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BACKGROUND: Besides medical consultations, various sources of information and support are available for melanoma patients (MP) in Germany from commercial and non-commercial providers; however, little is known about how they are perceived and accepted by MPs. MATERIAL AND METHODS: Between July and October 2016 a total of 529 melanoma patients were surveyed at 27 accredited German skin cancer centers by means of a standardized questionnaire. Their awareness and satisfaction with 12 given sources of information and counseling services (print, online and by telephone) were surveyed. The sources were recommended by renowned providers from the field of (dermatological) oncology for use by MPs. RESULTS: The MPs reported that the booklets called The blue advisor - skin cancer (Die Blauen Ratgeber - Hautkrebs, 43%) and Patient guidelines melanoma (Patientenleitlinie Melanom 24%) and the online domain www.hautkrebs-screening.de (23%) were the best known sources. These also met the information needs of the majority of users (65-80%). Booklets from commercial providers (between 8-16% known) were satisfactory for 42-56% of users. At 14% and 11%, respectively, the cancer counseling services (Krebsinformationsdienst) and INFONETZ Krebs as mainly telephone advisory offers were less well known. Few MPs were familiar with the skin cancer or melanoma booklets of the Austrian Cancer Aid and the Swiss Cancer League (2% each). CONCLUSION: The increased awareness and acceptance of booklets as well as information from principally non-commercial providers suggest that they are more often mediated to MPs and more frequently used and accepted by those affected.
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Servicios de Información , Melanoma , Neoplasias Cutáneas , Austria , Alemania , Conocimientos, Actitudes y Práctica en Salud , Humanos , Educación del Paciente como AsuntoRESUMEN
OBJECTIVE: To compare the long-term clinical efficacy of endovenous laser ablation (EVLA) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) incompetence. DESIGN: Investigator initiated two centre randomized controlled trial with 5 year follow up. MATERIALS AND METHODS: Interventions were performed on ambulatory and hospitalized patients at two vein centres, a university dermatology department (EVLA) and a specialized vein clinic (HLS). Four hundred patients suffering from GSV incompetence were assigned to EVLA or HLS of the GSV. One hundred and eighty five and 161 patients (=limbs), respectively, were treated per protocol. Main outcome measures were clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), Duplex detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), quality of life (Chronic Venous Insufficiency Questionnaire 2), side effects, and patient satisfaction 5 years after treatment. RESULTS: Two hundred and eighty one legs (81% of the study population) were evaluated with a median follow up of 60.4 (EVLA) and 60.7 months (HLS). Overall, REVAS was similarly observed in both groups: 45% (EVLA) and 54% (HLS), p = .152. Patients of the EVLA group showed significantly more clinical recurrences in the operated region (REVAS: same site): 18% vs. 5%, p = .002. In contrast, more different site recurrences were observed in the HLS group: 50% vs. 31%, p = .002. Duplex detected saphenofemoral refluxes occurred more frequently after EVLA: 28% vs. 5%, p < .001. Both treatments improved disease severity and quality of life without any difference. CONCLUSIONS: EVLA and HLS are comparably effective concerning overall REVAS, improvement of disease severity, and quality of life. In terms of same site clinical recurrence and saphenofemoral refluxes, HLS is superior to EVLA 5 years after treatment. CLINICAL TRIAL REGISTRATION: ISRCTN18322872.
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Procedimientos Endovasculares/métodos , Terapia por Láser , Vena Safena/cirugía , Várices/cirugía , Adolescente , Adulto , Femenino , Vena Femoral , Humanos , Ligadura , Masculino , Persona de Mediana Edad , Calidad de Vida , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Bites by poisonous snakes are rare dermatologic emergencies. A 43-year-old woman was bitten on her right forefinger by an adder during a hiking vacation in Austria. Her right arm and chest wall became swollen and then hemorrhagic, but she responded well to analgesics and immobilization. Administration of a specific antiserum was not necessary because of the lack of a systemic reaction.
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Servicios Médicos de Urgencia/métodos , Enfermedades de la Piel/etiología , Enfermedades de la Piel/terapia , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/terapia , Animales , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , ViperidaeRESUMEN
BACKGROUND: Members of the a disintegrin and metalloproteinase (ADAM) family are expressed in malignant tumors and participate in the pathogenesis of cancer. However, the presence of ADAM 10, 12, 17 and their role in basal cell carcinoma (BCC) have not been described. The purpose of this study was to investigate expression of ADAM 10, 12 and 17 in BCC. METHODS: Expression of ADAM 10, 12 and 17 was analyzed by immunohistochemistry in skin tissues obtained from 25 patients with different types of BCC. RESULTS: Immunoreactivity of ADAM 10, 12 and 17 was increased at the peripheral tumor margin compared with central areas of BCC tumor cell nests. Immunoreactivity of ADAM 10 and 12 was increased in the deep margin of invading tumor cell nests in mixed BCC. Focally increased expression of ADAM 12 was detected in squamous differentiated tumor cells of nodular BCC. In addition, immunoreactivity of ADAM 17 was increased in superficial BCC. CONCLUSIONS: ADAM 10, 12 and 17 showed different expression pattern in BCC histologic subtypes, indicating their different role in the BCC pathogenesis. Overexpression of ADAM 10, 12 and 17 immunoreactivity in deep invasion area of BCC indicates that these three proteases may play an important role in the locally invasive and highly destructive growth behavior of BCC. Additionally, we suggest that ADAM 17 may play an important role in early development of BCC.
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Proteínas ADAM/biosíntesis , Secretasas de la Proteína Precursora del Amiloide/biosíntesis , Carcinoma Basocelular/enzimología , Proteínas de la Membrana/biosíntesis , Neoplasias Cutáneas/enzimología , Proteína ADAM10 , Proteína ADAM12 , Proteína ADAM17 , Carcinoma Basocelular/patología , Humanos , Inmunohistoquímica , Neoplasias Cutáneas/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. PATIENTS AND METHODS: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. RESULTS: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. CONCLUSIONS: The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/secundario , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/análogos & derivados , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Polietilenglicoles , Estudios Prospectivos , Proteínas Recombinantes , Temozolomida , Resultado del TratamientoRESUMEN
A 71-year-old patient presented with diffuse and poorly circumscribed erythematous plaques of the abdominal skin, present for 5 months. Histology revealed a diffuse infiltration of the entire dermis with cytokeratin-positive signet-ring-cells. Subsequently, an extensive search for a primary adenocarcinoma uncovered a locally advanced signet-ring-cell gastric carcinoma. There were no metastases to other organs. This case shows the unusual clinical-diagnostic sequence of a patient with a signet-ring-cell-carcinoma of the stomach presenting with an erysipelas-like cutaneous metastasis of the abdominal skin.
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Neoplasias Abdominales/diagnóstico , Neoplasias Abdominales/secundario , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Erisipela/diagnóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/secundario , Neoplasias Gástricas/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
BACKGROUND: Late-type sensitizations against wood are rare and are mostly seen in patients with occupational contact with saw dust. Generally, commercial wooden products only lead to sensitization or dermatitis in cases when contact to the unprotected skin is direct, intensive and of longer duration, i.e. by wearing wooden jewelry or by playing wooden instruments. Causative for the sensitization process are ingredients of the wood core such as alkaloids, glycosides, anthrachinones, saponines, phenols, catechols, flavonoids, cumarins, and benzo-, naphtho-, furano-, and phenanthrenquinones and their precursors. CASE REPORT: We report the case of a 70-year-old patient who developed cheilitis after playing different wooden recorders made of African blackwood, rosewood, cedar, olive, and pear. METHODS: Patch testing with baseline series of contact allergens and saw dust of the recorders were performed as well as skin prick tests with common inhalant allergens and saw dust of the recorders. RESULTS: Patch testing showed sensitizations against African blackwood, rosewood, fragrance mix 2 and hydroxyisohexyl-3-cyclohexene carboxaldehyde. Skin prick testing was without pathological results. CONCLUSION: African blackwood and rosewood contain (S)-4'-hydroxy-4-methoxydalbergione and (S)-4-methoxydalbergione. As a result of the chemical affinity between the dalbergiones, cross-reactions between different woods are observed. The case presented shall show the diagnostic procedure in cases in which sensitizations against wood components are suspected.
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Clusterin (CLU) has been implicated in various cell functions involved in carcinogenesis and tumour progression. There are two known CLU protein isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is proapoptotic, and a secretory form (sCLU) is prosurvival. CLU expression has been associated with tumorigenesis of various malignancies, including tumours of prostate, colon, and breast. Furthermore, CLU expression is modulated by many factors that are believed to regulate tumour growth and/or apoptosis, including 1,25-dihydroxyvitamin D3, transforming growth factor beta-1, ultraviolet radiation, and IR. sCLU upregulation appears to be a general molecular stress response. Presently, preliminary results indicate that therapeutic modalities targeting CLU may be effective in cancer treatment. However, such strategies should make sure that nCLU is not eliminated or reduced. This review summarizes our present understanding of the importance of CLU in various physiological functions including tumour growth, and discusses its relevance to future cancer therapy.
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Clusterina/fisiología , Neoplasias/etiología , Apoptosis/fisiología , Biomarcadores de Tumor/genética , Ciclo Celular/fisiología , Clusterina/genética , Reparación del ADN , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias/patología , Neoplasias/fisiopatología , Neoplasias/terapia , Pronóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologíaRESUMEN
Prostate cancer is the most commonly diagnosed cancer in the majority of western countries. Due to their antiproliferative and proapoptotic activity, vitamin D analogues have been introduced recently as an experimental therapy for prostate cancer. Clusterin (CLU) is a glycoprotein that has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, and a secretory form (sCLU) is pro-survival. In this study, we analyzed whether proapoptotic and antiproliferative effects of 1,25(OH)(2)D(3) on LNCaP prostate cancer cells are modulated by expression of sCLU. Using colony forming assay, we studied the effect of treatment with different doses of 1,25(OH)(2)D(3) (10(-6), 10(-7), 10(-10)M) on proliferation of LNCaP cells that were stable transfected and over-express sCLU (LNT-1) as compared to empty vector-transfected cells (LN/C). We also measured apoptosis using TUNEL assay. sCLU over-expression protected against both antiproliferative (30%) and proapoptotic (15%) effects of 1,25(OH)(2)D(3), although this effect was statistically not significant. In conclusion, our findings demonstrate that expression of sCLU modulates growth regulatory effects of 1,25(OH)(2)D(3) in prostate cancer indicating that CLU interferes with vitamin D signalling pathways.
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Apoptosis/efectos de los fármacos , Calcitriol/farmacología , Clusterina/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Clusterina/genética , Humanos , Masculino , Neoplasias de la Próstata/genética , Sensibilidad y EspecificidadRESUMEN
The glycoprotein clusterin (CLU), has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. Both forms are implicated in various cell functions, including DNA repair, cell cycle regulation, and apoptotic cell death. CLU expression has been associated with tumorigenesis and the progression of various malignancies. In response to DNA damage, cell survival can be enhanced by activation of DNA repair mechanisms, while simultaneously stimulating energy-expensive cell cycle checkpoints that delay the cell cycle progression to allow more time for DNA repair. This review summarizes our current understanding of the role of clusterin in DNA repair, apoptosis, and cell cycle control and the relevance.
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Ciclo Celular , Clusterina/fisiología , Roturas del ADN de Doble Cadena , Reparación del ADN , Modelos Genéticos , Neoplasias/etiología , Neoplasias/genética , Apoptosis , Clusterina/genética , Humanos , Neoplasias/metabolismo , Isoformas de Proteínas/fisiologíaRESUMEN
BACKGROUND: The glycoprotein clusterin (CLU) has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. CLU expression has been associated with tumorigenesis and the progression of various malignancies. MATERIALS AND METHODS: The expression of CLU was studied immunohistochemically in paraffin sections of primary cutaneous malignant melanomas, metastases of malignant melanomas and acquired melanocytic naevi. Using PCR and Western blotting, the expression of CLU was also investigated in various vitamin D-responsive (MeWo, SK-MEL-28) and vitamin D-resistant melanoma cell lines (SK-MEL-5, SK-MEL-25), as well as in normal human melanocytes (NHM), along with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment. RESULTS: In contrast to acquired melanocytic naevi, CLU immunoreactivity was found in primary cutaneous malignant melanomas and metastases of malignant melanomas in situ. Both CLU protein and RNA were detected in melanoma cell lines and NHM. Treatment with 1,25(OH)2D3 modulated CLU's expression in vitamin D-responsive but not in -resistant melanoma cell lines. CONCLUSION: CLU may be of importance for the progression of malignant melanoma. The growth regulatory effects of 1,25(OH)2D3 in melanoma cell lines may, at least in part, be mediated via modulation of CLU expression.
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Calcitriol/farmacología , Clusterina/biosíntesis , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Masculino , Melanoma/patología , Melanoma/secundario , Persona de Mediana Edad , Neoplasias Cutáneas/secundarioRESUMEN
A human cell line (SCL-1) from a poorly differentiating cutaneous squamous cell carcinoma (SCC) ws studied through 20 passages during 2 years. Cells maintained their original morphology with low degree of keratinization, as indicated by light and electron microscopy. The keratin peptide pattern resembled the type in SCC tumors, and the corresponding filaments were detected by immunofluorescence at all passage levels. Cells did not grow in soft agar but formed tumor-like nodules in an "organotypic" culture assay (on lifted collagen gels) and grew invasively after transplantation to immunosuppressed inbred C3H mice. After injection into BALB/c nu/nu mice, tumors of SCC morphology were formed. The hypodiploid tumor stem-line was maintained for about 10 passages, when a shift to hyperploidy started, as determined by chromosome and DNA flow microfluorometric analyses. Two stable marker chromosomes (in 100 and 70% of the metaphases, respectively), involving chromosomes 7 and 9, strongly indicated a monoclonal origin of this cell line.
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Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/patología , Anciano , Animales , Biopsia , Carcinoma de Células Escamosas/genética , Línea Celular , Transformación Celular Neoplásica/patología , Femenino , Citometría de Flujo , Genotipo , Humanos , Cariotipificación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Neoplasias Cutáneas/genéticaRESUMEN
The process of monoclonal antibody (MAb) binding to tumor cells is greatly influenced by the biology of the respective antigen. This was concluded from an analysis of binding and release of MAbs and MAb fragments to melanoma cells at different concentration levels and different temperatures. With an antigen known to be stably expressed at the cell surface (i.e., Mr 97,000 protein) rapid binding of MAbs was observed at both 0 degrees C and 37 degrees C, and this was reversed by treatment with isoosmolar acid buffer. With another group of antigens, MAb binding increased continuously up to considerable levels at 37 degrees C, but not at 0 degrees C. Concomitantly, the portion of radioactive MAb not desorbable by acid buffer treatment increased, pointing to temperature-dependent internalization. With still another group of (glycolipid) antigens, the highest MAb binding was obtained with fixed cells at 0 degrees C. In this situation MAb release was particularly rapid, thus pointing to a shedding process.
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Anticuerpos Monoclonales/inmunología , Melanoma/inmunología , Complejo Antígeno-Anticuerpo/metabolismo , Antígenos/inmunología , Línea Celular , Humanos , Concentración de Iones de Hidrógeno , TemperaturaRESUMEN
Two cell lines (SCL-I and SCL-II) derived from squamous cell carcinomas of human skin were investigated during 4 years in culture. Both lines were tumorigenic in nude mice, and cells could be recultivated from xenografts. Growth in agar remained poor, but both cell lines developed abnormal stratified epithelial structures in organotypical cultures. The morphological and particularly ultrastructural characteristics remained typical in both cultures and xenografts. Keratinization slightly decreased, but nude mouse tumors differentiated as the original tumors, and this was reflected in keratin expression. Six major polypeptides (Mr 61,000, 57,000, 54,000, 51,000, 49,000, and 45,000) were similarly identified in both tumors and cell lines, also after animal passage, which was further substantiated by two-dimensional gel electrophoresis, but quantitative variations were found with different growth conditions. A distinct keratin cytoskeletal network was visualized in both lines by immunofluorescence, but only a few cells in SCL-II also expressed vimentin. Flow cytometry demonstrated 2c DNA stem lines for original tumors and derived lines. Early passages were hypodiploid by cytogenetic analysis of banded chromosomes. In SCL-I, a shift to tetraploidy occurred before passage 20 and remained stable throughout. In SCL-II, an incomplete shift to near tetraploidy and a stem line deviation were apparent, but later passages, nude mouse tumors, and cells recultured therefrom were hypodiploid (2c) again. Chromosome studies further revealed distinct stable marker chromosomes which showed additional structural aberrations with time in culture and after animal passage. Thus, phenotypically and genotypically, each squamous cell carcinoma and its derived cell line were distinct, and characteristics were preserved over long time periods in vitro and through in vivo passage.
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Carcinoma de Células Escamosas/fisiopatología , Neoplasias Cutáneas/fisiopatología , Animales , Carcinoma de Células Escamosas/genética , División Celular , Línea Celular , Bandeo Cromosómico , ADN de Neoplasias/análisis , Citometría de Flujo , Humanos , Cariotipificación , Queratinas/análisis , Cinética , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Cutáneas/genética , Trasplante HeterólogoRESUMEN
Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous-like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM-1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis.
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Antígenos/biosíntesis , Desarrollo Embrionario y Fetal/inmunología , Queratinocitos/inmunología , Enfermedades de la Piel/inmunología , Antígenos de Superficie/biosíntesis , Diferenciación Celular/inmunología , Transformación Celular Neoplásica , Expresión Génica , Cabello/inmunología , Humanos , Hiperplasia/inmunología , Inmunohistoquímica , Psoriasis/inmunología , Glándulas Sebáceas/inmunología , Piel/inmunología , Neoplasias Cutáneas/inmunología , Transfección , Verrugas/inmunologíaRESUMEN
The CD7(-) subset of CD4(+) T cells reflects a stable differentiation state of post-thymic helper T cells with CD45R0(+)CD45RA(-) 'memory' phenotype. Here we report that CD4(+)CD7(-) T cells are prone to increased spontaneous apoptosis in vitro compared to CD4(+)CD7(+) T cells. Spontaneous apoptosis is prevented by IL-15, but not by IL-2. Moreover, IL-15 increases Bcl-2 and decreases CD95/Fas expression of CD7(-), but not of CD7(+) T cells. Because IL-15 is physiologically not secreted but expressed in a membrane-bound form, we cocultured T cells with TNF-alpha stimulated fibroblasts that expose membrane IL-15. TNF-alpha stimulated fibroblasts rescue CD4(+)CD7(-) T cells from apoptosis whereas unstimulated fibroblasts do not. Rescue from apoptosis requires cell-cell contact and is abolished by addition of neutralizing antibodies to IL-15. We conclude that membrane IL-15 prevents accelerated apoptosis of CD4(+)CD7(-) T cells. This mechanism may contribute to accumulation of CD7(-) T cells in chronic inflammatory skin lesions.
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Antígenos CD7/análisis , Apoptosis , Linfocitos T CD4-Positivos/inmunología , Dermatitis/inmunología , Interleucina-15/farmacología , Subgrupos de Linfocitos T/inmunología , Apoptosis/efectos de los fármacos , Linfocitos T CD4-Positivos/citología , Células Cultivadas , Dermis/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Humanos , Memoria Inmunológica , Inmunofenotipificación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores de Interleucina-15 , Receptores de Interleucina-2/metabolismo , Subgrupos de Linfocitos T/clasificación , Subgrupos de Linfocitos T/citología , Factor de Necrosis Tumoral alfa/farmacología , Receptor fas/metabolismoRESUMEN
PURPOSE: To determine the predictive value of the angiogenic serum factors angiogenin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8) for the prognosis of patients with malignant melanoma. PATIENTS AND METHODS: Angiogenin, VEGF, bFGF, and IL-8 were measured in sera of 125 melanoma patients with different stages of disease and with or without current therapy including interferon alfa and different cytostatics in comparison with 30 healthy controls using enzyme-linked immunosorbent assay. RESULTS: Serum levels of angiogenin, VEGF, bFGF, and IL-8 were significantly increased in melanoma patients compared with healthy controls. Elevated serum concentrations of VEGF, bFGF, and IL-8 were associated with advanced disease stages and tumor burden. Cytostatic therapy of patients was accompanied by increased serum levels of angiogenin, bFGF, and IL-8. As shown by univariate analysis, elevated serum levels of VEGF (P = .0001 and .0036), bFGF (P < .00005 and < .00005), and IL-8 (P < .00005 and < .00005) were strongly correlated with a poor overall and progression-free survival, respectively. Multivariate analysis revealed stage of disease (P = .0238), tumor burden (P = .0347), VEGF (P = .0036), bFGF (P = .0252), and IL-8 (P = .0447) as independent predictive factors of overall survival. Tumor burden (P = .0081), VEGF (P = .0245), and IL-8 (P = .0089) were found as independent predictive factors of progression-free survival. CONCLUSION: Our data suggest that the angiogenic serum factors VEGF, bFGF, and IL-8 are useful predictive markers for overall and progression-free survival in melanoma patients.
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Sustancias de Crecimiento/sangre , Melanoma/sangre , Proteínas de Neoplasias/sangre , Análisis de Varianza , Inductores de la Angiogénesis/sangre , Biomarcadores/sangre , Factores de Crecimiento Endotelial/sangre , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Humanos , Interleucina-8/sangre , Linfocinas/sangre , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Ribonucleasa Pancreática/sangre , Análisis de Supervivencia , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
PURPOSE: Recently, the reverse-transcription polymerase chain reaction (RT-PCR) of tyrosinase messenger RNA (mRNA) was reported to be a useful tool for the detection of circulating tumor cells in the peripheral blood of melanoma patients. Our aim was to evaluate critically the diagnostic value of this marker by investigating a significant number of patients in different stages of the disease in a two-center study. PATIENTS AND METHODS: Different techniques of blood collection, RNA isolation, and RT-PCR were compared, and the detectability of tyrosinase mRNA was tested using nine different melanoma cell lines. The sensitivity of the method was confirmed by blood spiking experiments and the specificity by restriction enzyme analysis. Subsequently, a total of 153 blood samples from 137 individuals (30 healthy subjects, five basal cell carcinoma, and 102 melanoma patients) were investigated. RESULTS: The detection level of melanoma cells differed between the cell lines tested. However, we could reproducibly detect single melanoma cells by spiking whole blood samples from healthy volunteers. One of 43 patients with primary melanoma (2.3%), zero of 15 patients with regional metastasis (0%), and 12 of 44 patients with advanced disease (27.3%) were found to be RT-PCR positive. All blood samples obtained from controls and patients with basal cell carcinoma were tyrosinose mRNA negative. CONCLUSION: Our data support the recent doubts that the detection of circulating tumor cells in melanoma patients using the tyrosinase mRNA RT-PCR is not sensitive enough to be used either as a melanoma progression marker in early stages of the disease or to monitor therapy in advanced stages of the disease.
Asunto(s)
Biomarcadores de Tumor/sangre , ADN Complementario/biosíntesis , Melanoma/diagnóstico , Monofenol Monooxigenasa/genética , Células Neoplásicas Circulantes , ARN Mensajero/sangre , Humanos , Melanoma/sangre , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Transcripción Genética , Células Tumorales CultivadasRESUMEN
PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.
Asunto(s)
Ensayo de Inmunoadsorción Enzimática/normas , Melanoma/diagnóstico , Células Neoplásicas Circulantes , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , ADN de Neoplasias/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Melanoma/patología , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.