LncRNA HULC mediates radioresistance via autophagy in prostate cancer cells

Prostate cancer (PCa) is the second leading cause of cancer death in men. Irradiation is one of the available options for treatment of PCa, however, approximately 10-45% of PCa are resistant to irradiation. We aimed to explore the role of long non-coding RNA highly upregulated in liver cancer (HULC) in the sensitivity of PCa cells to irradiation. Survival rate, cell apoptosis, cycle, expressions of related proteins, and caspase-3 activity were assessed to explore the effects of HULC on sensitivity of PCa cells to irradiation. Expression of HULC in DU-145, PC3, LNCaP, and RWPE-1 cells was determined and the influence of HULC on DU-145 cells was explored. Then, PC3 cells aberrantly expressing HULC were implanted into NOD-SCID mice for tumor xenograft study. Changes of autophagy after aberrant expression of HULC in vivo and in vitro were tested. Furthermore, the interacted protein of HULC and involved signaling pathway were investigated. In PC3 and LNCaP cells under irradiation, survival rate and cell cycle were decreased and apoptosis was increased by HULC knockdown. HULC knockdown arrested PC3 cells at G0/G1 phase. DU-145 was sensitive to irradiation, and resistance to irradiation of DU-145 cells was enhanced by HULC overexpression. Moreover, HULC knockdown enhanced the sensitivity of PC3 xenografts to irradiation. HULC knockdown promoted autophagy through interaction with Beclin-1 and inhibition of mTOR, resulting in increased apoptosis. HULC knockdown improved sensitivity of PCa cells to irradiation both in vivo and in vitro. HULC suppressed Beclin-1 phosphorylation, thereby reduced autophagy, involving the mTOR pathway.

UVB suscetibilidade como fator de risco para o desenvolvimento da hanseníase virchowiana / UVB susceptibility as a risk factor to the development of lepromatous leprosy

FUNDAMENTOS: A radiação ultravioleta B (RUVB) é o mais importante fator ambiental capaz de modificar a função imunológica da pele humana. OBJETIVO: estudar a associação entre o fenótipo de suscetibilidade ou resistência à radiação RUVB e as formas polares da hanseníase. MATERIAL E MÉTODOS: foram avaliados 38 pacientes com hanseníase virchowiana (MHV) e 87 pacientes com hanseníase tuberculoide (MHT) de acordo com a classificação de Ridley e Jopling (1966). Todos os pacientes foram submetidos ao teste para determinação do fenótipo de suscetibilidade ou resistência à RUVB por meio da aplicação de um disco de dinitroclorobenzeno (DNCB) a 2 por cento em uma área de pele previamente irradiada com duas vezes a dose eritematosa mínima (DEM). Após 21 dias, outra aplicação de um disco similar de DNCB a 0,05 por cento na região escapular (área não exposta à RUVB) foi realizada para avaliar se houve sensibilização, com leitura após 48 horas. Os pacientes que apresentaram reação positiva ao DNCB foram considerados UVB-resistentes e o oposto foi considerado para aqueles que não apresentaram resposta (UVB-suscetíveis). RESULTADOS: A frequência de UVB-suscetíveis foi de 63,2 por cento (24 pacientes) no grupo MHV e 34,4 por cento (30 pacientes) no grupo MHT (OR = 3,26; IC = 1,36-7,87; x² = 7,73; p = 0,005). CONCLUSÃO: Os resultados sugerem que a UVB-suscetibilidade é um fator de risco para o desenvolvimento da MHV.

BACKGROUNDS: Ultraviolet radiation B (UVRB) is the most important environmental factor capable of altering the immune function of human skin. OBJECTIVE: To evaluate the association of the phenotypes of susceptibility or resistance to ultraviolet radiation B (UVRB) and the polar forms of leprosy. MATERIAL AND METHODS: We evaluated 38 patients with lepromatous leprosy (LL) and 87 patients with tuberculoid (TT) leprosy, according to the classification by Ridley and Jopling (1966). All the patients were submitted to a test to determine the phenotypes of susceptibility or resistance to UVRB through the application of a 2 percent dinitrochlorobenzene (DNCB) disc to a previously irradiated area with twice the minimal erythema dose (MED). After 21 days, a similar disc soaked in 0.05 percent DNCB was applied to the scapular area (unexposed to UVRB) to check for sensitiveness, with reading of the results after 48 hours. The patients that showed a positive reaction to DNCB were considered resistant (UVB-R) and those who did not show any reaction were considered susceptible (UVB-S). RESULTS: The frequency of UVB-S individuals was 63.2 percent (24 patients) in the LL group and 34.4 percent (30 patients) in the TT group (OR=3.26; IC=1.36 - 7.87; x²=7.73; p=0.005). CONCLUSION: Our results suggest that UVB-susceptibility is a risk factor to the development of lepromatous leprosy (LL).

Low dose hyper-radiosensitivity in human lung cancer cell line A549 and its possible mechanisms / 华中科技大学学报（医学）（英德文版）

The low dose hyper-radiosensitivity (HRS) in human lung cancer cell line A549 was investigated, the changes of ATM kinase, cell cycle and apoptosis of cells at different doses of radiation were observed, and the possible mechanisms were discussed. A549 cells in logarithmic growth phase were irradiated with (60)Co gamma-rays at doses of 0-2 Gy. Together with flow cytometry for precise cell sorting, cell survival fraction was measured by means of conventional colony-formation assay. The expression of ATM1981Ser-P protein was examined by Western blot 1 h after radiation. Apoptosis was detected by Hoechst 33258 fluorescent staining, and Annexin V-FITC/PI staining flow cytometry 24 h after radiation. Cell cycle distribution was observed by flow cytometry 6, 12 and 24 h after radiation. The results showed that the expression of ATM1981Ser-P protein was observed at 0.2 Gy, followed by an increase at >0.2 Gy, and reached the peak at 0.5 Gy, with little further increase as the dose exceeded 0.5 Gy. Twenty-four h after radiation, partial cells presented the characteristic morphological changes of apoptosis, and the cell apoptosis curve was coincident with the survival curve. As compared with control group, the cell cycle almost had no changes after exposure to 0.1 and 0.2 Gy radiation (P>0.05). After exposure to 0.3, 0.4 and 0.5 Gy radiation, G(2)/M phase arrest occurred 6 and 12 h after radiation (P<0.05), and the ratio of G(2)/M phase cells was decreased 24 h after radiation (P<0.05). It was concluded that A549 cells displayed the phenomenon of HRS/IRR. The mode of cell death was mainly apoptosis. The activity of ATM and cell cycle change may take an important role in HRS/IRR.

Spinal cord response to altered fractionation and re-irradiation: radiobiological considerations and role of bioeffect models.

The aim of radiation oncologist is to implement an uncomplicated loco regional control of cancer by radiation therapy. The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. The transformation of absorbed dose into a bioeffect dose is controlled by treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models have been proposed to predict the biological effect of radiotherapy treatments. Dale has proposed extrapolated response dose (ERD) equations for external beam therapy, intracavitary brachytherapy and interstitial brachytherapy. Within the context of the LQ model, the parameter which quantifies the overall biological effect on a given tissue is the biologically effective dose (BED) which is obtained by applying repopulation correction to ERD (Orton). Thames proposed the total effect (TE) concept based on the incomplete repair LQ model which accounts for the biological effect of a fractionated course of radiotherapy. Spinal cord myelitis limits the dose to tumours in the head and neck, thoracic and upper abdominal regions resulting in reduction of tumour control probability. Radiation myelopathy is one of the most devastating complications of clinical radiotherapy. Treatment techniques that are designed to minimize the risk of spinal cord injury are likely to underdose the tumour consequent failure to control the disease. Since radiation myelopathy results in severe and irreversible morbidity, it is important to establish the tolerance dose of the spinal cord. A number of patients have recently been reported to have developed radiation myelopathy following hyperfractionated accelerated radiotherapy. As the survival rates of patients increase, radiation oncologists are more frequently faced with the problem of treatment of late recurrence or second tumours situated within or close to previously treated site. A rationale for taking a decision in treating in such a condition is even more complex than the original condition and requires knowledge of the kinetics of decay of occult injury of the previous treatment. To test the validity of ERD, clinically reported data of altered fractionation to the spinal cord for 7 patients reported by Wong et al, Saunders et al and Bogaert et al, were analysed, ERD values were calculated and compared with compiled clinical literature data of 3233 patients for the incidence of spinal cord myelitis reported by Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al for conventional fractionation. ERD values were estimated with alpha/beta of 2.5 Gy for the conventional and altered fractionation data. To test the validity of TE concept for clinical data of re-irradiation tolerance of the spinal cord, the data of the 22 patients compiled by Nieder et al were used. Clinical data compiled from the literature of Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al, were used for comparison.

Frequencies of Micronuclei in Peripheral Lymphocytes in Korean Populations after Chronic Low-dose Radiation Exposure

The purpose of this study was to estimate predictive markers of intrinsic radiosensitivity in individuals who were exposed to occupational or environmental radiation. Throughout this process, the actual biohazard risks and base-line chromosome damage were evaluated in human population. Further studies were carried out to provide evidence for the existence of individual variations in age-dependent responses through micronuclei (MN) assay.Spontaneous frequencies not only vary greatly between individuals, but also working or living areas. It was shown that the increased level of spontaneous cell with MN was observed with increasing age. The relationship between radiosensitivity and the increased spontaneous level of MN may be in an inverse proportion. Ionizing radiation may be targeted mutagenic effects at the usual exposures of background levels that populations were exposed. Age and gender are the most important demographic variables in determining the MN index with frequencies in females, which were greater than those in males. The main life-style factors influencing the MN index in subjects were correlated significantly and positively with smoke. The results showed that an indicator of the genetic damaged rate in MN index in human populations significantly correlated with age, sex and life-style factors. So far, it is evident that with regard to the application of MN assay all future studies have to take into account the influence of age, gender, and life-style.In Conclusion, using micronuclei assay technique a large population can be easily monitored. This study illustrated that the MN assay may provide a high potential to ensure appropriate quality control and standard documentation protocol that can be used to monitor a large population exposed to radiation epidemiologically.

Estudo histomorfológico da cronologia do processo de reparo em feridas de extraçäo dental de ratos expostos à radiaçäo x 24 horas antes do ato cirúrgico / Histomorfologic study of the healing cronology process on dental extraction wound rats exposed to 24 hours radiation before the cirurgic procedures

O presente trabalho teve por objetivo estudar histomorfologicamente, a influência da radiaçäo X, 24 horas antes da extraçäo dental, sobre a cronologia do processo de reparo nas feridas decorrentes desta intervençäo. Foram empregados 60 ratos jovens. Estes ratos foram divididos em 2 grupos: Grupo Controle (I) e Grupo Irradiado (II). Os animais foram sacrificados aos 3, 7, 14, 28 e 40 dias após as extraçöes dentais. As peças obtidas sofreram o tratamento laboratorial de rotina para se obter lâminas corada com hematoxilina e eosina. Concluiu-se que: 1) Houve retardo no início da proliferaçäo fibroblástica e de vasos sanguíneos no Grupo Irradiado; 2) A irradiaçäo 24 horas antes do ato cirúrgico provocou um severo atraso na cronologia do processo de reparo alveolar

Adaptive response to ionizing radiation induced by low dose of gamma ray in human hepatoma cell lines

When cells are exposed to a low dose of a mutagenic or clastogenic agent, they often become less sensitive to the effects of a higher dose administered subsequently. Such adaptive responses were first described in Escherichia coli. Studies on mammalian cells have been limited to human lymphocytes exposed to low doses of an alkylating agent. In this study, the adaptive response to 1 cGy of gamma rays was investigated in human tumor cells using two human hepatoma cell lines, Hep G2 and Hep 3B. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results of this study indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher doses (50 cGy). The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 hour to 72 hours. In G2 chromatids, the adaptive response was observed both at short time intervals, as early as 1 hour, and at long time intervals. In S chromatids, however, the adaptive response was shown only at long time intervals. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the experimental groups. Therefore, it is suggested that the adaptive response can be observed in human hepatoma cell lines, which is first documented through this study.

Infusión intratumoral y parametrial del 3 nitrotriazole (AK-2123) en la radioterapia del cáncer de cuello uterino: estadios clínicos II - III resultados preliminares positivos / Intratumural insution and parametrial of 3 nitrotriazole (AK2123) in radiotherapy of cervix neoplasms

Basado en el efecto clínico diferencial de la acción de un nuevo radiosensibilizador de células hipóxicas, el AK-2123 (3-Nitro-1, 2, 4 - triazole), en el cáncer de cuello uterino localmente avanzado (estadíos II-B y III-B), se ha llevado a cabo un protocolo clínico fase I/II en 80 pacientes consecutivos a quienes se les inyectó intratumoralmente soluciones al 1 por ciento y 2 por ciento de AK-2123; 30 minutos antes de la administración de radioterapia externa. Los resultados preliminares muestran que las lesiones exofíticas responden mucho mejor que las endofíticas y el AK-2123 podría reemplazar al radium intracavitario para la variedad exofítica del estadío II-B del cáncer de cuello uterino, siendo la terapia estándard para esta neoplasia en nuestros pacientes. El tratamiento es bien tolerado y no desarrolla toxicidad neurológica.