RESUMEN
INTRODUCTION: High carcinogenic-risk human papillomaviruses (hrHPVs) are recognized as etiological agents of cervical cancer. Constant expression of the viral oncoproteins, E6 and E7, is required for maintenance of the malignant phenotype of tumor cells. The exact mechanism of regulation of viral oncogenes expression in tumor cells is not fully elucidated. THE PURPOSE: identification of viral noncoding RNAs (ncRNAs) in HPV16-positve cervical cancer. MATERIALS AND METHODS: The reverse transcription polymerase chain reactions were used to detect viral ncRNAs in HPV16-positve primary cervical squamous cell carcinomas and SiHa and CasKi cell lines. The knockdown technique with oligonucleotides complementary to ncRNAs was used to elucidate their functions. RESULTS: We have identified ncRNAs transcribed in the upstream regulatory region of HPV16 in the cervical carcinoma cell lines and in 32 out 32 cervical squamous cell carcinomas with episomal or integrated forms of HPV16 DNA. Knockdown of sense or antisense strains of ncRNAs by oligonucleotides results in a decrease or increase of the E6 and E7 oncogenes mRNA levels in cells, respectively. These changes of oncogenes mRNA levels are accompanied by the modulation of the levels of the p53 protein, the main target of the E6 oncoprotein. CONCLUSION: The presence of regulatory ncRNAs in all examined tumors and cell lines revealed for the first time indicates their necessity for maintenance of constant expression of E6 and E7 oncogenes in them. The findings can be useful for understanding of the fundamental aspects of the viral expression regulation in HPV16-positive tumors.
Asunto(s)
Alphapapillomavirus , Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Alphapapillomavirus/genética , Alphapapillomavirus/metabolismo , Carcinoma de Células Escamosas/genética , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Oligonucleótidos/metabolismo , Papillomaviridae/genética , Papillomaviridae/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Viral/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patologíaRESUMEN
The Landau-Lifshitz equation provides an efficient way to account for the effects of radiation reaction without acquiring the nonphysical solutions typical for the Lorentz-Abraham-Dirac equation. We solve the Landau-Lifshitz equation in its covariant four-vector form in order to control both the energy and momentum of radiating particles. Our study reveals that implicit time-symmetric collocation methods of the Runge-Kutta-Nyström type are superior in accuracy and better at maintaining the mass-shell condition than their explicit counterparts. We carry out an extensive study of numerical accuracy by comparing the analytical and numerical solutions of the Landau-Lifshitz equation. Finally, we present the results of the simulation of particle scattering by a focused laser pulse. Due to radiation reaction, particles are less capable of penetrating into the focal region compared to the case where radiation reaction is neglected. Our results are important for designing forthcoming experiments with high intensity laser fields.
Asunto(s)
Algoritmos , Modelos Químicos , Análisis Numérico Asistido por Computador , Fotones , Radioisótopos/análisis , Radioisótopos/química , Simulación por Computador , Matemática/métodosRESUMEN
Recently, much attention has been attracted to the problem of limitations on the attainable intensity of high power lasers [A. M. Fedotov et al., Phys. Rev. Lett. 105, 080402 (2010)]. The laser energy can be absorbed by electron-positron pair plasma produced from a seed by a strong laser field via the development of the electromagnetic cascades. The numerical model for a self-consistent study of electron-positron pair plasma dynamics is developed. Strong absorption of the laser energy in self-generated overdense electron-positron pair plasma is demonstrated. It is shown that the absorption becomes important for a not extremely high laser intensity I â¼ 10(24) W/cm(2) achievable in the near future.