular vestibule. The ulcer was 9×5.5 cm in size, and tissue destruction, necrosis was observed in the central portion, and the mandibular bone was exposed. On intraoral examination, tooth mobility and severe bone loss were evident. Due to the primary cutaneous origin of the lesion, BCC was considered as preliminary diagnosis. Biopsy was performed and diagnosis of BCC was confirmed. The diseased mandibular bone was resected and reconstructed with a surgical plate. The soft tissue defect was reconstructed with deltopectoral flap. The patient refused secondary stage plastic surgery. Although BCC is not a lethal malignancy, if left untreated and neglected, it can result in severe destruction, disfigurement, and even mortality.

  16. An unsupervised feature learning framework for basal cell carcinoma image analysis.

    Science.gov (United States)

    Arevalo, John; Cruz-Roa, Angel; Arias, Viviana; Romero, Eduardo; González, Fabio A

    2015-06-01

    The paper addresses the problem of automatic detection of basal cell carcinoma (BCC) in histopathology images. In particular, it proposes a framework to both, learn the image representation in an unsupervised way and visualize discriminative features supported by the learned model. This paper presents an integrated unsupervised feature learning (UFL) framework for histopathology image analysis that comprises three main stages: (1) local (patch) representation learning using different strategies (sparse autoencoders, reconstruct independent component analysis and topographic independent component analysis (TICA), (2) global (image) representation learning using a bag-of-features representation or a convolutional neural network, and (3) a visual interpretation layer to highlight the most discriminant regions detected by the model. The integrated unsupervised feature learning framework was exhaustively evaluated in a histopathology image dataset for BCC diagnosis. The experimental evaluation produced a classification performance of 98.1%, in terms of the area under receiver-operating-characteristic curve, for the proposed framework outperforming by 7% the state-of-the-art discrete cosine transform patch-based representation. The proposed UFL-representation-based approach outperforms state-of-the-art methods for BCC detection. Thanks to its visual interpretation layer, the method is able to highlight discriminative tissue regions providing a better diagnosis support. Among the different UFL strategies tested, TICA-learned features exhibited the best performance thanks to its ability to capture low-level invariances, which are inherent to the nature of the problem. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Automatic detection of basal cell carcinoma using telangiectasia analysis in dermoscopy skin lesion images.

    Science.gov (United States)

    Cheng, Beibei; Erdos, David; Stanley, Ronald J; Stoecker, William V; Calcara, David A; Gómez, David D

    2011-08-01

    Telangiectasia, dilated blood vessels near the surface of the skin of small, varying diameter, are critical dermoscopy structures used in the detection of basal cell carcinoma (BCC). Distinguishing these vessels from other telangiectasia, that are commonly found in sun-damaged skin, is challenging. Image analysis techniques are investigated to find vessels structures in BCC automatically. The primary screen for vessels uses an optimized local color drop technique. A noise filter is developed to eliminate false-positive structures, primarily bubbles, hair, and blotch and ulcer edges. From the telangiectasia mask containing candidate vessel-like structures, shape, size and normalized count features are computed to facilitate the discrimination of benign skin lesions from BCCs with telangiectasia. Experimental results yielded a diagnostic accuracy as high as 96.7% using a neural network classifier for a data set of 59 BCCs and 152 benign lesions for skin lesion discrimination based on features computed from the telangiectasia masks. In current clinical practice, it is possible to find smaller BCCs by dermoscopy than by clinical inspection. Although almost all of these small BCCs have telangiectasia, they can be short and thin. Normalization of lengths and areas helps to detect these smaller BCCs. © 2011 John Wiley & Sons A/S.

  18. Could cryosurgery be an alternative treatment for basal cell carcinoma of the vulva?

    Directory of Open Access Journals (Sweden)

    Verónica Garza-Rodríguez

    2014-01-01

    Full Text Available Basal cell carcinomas (BCC on the genital area account for less than 1% of all BCCs. Surgical management is indicated. Recurrence rate of vulvar BCC has been reported to be 10-20%. Mohs micrographic surgery (MMS is a superior surgical option. Other treatments include radiation and topical immuntherapy. Cryosurgery for vulvar BCC has not been reported. We present the case of a 88-year-old Hispanic woman with a vulvar ulcer that was confirmed as BCC by histopathology and treated with liquid nitrogen cryosurgery. Control biopsy was performed on day 90 was negative for BCC. No clinical evidence of recurrence was detected after one year. Although, the vulva is considered to be a high-risk site with respect to BCC and MMS is the gold standard for treatment, the delicate nature of the area may preclude complete removal by a surgical technique without compromising vital anatomical function. Liquid nitrogen cryosurgery uses the effects of extreme cold to effect deep destruction of the tumor and surrounding tissues. This is the first report of a vulvar BCC successfully treated with liquid nitrogen cryosurgery. We suggest this technique could be of benefit as an alternative treatment in cases where excisional procedures cannot be performed.

  19. Increase of bcl-2 Protein Expression in Aggressive Basal Cell Carcinoma of Head and Neck

    Directory of Open Access Journals (Sweden)

    Cláudia CAZAL

    2006-09-01

    Full Text Available Objective: The aim of this study was to verify the bcl-2 protein expression in 22 cutaneous basal cell carcinomas (BCC of the head and neck, and to compare it with its aggressive behavior. Method: Tumors were histologically classified in non-aggressive (BCC 1 and aggressive (BCC 2 and then submitted to the immunohistochemistry technique with the streptavidin-biotin peroxidase method using the anti-bcl-2 antibody. Results: After proceeding to morphological analysis, sixteen tumors (72.7% were considered aggressive and six (27.3% non-aggressive. Immunohistochemistry analysis showed that thirteen (59.1% lesions were positive staining and nine (40.9% were negative to the bcl-2 protein. Considering the positive lesions, 12 (92.3% were aggressive and one (7.7% non-aggressive. The relation between bcl-2 protein staining and the tumor aggressiveness was statistically significant (p<0.05 - Fisher's exact Test. Conclusion: The results suggest a relationship between the bcl-2 protein expression and the histological aggressiveness grade in the BCC of the head and neck group studied may exist.

  20. 1064 nm long-pulsed Nd:YAG laser treatment of basal cell carcinoma.

    Science.gov (United States)

    Ortiz, Arisa E; Anderson, R Rox; Avram, Mathew M

    2015-02-01

    Standard surgical and destructive treatments for basal cell carcinoma (BCC) can result in significant morbidity and scarring, stimulating the investigation of alternative non-surgical options. The objective of this study was to determine the safety, clinical, and histological efficacy of pulsed, high-fluence 1064 nm Nd:YAG laser therapy for the treatment of BCC on the trunk and extremities. This was a prospective, non-randomized, open-label clinical trial. Ten subjects with a biopsy-proven BCC less than 1.5 cm in diameter on the trunk or extremities received one treatment with a 10 milliseconds pulsed 1064 nm Nd:YAG laser. Standard excision was performed 1 month after laser treatment to confirm histologic clearance. The laser treatment was quick and well tolerated. There was complete histologic clearance after one treatment in 92% of the BCC tumors, overall. At higher fluences, there was 100% histologic clearance after one treatment. No significant adverse events were seen, including scarring. The 1064 nm long-pulsed Nd:YAG laser may offer a safe alternative for treating BCC off the face. A larger study is highly warranted to confirm these preliminary results. Lasers Surg. Med. 47:106-110, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  1. Treatment of Basal Cell Carcinomas with Pulsed Dye Laser: A Case Series

    Directory of Open Access Journals (Sweden)

    Norman Minars

    2012-01-01

    Full Text Available Background. Basal cell carcinoma (BCC is the most prevalent skin cancer. Because of its highly vascular characteristic, it is amendable to treatment with pulse dye laser (PDL. The goal of this study is to determine the safety and efficacy of PDL therapy for mostly facial BCCs. Materials and Methods. Sixteen men and thirteen women (29 total with 39 biopsy-proven BCCs were treated with 1–4 PDL (595 nm therapies at 2–4-week intervals. The treatment parameters included pulse energy of 15 J/cm 2, pulse length of 3 millisecond, with no dynamic cooling, and 7 mm spot size. The age of the patients was 30–90 years (mean 73 years. Response rates were evaluated by the clinical assessments with mean followup of 11 months. Results. Twenty-four patients with thirty-two tumors reached at least three months followup: 24/32 (75% tumors with complete resolution (mean 3 treatment sessions; 5/32 (16% tumors recurred; 3/32 (9% tumors with incomplete responses after four treatments. Minimal side effects and discomfort were experienced by the patients with PDL therapy. Conclusion. PDL is a safe, tolerable, and moderately effective method of treating various BCCs. The ideal niche and standardized settings for PDL treatment of BCCs are yet to be determined.

  2. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face.

    Science.gov (United States)

    Block, Alec M; Alite, Fiori; Diaz, Aidnag Z; Borrowdale, Richard W; Clark, Joseph I; Choi, Mehee

    2015-01-01

    Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

  3. Periocular Basal Cell Carcinoma Predictors for Recurrence and Infiltration of the Orbit

    Science.gov (United States)

    Furdova, Alena; Lukacko, Pavol

    2017-01-01

    Purpose: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the risk factors. Design: Retrospective, comparative, interventional case series. Methods: Data of all patients with BCC between 2008 and 2014 were reviewed for patient demographics, previous treatment options, tumor localization, and histopathologic subtype. Results: In group of 256 patients, orbital exenteration underwent 7 patients (2.7%). For 2 patients (5.1%), orbital exenteration was the first procedure performed. In the exenterated group, the most common tumor site was the medial cantus and lower eyelid, whereas in the overall group, it was the lower eyelid (P = 0.011). The proportion of patients initially treated with histopathologic result of infiltration of 1 margin was significantly higher in patients undergoing exenteration (P = 0.282). During the 7-year period observership, the authors have seen 13 recurrences (5.08%). In patients with recurrent BCC after surgery, the authors applied adjuvant high dose rate 192Ir brachytherapy. Neoadjuvant therapy with Vismodegib was effective in patient with biorbital infiltration after 1 side exenteration. Conclusions: Orbital invasion may be clinically silent. Recurrence rate of BCC in our group 5% corresponds to date in the literature. The exenteration for BCC may be significantly higher when the lesion involves a medial canthal location and lower eyelid and initial surgery does not include margin-controlled excision. PMID:27906855

  4. Combination Trimodality Therapy Using Vismodegib for Basal Cell Carcinoma of the Face

    Directory of Open Access Journals (Sweden)

    Alec M. Block

    2015-01-01

    Full Text Available Background. For large basal cell carcinomas (BCCs of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

  5. Confocal Microscopy–Guided Laser Ablation for Superficial and Early Nodular Basal Cell Carcinoma

    Science.gov (United States)

    Chen, Chih-Shan Jason; Sierra, Heidy; Cordova, Miguel; Rajadhyaksha, Milind

    2014-01-01

    Importance Laser ablation is a rapid and minimally invasive approach for the treatment of superficial skin cancers, but efficacy and reliability vary owing to lack of histologic margin control. High-resolution reflectance confocal microscopy (RCM) may offer a means for examining margins directly on the patient. Observations We report successful elimination of superficial and early nodular basal cell carcinoma (BCC) in 2 cases-, using RCM imaging to guide Er-:YAG laser ablation. Three-dimensional (3-D) mapping is feasible with RCM-, to delineate the lateral border and thickness of the tumor. Thus, the surgeon may deliver laser fluence and passes with localized control—ie, by varying the ablation parameters in sub-lesional areas with specificity that is governed by the 3-D topography of the BCC. We further demonstrate intra-operative detection of residual BCC after initial laser ablation and complete removal of remaining tumor by additional passes. Both RCM imaging and histologic sections confirm the final clearance of BCC. Conclusions and Relevance Confocal microscopy may enhance the efficacy and reliability of laser tumor ablation. This report represents a new translational application for RCM imaging, which, when combined with an ablative laser, may one day provide an efficient and cost-effective treatment for BCC. PMID:24827701

  6. A 5 year follow-up study of MAL-PDT treatment of Basal cell carcinoma and Actinic keratosis

    OpenAIRE

    2008-01-01

    Abstract Introduction: None melanoma skin cancer is divided into basal cell carcinoma and squamous cell carcinoma. The incidences of these tumours are increasing in the Caucasian population with increasing sun exposed leisure activities. Traditionally BCCs have been treated with excision surgery, but now several new treatment modalities have emerged. Photodynamic therapy is one of these new therapeutic options, but so far long follow-up data has been missing. Materials and Method: From ...

  7. The relationship between basal and squamous cell skin cancer and smoking related cancers

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    Sitas Freddy

    2011-12-01

    Full Text Available Abstract Background We compared the risk of being diagnosed with smoking-related cancers (lung, oral cavity, upper digestive and respiratory organs, bladder, kidney, anogenital cancers and myeloid leukaemia among people with squamous cell carcinoma (SCC or basal cell carcinoma of the skin (BCC, with risks found in the general population using data from an Australian population-based cancer registry. Methods People diagnosed with BCC or SCC in 1980-2003 reported to the Tasmanian Cancer Registry, Australia, were followed-up by linkage within the registry, until diagnosis of a subsequent smoking-related cancer, death, or until 31 December 2003. Risk of developing a future smoking-related cancer was assessed using age Standardised Incidence Ratios (SIR. Results People diagnosed with SCC had an increased risk of lung cancer (men: SIR = 1.89, 95% confidence interval: 1.61-2.21; women: SIR = 2.04, 1.42-2.83 and all other smoking-related cancers (men: SIR = 1.38, 1.19-1.60; women: SIR = 1.78, 1.34-2.33. Men with BCC had a significant increased risk of lung cancer (SIR = 1.26, 1.10-1.44 but not of any of the other smoking-related cancers (SIR = 1.09, 0.97-1.23. Conclusions Individuals with a history of SCC having an increased risk of developing smoking related cancers cancer suggests smoking as a common etiology. The relationship between BCC and smoking-related cancers is less certain.

  8. Pathway analysis for genome-wide association study of basal cell carcinoma of the skin.

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    Mingfeng Zhang

    Full Text Available BACKGROUND: Recently, a pathway-based approach has been developed to evaluate the cumulative contribution of the functionally related genes for genome-wide association studies (GWASs, which may help utilize GWAS data to a greater extent. METHODS: In this study, we applied this approach for the GWAS of basal cell carcinoma (BCC of the skin. We first conducted the BCC GWAS among 1,797 BCC cases and 5,197 controls in Caucasians with 740,760 genotyped SNPs. 115,688 SNPs were grouped into gene transcripts within 20 kb in distance and then into 174 Kyoto Encyclopedia of Genes and Genomes pathways, 205 BioCarta pathways, as well as two positive control gene sets (pigmentation gene set and BCC risk gene set. The association of each pathway with BCC risk was evaluated using the weighted Kolmogorov-Smirnov test. One thousand permutations were conducted to assess the significance. RESULTS: Both of the positive control gene sets reached pathway p-values<0.05. Four other pathways were also significantly associated with BCC risk: the heparan sulfate biosynthesis pathway (p  =  0.007, false discovery rate, FDR  =  0.35, the mCalpain pathway (p  =  0.002, FDR  =  0.12, the Rho cell motility signaling pathway (p  =  0.011, FDR  =  0.30, and the nitric oxide pathway (p  =  0.022, FDR  =  0.42. CONCLUSION: We identified four pathways associated with BCC risk, which may offer new insights into the etiology of BCC upon further validation, and this approach may help identify potential biological pathways that might be missed by the standard GWAS approach.

  9. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    Science.gov (United States)

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  10. Molecular mechanism: the human dopamine transporter histidine 547 regulates basal and HIV-1 Tat protein-inhibited dopamine transport.

    Science.gov (United States)

    Quizon, Pamela M; Sun, Wei-Lun; Yuan, Yaxia; Midde, Narasimha M; Zhan, Chang-Guo; Zhu, Jun

    2016-12-14

    Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% in H547P and 60% in H547D, respectively. These mutants did not alter DAT surface expression or surface DAT binding sites. H547 mutants attenuated Tat-induced inhibition of DA transport observed in WT hDAT. H547A displays a differential sensitivity to PMA- or BIM-induced activation or inhibition of DAT function relative to WT hDAT, indicating a change in basal PKC activity in H547A. These findings demonstrate that histidine547 on hDAT plays a crucial role in stabilizing basal DA transport and Tat-DAT interaction. This study provides mechanistic insights into identifying targets on DAT for Tat binding and improving DAT-mediated dysfunction of DA transmission.

  11. Immunoreactivity for alpha-smooth muscle actin characterizes a potentially aggressive subgroup of little basal cell carcinomas

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    L Pilloni

    2009-06-01

    Full Text Available Basal cell carcinoma (BCC is a very common malignant skin tumor that rarely metastatizes, but is often locally aggressive. Several factors, like large size (more than 3 cm, exposure to ultraviolet rays, histological variants, level of infiltration and perineural or perivascular invasion, are associated with a more aggressive clinical course. These morphological features seem to be more determinant in mideface localized BCC, which frequently show a significantly higher recurrence rate. An immunohistochemical profile, characterized by reactivity of tumor cells for p53, Ki67 and alpha-SMA has been associated with a more aggressive behaviour in large BCCs. The aim of this study was to verify if also little (less than 3 cm basal cell carcinomas can express immunohistochemical markers typical for an aggressive behaviour.

  12. In vitro testing of basal cytotoxicity: establishment of an adverse outcome pathway from chemical insult to cell death

    Science.gov (United States)

    Vinken, Mathieu; Blaauboer, Bas J.

    2017-01-01

    In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity. PMID:27939612

  13. In vitro testing of basal cytotoxicity: Establishment of an adverse outcome pathway from chemical insult to cell death.

    Science.gov (United States)

    Vinken, Mathieu; Blaauboer, Bas J

    2017-03-01

    In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells.

    Science.gov (United States)

    Smith, Stephen P; Scarpini, Cinzia G; Groves, Ian J; Odle, Richard I; Coleman, Nicholas

    2016-07-26

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of 'master regulators' for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.

  15. Comparative transcriptional profiling analysis of the two daughter cells from tobacco zygote reveals the transcriptome differences in the apical and basal cells

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    Hu Tian-Xiang

    2010-08-01

    Full Text Available Abstract Background In angiosperm, after the first asymmetric zygotic cell division, the apical and basal daughter cells follow distinct development pathways. Global transcriptome analysis of these two cells is essential in understanding their developmental differences. However, because of the difficulty to isolate the in vivo apical and basal cells of two-celled proembryo from ovule and ovary in higher plants, the transcriptome analysis of them hasn't been reported. Results In this study, we developed a procedure for isolating the in vivo apical and basal cells of the two-celled proembryo from tobacco (Nicotiana tabacum, and then performed a comparative transcriptome analysis of the two cells by suppression subtractive hybridization (SSH combined with macroarray screening. After sequencing, we identified 797 differentially expressed ESTs corresponding to 299 unigenes. Library sequence analysis successfully identified tobacco homologies of genes involved in embryogenesis and seed development. By quantitative real-time PCR, we validated the differential expression of 40 genes, with 6 transcripts of them specifically expressed in the apical or basal cell. Expression analysis also revealed some transcripts displayed cell specific activation in one of the daughter cells after zygote division. These differential expressions were further validated by in situ hybridization (ISH. Tissue expression pattern analysis also revealed some potential roles of these candidate genes in development. Conclusions The results show that some differential or specific transcripts in the apical and basal cells of two-celled proembryo were successfully isolated, and the identification of these transcripts reveals that these two daughter cells possess distinct transcriptional profiles after zygote division. Further functional work on these differentially or specifically expressed genes will promote the elucidation of molecular mechanism controlling early embryogenesis.

  16. Epoc-1: a POU-domain gene expressed in murine epidermal basal cells and thymic stromal cells.

    Science.gov (United States)

    Yukawa, K; Yasui, T; Yamamoto, A; Shiku, H; Kishimoto, T; Kikutani, H

    1993-11-15

    POU-domain transcription factors are known as developmental regulators which control organ development and cell phenotypes. In order to clarify the roles of POU-domain transcription factors in cell differentiation, we cloned a novel POU family gene, Epoc-1, from a murine thymus cDNA library. The amino acid (aa) sequence of the POU-specific domain of Epoc-1 is almost identical to those of Oct-1 and Oct-2. However, within the POU-homeodomain, 13 out of 60 aa differ between Epoc-1 and Oct-2. Recombinant Epoc-1 products were found to bind specifically to the octamer sequence. Epoc-1 was found to be expressed in skin, thymus, stomach and testis. In situ hybridization experiments and RNase protection assays indicated that Epoc-1 is expressed in the epidermal basal cells of the skin, which contain stem cells unipotent for keratinocyte differentiation and in thymic stromal elements. These results suggest that Epoc-1 might be one of the developmental regulators which controls epidermal development and thymic organogenesis.

  17. Clinical and histopathological characteristics of basal cell carcinoma in Chinese patients

    Institute of Scientific and Technical Information of China (English)

    CHANG Jian-min; GAO Xiao-man

    2013-01-01

    Background The clinical and histopathological characteristics of basal cell carcinoma (BCC) have been relatively well studied in Caucasian population.To characterize BCC in Chinese population,we analyzed the association of the histopathological subtypes with gender,age and anatomical location in this study.Methods The clinical and histopathological data of 243 BCC cases diagnosed at three hospitals in Beijing from January 2000 to April 2009 were reviewed retrospectively.Gender,age,location and histopathological subtype were analyzed.Results Among 243 patients enrolled,118 were males and 125 were females.The male/female ratio was 0.94∶1.The mean age was (65.16±12.62) years old.The head and neck were the most common sites of BCC (77.4%).Of the BCCs,53.9% were nodular,18.9% superficial and 18.5% infiltrative-morphoeic.The nodular,infiltrative-morphoeic and micronodular subtypes were predominant located on the head and neck,whereas the trunk was the most common location for the superficial subtype (P <0.05).The age at first presentation for females was lower than that for males (P<0.05).The age at first presentation for the superficial BCCs was younger than the non-superficial subtypes (P <0.05).Women with superficial BCC subtype visited hospital earlier than men (P <0.05).Conclusions Consistent with previous reports in Caucasian patient,our study find that different histopathological subtypes of BCC has distinct clinical features.It is speculated that the mechanisms underlining the pathogenesis of the superficial BCC may be different than those of non-superficial subtypes of BCC.

  18. Excision of periocular basal cell carcinoma guided by en face frozen section.

    Science.gov (United States)

    Tullett, Mark; Sagili, Suresh; Barrett, Andrew; Malhotra, Raman

    2013-09-01

    We describe a technique for monitoring excision margins in periocular basal cell carcinoma (BCC) using en face frozen sections and report outcomes. We excised periocular BCC with 3mm margins. An outer 1mm sliver of the perimeter of the specimen was mapped and sent for evaluation by en face frozen section. The central tumour mass was processed using routine paraffin sections. A further 3mm level was excised at the site of any affected margin and the outer 1mm sliver was again evaluated by frozen section. We identified 78 patients from November 2003 to July 2009; 67 had primary tumours and 11 (14%) had recurrent BCC of which 52 (66%) were located on the lower eyelid. Growth patterns were nodular (n=34, 43%), infiltrative (n=25, 32%), micronodular (n=12, 16%), and superficial (n=7, 9%). A third of BCC with a clinically nodular appearance showed additional histological patterns including infiltrative and micronodular growth patterns. Of 30 clinically nodular carcinomas, 29 were excised completely with one level, and one required 2 levels of excision for clearance after evaluation by frozen section. Mean follow-up was 23 months (range 2-60). There was one recurrence (1%). Excision of margins guided by en face frozen section is justified by the low rates of recurrence, and it can easily be taught or imported into hospital practice. Clinically nodular BCC have subclinical extensions that can be missed on bread loaf sectioning, which makes the sampling of margins a standard for periocular BCC. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  19. Reflectance confocal microscopy-guided laser ablation of basal cell carcinomas: initial clinical experience.

    Science.gov (United States)

    Sierra, Heidy; Yélamos, Oriol; Cordova, Miguel; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2017-08-01

    Laser ablation offers a procedure for precise, fast, and minimally invasive removal of superficial and early nodular basal cell carcinomas (BCCs). However, the lack of histopathological confirmation has been a limitation toward widespread use in the clinic. A reflectance confocal microscopy (RCM) imaging-guided approach offers cellular-level histopathology-like feedback directly on the patient, which may then guide and help improve the efficacy of the ablation procedure. Following an ex vivo benchtop study (reported in our earlier papers), we performed an initial study on 44 BCCs on 21 patients in vivo, using a pulsed erbium:ytterbium aluminum garnet laser and a contrast agent (aluminum chloride). In 10 lesions on six patients, the RCM imaging-guided detection of either presence of residual tumor or complete clearance was immediately confirmed with histopathology. Additionally, 34 BCCs on 15 patients were treated with RCM imaging-guided laser ablation, with immediate confirmation for clearance of tumor (no histopathology), followed by longer-term monitoring, currently in progress, with follow-up imaging (again, no histopathology) at 3, 6, and 18 months. Thus far, the imaging resolution appears to be sufficient and consistent for monitoring efficacy of ablation in the wound, both immediately postablation and subsequently during recovery. The efficacy results appear to be promising, with observed clearance in 19 cases of 22 cases with follow-ups ranging from 6 to 21 months. An additional 12 cases with 1 to 3 months of follow-ups has shown clearance of tumor but a longer follow-up time is required to establish conclusive results. Further instrumentation development will be necessary to cover larger areas with a more automatically controlled instrument for more uniform, faster, and deeper imaging of margins. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  20. Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome.

    Science.gov (United States)

    Yasar, Binnaz; Byers, Helen J; Smith, Miriam J; Lear, John; Oudit, Deemesh; Bholah, Zaynab; Roberts, Stephen A; Newman, William G; Evans, D Gareth

    2015-05-01

    Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04-2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR=1.44, 95% CI: 1.08-1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR=2.48, 95% CI: 1.47-4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.

  1. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma

    Science.gov (United States)

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul

    2017-01-01

    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  2. Basal cell carcinoma of the outer nose: Overview on surgical techniques and analysis of 312 patients

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2014-01-01

    Full Text Available Background: Basal cell carcinoma of the nose is common, with a potential of local recurrence and high-risk features. Materials and Methods: We provide a review on anatomy of the nose, tumour surgery and defect closure on the nose. We analysed our own patients with nasal BCC of a 24 months period. Results: We identified 321 patients with nasal BCC. There was a predominance of female patients of 1.2 to 1. The mean age was 74.8 years. Slow Mohs technique was employed for all tumours until 3D tumour-free margins were achieved. That resulted on average in 1.8 ± 0.7 Mohs stages. The most common histologic types were solitary (n = 182, morpheic (79, and micronodular (20, Perineural infiltration was evident in 56 tumours. Primary closure after mobilisation of soft tissue was possible in 105 BCCs. Advancement flaps were used in 91 tumours, rotation flaps in 47, transposition flaps in 34 tumours, and combined procedures in 6 cases. In 36 patients full-thickness skin grafting was performed. In two patients healing by second intention was preferred. Partial flap loss was seen in four patients (1.4%. All of them had significant underlying pathologies. None of the tumours treated showed a relapse during the observation time. However, this is a limitation of the present study since follow-up was on average only 10 months. Conclusions: BCCs of the nose are common. Only 3D-controlled micrographic surgery (Mohs or slow Mohs guarantee a high rate of complete tumour removal and a very low risk of recurrence.

  3. 18-FDG PET/CT assessment of basal cell carcinoma with vismodegib.

    Science.gov (United States)

    Thacker, Curtis A; Weiss, Glen J; Tibes, Raoul; Blaydorn, Lisa; Downhour, Molly; White, Erica; Baldwin, Jason; Hoff, Daniel D; Korn, Ronald L

    2012-10-01

    The use of 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib. Fourteen subjects with BCC were imaged with 18-FDG PET/CT for lesion identification and response categorizing (European Organisation for Research and Treatment for Cancer [EORTC] and PET response criteria in solid tumors [PERCIST] 1.0). Several parameters including metabolic activity of target lesions, site of disease presentation and spread, treatment response, and prognostic significance of metabolic activity following therapy were evaluated. All subjects exhibited at least one hypermetabolic lesion. Most subjects had only four organ systems involved at study enrollment: skin-muscle (93%), lung (57%), lymph nodes (29%), and bone (21%). SUVmax measured across all lesions decreased (median 33%, SD ± 45%) following therapy with metabolic activity normalizing or disappearing in 42% of lesions. No significant difference was observed between EORTC and PERCIST 1.0. Subjects that demonstrated at least a 33% reduction in SUVmax from baseline had a significantly longer progression-free survival (PFS) (median 17 months, 95% confidence interval [CI] ±4 months vs. 9 months, 95% CI ±5 months, P = 0.038) and overall survival (OS) (median 24 months, 95% CI ±4 months vs. 17 months, 95% CI ±13 months, P = 0.019). BCC lesions are hypermetabolic on 18-FDG PET/CT. A decrease in SUVmax was associated with improved PFS and OS. These results further support the incorporation of 18-FDG PET/CT scans in advanced BCC management.

  4. Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial.

    Science.gov (United States)

    Dessinioti, Clio; Plaka, Michaela; Stratigos, Alexander J

    2014-05-01

    The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a Phase II, international, multicenter clinical trial evaluating the efficacy and safety of vismodegib 150 mg once daily in patients with locally advanced or metastatic BCC. Vismodegib has been approved for the treatment of adult patients with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy. This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics.

  5. Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Pricl, Sabrina; Cortelazzi, Barbara; Dal Col, Valentina; Marson, Domenico; Laurini, Erik; Fermeglia, Maurizio; Licitra, Lisa; Pilotti, Silvana; Bossi, Paolo; Perrone, Federica

    2015-02-01

    Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss-of-function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Targeting this pathway with vismodegib, a novel SMO inhibitor, results in impressive tumor regression in patients harboring genetic defects in this pathway. However, a secondary mutation in SMO has been reported in medulloblastoma patients following relapse on vismodegib to date. This mutation preserves pathway activity, but appears to confer resistance by interfering with drug binding. Here we report for the first time on the molecular mechanisms of resistance to vismodegib in two BCC cases. The first case, showing progression after 2 months of continuous vismodegib (primary resistance), exhibited the new SMO G497W mutation. The second case, showing a complete clinical response after 5 months of treatment and a subsequent progression after 11 months on vismodegib (secondary resistance), exhibited a PTCH1 nonsense mutation in both the pre- and the post-treatment specimens, and the SMO D473Y mutation in the post-treatment specimens only. In silico analysis demonstrated that SMO(G497W) undergoes a conformational rearrangement resulting in a partial obstruction of the protein drug entry site, whereas the SMO D473Y mutation induces a direct effect on the binding site geometry leading to a total disruption of a stabilizing hydrogen bond network. Thus, the G497W and D473Y SMO mutations may represent two different mechanisms leading to primary and secondary resistance to vismodegib, respectively.

  6. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype

    OpenAIRE

    Wiese, David A.; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Kiupel, Matti

    2013-01-01

    Background Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer s...

  7. Cholinergic modulation differs between basal and apical dendritic excitation of hippocampal CA1 pyramidal cells.

    Science.gov (United States)

    Leung, L Stan; Péloquin, Pascal

    2010-08-01

    We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink-PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX-116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.

  8. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being...... introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  9. A study of the radiation effects on the basal cell of the rat tongue epithelium according to the exposure timing

    Energy Technology Data Exchange (ETDEWEB)

    Na, Chun Hwa; You, Dong Soo [Dept. of Oral and Maxillofacial Radiology, Graduate School, Seoul National University, Seoul (Korea, Republic of)

    1995-08-15

    The purpose of this study was to investigate chronic radiation effects on the basal cell of the rat epithelium according to different irradiation timing. Forty-two female rats were divided into 5 experimental groups according to different irradiation timing and were irradiated single dose of 396 cGy by MK cell irradiator using Cs-137. Experimental rats were sacrificed at the 2nd week, 4th week and 6th week after birth. The specimens were examined with light microscope and transmission electron microscope. The following results were obtained: 1. The first changes after irradiation were vacuoles. The vacuoles were chiefly observed in the cytoplasm, perinuclei area, and nuclei. 2. The most severe degenerative changes in the basal cell layer were observed in all experimental groups. ; cellular disarragement, vacuole formation, widening of intercellular space, enlarged mitochondria and rER, and chromatin clumping were seen. 3. The cellular degenerative changes were most severe at the 4th week after birth in all experimental group, and the basal cell hyperplasia was seen at the 6th week in the most of experimental groups. 4. The experimental groups 3 and 4 show more severe and more prolonged cellular degeneration than experimental groups 1 and 2, which were irradiated in pregnancy, and experimental group 5, which was irradiated after tongue maturation.

  10. Papular Epidermal Nevus with Skyline Basal Cell Layer (PENS): Three New Cases and Review of the Literature.

    Science.gov (United States)

    Luna, Paula C; Pannizardi, Anabel A; Martin, Carolina I; Vigovich, Felix; Casas, José G; Larralde, Margarita

    2016-05-01

    Papular epidermal nevus with skyline basal cell layer (PENS) is a recently described type of epidermal nevus with characteristic histopathologic findings, mainly regular, rectangular acanthosis and a well-demarcated basal cell layer with clear palisading and separation between basal cell nuclei and the first row of Malpighian cell nuclei. Although the first reports described randomly distributed lesions appearing sporadically in otherwise healthy patients, cases of Blaschkoid distribution, lesions associated with extracutaneous manifestations, and familial cases have been reported. We performed a review of the clinical charts of all patients with histologic diagnosis of PENS in our hospital. We evaluated epidemiologic, clinical, and histologic features. We then reviewed the literature with a particular emphasis on the presence or absence of extra-cutaneous associations. Three patients with PENS are described. One had a single lesion, one had three lesions, and one, a patient with mild developmental delay, a curved penis, and hypospadias, had multiple lesions. The probability of having extracutaneous manifestations is 6.3 times as great in individuals with more than four lesions. Therefore these patients may need closer follow-up. © 2016 Wiley Periodicals, Inc.

  11. Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

    Science.gov (United States)

    Ikeda, Sadakatsu; Goodman, Aaron M; Cohen, Philip R; Jensen, Taylor J; Ellison, Christopher K; Frampton, Garrett; Miller, Vincent; Patel, Sandip P; Kurzrock, Razelle

    2016-01-01

    Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden. PMID:27942391

  12. Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.

    Directory of Open Access Journals (Sweden)

    Tjinta Brinkhuizen

    Full Text Available BACKGROUND: Basal cell carcinoma (BCC is the most common cancer in Caucasians. Trichoepithelioma (TE is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1 and mechanistic/mammalian target of rapamycin (mTOR are key players in these pathways. OBJECTIVES: To determine whether HIF1/mTOR signalling is involved in BCC and TE. METHODS: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45 and TE (n = 35 samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%. RESULTS: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3, 73% and 75% (CAIX, 79% and 86% (GLUT1, 50% and 19% (HIF1α, 89% and 88% (pAKT, 55% and 61% (pS6, 15% and 25% (pMTOR, 44% and 63% (PHD2 and 44% and 49% (VEGF-A. CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. CONCLUSIONS: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

  13. Development of edge-activated liposomes for siRNA delivery to human basal epidermis for melanoma therapy.

    Science.gov (United States)

    Dorrani, Mania; Garbuzenko, Olga B; Minko, Tamara; Michniak-Kohn, Bozena

    2016-04-28

    Delivery of macromolecules such as siRNA into cells that reside in the basal epidermis of the skin is a major challenge due to the transport barriers that need to be overcome. siRNAs have potential therapeutic applications in various dermatological diseases such as psoriasis, atopic dermatitis, and cancer. Unfortunately, a low permeability of siRNA through the stratum corneum and epidermis has significantly limited its use for topical application. The objective of this study was to develop a topical siRNA delivery system that can permeate through the stratum corneum and viable epidermis and efficiently deposit therapeutic levels of siRNA to the basal epidermis/upper dermis where melanoma cells reside. To achieve this objective, a series of liposome compositions that contained various concentrations of edge activator in their structures were prepared and then complexed with siRNA at different ratios to generate a small library of liposome-siRNA complexes (lipoplexes) with different physicochemical properties. In this study we used melanoma as a disease model. Through use of quantitative imaging analysis, we identified the necessary design parameters for effective permeation of lipoplexes through the skin layers and deposition at the upper dermis. The ability of the formulated lipoplexes to internalize into melanoma cells, knockdown the expression of the BRAF protein and induce cell death in melanoma cells was studied by fluorescent microscopy, in-cell immunofluorescence assay and WST-1 cell proliferation assay. By providing direct quantitative and qualitative microscopy evidence, the results of this study demonstrate for the first time that the passive delivery of an edge-activated liposomal formulation can effectively carry siRNA through the stratum corneum and deposit it at the lower epidermis/upper dermis.

  14. Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

    Science.gov (United States)

    Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

    2015-10-01

    The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

  15. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

    Science.gov (United States)

    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  16. 腮腺基底细胞腺瘤的CT诊断%Diagnosis of Parotid Basal cell adenoma with CT

    Institute of Scientific and Technical Information of China (English)

    曾祥民; 李家开

    2010-01-01

    Objective To evaluate the CT findings of the parotid basal cell adenoma and it's diagnostic value.Methods The CT appearances of 10 patients with parotid basal cell adenoma confirmed by histopathology were reviewed retrospectively.The plain and the contrast-enhanced CT scan were performed in all cases.Results The well-defined mass in varied size with marked enhancement in contrast-enhanced CT imagines,in which the CT value increased to 200Hu maximally(average,84Hu),were the pathognomonic CT characteristics of the parotid basal cell adenoma.Conclusion The qualitative diagnosis of the parotid basal cell adenoma could be made based on the CT findings combined with some valuable clinical information before operation.%目的 探讨基底细胞腺瘤的CT表现特点及其临床应用价值.方法 回顾分析经手术及病理证实的10例腮腺基底细胞腺瘤的CT表现,所有患者均进行了腮腺CT平扫及增强扫描.结果 边界清楚、大小不等、增强扫描显著强化的软组织块影是腮腺基底细胞腺瘤的特征性CT表现,增强扫描较平扫CT值增加最高约200 Hu,平均增加84 Hu.结论 腮腺基底细胞腺瘤CT表现具有一定特征性,结合临床特点能够在术前作出定性诊断.

  17. Cyclical and patch-like GDNF distribution along the basal surface of Sertoli cells in mouse and hamster testes.

    Directory of Open Access Journals (Sweden)

    Takeshi Sato

    Full Text Available BACKGROUND AND AIMS: In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs through GDNF family receptor α1 (GFRα1. It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.

  18. Research Techniques Made Simple: Noninvasive Imaging Technologies for the Delineation of Basal Cell Carcinomas.

    Science.gov (United States)

    Que, Syril Keena T

    2016-04-01

    In this article we discuss the development of noninvasive imaging modalities to help delineate tumor margins of basal cell carcinomas in the setting of Mohs micrographic surgery. A review of the available literature reveals that dermoscopy can help delineate basal cell carcinomas before surgical removal but that it has no benefit over clinical inspection in reducing the number of Mohs stages. In contrast, fluorescence confocal microscopy has a sensitivity of 88-96% and specificity of 89-99% for the detection of basal cell carcinomas and can potentially serve as a rapid means for tumor evaluation on ex vivo specimens. Optical coherence tomography has shown some success in the presurgical evaluation of tumor margins in vivo, before surgical excision. With ongoing developments in device portability, speed of image retrieval, and image resolution, these technologies are likely to gain traction in cutaneous oncology research and practice. It is therefore important for dermatology clinicians and researchers to understand the mechanisms, principal uses, advantages, and limitations of each device.

  19. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    Science.gov (United States)

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  20. Anatomia microcirúgica da substâcia perfurada anterior basal humana Microsurgical anatomy of the human basal anterior perforated substance

    Directory of Open Access Journals (Sweden)

    Arlindo Alfredo Silveira D’Ávila

    2006-06-01

    Full Text Available A substância perfurada anterior constitui referencial na base do encéfalo. Localizada acima da bifurcação subaracnóidea da artéria carótida interna em sua porção basal e junto à artéria comunicante anterior na face inter-hemisférica, é transfixada por ramos perfurantes dirigidos aos núcleos telencefálicos corticais, cápsula interna e parte do tálamo. Por injeção intravascular de gelatina carminada, resina de Batson e látex, analisamos 50 hemisférios cerebrais humanos adultos de ambos os sexos, sob o microscópio cirúrgico. Objetivamos contribuir para a determinação da origem, número e topografia dos ramos destinados a essa região, seu curso, anastomoses e territórios de penetração. Propusemo-nos também a analisar a contribuição da artéria comunicante anterior à substância perfurada anterior. Foram encontradas variações anatômicas, incluindo anastomoses, envolvendo principalmente a artéria cerebral média e a artéria coróidea anterior. Estes conhecimentos são de interesse clínico-cirúrgico em razão da freqüência de patologias vasculares e tumorais a ela relacionadas.The anterior perforated substance (APS is a landmark in the basal forebrain. It has a basal face located above the carotid bifurcation in the subarachnoid space, and an interhemispheric one. It is the site of passage of the arteries to the caudate nucleus, putamen, internal capsule, adjacent areas of the globus pallidus and thalamus. Fifty hemispheres from twenty-five adult cadavers were obtained. The arteries were perfused with colored latex, Batson’s resin and gelatin colored with carmine. Using a surgical microscope we have determined the origin, local and number of origin from the parent vessel. The sites of penetration in the mediolateral and anteroposterior direction were also recorded. The anterior communicating artery contribution to the basal APS was reviewed. Significant vascular variations and anastomoses were encountered

  1. Enhancement of Bleomycin Sensitivity in Human Lung Cancer Cell ...

    African Journals Online (AJOL)

    cytotoxic effect of bleomycin in the adenocarcinoma human alveolar basal epithelial A549 cell line. Methods: The .... advantageous (at 100 mg/kg body weight) in increasing the ... Cobalt-60 (60Co) gamma radiation at a sublethal dose of 8 Gy ...

  2. Effect of propionyl-L-carnitine on human endothelial cells

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Scheffer, M.A.

    1991-01-01

    A possible protective effect of propionyl-L-carnitine on human endothelial cells was studied both under basal culture conditions and in the presence of agents capable of influencing oxidative damage, such as glucose/glucose oxidase and oxidized low-density lipoproteins. Propionyl-L-carnitine had no

  3. Transcription profile analysis reveals that zygotic division results in uneven distribution of specific transcripts in apical/basal cells of tobacco.

    Directory of Open Access Journals (Sweden)

    Ligang Ma

    Full Text Available BACKGROUND: Asymmetric zygotic division in higher plants results in the formation of an apical cell and a basal cell. These two embryonic cells possess distinct morphologies and cell developmental fates. It has been proposed that unevenly distributed cell fate determinants and/or distinct cell transcript profiles may be the underlying reason for their distinct fates. However, neither of these hypotheses has convincing support due to technical limitations. METHODOLOGY/PRINCIPAL FINDINGS: Using laser-controlled microdissection, we isolated apical and basal cells and constructed cell type-specific cDNA libraries. Transcript profile analysis revealed difference in transcript composition. PCR and qPCR analysis confirmed that transcripts of selected embryogenesis-related genes were cell-type preferentially distributed. Some of the transcripts that existed in zygotes were found distinctly existed in apical or basal cells. The cell type specific de novo transcription was also found after zygotic cell division. CONCLUSIONS/SIGNIFICANCE: Thus, we found that the transcript diversity occurs between apical and basal cells. Asymmetric zygotic division results in the uneven distribution of some embryogenesis related transcripts in the two-celled proembryos, suggesting that a differential distribution of some specific transcripts in the apical or basal cells may involve in guiding the two cell types to different developmental destinies.

  4. PHOTODYNAMIC THERAPY IN PATIENTS WITH DIFFERENT CLINICAL FORMS OF BASAL CELL CARCINOMA OF THE SKIN

    Directory of Open Access Journals (Sweden)

    O. V. Matveeva

    2014-01-01

    Full Text Available Background: Photodynamic therapy is frequently applied for non-invasive destruction of basal cell carcinomas (BCC of the skin; though, there is lack of evidence for efficacy of the method. Aim: To assess objective response of BCCs to photodynamic therapy with intralesional administration of photosensitizer Radachlorin in patients with different clinical forms, stages, flow patterns and localization of BCC. Materials and methods: 45  stage I–II BCCs patients with primary and recurrent solitary (ulcerative, superficial, scleroderma-like and nodular forms and multiple lesions (predominantly Т₁– Т₂N₀M₀, with difficult to treat localization and high risk of recurrence were included during the period from March 2004 to March 2007. All patients received one cycle of photodynamic therapy with intralesional Radachlorin (0.5–1  ml/1  cm² tumor surface and irradiation dose 300  J/cm² (wavelength 662 nm. A primary outcome measure was grade of clinical and cytological lesion regression after three months. Secondary outcome measure was stable clinical and cytological reaction at the lesion site. In the long-term, lesion recurrence was assessed yearly during 5 years. Results: Complete regression of BCCs was found in 43  (95.5% patients and 47  (95.9% lesions. In 2 (4.5% patients with partial regression of 2 (4.1% lesions repeated cycles of photodynamic therapy resulted in complete response. In BCCs Т₁N₀M₀, early outcome was independent from the clinical form of the diseases; by contrast, in BCCs Т₂N₀M₀, treatment of scleroderma-like BCCs was non-significantly less effective (66.7% compared to nodular, surface (100% for both and ulcerative (92.8% forms. In the long-term, 1  tumor recurrence was observed after 29 months at the site of completely regressed ulcerative lesion. Conclusion: Photodynamic therapy with intralesional administration of photosensitizer Radachlorin is an effective treatment method for different

  5. Stem cell derived basal forebrain cholinergic neurons from Alzheimer's disease patients are more susceptible to cell death.

    Science.gov (United States)

    Duan, Lishu; Bhattacharyya, Bula J; Belmadani, Abdelhak; Pan, Liuliu; Miller, Richard J; Kessler, John A

    2014-01-08

    An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a constant feature of Alzheimer's disease (AD) and is associated with deficits in spatial learning and memory. Induced pluripotent stem cells (iPSCs) derived from patients with AD as well as from normal controls could be efficiently differentiated into neurons with characteristics of BFCNs. We used BFCNs derived from iPSCs to model sporadic AD with a focus on patients with ApoE3/E4 genotypes (AD-E3/E4). BFCNs derived from AD-E3/E4 patients showed typical AD biochemical features evidenced by increased Aβ42/Aβ40 ratios. AD-E3/E4 neurons also exhibited altered responses to treatment with γ-secretase inhibitors compared to control BFCNs or neurons derived from patients with familial AD. BFCNs from patients with AD-E3/E4 also exhibited increased vulnerability to glutamate-mediated cell death which correlated with increased intracellular free calcium upon glutamate exposure. The ability to generate BFCNs with an AD phenotype is a significant step both for understanding disease mechanisms and for facilitating screening for agents that promote synaptic integrity and neuronal survival.

  6. Laminin-511 and integrin beta-1 in hair follicle development and basal cell carcinoma formation

    Directory of Open Access Journals (Sweden)

    Williams Samantha

    2010-11-01

    Full Text Available Abstract Background Initiation of the hair follicle placode and its subsequent growth, maturation and cycling in post-natal skin requires signaling interactions between epithelial cells and adjacent dermal cells and involves Shh signaling via the primary cilium. Previous reports have implicated laminins in hair follicle epithelial invagination. Results Here we use a human BCC model system and mouse mutants to re-evaluate the role of laminin-511 in epithelial invagination in the skin. Blocking laminin 511 and 332 in BCCs maintains primary cilia and Shh signalling, but prevents invagination. Similarly, in laminin-511 and dermal beta-1 integrin mutants, dermal papilla development and primary cilia formation are normal. Dermal beta-1 integrin mutants have normal hair follicle development. Conclusions Our data provides support for a primary role of laminin-511 promoting hair follicle epithelial downgrowth without affecting dermal primary cilia and Shh target gene induction.

  7. The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model.

    Science.gov (United States)

    Bouez, Charbel; Reynaud, Caroline; Noblesse, Emmanuelle; Thépot, Amélie; Gleyzal, Claudine; Kanitakis, Jean; Perrier, Eric; Damour, Odile; Sommer, Pascal

    2006-03-01

    Lysyl oxidase initiates the enzymatic stage of collagen and elastin cross-linking. Among five isoforms comprising the lysyl oxidase family, LOX is the better studied. LOX is associated to an antitumor activity in ras-transformed fibroblasts, and its expression is down-regulated in many carcinomas. The aim of this work was to shed light on LOX functions within the epidermis by studying its expression in human basal and squamous cell carcinomas and analyzing the effect of its enzymatic activity inhibition and protein absence on human keratinocytes behavior in a skin equivalent. In both carcinomas, LOX expression by epidermal tumor cells was lacking, while it was up-regulated around invading tumor cells in association with the stromal reaction. Lysyl oxidase activity inhibition using beta-aminoproprionitrile in a skin equivalent model prepared with both primary human keratinocytes and HaCaT cell line affected keratin 10 and filaggrin expression and disorganized the collagen network and the basement membrane. In spite of all these changes, no invasion phenotype was observed. Modelization of the invasive phenotype was only noticed in the skin equivalent developed with LOX antisense HaCaT cell line, where the protein LOX is specifically absent. Our results clearly indicate that lysyl oxidase enzymatic activity is essential not only for the integrity maintenance of the dermis but also for the homeostasis of the epidermis. Moreover, LOX protein plays a role in the skin carcinomas and invasion but not through its enzymatic activity.

  8. Time-course of coherence in the human basal ganglia during voluntary movements

    Science.gov (United States)

    Talakoub, Omid; Neagu, Bogdan; Udupa, Kaviraja; Tsang, Eric; Chen, Robert; Popovic, Milos R.; Wong, Willy

    2016-01-01

    We are interested in characterizing how brain networks interact and communicate with each other during voluntary movements. We recorded electrical activities from the globus pallidus pars interna (GPi), subthalamic nucleus (STN) and the motor cortex during voluntary wrist movements. Seven patients with dystonia and six patients with Parkinson’s disease underwent bilateral deep brain stimulation (DBS) electrode placement. Local field potentials from the DBS electrodes and scalp EEG from the electrodes placed over the motor cortices were recorded while the patients performed externally triggered and self-initiated movements. The coherence calculated between the motor cortex and STN or GPi was found to be coupled to its power in both the beta and the gamma bands. The association of coherence with power suggests that a coupling in neural activity between the basal ganglia and the motor cortex is required for the execution of voluntary movements. Finally, we propose a mathematical model involving coupled neural oscillators which provides a possible explanation for how inter-regional coupling takes place. PMID:27725721

  9. Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas.

    Science.gov (United States)

    Boaventura, Paula; Pereira, Dina; Mendes, Adélia; Batista, Rui; da Silva, André Ferreira; Guimarães, Isabel; Honavar, Mrinalini; Teixeira-Gomes, José; Lopes, José Manuel; Máximo, Valdemar; Soares, Paula

    2014-01-01

    Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented. The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC. 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients. The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation. Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  11. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  12. Risk factors for basal cell carcinoma: a case-control study

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    Marcus Maia

    1995-02-01

    Full Text Available A controlled trial was performed with the purpose of investigating which factors could be considered of significant risk for the development of basal cell carcinoma. A total of 259 cases of basal cell carcinoma diagnosed from July 1991 to July 1992 were compared with 518 controls matched for age and sex. All subjects in both groups were white. Protocol data were submitted to statistical analysis by the chi-square test and by multiple conditional logistic regression analysis and the following conclusions were reached: 1 light skin color (types I and II of the Fitzpatrick classification, odds ratio of 2.8; outdoor work under constant sunlight, odds ratio of 5.0; the presence of actinic lesions due to exposure to the sun, odds ratio of 4.9, are risk factors perse. 2 Type III skin in the Fitzpatrick classification only represents a risk factor when the patient reports a history of intense sunburns, but not in the absence of such a history. 3 Sunburns per se do not represent a risk factor althorig the point made in item 2 of these conclusions is valid. 4 Other suspected risk factors whose significance was not confirmed by multiple conditioned logistic regression analysis were: residence in rural areas, light eyes and blond hair color, extent of the awareness of the "sun x skin cancer" relationship, familial occurrence of skin cancer, excessive exposure to the sun, and freckles appearing in childhood.Realizou-se estudo controlado para investigar quais os fatores de risco, para o desenvolvimento do carcinoma basocelular, são significantes. Foram utilizados 259 casos de carcinoma basocelular (diagnosticados entre julho de 1991 e julho de 1992 e 518 controles, pareados segundo sexo e idade. Submetidos os dados constantes do protocolo à análise estatística (Qui-quadrado e Regressão Logística Múltipla Condicional, foi possível obter as seguintes conclusões na população estudada: 1 - Representam fatores de risco, por si só: - as peles claras de

  13. Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

    2015-06-01

    The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ~80% decrease in the IAS tone, whereas that of RAS lead to ~20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS.

  14. Bivariate analysis of basal serum anti-Mullerian hormone measurements and human blastocyst development after IVF

    LENUS (Irish Health Repository)

    Sills, E Scott

    2011-12-02

    Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+\\/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+\\/- SD) terminal serum estradiol during IVF was 5929 +\\/- 4056 pmol\\/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol\\/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.

  15. The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

    Science.gov (United States)

    Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

    2014-01-01

    For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

  16. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitrugno Valentina

    2010-11-01

    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  17. Giant epithelial malignancies (basal cell carcinoma, squamous cell carcinoma: A series of 20 tumors from a single center

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2012-01-01

    Full Text Available Background: Among nonmelanoma skin cancer (NMSC, basal cell carcinoma (BCC, and squamous cell carcinoma (SCC are the most common. Giant NMSCs have occasionally reported in the medical literature with particular problems related to diagnosis and treatment. The aim of this study was to analyze patients, treatment, and outcome with giant BCC/SCC. Materials and Methods: We analyzed our files between January 1, 2008, and December 31, 2011, of an academic teaching hospital in the dermatology department. Patients were analyzed according to demographic factors, clinical presentation, histopathology, treatment, and outcome. American Society of Anesthesiology physical status system was used to assess the fitness of patients before surgery. Results: The frequency of giant NMSC was estimated as 0.4% for both tumor entities. 80% of giant BCC patients were female and 100% of giant SCC patients were male. The mean age was 81.5 ± 8.5 years for BCC and 79.5 ± 11.4 years for SCC. The major anatomical site was the scalp. Four of 10 BCCs were classified metatypic (basosquamous. Perineural infiltration was seen in 5 NMSCs. Seventy percent of patients had an ASA score ≥3. Surgery was performed in general anaesthesia in 5 (BCC and 6 (SCC patients, respectively. All other patients were operated in local or tumescence anesthesia. Blood transfusions were necessary in five patients. The primary treatment was delayed Mohs technique. Defect closure was realized with rotational flaps in most cases. Neoadjuvant chemoimmune therapy and adjuvant combined cetuximab/radiotherapy have been performed in three patients. We observed three deaths, all unrelated to NMSC. 75% of patients achieved complete remission. Conclusions: Giant NMSC is uncommon but not rare. These tumors are high-risk subtypes. Treatment needs an interdisciplinary approach.

  18. Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea

    Science.gov (United States)

    Zhang, Shasha; Chen, Yan; Zhang, Xiaoli; Wang, Lei; Tang, Mingliang; Shi, Haibo; Bird, Phillip I.; Li, Huawei; Chai, Renjie

    2016-01-01

    Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future. PMID:27070092

  19. The Action of Discoidin Domain Receptor 2 in Basal Tumor Cells and Stromal Cancer-Associated Fibroblasts Is Critical for Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Callie A.S. Corsa

    2016-06-01

    Full Text Available High levels of collagen deposition in human and mouse breast tumors are associated with poor outcome due to increased local invasion and distant metastases. Using a genetic approach, we show that, in mice, the action of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2 in both tumor and tumor-stromal cells is critical for breast cancer metastasis yet does not affect primary tumor growth. In tumor cells, DDR2 in basal epithelial cells regulates the collective invasion of tumor organoids. In stromal cancer-associated fibroblasts (CAFs, DDR2 is critical for extracellular matrix production and the organization of collagen fibers. The action of DDR2 in CAFs also enhances tumor cell collective invasion through a pathway distinct from the tumor-cell-intrinsic function of DDR2. This work identifies DDR2 as a potential therapeutic target that controls breast cancer metastases through its action in both tumor cells and tumor-stromal cells at the primary tumor site.

  20. Papular Epidermal Nevus with “Skyline” Basal Cell Layer Syndrome – Natural Course: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Carole Anouk Zahn

    2017-01-01

    Full Text Available Papular epidermal nevus with “skyline” basal cell layer (PENS is a very rare type of keratinocytic nevus and is associated with extracutaneous findings such as neurological symptoms in about 50% of the cases. Therefore, it is also referred to as PENS syndrome. Clinically visible hyperkeratotic papules and plaques already appear at birth or shortly thereafter, while neurological symptoms such as epilepsy and mental retardation manifest themselves during childhood. Genetics suggests gonadal mosaicism as a possible cause for the disease. Another hypothesis is that genetic mutation can occur in a mendelian trait or through a paradominant inheritance.

  1. Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC-0449).

    Science.gov (United States)

    Meani, Rowena E; Lim, Shueh-Wen; Chang, Anne Lynn S; Kelly, John W

    2014-08-01

    Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti-tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response.

  2. Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

    Science.gov (United States)

    Iftimia, Nicusor; Peterson, Gary; Chang, Ernest W.; Maguluri, Gopi; Fox, William; Rajadhyaksha, Milind

    2016-01-01

    We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ˜1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ˜7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ˜600 μm, and agreement with histology was within about ±50 μm.

  3. Relationship between spatial pattern of basal bodies and membrane skeleton (epiplasm) during the cell cycle of Tetrahymena: cdaA mutant and anti-membrane skeleton immunostaining.

    Science.gov (United States)

    Kaczanowska, J; Buzanska, L; Ostrowski, M

    1993-01-01

    Microtubular basal bodies and epiplasm (membrane skeleton) are the main components of the cortical skeleton of Tetrahymena. The aim of this report was to study functional interactions of basal bodies and epiplasm during the cell cycle. The cortex of Tetrahymena cells was stained with anti-epiplasm antibody. This staining produced a bright epiplasmic layer with a dark pattern of unstained microtubular structures. The fluorescence of the anti-epiplasm antibody disappeared at sites of newly formed microtubular structures, so the new basal body domains and epiplasmic layer could be followed throughout the cell cycle. Different patterns of deployment of new basal bodies were observed in early and advanced dividers. In advanced dividers the fluorescence of the epiplasmic layer diminished locally within the forming fission line where the polymerization of new basal bodies largely extincted. In wild type Tetrahymena, the completion of the micronuclear metaphase/anaphase transition was associated with a transition from the pattern of new basal body deployment and epiplasm staining of the early divider to the pattern of the advanced dividers. The signal for the fission line formation in Tetrahymena (absent in cdaA1 Tetrahymena mutationally arrested in cytokinesis) brings about 1) transition of patterns of deployment of basal bodies and epiplasmic layer on both sides of the fission line; and 2) coordination of cortical divisional morphogenesis with the micronuclear mitotic cycle.

  4. Cell encoding recombinant human erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A.K.; Withy, R.M.; Zabrecky, J.R.; Masiello, N.C.

    1990-09-04

    This patent describes a C127 cell transformed with a recombinant DNA vector. It comprises: a DNA sequence encoding human erythropoietin, the transformed cell being capable of producing N-linked and O-linked glycosylated human erythropoietin.

  5. Dark cells in human oral leukoplakias

    Energy Technology Data Exchange (ETDEWEB)

    Klein-Szanto, A.J.P. (Oak Ridge National Lab., TN); Sega, M.; Banoczy, J.; Albrecht, M.

    1982-01-01

    Dark basal keratinocytes, characterized by a strong affinity for basic dyes and by electron density of cytoplasm and nucleus, could be recognized in eleven oral leukoplakias. The percentage of dark cells was higher in the group comprising leukoplakias verrucosa, and erosiva (28% of the basal cells) than in the leukoplakia simplex group (10%). The presence of these cells is a good indicator of the degree of histological dysplasia and correlates well with the preneoplastic potential of these lesions.

  6. Mutation Screening of 1,237 Cancer Genes across Six Model Cell Lines of Basal-Like Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Eleonor Olsson

    Full Text Available Basal-like breast cancer is an aggressive subtype generally characterized as poor prognosis and lacking the expression of the three most important clinical biomarkers, estrogen receptor, progesterone receptor, and HER2. Cell lines serve as useful model systems to study cancer biology in vitro and in vivo. We performed mutational profiling of six basal-like breast cancer cell lines (HCC38, HCC1143, HCC1187, HCC1395, HCC1954, and HCC1937 and their matched normal lymphocyte DNA using targeted capture and next-generation sequencing of 1,237 cancer-associated genes, including all exons, UTRs and upstream flanking regions. In total, 658 somatic variants were identified, of which 378 were non-silent (average 63 per cell line, range 37-146 and 315 were novel (not present in the Catalogue of Somatic Mutations in Cancer database; COSMIC. 125 novel mutations were confirmed by Sanger sequencing (59 exonic, 48 3'UTR and 10 5'UTR, 1 splicing, with a validation rate of 94% of high confidence variants. Of 36 mutations previously reported for these cell lines but not detected in our exome data, 36% could not be detected by Sanger sequencing. The base replacements C/G>A/T, C/G>G/C, C/G>T/A and A/T>G/C were significantly more frequent in the coding regions compared to the non-coding regions (OR 3.2, 95% CI 2.0-5.3, P<0.0001; OR 4.3, 95% CI 2.9-6.6, P<0.0001; OR 2.4, 95% CI 1.8-3.1, P<0.0001; OR 1.8, 95% CI 1.2-2.7, P = 0.024, respectively. The single nucleotide variants within the context of T[C]T/A[G]A and T[C]A/T[G]A were more frequent in the coding than in the non-coding regions (OR 3.7, 95% CI 2.2-6.1, P<0.0001; OR 3.8, 95% CI 2.0-7.2, P = 0.001, respectively. Copy number estimations were derived from the targeted regions and correlated well to Affymetrix SNP array copy number data (Pearson correlation 0.82 to 0.96 for all compared cell lines; P<0.0001. These mutation calls across 1,237 cancer-associated genes and identification of novel variants will aid in

  7. Head and neck basal cell carcinoma prevalence in individuals submitted to childhood X-ray epilation for tinea capitis treatment.

    Science.gov (United States)

    Boaventura, Paula; Oliveira, Rosa; Pereira, Dina; Soares, Paula; Teixeira-Gomes, José

    2012-01-01

    A higher prevalence for basal cell carcinoma (BCC) has been associated with radiation, namely with tinea capitis epilation treatment. To evaluate the prevalence of head and neck basal cell carcinoma (BCC) and to identify the major risk factors for BCC in individuals irradiated in childhood for tinea capitis treatment. We clinically observed 1,308 individuals from an original cohort of 5,356 irradiated between 1950 and 1963, registering previous skin lesions excisions and proposing for surgery all the suspicious lesions detected. In 585 participants, 47 with BCC, the skin pigmentation was measured. The overall prevalence of BCC was 8.0% and of multiple BCC was 2.4%. Both total (14.7%) and multiple BCC (6.6%) were significantly more common in the individuals who had received a higher radiation dose. Multiple BCC was more prevalent (3.7%) in younger irradiated individuals and total BCC (9.4%) in women. Participants with BCC and without BCC presented similar skin pigmentation. Younger age at irradiation, higher dose and female gender increased the risk of developing BCC in these irradiated individuals.

  8. Nevoid basal cell carcinoma syndrome with a unilateral giant ovarian fibroma in a Japanese 6-year-old girl.

    Science.gov (United States)

    Jimbo, Takahiro; Masumoto, Kouji; Urita, Yasuhisa; Takayasu, Hajime; Shinkai, Toko; Uesugi, Toru; Gotoh, Chikashi; Sakamoto, Naoya; Sasaki, Takato; Oto, Tatsuyuki; Fukushima, Takashi; Noguchi, Emiko; Nakano, Yoshiro

    2014-05-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by basal cell carcinoma, skeletal abnormalities, benign tumors including ovarian fibroma, and various other phenotypic expressions. Ovarian fibromas in NBCCS before puberty are very rare. We report a 6-year-old prepubescent girl with NBCCS showing skeletal abnormalities, medulloblastoma, and ovarian fibromas. The patient was referred to our hospital owing to abdominal distension. On admission, a huge elastic hard tumor was palpable and computed tomography showed a huge tumor of the left ovary. We performed a left salpingo-oophorectomy and diagnosed the tumor as a benign fibroma. Further examination of the computed tomography images showed skeletal abnormalities. In addition, the patient had a history of medulloblastoma at the age of 4 years. Therefore, we diagnosed NBCCS. A genetic examination indicated a novel 1 bp deletion in exon 18 (c.3055delG). Sequence analysis of exon 18 using DNA from the ovarian tumor revealed a mutant allele (c.3055delG) dominant to the wild-type allele, thus suggesting loss of heterozygosity in the PTCH1 gene, which is known to be associated with NBCCS. Conclusion On the basis of our experience, physicians treating pediatric ovarian tumors should be aware that such huge benign ovarian tumors may be a phenotype of NBCCS, as shown in our patient. In addition, genetic examination focusing on the PTCH1 gene might be important for diagnosis of NBCCS in pediatric patients.

  9. Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

    Science.gov (United States)

    Rodrigues, A L; Carvalho, A; Cabral, R; Carneiro, V; Gilardi, P; Duarte, C P; Puente-Prieto, J; Santos, P; Mota-Vieira, L

    2014-07-25

    Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

  10. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma

    Science.gov (United States)

    GHITA, MIHAELA A.; CARUNTU, CONSTANTIN; ROSCA, ADRIAN E.; KALESHI, HARILLAQ; CARUNTU, ANA; MORARU, LILIANA; DOCEA, ANCA OANA; ZURAC, SABINA; BODA, DANIEL; NEAGU, MONICA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC. PMID:27123056

  11. Rotating cell culture systems for human cell culture: human trophoblast cells as a model.

    Science.gov (United States)

    Zwezdaryk, Kevin J; Warner, Jessica A; Machado, Heather L; Morris, Cindy A; Höner zu Bentrup, Kerstin

    2012-01-18

    -grown cells are able to respond to chemical and molecular gradients in three dimensions (i.e. at their apical, basal, and lateral surfaces) because they are cultured on the surface of porous microcarrier beads. When grown as two-dimensional monolayers on impermeable surfaces like plastic, cells are deprived of this important communication at their basal surface. Consequently, the spatial constraints imposed by the environment profoundly affect how cells sense and decode signals from the surrounding microenvironment, thus implying an important role for the 3-D milieu. We have used the RCCS to engineer biologically meaningful 3-D models of various human epithelial tissues. Indeed, many previous reports have demonstrated that cells cultured in the RCCS can assume physiologically relevant phenotypes that have not been possible with other models. In summary, culture in the RCCS represents an easy, reproducible, high-throughput platform that provides large numbers of differentiated cells that are amenable to a variety of experimental manipulations. In the following protocol, using EVTs as an example, we clearly describe the steps required to three-dimensionally culture adherent cells in the RCCS.

  12. Functional characterization of UCP1 in mammalian HEK293 cells excludes mitochondrial uncoupling artefacts and reveals no contribution to basal proton leak.

    Science.gov (United States)

    Jastroch, Martin; Hirschberg, Verena; Klingenspor, Martin

    2012-09-01

    Mechanistic studies on uncoupling proteins (UCPs) not only are important to identify their cellular function but also are pivotal to identify potential drug targets to manipulate mitochondrial energy transduction. So far, functional and comparative studies of uncoupling proteins in their native environment are hampered by different mitochondrial, cellular and genetic backgrounds. Artificial systems such as yeast ectopically expressing UCPs or liposomes with reconstituted UCPs were employed to address crucial mechanistic questions but these systems also produced inconsistencies with results from native mitochondria. We here introduce a novel mammalian cell culture system (Human Embryonic Kidney 293 - HEK293) to study UCP1 function. Stably transfected HEK293 cell lines were derived that contain mouse UCP1 at concentrations comparable to tissue mitochondria. In this cell-based test system UCP1 displays native functional behaviour as it can be activated with fatty acids (palmitate) and inhibited with purine nucleotides guanosine-diphosphate (GDP). The catalytic centre activity of the UCP1 homodimer in HEK293 is comparable to activities in brown adipose tissue supporting functionality of UCP1. Importantly, at higher protein levels than in yeast mitochondria, UCP1 in HEK293 cell mitochondria is fully inhibitable and does not contribute to basal proton conductance, thereby emphasizing the requirement of UCP1 activation for therapeutic purposes. These findings and resulting analysis on UCP1 characteristics demonstrate that the mammalian HEK293 cell system is suitable for mechanistic and comparative functional studies on UCPs and provides a non-confounding mitochondrial, cellular and genetic background.

  13. Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

    Science.gov (United States)

    Appel, T; Bierhoff, E; Appel, K; von Lindern, J-J; Bergé, S; Niederhagen, B

    2003-06-01

    We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

  14. Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells.

    Science.gov (United States)

    Siupka, Piotr; Hersom, Maria Ns; Lykke-Hartmann, Karin; Johnsen, Kasper B; Thomsen, Louiza B; Andresen, Thomas L; Moos, Torben; Abbott, N Joan; Brodin, Birger; Nielsen, Morten S

    2017-07-01

    Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process. Here, we elucidate the endosomal trafficking of the retrograde transported cation-independent mannose-6-phosphate receptor (MPR300) in primary cultures of brain endothelial cells (BECs) of porcine and bovine origin. Receptor expression and localisation of MPR300 in the endo-lysosomal system and trafficking of internalised receptor are analysed. We also demonstrate that MPR300 can undergo bidirectional apical-basal trafficking in primary BECs in co-culture with astrocytes. This is, to our knowledge, the first detailed study of retrograde transported receptor trafficking in BECs, and the study demonstrates that MPR300 can be transported from the luminal to abluminal membrane and reverse. Such trafficking of MPR300 suggests that retrograde transported receptors in general may provide a mechanism for transport of pharmaceuticals into the brain.

  15. Identification of intermediate cell types by keratin expression in the developing human prostate

    NARCIS (Netherlands)

    Xue, Y; Smedts, F; Debruyne, FMJ; de la Rosette, JJMCH; Schalken, JA

    1998-01-01

    BACKGROUND. The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in

  16. Identification of intermediate cell types by keratin expression in the developing human prostate

    NARCIS (Netherlands)

    Xue, Y; Smedts, F; Debruyne, FMJ; de la Rosette, JJMCH; Schalken, JA

    1998-01-01

    BACKGROUND. The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in ea

  17. Basal buffer systems for a newly glycosylated recombinant human interferon-β with biophysical stability and DoE approaches.

    Science.gov (United States)

    Kim, Nam Ah; Song, Kyoung; Lim, Dae Gon; Hada, Shavron; Shin, Young Kee; Shin, Sangmun; Jeong, Seong Hoon

    2015-10-12

    The purpose of this study was to develop a basal buffer system for a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a), termed R27T, to optimize its biophysical stability. The protein was pre-screened in solution as a function of pH (2-11) using differential scanning calorimetry (DSC) and dynamic light scattering (DLS). According to the result, its experimental pI and optimal pH range were 5.8 and 3.6-4.4, respectively. Design of experiment (DoE) approach was developed as a practical tool to aid formulation studies as a function of pH (2.9-5.7), buffer (phosphate, acetate, citrate, and histidine), and buffer concentration (20 mM and 50 mM). This method employed a weight-based procedure to interpret complex data sets and to investigate critical key factors representing protein stability. The factors used were Tm, enthalpy, and relative helix contents which were obtained by DSC and Fourier Transform Infrared spectroscopy (FT-IR). Although the weights changed by three responses, objective functions from a set of experimental designs based on four buffers were highest in 20 mM acetate buffer at pH 3.6 among all 19 scenarios tested. Size exclusion chromatography (SEC) was adopted to investigate accelerated storage stability in order to optimize the pH value with susceptible stability since the low pH was not patient-compliant. Interestingly, relative helix contents and storage stability (monomer remaining) increased with pH and was the highest at pH 4.0. On the other hand, relative helix contents and thermodynamic stability decreased at pH 4.2 and 4.4, suggesting protein aggregation issues. Therefore, the optimized basal buffer system for the novel biobetter was proposed to be 20 mM acetate buffer at pH 3.8±0.2. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Cell size and basal metabolic rate in hummingbirds Tamaño celular y tasa metabólica basal en picaflores

    National Research Council Canada - National Science Library

    Juan C. Opazo; Mauricio Soto-Gamboa; Maria José Fernández

    2005-01-01

    .... Knowing that cell size is proportional to C-value, in this study we tested for a relationship between mean corpuscular volume of red blood cells and BMR in four species of hummingbirds ranging from 4 to 20 g...

  19. Initial basal cell carcinomas diagnosed in the National Campaign for Skin Cancer Prevention are smaller than those identified by the conventional medical referral system*

    Science.gov (United States)

    Wakiyama, Thweicyka Pinheiro; França, Maria Laura Marconi; Carvalho, Larissa Pierri; Marques, Mariangela Esther Alencar; Miot, Hélio Amante; Schmitt, Juliano Vilaverde

    2017-01-01

    BACKGROUND Basal cell carcinoma is the malignant tumor most often diagnosed in the National Campaign for Skin Cancer Prevention (NCSCP). Little is known about the profile of these lesions compared to the profile of lesions diagnosed by conventional routes of public dermatological care. OBJECTIVE To identify if basal cell carcinomas identified in prevention campaigns and referred to surgery are smaller than those routinely removed in a same medical institution. METHODS Cross-sectional study including tumors routed from 2011-2014 campaigns and 84 anatomopathological reports of outpatients. RESULTS The campaigns identified 223 individuals with suspicious lesions among 2,531 examinations (9%), with 116 basal cell carcinomas removed. Anatomopathological examinations revealed that the primary lesions identified in the national campaigns were smaller than those referred to surgery by the conventional routes of public health care (28 [13-50] x 38 [20-113] mm2, p <0.01). On the other hand, after a mean follow-up of 15.6 ± 10.3 months, 31% of cases identified in campaigns showed new basal cell carcinoma lesions. STUDY LIMITATIONS Retrospective study and inaccuracies in the measurements of the lesions. CONCLUSIONS The NCSCP promotes an earlier treatment of basal cell carcinomas compared to patients referred to surgery by the conventional routes of public health care, which can result in lower morbidity rates and better prognosis. PMID:28225952

  20. Expression of PinX1 and hTERT in basal cell carcinoma and their implications

    Institute of Scientific and Technical Information of China (English)

    Long Qin; Jing Ge

    2015-01-01

    Objective This study aimed to investigate the expression and significance of PIN2/TERF1 interacting, telomerase inhibitor 1 (PinX1) and human telomerase reverse transcriptase (hTERT) in basal cel carcino-ma (BCC). Methods Real-time polymerase chain reaction and immunohistochemistry were performed to quantify the mRNA expressions and integrated optical density (IOD), respectively, of PinX1 and hTERT in BCC specimens (n = 30), as wel as in normal skin specimens (n = 15). Results The mRNA expression level and IOD of PinX1 in the BCC samples were both significantly lower than those in the control specimens (P 0.05). Conclusion Downregulation of PinX1 and upregulation of hTERT expression may be associated with the activation and maintenance of telomerases in the induction of BCC.

  1. Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Xiaoti Xu

    2015-09-01

    Full Text Available Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

  2. Peculiarities of cell-cell interactions in basal decidual membrane at vaginitis associated with contamination by opportunistic microorganisms

    Directory of Open Access Journals (Sweden)

    L. R. Mustafina

    2012-01-01

    Full Text Available An important role in anti-infection protection during pregnancy belongs to local immunity mechanisms. At contamination of lower genital tracts by Ureaplasma urealyticum and Mycoplasma hominis, the activation of natural killers in basal decidual membrane was absent, which can be considered as a marker of immune compromise of women in the aspect of reliability of control of the population of urinogenital opportunistic flora and prognostic factor of possible intrauterine infection.

  3. Correlation of hepatitis C and prostate cancer, inverse correlation of basal cell hyperplasia or prostatitis and epidemic syphilis of unknown duration

    Directory of Open Access Journals (Sweden)

    Annika Krystyna

    2011-04-01

    Full Text Available PURPOSE: The accuracy of prostate specific antigen (PSA to detect prostate cancer has not yet been determined. Autopsy evidence suggests one-third of men have evidence of prostate cancer. Correlation between prostate cancer and sexually transmitted infection is indeterminate. MATERIALS AND METHODS: A retrospective database was created of all men who underwent transrectal ultrasound guided prostate biopsy over 3 years. Men were 49% African or African Caribbean, and 51% Central or South American. Information about prostate specific antigen, cholesterol, hepatitis A, B and C, human immunodeficiency virus, syphilis, tuberculin skin testing and histology were collected. RESULTS: Hepatitis C antibody detection correlated with prostate cancer OR 11.2 (95% CI 3.0 to 72.4. The odds of prostate cancer increased annually (p = 0.0003. However, no correlation was found between prostate cancer and the following: PSA, biopsy date, repeat biopsy, more than 12 cores at biopsy, total cholesterol, high density lipoprotein, triglycerides, low density lipoprotein, risk measure reported with free and total PSA, hepatitis B surface antibody, high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Histologic prostatitis and basal cell hyperplasia were inversely correlated with prostate cancer. Syphilis of unknown duration occurred in 17% of men with indeterminate correlation to prostate cancer. CONCLUSION: In inner city men of African and African-Caribbean, or Central and South American descent, prostate specific antigen levels did not correlate with prostate cancer. Hepatitis C antibody detection correlates significantly with prostate cancer. One prostate biopsy is sufficient to diagnose statistically significant prostate cancer. Histologic prostatitis and basal cell hyperplasia decrease odds of prostate cancer. Atypical small acinar proliferation may not correlate to prostate cancer and is pending further investigation. Men should be

  4. Basal Cell Carcinoma is as Common as the Sum of all Other Cancers: Implications for Treatment Capacity.

    Science.gov (United States)

    Holm, Ann-Sofie; Nissen, Christoffer V; Wulf, Hans Christian

    2016-05-01

    Reliable estimates of disease incidence are fundamental to planning future healthcare services. However, in many countries registration of basal cell carcinoma (BCC) is often non-existent. This study examines how many BCC treatments were carried out in Denmark in 2013. The Danish Cancer Registry and the Danish Pathology Registry were used to examine how many BCC treatments were registered, and a test sample was taken from Bispebjerg Hospital to examine the number treated but not registered. The study showed that 21.7% of BCC treatments were performed solely on a clinical diagnosis. Furthermore, some records are inadequate in relation to BCC registration, as BCCs treated are 3 times the number of individuals in the Danish Cancer Registry, and there are nearly as many BCCs as the sum of all other cancers. The increasing BCC incidence will result in difficulties in ensuring treatment capacity.

  5. Intricate correlation and biological behavior of keratocyst in nevoid basal cell carcinoma syndrome: A comprehensive review of literature

    Directory of Open Access Journals (Sweden)

    Asha Raj

    2013-01-01

    Full Text Available The odontogenic keratocysts (OKC usually represent a particular entity that has been of interest mainly due to biological aggressiveness and to its frequent recurrence. Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome is a hereditary condition characterized by a wide-range of developmental abnormalities and a predisposition to neoplasms. There are several possible reasons why OKC recur so frequently and require meticulous surgical planning and execution. This mini review has attempted to show that there is a lack of published evidence regarding the cause of frequent recurrent of OKC that presented in NBCCS. However, the findings of the study revealed differences in opinion regarding the treatment modalities, which necessitates further long term clinical studies that could precisely document certain reliable guidelines in this perspective.

  6. Surface-Enhanced Raman Spectroscopy Study of 4-ATP on Gold Nanoparticles for Basal Cell Carcinoma Fingerprint Detection

    Science.gov (United States)

    Quynh, Luu Manh; Nam, Nguyen Hoang; Kong, K.; Nhung, Nguyen Thi; Notingher, I.; Henini, M.; Luong, Nguyen Hoang

    2016-05-01

    The surface-enhanced Raman signals of 4-aminothiophenol (4-ATP) attached to the surface of colloidal gold nanoparticles with size distribution of 2 to 5 nm were used as a labeling agent to detect basal cell carcinoma (BCC) of the skin. The enhanced Raman band at 1075 cm-1 corresponding to the C-S stretching vibration in 4-ATP was observed during attachment to the surface of the gold nanoparticles. The frequency and intensity of this band did not change when the colloids were conjugated with BerEP4 antibody, which specifically binds to BCC. We show the feasibility of imaging BCC by surface-enhanced Raman spectroscopy, scanning the 1075 cm-1 band to detect the distribution of 4-ATP-coated gold nanoparticles attached to skin tissue ex vivo.

  7. Treatment of margin positive basal cell carcinoma with vismodegib: case report and consideration of treatment options and their implications.

    Science.gov (United States)

    Bayers, Stephanie; Kapp, Daniel L; Beer, Kenneth R; Slavin, Benjamin

    2013-10-01

    Historically, basal cell carcinomas (BCCs) that are neither surgically resectable nor candidates for radiation therapy have had few treatment options. The hedgehog pathway inhibitor, vismodegib, represents a new opportunity for the treatment of such patients. Vismodegib has approval from the United States Food and Drug Administration for treatment of metastatic BCC, locally advanced BCC recurring after surgery, and BCC that is not treatable via surgery or radiation. We present the case of a patient with a BCC infiltrating the spinal column that was neither possible to fully remove surgically nor a candidate for primary treatment with radiation. Treatment with vismodegib followed by adjuvant radiation therapy resulted in complete disease clearance. Vismodegib represents a promising treatment option for patients with surgically non-resectable BCCs that are not candidates for radiation therapy. Mechanism of action, benefits, and adverse events of vismodegib are reviewed, along with a brief discussion on newer options in the hedgehog inhibitor class.

  8. Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum.

    Science.gov (United States)

    Fife, Douglas; Laitinen, Marko A; Myers, David J; Landsteiner, Pamela B

    2017-03-01

    Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow-up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted.

  9. Exposure to sun radiation as a risk factor for the occurrence of basal cell carcinoma in the Montenegrian population

    Directory of Open Access Journals (Sweden)

    Maksimović Nataša

    2006-01-01

    Full Text Available Backgound/aim: Basal cell carcinoma (BCC is the most frequent form of carcinomas in the whites. Among the environmental factors, the most important risk factor for its occurrence is the exposure to sun radiation. The aim of this study was to assess the role of the sun radiation in the development of basal cell carcinoma BCC in the Montenegrian population. Methods. A case-control study was conducted in a period from 2002-2003. The study group included 100 histopatologically confirmed cases with BCC, while the control group included 100 patients from the same population, who did not present skin cancer and who were individually matched with the cases from the study group by sex and age (± 5 years. All the participants were interviewed using an epidemiological questionnaire. For statistical analysis, the χ2 test and univariate logistic regression analysis were used. Results. The risk for development of BCC was increased in the persons: that always had burns with no tan during the exposure to sunlight (OR = 1.75; 95% CI = 1.20-2.55; p = 0.003; that developed sunburns after two hours of the exposure to sunlight (OR = 3.72; 95% CI = 2.39-5.79; p < 0.001 that kept light tan or remained without changes in childhood and adolescence after the repeated exposures to sunlight (OR = 2.92; 95% CI = 1.89-4.52; p < 0.001 that often had severe and painful sunburns (OR = 4.48; 95% CI = 2.74-7.33; p < 0.001. Conclusion. Our study confirmed the significance of sunlight exposure for the development of BCC.

  10. Electronic brachytherapy for superficial and nodular basal cell carcinoma: a report of two prospective pilot trials using different doses

    Directory of Open Access Journals (Sweden)

    Rosa Ballester-Sánchez

    2016-01-01

    Full Text Available Purpose : Basal cell carcinoma (BCC is a very common cancer in the Caucasian population. Treatment aims to eradicate the tumor with the lowest possible functional and aesthetic impact. Electronic brachytherapy (EBT is a treatment technique currently emerging. This study aims to show the outcomes of two consecutive prospective pilot clinical trials using different radiation doses of EBT with Esteya® EB system for the treatment of superficial and nodular basal cell carcinoma. Material and methods : Two prospective, single-center, non-randomized, pilot studies were conducted. Twenty patients were treated in each study with different doses. The first group (1 was treated with 36.6 Gy in 6 fractions of 6.1 Gy, and the second group (2 with 42 Gy in 6 fractions of 7 Gy. Cure rate, acute toxicity, and late toxicity related to cosmesis were analyzed in the two treatment groups. Results: In group 1, a complete response in 90% of cases was observed at the first year of follow-up, whereas in group 2, the complete response was 95%. The differences with reference to acute toxicity and the cosmetic results between the two treatment groups were not statistically significant. Conclusions : Our initial experience with Esteya® EB system to treat superficial and nodular BCC shows that a dose of 36.6 Gy and 42 Gy delivered in 6 fraction of 7 Gy achieves a 90% and 95% clinical cure rate at 1 year, respectively. Both groups had a tolerable toxicity and a very good cosmesis. The role of EBT in the treatment of BCC is still to be defined. It will probably become an established option for selected patients in the near future.

  11. Correlation of " in vivo" microcirculation and degeneration of the basal cells of the epithelium in lingual lichen planus

    Directory of Open Access Journals (Sweden)

    Scardina G

    2009-01-01

    Full Text Available Background: Oral lichen planus is an inflammatory chronic disease with an autimmune pathogenesis and unknown etiology that affects oral mucosa, with or without the involvement of the skin and other mucous membranes. The principal histological characteristics are the degeneration of the basal cell layer and the abnormal infiltration of inflammatory cells into the subepithelial layer of connective tissue. Objectives: This study is aimed to appraise if lingual lichen planus (LLP is sustained by alteration of the oral microcirculation and if this abnormal vascularisation increases the degeneration of basal keratinocytes and the disruption of the basement membrane. Materials and Methods: Fifteen patients with a histological diagnosis of LLP with higher degree of degeneration of the basement membrane, fifteen LLP patients with lower degree of basement membrane (BM degeneration and fifteen healthy patients were included in the study. The microcirculation of the left margin of the lingual mucosa of all the patients and subjects was analysed with the videocapillaroscopy. The following parameters were analyzed on each capillaroscopic image: c0 apillary loop length, loop diameter, and capillary density. The results obtained by videocapillaroscopy software were subjected to statistical analysis using Mann Whitney U-test (P < 0.001. Statistical analysis was performed using PAST software, v. 1.53. Results: Capillary density, loop length, and total diameter showed statistically significant differences between LLP patients with histologically lower degree of BM degeneration and healthy subjects and a meaningful significant difference between LLP patients with higher degree of BM degeneration. Conclusions: A remarkable increase in capillary density was showed by videocapillaroscopic exam. The increased value of the density could be associated with angiogenesis mechanism and it could be an indicator of the evolutionary condition of LLP. Videocapillaroscopy may be

  12. Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

    Science.gov (United States)

    Skowron, K. B.; Pitroda, S. P.; Namm, J. P.; Balogun, O.; Beckett, M. A.; Zenner, M. L.; Fayanju, O.; Huang, X.; Fernandez, C.; Zheng, W.; Qiao, G.; Chin, R.; Kron, S. J.; Khodarev, N. N.; Posner, M. C.; Steinberg, G. D.; Weichselbaum, R. R.

    2016-01-01

    Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients. PMID:27775025

  13. Basal energy expenditure measured by indirect calorimetry in patients with squamous cell carcinoma of the esophagus.

    Science.gov (United States)

    Becker Veronese, Camila Beltrame; Guerra, Léa Teresinha; Souza Grigolleti, Shana; Vargas, Juliane; Pereira da Rosa, André Ricardo; Pinto Kruel, Cleber Dario

    2013-01-01

    Antecedentes: La determinación del gasto energético basal (GEB) es esencial para la planificación de la terapia nutricional en pacientes con cáncer de esófago. Objetivos: El objetivo de este estudio fue determinar GEB por calorimetría indirecta (CI) en pacientes con carcinoma de células escamosas del esófago (CCS). Métodos: Estudio transversal con 30 pacientes ingresados con el diagnóstico de CCS que se sometieron CI antes de iniciar la terapia contra el cáncer. La abeja se evaluó con CI y estimó por medio de la ecuación de Harris-Benedict (EHB). La evaluación nutricional se realizó utilizando los parámetros antropométricos (índice de masa corporal, circunferencia del brazo, el pliegue del tríceps, circunferencia muscular del brazo y pérdida de peso), parámetros bioquímicos (albúmina, transferrina y la proteína C-reactiva) y bioimpedancia tetrapolar para evaluar la composición corporal (grasa masa). Además, la capacidad pulmonar se midió y la estadificación clínica del cáncer establecido por el método TNM. Resultados: La media de la abeja para la ecuación CI y Harris-Benedict fueron 1421,8 ± 348,2 kcal / día y 1310,6 ± 215,1 kcal / día, respectivamente. No se encontró asociación entre GEB medido por CI y la estadificación clínica (p = 0,255) o el índice Tiffeneau (p = 0,946). No se encontraron asociaciones significativas entre GEB medidos por dosis de CI y alteración de la transferrina, albúmina y proteína C reactiva (p = 0,364, 0,309 y 0,780, respectivamente). Los factores más asociados con GEB fueron el IMC y la masa libre de grasa. Conclusión: La abeja de los pacientes con CCS fue subestimada cuando se utiliza el EHB, y el resultado sobreestimado cuando se incorpora un factor de d2013 con el EHB. Por lo tanto, a pesar de las dificultades de aplicación práctica de CI, su uso debe ser considerado.

  14. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

    OpenAIRE

    Moina Hasni Ebou; Amrit Singh-Estivalet; Jean-Marie Launay; Jacques Callebert; François Tronche; Pascal Ferré; Jean-François Gautier; Ghislaine Guillemain; Bernadette Bréant; Bertrand Blondeau; Jean-Pierre Riveline

    2016-01-01

    International audience; Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synth...

  15. Elucidating the Tumor-Suppressive Role of SLITs in Maintaining the Basal Cell Niche

    Science.gov (United States)

    2011-10-01

    of both the glandular epithelium and vasculature and promotes metastasis formation. Int J Oncol. 2009;35(3):525–36. 10. Marlow R, Strickland P, Lee JS...organize tissue structure, including cells in the breast stem cell niche, and to generate the barrier between epithelium and stroma by secreting the...Macias H., Cardiff R.D., Sukumar S., Hinck. 2008. SLITs suppress tumor growth and microenvironment by silencing Sdf1/Cxcr4 within breast epithelium

  16. Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: Linkage and loss of heterozygosity

    Energy Technology Data Exchange (ETDEWEB)

    Chenevix-Trench, G.; Wicking, C.; Berkman, J.; Sharpe, H.; Hockey, A.; Haan, E.; Oley, C.; Ravine, D.; Turner, A.; Searle, J. (and others)

    1993-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North Americal and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCs gene is probably a tumor-suppressor gene. In this study the authors have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity. They have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. 21 refs., 3 figs., 2 tabs.

  17. [Prenatal diagnosis with fetal cells in maternal blood: report of experiences in Basal].

    Science.gov (United States)

    Holzgreve, W; Troeger, C; Schatt, S; Vial, Y; Louwen, F; Gloning, K; Hahn, S

    1998-10-24

    Currently prenatal diagnosis relies on invasive procedures such as chorion villus sampling (CVS) or amniocentesis (AC). Many parents are reluctant to expose themselves and their child to the small, but significant risk posed by these procedures to mother and child. There is, hence, a great need for a risk-free non-invasive alternative. To achieve this goal most research has been focussed on enriching fetal cells from the blood of pregnant women. The erythroblast has emerged as the target cell of choice, since it is abundant in the early fetus, rare in normal adult blood, and since it has a very short half life, there is no risk of obtaining cells from previous pregnancies. Most enrichment protocols rely either on magnetic- or fluorescent activated cell sorting (MACS and FACS) using fetal specific antibodies. These enriched cells can be examined by FISH (fluorescence in-situ hybridisation) for the presence of the most common fetal chromosomal aneuploidies (13, 18, 21, X and Y) or by polymerase chain reaction (PCR) on singly manipulated cells for genetic disorders. The efficacy in detecting fetal aneuploidies is currently being evaluated in a phase II clinical trial under the auspices of the NIH-NICHD, the so-called NIFTY Trial, in which our group is a participant. By modifying our enrichment protocols we have recently been able to obtain detection sensitivities of almost 80%, thereby renewing our optimism that this methodology provides a solid basis for an effective non-invasive prenatal diagnostic test.

  18. Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential?

    DEFF Research Database (Denmark)

    Rossen, K; Dahlstrøm, K K; Mercurio, A M;

    1994-01-01

    We have studied the expression of alpha 6 beta 4 integrin, a carcinoma laminin receptor in ten squamous cell carcinomas (SCCs) and ten basal cell carcinomas (BCCs) of the skin in order to examine whether changes in alpha 6 beta 4 integrin expression may be related to invasive and metastatic...... the expression of the alpha 6 and the beta 4 subunits paralleled each other, showing an increased intensity and loss of polarity. The BCCs, however, showed consistently decreased expression of both the alpha 6 and the beta 4 subunits. The results of our study, as well as those of other studies, support...

  19. Effect of the hydrophobic basal layer of thermoresponsive block co-polymer brushes on thermally-induced cell sheet harvest.

    Science.gov (United States)

    Matsuzaka, Naoki; Takahashi, Hironobu; Nakayama, Masamichi; Kikuchi, Akihiko; Okano, Teruo

    2012-01-01

    Thermoresponsive poly(benzyl methacrylate)-b-poly(N-isopropylacrylamide) (PBzMA-b-PIPAAm) block co-polymer brush surfaces were prepared by surface-initiated two-step reversible addition-fragmentation chain transfer radical (RAFT) polymerization. PBzMA brushes were fabricated on azoinitiator-immobilized glass substrates in the presence of dithiobenzoate (DTB) compound as a RAFT agent. The amount of grafted polymer was regulated by initial monomer concentrations. The second thermoresponsive blocks were added to the RAFT-related DTB groups located at PBzMA termini through the propagation of PIPAAm chains, resulting in formation of PBzMA-b-PIPAAm brushes. Surface characteristics of the block co-polymer brushes and its influence on thermally regulated cellular behavior were investigated using bovine carotid artery endothelial cells (BAECs), compared with PIPAAm brush surfaces. Cell adhesion/detachment behavior on thermoresponsive polymer brush surfaces significantly depended on their individual polymer architectures and chemical compositions of grafted polymers. Low-temperature treatment at 20°C, below the phase-transition temperature of PIPAAm, induced the spontaneous detachment of adhering cells from the PBzMA-b-PIPAAm brush surfaces with a higher rate than that from PIPAAm brush surfaces. In addition, the cell-repellent effect of the hydrophobic basal layer successfully accelerated for harvesting BAEC sheets from the block co-polymer brush surfaces. Unique features of thermoresponsive block co-polymer brush architectures can be applied to control cell-adhesion strength for enhancing cell adhesion or accelerating cell detachment.

  20. Basal chromatin modification at the IL-4 gene in helper T cells

    Energy Technology Data Exchange (ETDEWEB)

    Grogan, Jane L.; Wang, Zhi-En; Stanley, Sarah; Harmon, Brian; Loots, Gaby G.; Rubin, Edward M.; Locksley, Richard M.

    2003-04-15

    Chromatin immunoprecipitations in naive CD4, but not CD8, T cells, demonstrated association of the IL-4 promoter with acetylated histone. Histone modifications and rapid IL-4 transcription were absent in conserved noncoding sequence 1 (CNS-1){sup -/-} cells lacking an 8-kb-distant enhancer in the IL-4/IL-13 intergenic region, but also in CD4{sup -/-} and Itk{sup -/-} cells, which have similar Th2 deficiencies. Histones associated with the IL-13 promoter were not similarly acetylated in naive T cells, but became acetylated in differentiated Th2 cells. Conversely, Th1 differentiation induced histone methylation at the type 2 cytokine locus. Like CD4{sup -/-} and Itk{sup -/-} mice, CNS-1{sup -/-} BALB/c mice were highly resistant to the Th2-inducing protozoan, Leishmania major. CNS-1 deficiency led to failure of IL-4 gene repositioning to heterochromatin after Th1 polarization, possibly related to the presence of reiterative Ikaros binding sites in the intergenic element. Hyperacetylation of nonexpressed genes may serve to mark lineage-specific loci for rapid expression and further modification.

  1. Inoperable metastatic giant basal cell trunk carcinoma: radiotherapy can be useful; Carcinome basocellulaire geant du tronc metastatique inoperable: la radiotherapie peut etre utile

    Energy Technology Data Exchange (ETDEWEB)

    Mania, A.; Durando, X.; Lapeyre, M. [Centre Jean-Perrin, Clermont-Ferrand (France); Barthelemy, I. [CHU Estaing, Clermont-Ferrand (France)

    2011-10-15

    The authors evoke some characteristics of the basal cell carcinoma (slow evolution, local morbidity) and report and discuss the case of a giant basal cell trunk carcinoma, associated with several symptoms (pain, bleeding, anaemia), already metastatic at the moment of diagnosis, and locally treated by irradiation. Due to its size and expansion, this carcinoma was considered as inoperable. An external radiotherapy has been performed and resulted in a significant clinical tumour reduction. But the metastatic risk is high in such cases. Radiotherapy is then a therapeutic option for a local treatment with a durable efficiency. Short communication

  2. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

  3. Basal-subtype and MEK-Pl3K feedback signaling determine susceptibility of breast cancer cells to MEK inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Mirzoeva, Olga K.; Das, Debopriya; Heiser, Laura M.; Bhattacharya, Sanchita; Siwak, Doris; Gendelman, Rina; Bayani, Nora; Wang, Nicholas J.; Neve, Richard M.; Knight, Zachary; Feiler, Heidi S.; Gascard, Philippe; Parvin, Bahram; Spellman, Paul T.; Shokat, Kevan M.; Wyrobek, Andrew J.; Bissell, Mina J.; McCormick, Frank; Kuo, Wen-Lin; Mills, Gordon B.; Gray, Joe W.; Korn, W. Michael

    2009-01-23

    Specific inhibitors of MEK have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We employed a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth-inhibition by small-molecule MEK inhibitors. Activation of the PI3 kinase pathway in response to MEK inhibition through a negative MEK-EGFR-PI3 kinase feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3 kinase produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies.

  4. Pathway analysis of expression-related SNPs on genome-wide association study of basal cell carcinoma

    Science.gov (United States)

    Li, Xin; Liang, Liming; De Vivo, Immaculata; Tang, Jean Y.; Han, Jiali

    2016-01-01

    Genome-wide association studies (GWASs) have primarily focused on the association between individual genetic markers and risk of disease. We applied a novel approach that integrates skin expression-related single-nucleotide polymorphisms (eSNPs) and pathway analysis for GWAS of basal cell carcinoma (BCC) to identify potential novel biological pathways. We evaluated the associations between 70,932 skin eSNPs and risk of BCC among 2,323 cases and 7,275 controls of European ancestry, and then assigned them to the pathways defined by KEGG, GO, and BioCarta databases. Three KEGG pathways (colorectal cancer, actin cytoskeleton, and BCC), two GO pathways (cellular component disassembly in apoptosis, and nucleus organization), and four BioCarta pathways (Ras signaling, T cell receptor signaling, natural killer cell-mediated cytotoxicity, and links between Pyk2 and Map Kinases) showed significant association with BCC risk with p-value<0.05 and FDR<0.2. These pathways also ranked at top in sensitivity analyses. Two positive controls in KEGG, the hedgehog pathway and the BCC pathway, showed significant association with BCC risk in both main and sensitivity analyses. Our results indicate that SNPs that are undetectable by conventional GWASs are significantly associated with BCC when tested as pathways. Biological studies of these gene groups suggest their potential roles in the etiology of BCC. PMID:27367190

  5. MicroRaman Spectroscopy and Raman Imaging of Basal Cell Carcinoma

    Science.gov (United States)

    Short, M. A.; Zeng, H.; Lui, H.

    2005-03-01

    We have measured the Raman spectra of normal and cancerous skin tissues using a confocal microRaman spectrograph with a sub-micron spatial resolution. We found that the Raman spectrum of a cell nucleolus is different from the spectra measured outside the nucleolus and considerably different from those measured outside the nucleus. In addition, we found significant spectroscopic differences between normal and cancer-bearing sites in the dermis region. In order to utilize these differences for non-invasive skin cancer diagnosis, we have developed a Raman imaging system that clearly demonstrates the structure, location and distribution of cells in unstained skin biopsy samples. Our method is expected to be useful for the detection and characterization of skin cancer based on the known distinct cellular differences between normal and malignant skin.

  6. **-Postprandial pancreatic [(11)C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release.

    Science.gov (United States)

    Steiner, Emanuel; Kazianka, Lukas; Breuer, Robert; Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus; Stimpfl, Thomas; Reiter, Birgit; Karanikas, Georgios; Miholic, Johannes

    2017-03-01

    [S-methyl-(11)C]-L-methionine ([(11)C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [(11)C]MET uptake. Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [(11)C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. The uptake of [(11)C]MET in the pancreas was significantly higher (p insulin AUC60 (R(2) = 0.66,p insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of (11)C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R(2) = 0.78, p < 0.0001). Postprandial [(11)C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.

  7. Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308

    DEFF Research Database (Denmark)

    Skov, Lone; Allen, Michael H; Bang, Bo

    2003-01-01

    The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to play a central role. A single base pair polymorphism at position --308 in the promoter region of the TNF-alpha gene associated with an enhance...... with increased TNF-alpha production and BCC and necessary.......The mechanisms underlying induction of UVB-induced immunosuppression are not fully understood, but tumor necrosis factor alpha (TNF-alpha) is suggested to play a central role. A single base pair polymorphism at position --308 in the promoter region of the TNF-alpha gene associated with an enhanced...... secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were...

  8. Crosstalks between myo-inositol metabolism, programmed cell death and basal immunity in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Ping Hong Meng

    Full Text Available BACKGROUND: Although it is a crucial cellular process required for both normal development and to face stress conditions, the control of programmed cell death in plants is not fully understood. We previously reported the isolation of ATXR5 and ATXR6, two PCNA-binding proteins that could be involved in the regulation of cell cycle or cell death. A yeast two-hybrid screen using ATXR5 as bait captured AtIPS1, an enzyme which catalyses the committed step of myo-inositol (MI biosynthesis. atips1 mutants form spontaneous lesions on leaves, raising the possibility that MI metabolism may play a role in the control of PCD in plants. In this work, we have characterised atips1 mutants to gain insight regarding the role of MI in PCD regulation. METHODOLOGY/PRINCIPAL FINDINGS: - lesion formation in atips1 mutants depends of light intensity, is due to PCD as evidenced by TUNEL labelling of nuclei, and is regulated by phytohormones such as salicylic acid - MI and galactinol are the only metabolites whose accumulation is significantly reduced in the mutant, and supplementation of the mutant with these compounds is sufficient to prevent PCD - the transcriptome profile of the mutant is extremely similar to that of lesion mimic mutants such as cpr5, or wild-type plants infected with pathogens. CONCLUSION/SIGNIFICANCE: Taken together, our results provide strong evidence for the role of MI or MI derivatives in the regulation of PCD. Interestingly, there are three isoforms of IPS in Arabidopsis, but AtIPS1 is the only one harbouring a nuclear localisation sequence, suggesting that nuclear pools of MI may play a specific role in PCD regulation and opening new research prospects regarding the role of MI in the prevention of tumorigenesis. Nevertheless, the significance of the interaction between AtIPS1 and ATXR5 remains to be established.

  9. Adenoma de células basales parotídeo: Revisión a propósito de cuatro casos Basal cell adenoma of the parotid: A revision based on four cases

    Directory of Open Access Journals (Sweden)

    M.J. Pastor Fortea

    2005-04-01

    Full Text Available El adenoma de células basales es un tipo específico de adenoma con una apariencia histológica uniforme y monomorfa, en el que predominan las células basaliodes sin el componente mixocondroide del tumor mixto. Atendiendo a su morfología pueden ser divididos en cuatro subtipos: sólido, tubular, trabecular y membranoso. Presentamos cuatro casos de adenoma de células basales localizados en glándula parótida: uno de tipo sólido, uno de tipo trabecular y dos de tipo membranoso, tratados mediante parotidectomía superficial conservadora en todos los casos. Esta división en distintos patrones morfológicos tiene una finalidad descriptiva, salvo en el subtipo membranoso por su mayor tendencia a la multifocalidad y a la recidiva, su ocasional transformación maligna, así como por su posible asociación en un tercio de los casos a tumores ecrinos dermales. Esto implica un seguimiento más estrecho y un despistaje de posibles lesiones cutáneas asociadas.The basal cell adenoma is a specific type of adenoma, with a uniform, monomorphous histologic appearance that is dominated by basaloid cells and that does not have the myxochondroid tissue characteristic of mixed tumors. It may be divided on the basis of its morphologic pattern into four subtypes: solid, tubular, trabecular and membranous. We report four cases of basal cell adenoma subdivided as follows: one solid, one trabecular and two membranous subtypes. In all cases a conservative superficial parotidectomy was the treatment. Morphologic identification of the specific subtype is for descriptive purposes, except in the case of the membranous type, due to its tendency to be multifocal, its high recurrence rate, its occasional malignant transformation and its possible association in about onethird of the reported cases with dermal cylindromas. A close followup and screening of skin lesions is suggested for these tumors.

  10. Diagnostic and pathogenetic role of café-au-lait macules in nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Ponti Giovanni

    2012-10-01

    Full Text Available Abstract Café au lait spots (CALS are common dermatologic findings that can at the same time arise in a variety of pathologic conditions such as Neurofibromatosis type 1 (NF1, together with numerous hereditary syndromes for which they represent either diagnostic criteria or associated elements (McCune Albright, Silver-Russell, LEOPARD, Ataxia-Telangiectasia. A review of the literature also revealed two cases of association with NBCCS. We report here the case of a female proband with CALS associated to Nevoid Basal Cell Carcinoma Syndrome (NBCCS with known PTCH1 germline mutation (C.1348-2A>G who had been misdiagnosed with NF1 in her childhood because of 5 CALS and cutaneous nodules. The patient presented a giant cell tumor of the skin, palmar and calcaneal epidermoidal cystic nodules, odontogenic keratocystic tumors and deformity of the jaw profile. Her family history brought both her brother and father to our attention because of the presence of KCOTs diagnosed at early age: after genetic testing, the same PTCH1 germline mutation was identified in the three family members. Clinical criteria are used for discerning NF1 diagnosis (size, number and onset age, while there are no definite guidelines concerning CALS except for their presence. In our experience, we have noted an association of CALS with NBCCS; this seems interesting because we already know clinical criteria are a dynamic entity and can be modified by epidemiologic evidences.

  11. Proliferative activity of epidermal basal cells after wounding. AgNOR counts compared with bromodeoxyuridine reactivity in rats.

    Science.gov (United States)

    Rebolledo Godoy, A P; Rebolledo Godoy, M; Meissner, C; Oehmichen, M

    2001-04-01

    Quantitative changes in nucleolus organizer regions (NORs) are known markers of proliferation that can be demonstrated by a specific silver staining technique on paraffin-embedded sections. Wounding of skin induces proliferation of basal epidermal cells at the wound margin. The degree of proliferation depends on the survival time and can be measured by morphometric assessment of argyrophilic NORs (AgNORs). Following incision wounding of the pinnae, rats were allowed to survive for different intervals (7 rats per interval) up to 120 hours. Before each sacrifice, biopsies were taken and incubated in a bromodeoxyuridine (BrdU) solution, embedded in paraffin, and stained with an antibody against BrdU. At the same time morphometric analysis of AgNOR counts was performed on sections made from the same material. BrdU incorporating nuclei were assessed by simple counting, whereas morphometric analysis of AgNOR counts was computer aided. Both methods revealed an increase in the number of proliferating cells, a plateau phase being reached after about 36 hours, followed by a decline after about 70 hours. Both methods thus allowed a reliable temporal classification of the skin injury according to survival time. The molecular background of the AgNOR changes in relation to the proliferation of cellular elements is discussed in detail.

  12. Thomsen-Friedenreich (T) antigen as marker of myoepithelial and basal cells in the parotid gland, pleomorphic adenomas and adenoid cystic carcinomas. An immunohistological comparison between T and sialosyl-T antigens, alpha-smooth muscle actin and cytokeratin 14

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Christensen, M

    1995-01-01

    Controversy centres on the role and identification of myoepithelial (MEC) and basal cells in salivary gland tumours, and recent studies suggest that both basal cells and myoepithelial cells participate in the formation of salivary gland tumours. We have correlated the expression of different well...

  13. Prolactin-induced prostate tumorigenesis links sustained Stat5 signaling with the amplification of basal/stem cells and emergence of putative luminal progenitors.

    Science.gov (United States)

    Sackmann-Sala, Lucila; Chiche, Aurélie; Mosquera-Garrote, Nerea; Boutillon, Florence; Cordier, Corinne; Pourmir, Ivan; Pascual-Mathey, Luz; Kessal, Karima; Pigat, Natascha; Camparo, Philippe; Goffin, Vincent

    2014-11-01

    Current androgen ablation therapies for prostate cancer are initially successful, but the frequent development of castration resistance urges the generation of alternative therapies and represents an important health concern. Prolactin/signal transducer and activator of transcription 5 (STAT5) signaling is emerging as a putative target for alternative treatment for prostate cancer. However, mechanistic data for its role in development or progression of prostate tumors are scarce. In vivo mouse studies found that local prolactin induced the amplification of prostate epithelial basal/stem cells. Because these cells are proposed cells of origin for prostate cancer and disease recurrence, we looked further into this amplification. Our results indicated that sustained Stat5 activation was associated with the occurrence of abnormal basal/stem cell clusters in prostate epithelium of prostate-specific prolactin-transgenic mice. Analysis of epithelial areas containing these clusters found high proliferation, Stat5 activation, and expression of stem cell antigen 1. Furthermore, enhanced prolactin signaling also led to amplification of a luminal cell population that was positive for stem cell antigen 1. These cells may originate from amplified basal/stem cells and might represent important progenitors for tumor development in prostate epithelium. These data provide a deeper understanding of the initial stages of prostate tumorigenesis induced by prolactin to help determine whether this hormone or its downstream messengers could be useful targets for prostate cancer treatment in the future.

  14. Basal Ganglia Structures Differentially Contribute to Verbal Fluency: Evidence from Human Immunodeficiency Virus (HIV)-Infected Adults

    Science.gov (United States)

    Thames, April D.; Foley, Jessica M.; Wright, Matthew J.; Panos, Stella E.; Ettenhofer, Mark; Ramezani, Amir; Streiff, Vanessa; El-Saden, Suzie; Goodwin, Scott; Bookheimer, Susan Y.; Hinkin, Charles H.

    2012-01-01

    Background: The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to…

  15. The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

    Science.gov (United States)

    Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

    2013-01-01

    Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

  16. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma : a single blind, non-inferiority, randomised controlled trial

    NARCIS (Netherlands)

    Arits, Aimee H. M. M.; Mosterd, Klara; Essers, Brigitte A. B.; Spoorenberg, Eefje; Sommer, Anja; De Rooij, Michette J. M.; van Pelt, Han P. A.; Quaedvlieg, Patricia J. F.; Krekels, Gertruud A. M.; van Neer, Pierre A. F. A.; Rijzewijk, Joris J.; van Geest, Adrienne J.; Steijlen, Peter M.; Nelemans, Patty J.; Kelleners-Smeets, Nicole W. J.

    Background Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We

  17. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous...

  18. Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study

    Science.gov (United States)

    Delpueyo, Xana; Vilaseca, Meritxell; Royo, Santiago; Ares, Miguel; Rey-Barroso, Laura; Sanabria, Ferran; Puig, Susana; Pellacani, Giovanni; Noguero, Fernando; Solomita, Giuseppe; Bosch, Thierry

    2017-06-01

    This article proposes a multispectral system that uses the analysis of the spatial distribution of color and spectral features to improve the detection of skin cancer lesions, specifically melanomas and basal cell carcinomas. The system consists of a digital camera and light-emitting diodes of eight different wavelengths (414 to 995 nm). The parameters based on spectral features of the lesions such as reflectance and color, as well as others empirically computed using reflectance values, were calculated pixel-by-pixel from the images obtained. Statistical descriptors were calculated for every segmented lesion [mean (x˜), standard deviation (σ), minimum, and maximum]; descriptors based on the first-order statistics of the histogram [entropy (Ep), energy (En), and third central moment (μ3)] were also obtained. The study analyzed 429 pigmented and nonpigmented lesions: 290 nevi and 139 malignant (95 melanomas and 44 basal cell carcinomas), which were split into training and validation sets. Fifteen parameters were found to provide the best sensitivity (87.2% melanomas and 100% basal cell carcinomas) and specificity (54.5%). The results suggest that the extraction of textural information can contribute to the diagnosis of melanomas and basal cell carcinomas as a supporting tool to dermoscopy and confocal microscopy.

  19. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma : a single blind, non-inferiority, randomised controlled trial

    NARCIS (Netherlands)

    Arits, Aimee H. M. M.; Mosterd, Klara; Essers, Brigitte A. B.; Spoorenberg, Eefje; Sommer, Anja; De Rooij, Michette J. M.; van Pelt, Han P. A.; Quaedvlieg, Patricia J. F.; Krekels, Gertruud A. M.; van Neer, Pierre A. F. A.; Rijzewijk, Joris J.; van Geest, Adrienne J.; Steijlen, Peter M.; Nelemans, Patty J.; Kelleners-Smeets, Nicole W. J.

    2013-01-01

    Background Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We asses

  20. Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex.

    Science.gov (United States)

    LaMonica, Bridget E; Lui, Jan H; Hansen, David V; Kriegstein, Arnold R

    2013-01-01

    The human neocortex is increased in size and complexity as compared with most other species. Neocortical expansion has recently been attributed to protracted neurogenesis by outer radial glial cells in the outer subventricular zone, a region present in humans but not in rodents. The mechanisms of human outer radial glial cell generation are unknown, but are proposed to involve division of ventricular radial glial cells; neural stem cells present in all developing mammals. Here we show that human ventricular radial glial cells produce outer radial glial cells and seed formation of the outer subventricular zone via horizontal divisions, which occur more frequently in humans than in rodents. We further find that outer radial glial cell mitotic behaviour is cell intrinsic, and that the basal fibre, inherited by outer radial glial cells after ventricular radial glial division, determines cleavage angle. Our results suggest that altered regulation of mitotic spindle orientation increased outer radial glial cell number, and ultimately neuronal number, during human brain evolution.

  1. Chronic TNFalpha and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis.

    Science.gov (United States)

    Bézaire, Véronic; Mairal, Aline; Anesia, Rodica; Lefort, Corinne; Langin, Dominique

    2009-09-17

    We examined the effects of chronic TNFalpha and dibutyryl-cAMP (Db-cAMP) pre-treatment on the lipolytic machinery of human hMADS adipocytes. TNFalpha decreased adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin (PLIN) protein content. Conversely, Db-cAMP increased ATGL and HSL protein content but prevented PLIN phosphorylation, the net result being accentuated basal lipolysis. In forskolin-stimulated conditions, TNFalpha and Db-cAMP pre-treatment decreased stimulated TG-hydrolase activity and impaired PLIN phosphorylation. Together, this resulted in a severely attenuated response to forskolin-stimulated lipolysis.

  2. Imiquimod 5% cream for the treatment of large nodular basal cell carcinoma at the medial canthal area

    Science.gov (United States)

    Karabulut, Gamze Ozturk; Kaynak, Pelin; Ozturker, Can; Fazil, Korhan; Ocak, Osman Bulut; Taskapılı, Muhittin

    2017-01-01

    Context (Background): Imiquimod (IMQ) 5% cream is an immunomodulatory and antitumorigenic agent, which was used as a topical treatment regimen, who had periocular basal cell carcinoma (BCC). Aim: This study aims to present three cases with large BCC at the medial canthal area treated with IMQ 5% cream. Materials and Methods: IMQ 5% cream was used in three patients with ages 45, 49, and 73 who preferred medical treatment over surgery. Following incisional biopsy IMQ cream was used once a day, 5 times a week and the patients were followed up weekly during 12 week treatment period and monthly after the clearance of the lesion. Results: Erythema and erosion on the surface of the lesion, injection of conjunctiva, burning and itching sensation, epiphora and punctate keratitis were seen in all patients during the treatment period. The ophthalmic side effects could be managed by topical lubricating eye drops and the inflammatory reactions resolved within 1 month after cessation of therapy. The patients were followed up for at least 3 years without tumor recurrence and the biopsies taken from the suspected area were found to be tumor free. Conclusion: Surgical excision of carcinoma of the eyelid at medial canthal area can be difficult without causing damage to the lacrimal system and reconstruction of the defect may need grafts or flaps. IMQ may provide an alternative therapy to surgery in certain cases. PMID:28300740

  3. Six Years of Experience in Photodynamic Therapy for Basal Cell Carcinoma: Results and Fluorescence Diagnosis from 191 Lesions

    Directory of Open Access Journals (Sweden)

    M. Fernández-Guarino

    2014-01-01

    Full Text Available Background. Photodynamic therapy (PDT has become a therapeutic option for basal cell carcinoma (BCC in the last decade. Objectives. To study the results and predictors of BCC response to treatment with PDT and to evaluate fluorescence diagnosis of BCC. Methods. A descriptive, retrospective, and observational study was carried out. Patients with biopsy-confirmed BCC who were treated with methyl aminolevulinate and red light according to standard treatment protocols (2 sessions separated by 2 weeks, 630 nm, 37 J/cm2, 8 minutes, Aktilite were selected. Response was scored as clinically complete and incomplete and the patients were followed up every three months. Results. Data from 191 BCC in 181 patients with a mean age of 69.55 years and a mean follow-up period of 34.4 months were collected. The overall response was 74% of the BCC treated, with the best response in superficial BCC with a 95% of complete response. The regression analysis revealed that the superficial histological type was the primary factor predictive of a complete response. Conclusions. In the treatment of BCC with PDT, the most significant factor for predicting response is the histological type.

  4. Robust demarcation of basal cell carcinoma by dependent component analysis-based segmentation of multi-spectral fluorescence images.

    Science.gov (United States)

    Kopriva, Ivica; Persin, Antun; Puizina-Ivić, Neira; Mirić, Lina

    2010-07-02

    This study was designed to demonstrate robust performance of the novel dependent component analysis (DCA)-based approach to demarcation of the basal cell carcinoma (BCC) through unsupervised decomposition of the red-green-blue (RGB) fluorescent image of the BCC. Robustness to intensity fluctuation is due to the scale invariance property of DCA algorithms, which exploit spectral and spatial diversities between the BCC and the surrounding tissue. Used filtering-based DCA approach represents an extension of the independent component analysis (ICA) and is necessary in order to account for statistical dependence that is induced by spectral similarity between the BCC and surrounding tissue. This generates weak edges what represents a challenge for other segmentation methods as well. By comparative performance analysis with state-of-the-art image segmentation methods such as active contours (level set), K-means clustering, non-negative matrix factorization, ICA and ratio imaging we experimentally demonstrate good performance of DCA-based BCC demarcation in two demanding scenarios where intensity of the fluorescent image has been varied almost two orders of magnitude.

  5. Superpulsed CO2 Laser with Intraoperative Pathologic Assessment for Treatment of Periorbital Basal Cell Carcinoma Involving Eyelash Line

    Directory of Open Access Journals (Sweden)

    Ali Ebrahimi

    2014-01-01

    Full Text Available Background. Periorbital basal cell carcinoma (BCC is considered a high risk case because it is associated with high rate of recurrence and complication. Superpulsed CO2 laser with intraoperative pathologic assessment could be an alternative and appropriate treatment for periocular lesions where Mohs micrographic surgery is not available. Objective. To evaluate the efficacy of superpulsed CO2 laser therapy with intraoperative pathologic assessment on periocular BCC involving eyelash line. Method. This follow-up study was performed on 20 patients with a total of 21 BCC lesions that were pathologically documented. Firstly, debulkation of tumoral mass was done by curettage. Then, irradiation and intraoperative pathologic evaluation were done by concurrent CO2 laser. The patients were followed up for a period of 36 months. Results. Out of 21 lesions, the nodular type accounted for 15 (71.4% lesions, and 12 (57.1% lesions were seen in the lower lid as the most common clinical type and site involvement. Twenty BCC lesions (95.2% were treated after one session. Damage to eyelash was seen in 2 (10% patients, but ectropion and other complications were not seen in any patient. Conclusion. Treatment with superpulsed CO2 laser and intraoperative pathologic evaluation for periorbital BCC lesions much close to conjunctiva could be an effective method with minimal complications without major danger of recurrence. This modality can be used with care in the inner canthus and high risk pathologic lesions.

  6. Basal cell adenoma-clinicopathological, immunohistochemical analysis and surgical considerations of a rare salivary gland tumor with review of literature

    Directory of Open Access Journals (Sweden)

    A D Bhagat Singh

    2015-01-01

    Full Text Available Introduction: Basal cell adenoma (BCA of the salivary glands is a rare benign salivary gland tumour. Differentiation of BCA from varied entities involving maxillofacial area is mandatory. Aim: To analyze the clinicopathological, histopathologic features, immunohistochemcal analysis and surgical considerations of this rare entity. Materials and Methods: This study included 12 cases of BCA from archives of department reported over the period of 13 years. All the pertaining clinicopathologic features such as incidence, age, sex and site of lesions were assessed. Tissue sections were stained by using panel of immunohistochemical markers, i.e. Pan CK, CK 5/6 and S100, Calponin, p63, CD 117 and smooth muscle actin. Results: BCA was observed in 26-52 years age group (mean age, 38.75 years with female propensity of 7:5 male to female ratio. It is seen more commonly in parotid gland, followed by upper lip, buccal mucosa and palate. Solid type is the most common histopathologic type followed by tubular, membranous and trabecular. Only one case of membranous type of BCA showed recurrence. Pan CK, CK 5/6 showed strong immunoreactivity, calponin showed moderate staining, p63 and Ki-67 mild staining, whereas CD 117 and SMA showed negative immunostaining. Conclusion: Vigilant comprehensive analysis of all the pertaining clinicopathologic and histopathologic features and immunohistochemical analysis are required for differentiating from other lesions with basaloid differentiation having varying prognosis.

  7. Vismodegib, itraconazole and sonidegib as hedgehog pathway inhibitors and their relative competencies in the treatment of basal cell carcinomas.

    Science.gov (United States)

    Wahid, Mohd; Jawed, Arshad; Mandal, Raju K; Dar, Sajad A; Khan, Saif; Akhter, Naseem; Haque, Shafiul

    2016-02-01

    The advent of more sophisticated studies published has clarified the understating of the root cause of various skin cancers or basal cell carcinomas (BCCs). The remarkable role is played by the comprehensive work done on unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The defective Hh pathway has been found as the major cause for BCCs as activated Hh signaling within primary cilia plays a key role in the pathogenesis of BCCs. The BCC accounts for up to 40% of all cancers in the US, with growing incidences in other countries as well. Thus, it is considered to be utmost important by the researchers all over the world developing drugs for the treatment of skin cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and sonidegib have shown promising results inhibiting the awry function of Hh pathway resulting in treatment of different forms of skin cancers. These drugs have shown positive results but failed to prove their potential as expected. Vismodegib and sonidegib are better but fail in case of resistant tumors. This review article describes the mechanism of actions of these Hh pathway inhibitors and provides the rationale for their effectiveness/non-effectiveness for the treatment of metastatic or locally advanced BCC.

  8. Functional heterogeneity within the CD44 high human breast cancer stem cell-like compartment reveals a gene signature predictive of distant metastasis

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Terp, Mikkel Green; Christensen, Anne G

    2012-01-01

    The CD44(hi) compartment in human breast cancer is enriched in tumor-initiating cells; however the functional heterogeneity within this subpopulation remains poorly defined. We used a triple-negative breast cancer cell line with a known bi-lineage phenotype to isolate and clone CD44(hi) single......-cells that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively. Herein we demonstrate in this and other triple-negative breast cancer cell lines that rather than CD44(hi)/CD24(-) mesenchymal-like Basal B cells, the CD44(hi)/CD24(lo) epithelioid Basal A cells retained classical cancer stem cell...... of estrogen receptor-negative human breast cancers. These findings strongly favor functional heterogeneity in the breast cancer cell compartment and hold promise for further refinements of prognostic marker profiling. Our work confirms that, in addition to cancer stem cells with mesenchymal-like morphology...

  9. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, P; Tornøe, Jens

    2010-01-01

    Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device...

  10. HCMV Infection Depress NGF Expression in Human Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    Hai-tao WANG; Bin WANG; Zhi-jun LIU; Zhi-qiang BAI; Ling LI; Dong-meng QIAN; Zhi-yong YAN; Xu-xia SONG

    2009-01-01

    Human cytomegalovirus (HCMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, RT-PCR and Western Blotting were performed to quantify the regulation of endogenic nerve growth factor expression in neuroglia cells by HCMV infection. The results showed that basal, endogenous NGF expression in U251 was unchanged during early HCMV infection. NGF expression is strongly down-regulated during the latent phase of infection. These results suggest that HCMV can depress the NGF expression in U251 cells.

  11. Clinical, dermoscopic and histological features of a combined tumor composed of a melanoma in situ, a basal cell carcinoma and an intradermal naevus

    Directory of Open Access Journals (Sweden)

    Massimiliano Scalvenzi

    2012-12-01

    Full Text Available The combined tumors are neoplasms consisting of 2 or more distinct cell population that are intimately admixed. The presence of more than one neoplasm in the same lesion comprising melanocytes and keratinocytes are rare but well documented. We report a case of a 65-year-old man with a melanoma in situ, a basal cell carcinoma and an intradermal naevus in collision that clinically appeared as a single lesion. Clinical, dermoscopic and histological features are discussed.

  12. Expressão de marcadores de proliferação celular e apoptose em carcinoma basocelular Markers expression of cell proliferation and apoptosis in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Marília de Pádua Dornelas Corrêa

    2009-12-01

    Full Text Available FUNDAMENTOS: O carcinoma basocelular é o câncer mais comum em humanos. Estudos que utilizam recursos da biologia molecular e genética, associados à histomorfologia, permitem a identificação de fatores de risco no desenvolvimento de lesões mais recorrentes e agressivas. OBJETIVO: Correlacionar a expressão dos marcadores de apoptose (p53 e Bcl-2 e proliferação celular (Ki-67 e PCNA com os indicadores histológicos de gravidade do tumor. MÉTODOS: Estudaram-se cinco amostras das formas nodular, morfeiforme e superficial, respectivamente, e um grupo-controle com três pacientes livres de lesão. Empregou-se o teste de Mann-Whitney na comparação da expressão desses marcadores com a forma de apresentação do carcinoma basocelular. RESULTADOS: Verificou-se que a marcação do Bcl-2 foi expressiva nos CBCs ditos agressivos (variantes morfeiforme e nodular. Dos tumores estudados, 66,7% (n = 10 indicaram fortemente o p53. Nossos resultados mostram maior expressão do Ki-67 no carcinoma basocelular nodular e superficial, sem expressão nos controles. O PCNA mostrou forte marcação em todos os tipos de tumores e nos controles. CONCLUSÃO: Os achados nos permitem concluir que o Bcl-2 e o p53 apresentam tendência para diagnosticar gravidade do carcinoma basocelular e o Ki-67, por seu comportamento variável, não pode ser considerado como marcador de gravidade, assim como o PCNA, que não foi um bom marcador de proliferação celular.BACKGROUND: - Basal cell carcinoma is the most common form of human cancer. Studies employing molecular and genetic biology techniques, associated with histomorphology, lead to the identification of risk factors in the development of more recurring and aggressive lesions. OBJECTIVE - To correlate markers expression of apoptosis (p53 and bcl-2 and cell proliferation (Ki-67 and PCNA with histological indicators of tumor severity. METHODS - Five samples of the nodular, morpheaform and superficial types of carcinoma

  13. Diffusion inside living human cells

    DEFF Research Database (Denmark)

    Leijnse, N.; Jeon, J. -H.; Loft, Steffen

    2012-01-01

    Naturally occurring lipid granules diffuse in the cytoplasm and can be used as tracers to map out the viscoelastic landscape inside living cells. Using optical trapping and single particle tracking we found that lipid granules exhibit anomalous diffusion inside human umbilical vein endothelial...... cells. For these cells the exact diffusional pattern of a particular granule depends on the physiological state of the cell and on the localization of the granule within the cytoplasm. Granules located close to the actin rich periphery of the cell move less than those located towards to the center...... of the cell or within the nucleus. Also, granules in cells which are stressed by intense laser illumination or which have attached to a surface for a long period of time move in a more restricted fashion than those within healthy cells. For granules diffusing in healthy cells, in regions away from the cell...

  14. **-Postprandial pancreatic [{sup 11}C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Emanuel; Kazianka, Lukas; Breuer, Robert; Miholic, Johannes [Medical University of Vienna, Department of Surgery, Vienna (Austria); Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus [Medical University of Vienna, Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Stimpfl, Thomas; Reiter, Birgit [Medical University of Vienna, Clinical Institute of Laboratory Medicine, Forensic Toxicology, Vienna (Austria); Karanikas, Georgios [Medical University of Vienna, Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Divisional Head PET-PET/CT (Nuclear Medicine), Vienna (Austria)

    2017-03-15

    patients after PD (R{sup 2} = 0.78, p < 0.0001). Postprandial [{sup 11}C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function. (orig.)

  15. Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

    Science.gov (United States)

    Zhang, Mingfeng; Liang, Liming; Morar, Nilesh; Dixon, Anna L; Lathrop, G Mark; Ding, Jun; Moffatt, Miriam F; Cookson, William O C; Kraft, Peter; Qureshi, Abrar A; Han, Jiali

    2012-04-01

    Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

  16. Epidemiology of basal and squamous cell carcinoma in Belgium: the need for a uniform and compulsory registration.

    Science.gov (United States)

    Callens, J; Van Eycken, L; Henau, K; Garmyn, M

    2016-11-01

    Non-melanoma skin cancer (NMSC) is the most common type of cancer among Caucasians, however, few data exist on its incidence. Because of a sheer volume of these tumours, NMSC is often not systematically registered. To describe and analyse the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Belgium. Incidence data of BCC and SCC, including multiple primary skin tumours in the same patient, were extracted from the Belgian Cancer Registry from 2004 to 2012 (predominantly coming from pathology notifications). Belgian legislation makes cancer registration compulsory for oncological care programmes and for all pathological anatomy laboratories. Between 2004 and 2012, 113 254 BCC and 33 153 SCC cases were reported in Belgium. A total of 130 339 patients had 146 407 tumours. Approximately, 10% of the patients (12 759 patients) had multiple tumours. The world age-standardised incidence rate (WSR) for BCC increased from 36.9 in 2004 to 98.4 per 100 000 person years in 2012 for males and from 34.2 in 2004 to 102.0 in 2012 for females. For SCC, the WSR increased from 14.9 in 2004 to 24.7 in 2012 for males and from 6.8 in 2004 to 13.5 in 2012 for females. From 2004 to 2012, the incidence of BCC and SCC markedly rose in Belgium, as also seen worldwide. Known causes are increased sun exposure caused by changed sunlight-related behaviour (increased outdoor activities and holidays, use of tanning beds and changes in clothing style), ageing and improved registration. Because of their high and increasing incidence, these cancers will have major implications on healthcare planning and preventive measures. Therefore, we recommend compulsory registration, whenever is possible, of BCC and SCC, although it is an ambitious objective, especially in countries with a high burden of these tumours and in countries where registration is currently unavailable. © 2016 European Academy of Dermatology and Venereology.

  17. Basal cell carcinoma

    Science.gov (United States)

    ... treat cancers that are not large or deep Mohs surgery: Removing a layer of skin and looking ... Philadelphia, PA: Elsevier Saunders; 2014:chap 22. U.S. Food and Drug Administration. FDA sheds light on sunscreens. ...

  18. Basal Cell Carcinoma

    Science.gov (United States)

    ... Boards study tools Online Learning Center Meetings and events Make a difference Career planning Media Relations Toolkit AAD apps Academy meeting Chronic urticaria—for members Chronic urticaria—for public Dermatology World Dialogues in Dermatology JAAD Mohs AUC ...

  19. Cell type complexity in the basal metazoan Hydra is maintained by both stem cell based mechanisms and transdifferentiation.

    Science.gov (United States)

    Siebert, Stefan; Anton-Erxleben, Friederike; Bosch, Thomas C G

    2008-01-01

    Understanding the mechanisms controlling the stability of the differentiated cell state is a fundamental problem in biology. To characterize the critical regulatory events that control stem cell behavior and cell plasticity in vivo in an organism at the base of animal evolution, we have generated transgenic Hydra lines [Wittlieb, J., Khalturin, K., Lohmann, J., Anton-Erxleben, F., Bosch, T.C.G., 2006. Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis. Proc. Natl. Acad. Sci. U. S. A. 103, 6208-6211] which express eGFP in one of the differentiated cell types. Here we present a novel line which expresses eGFP specifically in zymogen gland cells. These cells are derivatives of the interstitial stem cell lineage and have previously been found to express two Dickkopf related genes [Augustin, R., Franke, A., Khalturin, K., Kiko, R., Siebert, S. Hemmrich, G., Bosch, T.C.G., 2006. Dickkopf related genes are components of the positional value gradient in Hydra. Dev. Biol. 296 (1), 62-70]. In the present study we have generated transgenic Hydra in which eGFP expression is under control of the promoter of one of them, HyDkk1/2/4 C. Transgenic Hydra recapitulate faithfully the previously described graded activation of HyDkk1/2/4 C expression along the body column, indicating that the promoter contains all elements essential for spatial and temporal control mechanisms. By in vivo monitoring of eGFP+ gland cells, we provide direct evidence for continuous transdifferentiation of zymogen cells into granular mucous cells in the head region. We also show that in this tissue a subpopulation of mucous gland cells directly derives from interstitial stem cells. These findings indicate that both stem cell-based mechanisms and transdifferentiation are involved in normal development and maintenance of cell type complexity in Hydra. The results demonstrate a remarkable plasticity in the differentiation capacity of cells in an organism which diverged before

  20. Basal/HER2 breast carcinomas: integrating molecular taxonomy with cancer stem cell dynamics to predict primary resistance to trastuzumab (Herceptin).

    Science.gov (United States)

    Martin-Castillo, Begoña; Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cufí, Silvia; Moreno, José Manuel; Corominas-Faja, Bruna; Urruticoechea, Ander; Martín, Ángel G; López-Bonet, Eugeni; Menendez, Javier A

    2013-01-15

    High rates of inherent primary resistance to the humanized monoclonal antibody trastuzumab (Herceptin) are frequent among HER2 gene-amplified breast carcinomas in both metastatic and adjuvant settings. The clinical efficacy of trastuzumab is highly correlated with its ability to specifically and efficiently target HER2-driven populations of breast cancer stem cells (CSCs). Intriguingly, many of the possible mechanisms by which cancer cells escape trastuzumab involve many of the same biomarkers that have been implicated in the biology of CS-like tumor-initiating cells. In the traditional, one-way hierarchy of CSCs in which all cancer cells descend from special self-renewing CSCs, HER2-positive CSCs can occur solely by self-renewal. Therefore, by targeting CSC self-renewal and resistance, trastuzumab is expected to induce tumor shrinkage and further reduce breast cancer recurrence rates when used alongside traditional therapies. In a new, alternate model, more differentiated non-stem cancer cells can revert to trastuzumab-refractory, CS-like cells via the activation of intrinsic or microenvironmental paths-to-stemness, such as the epithelial-to-mesenchymal transition (EMT). Alternatively, stochastic transitions of trastuzumab-responsive CSCs might also give rise to non-CSC cellular states that lack major attributes of CSCs and, therefore, can remain "hidden" from trastuzumab activity. Here, we hypothesize that a better understanding of the CSC/non-CSC social structure within HER2-overexpressing breast carcinomas is critical for trastuzumab-based treatment decisions in the clinic. First, we decipher the biological significance of CSC features and the EMT on the molecular effects and efficacy of trastuzumab in HER2-positive breast cancer cells. Second, we reinterpret the genetic heterogeneity that differentiates trastuzumab-responders from non-responders in terms of CSC cellular states. Finally, we propose that novel predictive approaches aimed at better forecasting

  1. Positive and negative regulation of the human heme oxygenase-1 gene expression in cultured cells.

    Science.gov (United States)

    Takahashi, S; Takahashi, Y; Ito, K; Nagano, T; Shibahara, S; Miura, T

    1999-10-28

    To elucidate the regulation of the human heme oxygenase-1 (hHO-1) gene expression, we assessed approximately 4 kb of the 5'-flanking region of the hHO-1 gene for basal promoter activity and sequenced approximately 2 kb of the 5'-flanking region. A series of deletion mutants of the 5'-flanking region linked to the luciferase gene was constructed. Basal level expression of these constructs was tested in HepG2 human hepatoma cells and HeLa cervical cancer cells. By measuring luciferase activity, which was transiently expressed in the transfected cells, we found a positive regulatory region at position -1976 to -1655 bp. This region functions in HepG2 cells but not in HeLa cells. A negative regulatory region was also found at position -981 to -412 bp that functions in both HepG2 cells and HeLa cells.

  2. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and......Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self...... of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from...

  3. External beam radiotherapy for basal cell carcinoma. Local control and cosmetic outcome; Strahlentherapie des Basalzellkarzinoms. Lokale Kontrolle und kosmetisches Ergebnis

    Energy Technology Data Exchange (ETDEWEB)

    Seegenschmiedt, M.H.; Oberste-Beulmann, S.; Guntrum, F.; Olschewski, T. [Krankenhaus Essen (Germany). Klinik fuer Radioonkologie, Strahlentherapie und Nuklearmedizin; Lang, E.; Lang, B. [Praxis fuer Dermatologie, Essen (Germany)

    2001-05-01

    Background: The basal cell carcinoma which is often occurring in the elderly can be well treated by surgery. For large and recurrent lesions and in cosmetically difficult locations external beam radiotherapy provides an equally effective treatment alternative. Patients and Methods: From 1986 to 1999, 60 females and 39 males received primary radiotherapy for a total of 127 histologically verified basal cell carcinoma lesions. Tumors were mostly localized in the face at the temple, nose and forehead. Radiotherapy was applied with orthovoltage equipment and energies of up to 100 kV. Single doses ranged from 2 to 5 Gy related to the 80%-isodose depth. Weekly doses ranged from 8 to 25 Gy and total doses from 25 to 60 Gy. The mean follow-up period was 36{+-}21 months. The acute sequelae were scored according to CTC criteria. Radiogenic late effects as single events were related to the radiation portal. Results: 3 months after treatment all besides one patient (99%) experienced complete tumor remission (CR). In all cases, acute radiation reaction occurred within the radiation portal: CTC Grade 1 in 100%, CTC Grade 2 in 54% and CTC Grade 3 in 30% of the cases. All side effects regressed under simple local measures without further complications. Late sequelae were observed in three cases. Overall cosmetic outcome was good to excellent in almost all patients (98%). In two cases (2%) a local recurrence was observed 6 and 20 months after radiotherapy. Conclusion: External beam (orthovoltage) radiotherapy is very effective and yields high tumor control rates and good cosmetic results in long-term follow-up. Former dermatological treatment concepts should be replaced by an ICRU-based radiophysical dose prescription and should respect the newer radiobiological fractionation principles. (orig.) [German] Hintergrund: Das Basaliom oder Basalzellkarzinom ist ein im Alter haeufig vorkommender Hauttumor, der chirurgisch gut behandelbar ist. Bei grossen und rezidivierenden Tumoren und

  4. Surgical Treatment of Facial Basal Cell Carcinoma: Patient-Based Assessment of Clinical Outcome in a Prospective Cohort Study.

    Science.gov (United States)

    Ofaiche, Joséphine; Lopez, Raphael; Bérard, Emilie; André, Aymeric; Bulai-Livideanu, Cristina; Méresse, Thomas; Vairel, Benjamin B; Grolleau, Jean-Louis; Paul, Carle; Meyer, Nicolas

    2016-01-01

    There are limited data on the esthetic, functional, and morphological outcomes of surgical treatment of facial basal cell carcinoma (BCC). The aim of our study was to assess the determinants of the evaluation of both the patients and the investigator of the esthetic, functional, and morphological impact of the surgical treatment of facial BCC. A prospective observational study evaluated 111 patients treated surgically for facial BCCs (n = 135 BCCs), using the Patient and Observer Scar Assessment Scale (POSAS), a validated and reliable scale designed for the evaluation of all types of scars by professionals and patients. Scar assessment rated by the patients was very good. Skin aging was associated with a better surgical outcome as evaluated by POSAS (OR = 0.30, 95% CI: 0.09-0.98; p = 0.04). Conversely, histologically infiltrative or sclerosing BCC (OR = 2.33, 95% CI: 0.95-5.71; p = 0.06) was independently associated with poorer POSAS. In terms of the investigator's evaluation, aging signs (protective factor: OR = 0.17, 95% CI: 0.04-0.73; p = 0.01), location on the H-zone of the face (risk factor: OR = 2.95, 95% CI: 1.07-8.15; p = 0.03), and histologically infiltrative or sclerosing BCC (risk factor: OR = 2.89, 95% CI: 1.01-8.29; p = 0.04) were independently associated with POSAS. Esthetic, functional, and morphological outcomes of facial BCC surgery provide high patient satisfaction overall. Taking wider margins requires specific measures to improve the surgical outcome. © 2016 S. Karger AG, Basel.

  5. Indoor tanning and the MC1R genotype: risk prediction for basal cell carcinoma risk in young people.

    Science.gov (United States)

    Molinaro, Annette M; Ferrucci, Leah M; Cartmel, Brenda; Loftfield, Erikka; Leffell, David J; Bale, Allen E; Mayne, Susan T

    2015-06-01

    Basal cell carcinoma (BCC) incidence is increasing, particularly in young people, and can be associated with significant morbidity and treatment costs. To identify young individuals at risk of BCC, we assessed existing melanoma or overall skin cancer risk prediction models and built a novel risk prediction model, with a focus on indoor tanning and the melanocortin 1 receptor gene, MC1R. We evaluated logistic regression models among 759 non-Hispanic whites from a case-control study of patients seen between 2006 and 2010 in New Haven, Connecticut. In our data, the adjusted area under the receiver operating characteristic curve (AUC) for a model by Han et al. (Int J Cancer. 2006;119(8):1976-1984) with 7 MC1R variants was 0.72 (95% confidence interval (CI): 0.66, 0.78), while that by Smith et al. (J Clin Oncol. 2012;30(15 suppl):8574) with MC1R and indoor tanning had an AUC of 0.69 (95% CI: 0.63, 0.75). Our base model had greater predictive ability than existing models and was significantly improved when we added ever-indoor tanning, burns from indoor tanning, and MC1R (AUC = 0.77, 95% CI: 0.74, 0.81). Our early-onset BCC risk prediction model incorporating MC1R and indoor tanning extends the work of other skin cancer risk prediction models, emphasizes the value of both genotype and indoor tanning in skin cancer risk prediction in young people, and should be validated with an independent cohort. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Basal Cell Nevus Syndrome. A Case Presentation Síndrome de Gorlin. Presentación de caso.

    Directory of Open Access Journals (Sweden)

    Orlando Sotolongo Terry

    2007-02-01

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    Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

    El síndrome de Gorlin es una entidad infrecuente, de muy baja incidencia según reportes de la literatura médica. Se caracteriza por un grupo considerable de alteraciones que se presentan de manera variable en el organismo y lesiones localizadas en la región maxilofacial. Se presentó el caso de un paciente de 61 años de edad, masculino, de raza blanca, procedente de la zona urbana de Cienfuegos, con la referencia familiar de numerosas deformidades físicas desde su nacimiento: retraso mental, presencia de lunares a partir de la primera década de la vida y aumento de volumen del cuerpo mandibular. El diagnóstico, apoyado en exámenes clínicos y radiológicos, así como en estudios histopatológicos, fue la presencia de queratoquistes.

  7. [Autoimmunity factor in chronic gastritis: incidence of antiparietal cell antibodies and their relation to antral histology and basal blood gastrins].

    Science.gov (United States)

    Schraier, M; Katz, S; Pest, S; Chiocca, J C; Costa, J A

    1983-01-01

    In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.

  8. Immunohistochemical markers of advanced basal cell carcinoma: CD56 is associated with a lack of response to vismodegib.

    Science.gov (United States)

    Castillo, Jean-Marie; Knol, Anne-Chantal; Nguyen, Jean-Michel; Khammari, Amir; Saint-Jean, Mélanie; Dreno, Brigitte

    2016-10-01

    Vismodegib is an effective treatment for advanced basal cell carcinoma (BCC), but primary resistance to vismodegib remains to be elucidated. Alternative approaches are warranted to help selecting patients most likely to be responsive to treatment. The identification of immunohistochemical markers may support this perspective, as well as better understanding of resistance mechanisms. To determine the level of expression of CD56, PDGF-R, CD117, MMP9, TIMP3, and CXCR4 in advanced BCC, and explore whether expression levels are associated with non-response to vismodegib. A cross-sectional study was conducted. Immunohistochemical markers were selected based on their roles in tumour proliferation and/or migration in skin tumours. Tissue samples included pretreatment advanced BCC samples from patients treated with vismodegib, with an available response after six months of treatment. Regression optimised models were used to build hypotheses regarding a possible association between expression levels and non-response to vismodegib, which was then tested by logistic regression. Twenty-three patients were included. The percentage of samples expressing markers ranged from 43.5% (CD117) to 91.3% (CXCR4). CD56 expression was significantly associated with an increased risk of non-response to vismodegib (OR = 5.5; CI 95%: 3.4-29.8; p = 0.0488); a similar association was suggested for CXCR4 (p = 0.066), but not identified for other markers. These results provide a better understanding of the expression of immunohistochemical markers in advanced BCC. Further detailed analysis of CD56 expression may provide insights into guiding further investigation of the correlation between this marker and non-response to vismodegib.

  9. Diagnosis of Basal Cell Carcinoma by Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial

    Science.gov (United States)

    Alkemade, Hans A.C; Maessen-Visch, Birgitte; Hendriks, Jan C.M; van Erp, Piet E.J; Adang, Eddy M.M; Gerritsen, Marie-Jeanne P

    2016-01-01

    Background Skin cancer, including basal cell carcinoma (BCC), has become a major health care problem. The limitations of a punch biopsy (at present the gold standard) as diagnostic method together with the increasing incidence of skin cancer point out the need for more accurate, cost-effective, and patient friendly diagnostic tools. In vivo reflectance confocal microscopy (RCM) is a noninvasive imaging technique that has great potential for skin cancer diagnosis. Objective To investigate whether in vivo RCM can correctly identify the subtype of BCC and to determine the cost-effectiveness of RCM compared with punch biopsy (usual care). Study design: Randomized controlled multicenter trial. Methods On the basis of 80% power and an alpha of 0.05, 329 patients with lesions clinically suspicious for BCC will be included in this study. Patients will be randomized for RCM or for a punch biopsy (usual care). When a BCC is diagnosed, surgical excision will follow and a follow-up visit will be planned 3 months later. Several questionnaires will be filled in (EQ-5D, EQ-5D VAS, iMTA PCQ, and TSQM-9). We will perform statistical analysis, cost-effectiveness, and patient outcome analysis after data collection. Results This research started in January 2016 and is ethically approved. We expect to finish this study at the end of 2018. Conclusions In this study, we will investigate whether RCM is at least as good in identifying BCC subtypes as conventional pathological investigation of skin biopsies. Anticipating that RCM is found to be a cost-effective alternative, it saves on direct medical consumption like labor of the pathologist and other medical personnel as well as materials related to treatment failure with at least equal effectiveness. Trial Registration Clinicaltrials.gov NCT02623101; https://clinicaltrials.gov/ct2/show/NCT02623101 (Archived by WebCite at http://www.webcitation.org/6id54WQa2) PMID:27363577

  10. Family History of Skin Cancer is Associated with Early-Onset Basal Cell Carcinoma Independent of MC1R Genotype

    Science.gov (United States)

    Berlin, Nicholas L.; Cartmel, Brenda; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.; Ferrucci, Leah M.

    2015-01-01

    Background As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual’s risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin-1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Materials and Methods Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale Dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. Results A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80–3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74–3.35). Conclusions Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90–7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. PMID:26381319

  11. Molecular genetic mechanisms of basal cell carcinoma%基底细胞癌的分子遗传机制研究进展

    Institute of Scientific and Technical Information of China (English)

    陈洁; 陈明华

    2012-01-01

    基底细胞癌是一种最为常见的皮肤癌.近年来研究表明,SHH信号通路的变异在基底细胞癌的发生中起到一个关键的作用,SHH通路的重要成