RESUMEN
Xeroderma Pigmentosum is an autosomal recessive disease characterized by increased sensitivity to ultraviolet radiation. Adjuvant radiotherapy (RT) is an important locoregional treatment modality for high-risk skin squamous cell cancers (SCCs). We present a case of an adult with high-risk skin SCC treated with standard adjuvant RT and followed-up for >4 years with acceptable side effects.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Xerodermia Pigmentosa , Adulto , Carcinoma de Células Escamosas/radioterapia , Células Epiteliales , Humanos , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/radioterapia , Rayos Ultravioleta , Xerodermia Pigmentosa/complicaciones , Xerodermia Pigmentosa/diagnóstico , Xerodermia Pigmentosa/radioterapiaRESUMEN
Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.
Asunto(s)
Ácido Aminolevulínico/farmacología , Antineoplásicos/farmacología , Queratosis Actínica/radioterapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Animales , Enfermedad de Bowen/radioterapia , Carcinoma Basocelular/radioterapia , Queilitis/radioterapia , Europa (Continente) , Glucosa/química , Glutamina/química , Humanos , Porfirinas/química , Exposición a la Radiación , Luz Solar , Factores de Tiempo , Xerodermia Pigmentosa/radioterapiaAsunto(s)
Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/radioterapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/radioterapia , Xerodermia Pigmentosa/diagnóstico , Xerodermia Pigmentosa/radioterapia , Carcinoma Basocelular/complicaciones , Niño , Humanos , Masculino , Neoplasias Cutáneas/complicaciones , Resultado del Tratamiento , Xerodermia Pigmentosa/complicacionesRESUMEN
Ex vivo cutaneous gene therapy is an alternative treatment for recessively inherited diseases with cutaneous traits. It relies on the transfer in cultured epidermal keratinocytes of the wild-type allele of the gene whose mutation is responsible for the disease. As for severely burnt patients, epithelial sheets developed from genetically corrected cells may then be grafted back to the patients. Long term correction and graft take depend on the genetic correction of stem cells. Success of such an approach has recently been reported in the case of one patient suffering from a severe case of junctional epidermolysis bullosae. Here we report a method for safely selecting keratinocytes populations after genetic manipulation. The method is non invasive and non immunogenic and allows high enrichment of genetically manipulated stem keratinocytes. This could perhaps contribute to ex vivo gene therapy approaches of cancer prone genodermatoses such as xeroderma pigmentosum.
Asunto(s)
Células Epidérmicas , Epidermis/fisiología , Terapia Genética/métodos , Células Madre/citología , Células Madre/fisiología , Xerodermia Pigmentosa/genética , Xerodermia Pigmentosa/terapia , Folículo Piloso/citología , Folículo Piloso/fisiología , Humanos , Mutación , Neoplasias Inducidas por Radiación , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversos , Xerodermia Pigmentosa/radioterapiaRESUMEN
The XPF and ERCC1 proteins form a tight complex and function as an endonuclease to incise on the 5'-side of pyrimidine dimers in DNA. Levels of both proteins are extremely low in group F xeroderma pigmentosum (XP-F) cells. We transfected XP-F cells with the plasmids expressing XPF or ERCC1 and examined levels of both proteins in the cells. Although XP-F cells are sensitive to UV and mitomycin C (MMC), cells overexpressing XPF expressed ERCC1 as well and resistance to UV and MMC was restored to the normal level. In contrast, cells overexpressing ERCC1 did not express XPF and were still sensitive to UV and MMC. These results indicate that both the XPF and ERCC1 proteins are required to repair UV- and MMC-induced DNA damage. Even though a high level of ERCC1, which has been presumed to be a catalytic subunit of the endonuclease, is stably present in XP-F cells, ERCC1 protein alone cannot carry out excision repair completely.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Endonucleasas , Mitomicina/farmacología , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Proteínas/fisiología , Xerodermia Pigmentosa/genética , Células Clonales , Reparación del ADN/genética , Proteínas de Unión al ADN/efectos de los fármacos , Proteínas de Unión al ADN/efectos de la radiación , Femenino , Humanos , Regiones Promotoras Genéticas , Proteínas/efectos de los fármacos , Proteínas/efectos de la radiación , Transfección , Rayos Ultravioleta , Xerodermia Pigmentosa/tratamiento farmacológico , Xerodermia Pigmentosa/radioterapiaRESUMEN
Women with breast cancer and a family history of breast cancer and some with sporadic breast cancer are deficient in the repair of radiation-induced DNA damage compared with normal donors with no family history of breast cancer. DNA repair was measured indirectly by quantifying chromatid breaks in phytohaemagglutinin (PHA)-stimulated blood lymphocytes after either X-irradiation or UV-C exposure, with or without post treatment with the DNA repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara-C). We have correlated chromatid breaks with unrepaired DNA strand breaks using responses to X-irradiation of cells from xeroderma pigmentosum patients with well-characterised DNA repair defects or responses of repair-deficient mutant Chinese hamster ovary (CHO) cells with or without transfected human DNA repair genes. Deficient DNA repair appears to be a predisposing factor in familial breast cancer and in some sporadic breast cancers.
Asunto(s)
Neoplasias de la Mama/etiología , Reparación del ADN , Animales , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Células CHO/fisiología , Células CHO/efectos de la radiación , Cromátides/efectos de la radiación , Cricetinae , Citarabina/farmacología , Daño del ADN , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Reparación del ADN/efectos de la radiación , ADN de Neoplasias/efectos de la radiación , Femenino , Humanos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/efectos de la radiación , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Fitohemaglutininas/farmacología , Factores de Riesgo , Transfección , Rayos Ultravioleta , Rayos X , Xerodermia Pigmentosa/metabolismo , Xerodermia Pigmentosa/patología , Xerodermia Pigmentosa/radioterapiaRESUMEN
A recombinant nonreplicating human adenovirus type 5, Ad5HCMVsp1lacZ, expressing the lacZ gene under control of the human cytomegalovirus immediate early promoter, was used to assess the effect of heat-shock (HS) on DNA repair of a UV-damaged reporter gene. Host cell reactivation (HCR) of beta-galactosidase (beta-gal) activity for UV-irradiated Ad5HCMVsp1lacZ was used as an indicator of DNA repair in the transcribed strand of an active gene. Repair was examined in heat-shock (HS) pretreated and mock-treated normal fibroblasts, normal lung epithelial cells, xeroderma pigmentosum group A, C, D and G fibroblasts (XP-A, XP-C, XP-D and XP-G), Cockayne's syndrome group A fibroblasts (CS-A), SV40-transformed normal fibroblasts (GM637f) and 5 tumour cell lines (SKOV-3, HeLa, HT29, SCC-25 and U20S). HS enhanced reactivation (HSER) of the reporter gene was detected in normal cells, HT29 tumour cells and XP-C fibroblasts. HSER was reduced or absent in all other XP, CS and tumour cell lines tested. HSER in normal and XP-C cell lines, but not CS-A, XP-A, XP-D or XP-G cells, suggests that HS treatment can enhance the repair of UV-damaged DNA through an enhancement of transcription coupled repair (TCR) or a mechanism which involves the TCR pathway. Since this response was absent in the SV40-transformed fibroblast cell line and 4 of 5 tumour cell lines examined, HSER of beta-gal activity for UV-irradiated Ad5HCMVsp1lacZ also requires some cellular function(s) affected by transformation.
Asunto(s)
Reparación del ADN , Genes Reporteros/efectos de la radiación , Calor , Transcripción Genética , Línea Celular Transformada , Fibroblastos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Células Tumorales Cultivadas , Rayos Ultravioleta , Xerodermia Pigmentosa/genética , Xerodermia Pigmentosa/patología , Xerodermia Pigmentosa/radioterapia , beta-Galactosidasa/genética , beta-Galactosidasa/efectos de la radiaciónRESUMEN
Our experience reported here, as well as a review of the literature, suggests that radiation therapy can be used in the palliative treatment of XP-related malignancy. However, radiation therapy should be used with caution in XP patients with an anticipated prolonged life expectancy, because the late side effects of ionizing radiation in XP are not well known.
Asunto(s)
Neoplasias Cutáneas/radioterapia , Xerodermia Pigmentosa/radioterapia , Adulto , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Relación Dosis-Respuesta en la Radiación , Resultado Fatal , Humanos , Masculino , Neoplasias de la Parótida/patología , Neoplasias Cutáneas/diagnóstico , Rayos X , Xerodermia Pigmentosa/diagnósticoAsunto(s)
Sarcoma de Kaposi/terapia , Xerodermia Pigmentosa/terapia , Antineoplásicos/uso terapéutico , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Interferón Tipo I/uso terapéutico , Proteínas Recombinantes , Sarcoma de Kaposi/etiología , Xerodermia Pigmentosa/tratamiento farmacológico , Xerodermia Pigmentosa/radioterapiaRESUMEN
The treatment of radiation damages of the integumentary tissues is a complicated problem of reconstructive plastic surgery. The condition of the tissues in the irradiated zone do not allow wide application of the traditional methods. Microsurgical autotransplantation of the greater omentum provides the possibility for adequate closure of the radiation ulcers. Operations were conducted on 9 patients with such ulcers of various localization; the cosmetic and functional result was good in 7 of them.
Asunto(s)
Epiplón/trasplante , Traumatismos por Radiación/cirugía , Adulto , Neoplasias de la Mama/radioterapia , Carcinoma Basocelular/radioterapia , Femenino , Humanos , Masculino , Microcirugia , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Radioterapia/efectos adversos , Neoplasias Cutáneas/radioterapia , Xerodermia Pigmentosa/radioterapiaRESUMEN
Xeroderma pigmentosum (XP), is a rare, autosomal recessive disease with sun sensitivity and multiple neoplasms in association with reduced DNA repair. As a reflection of the clinical consequences of deficient DNA repair, XP serves as a model for determining the effects of proficient DNA repair. To estimate the risk of developing neoplasms in XP, we abstracted reports of 726 XP patients (from 41 countries) published from 1874 to 1982. Despite limitations of a literature survey, the XP patients under age 20 years had an estimated 2000-fold increase in frequency of basal cell and squamous cell carcinoma of the skin, of cutaneous melanoma, of cancer of the anterior eye, and of cancer of the anterior tongue, in comparison to the general population. These sites are all potentially exposed to u.v. radiation, a strong carcinogen which produces DNA damage that is poorly repaired by XP cells. XP patients under age 20 years also had an estimated 12-fold increase in occurrence of neoplasms in sites not exposed to u.v. radiation. Among the XP patients under age 40 years with internal cancer, there was a disproportionate representation of malignant neoplasms of the brain (especially sarcomas), and oral cavity (excluding tongue) compared to US whites under age 40 years. These internal neoplasms may be related to exposure to chemical environmental carcinogens that cause DNA damage which, like u.v.-induced damage, is poorly repaired by XP cells. These reports provide no evidence of an increase in XP of common lethal neoplasms such as lymphomas, or female genital tract or endocrine system cancers. These findings suggest that DNA repair plays a role in protection against u.v.-induced neoplasia and in protection against some internal neoplasms in the general population.
Asunto(s)
Reparación del ADN , Neoplasias/etiología , Neoplasias Cutáneas/etiología , Xerodermia Pigmentosa/complicaciones , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/etiología , Niño , Preescolar , Neoplasias del Ojo/etiología , Femenino , Humanos , Lactante , Masculino , Melanoma/etiología , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/etiología , Riesgo , Neoplasias de la Lengua/etiología , Terapia Ultravioleta/efectos adversos , Xerodermia Pigmentosa/radioterapiaAsunto(s)
Neoplasias Encefálicas/radioterapia , Aberraciones Cromosómicas , Linfocitos/ultraestructura , Meduloblastoma/radioterapia , Enfermedades de la Piel/radioterapia , Xerodermia Pigmentosa/radioterapia , Neoplasias Encefálicas/complicaciones , Niño , Preescolar , Humanos , Linfocitos/efectos de la radiación , Masculino , Meduloblastoma/complicaciones , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Enfermedades de la Piel/complicaciones , Xerodermia Pigmentosa/complicacionesRESUMEN
A new technique has been developed for studying the extent of repair of UV-radiation damage to DNA in human cells. It is easy to use, has excellent sensitivity, and provides rapid quantitative estimates of repair. UV-irradiated cells whose DNA has been previously labeled with a radioisotope are grown after irradiation in non-radioactive bromodeoxyuridine, which is incorporated at the breaks induced by repair enzymes. After a period of growth in the thymidine analog the cells are exposed to a large flux of 313 nm radiation and then lysed on top of an alkaline sucrose gradient. Bromodeoxyuridine-containing sections of the DNA are thus selectively photolysed. Sedimentation in the alkaline gradient reveals the average molecular weight of disrupted segments and gives a measure of the number of breaks induced by repair enzymes over the whole period allowed for repair. The large change in average molecular weight observed upon exposure of normal repairing cells to 313 nm radiation is not observed in the repair-deficient cells from patients with xeroderma pigmentosum. The quantitative aspects of this assay for repair and its sensitivity should make it applicable to the study of repair induced by agents other than UV radiation.