Effect of 17AAG-cypate polymer micelle on radio-sensitivityof A549 cells / 中华放射肿瘤学杂志

Objective To investigate the radiosensitizing effect of 17AAG-cypate micelles on human non-small cell lung cancer A549 cells and its possible mechanism.Methods (1) A single-hit multi-target model formula was used to analyze the radiosensitizing effects of 17AAG-M and 17AAG-cypate-M.(2) The effects of 17AAG-cypate-M on the viability of A549 cells under laser and X-ray irradiation were analyzed by MTT assay.(3) The effect of the drugs on the cell senescence was observed by β-galactosidase staining assay.(4) The effects of different treatment conditions on DNA damage repair were analyzed by γ-H2AX immunofluorescence staining assay.(5) The expression of p-Erk1/2 and p-Akt was measured by Western blot.The paired t test was used for analyzing the differences between groups.Results Compared with the X-ray irradiation group,the X-ray+17AAG-cypate-M group had a lower mean lethal dose and a sensitization enhancement ratio greater than 1,indicating that 17AAG-cypate-M had a radiosensitizing effect.Compared with the 17AAG-M group,the 17AAG-cypate-M group showed significantly lower cell viability (P<0.01),a significantly higher percentage of aging cells (P<0.01),and significantly further delayed DNA damage repair (P<0.01).And the 17AAG-cypate-M group had lower expression of p-Erk1/2 and p-Akt than the 17AAG-M group.Conclusions Compared with 17AAG-M,17AAG-cypate-M has a higher radiosensitizing effect on A549 cells.The mechanism might be inducing the cell senescence,delaying DNA damage repair,and inhibiting the expression of p-Erk1/2 and p-Akt.

The effect of oxaplatin on enhancing radiosensitivity in human hepatocellular carcinoma cell line HepG2 / 中华放射肿瘤学杂志

Objective To explore the effect of oxaliplatin ( OXA) on enhancing radiosensitivity in human hepatocellular carcinoma cell line HepG2 . Methods 50% inhibition concentration ( IC50 ) of HepG2 cells treated with OXA was measured by using MTT method at 6, 12, 24, 48 hours. Then clone formation assay was applied to obtain sensitizing enhancement ratio ( SER) of OXA combing IR, according to the survival fraction of three groups 10?14 days after treatments:placebo?treated group ( C) ,radiation group ( IR, single dose of 1 Gy,2 Gy,4 Gy,6 Gy,8 Gy,10 Gy) and IR synchronizing OXA group ( IR+3 mg/L OXA) . The proportions of cell apoptosis were analyzed using flow cytometry at 24 hours after treatment. At last, we semi?quantitative tested the expression of extracellular regulated protein kinase 1/2 ( ERK 1/2 ) and DNA damage repair protein Ku?70 of the C,IR and IR+OXA groups. Statistical analysis was performed by T test. Results The IC50 of OXA on HepG2 cells is 54?4 mg/L at 6 hours,29?1 mg/L at 12 hours,17?8 mg/L at 24 hours and 10?5 mg/L at 48 hours.3 mg/L was selected in clone formation assay at which 80?90% HepG2 cells survived at 24 hours. The SER ( SF2 ) is calculated as 1?59. Flow cytometry showed the proportion of survival cells in IR+OXA group is significantly lower than those of IR group ( P=0?005) ,OXA group ( P=0?008) and C group ( P=0?001) . The expressions of ERK 1/2 were inhibited in IR and IR+OXA groups compared by that of control group. But the expression of ERK 1/2 in IR group showed increasing after 48 hours which was higher than that of IR+OXA group. For Ku?70,the changes of expression were similar with that of ERK 1/2. Conclusion Oxaliplatin presented enhancing radiosensitivity in human hepatocellular carcinoma cell line HepG2 in vitro.

The radiosensitizing effect of nano-gold and nano-silver particles in HepG2 hepatocellular carcinoma cell / 中华放射肿瘤学杂志

Objective To study the radiosensitizing effect of nano-gold nano-silver particles in hepatocellular carcinoma cells (HepG2) in vitro and the possible mechanisms.Methods MTT assay and clonogenic assay were performed to determine the killing effect of nano-gold and nano-silver particles in HepG2 cells.Flow-cytometry was used to measure cell apoptosis and cell cycle distribution.Western blotting was used to measure the expression of Caspase-3,Bax and Bcl-2.ELIASA was used to determine the content of catalase (CAT),superoxide dismutase (SOD),and total glutathione (GSH).Results Nano-gold and nano-silver particles inhibited the proliferation of HepG2 cells with IC50 of 6.51 μg/ml and 2.47 μg/ml,respectively.Nano-gold and nano-silver particles significantly enhanced the radiosensitivity of HepG2 cells.Obtained by Dq,the SER of 1/5 IC50 nano-gold and nano-silver particles were 1.37 and 1.48,and 1/10IC50 with 1.11 and 1.09.Nano-gold and nano-silver particles increased the expression of Caspase-3 and Bax and reduced the exprcssion of Bcl-2.CAT,SOD and total GSH were significantly reduced.Conclusions Nano-gold and nano-silver particles can enhance the radiation sensitivity of HepG2 cells.Specific sensitizing mechanism may be the activation of the mitochondrial apoptosis pathway and the induction of reactive oxygen species in apoptotic pathways,which ultimately induces apoptosis.

A phase Ⅲ multicenter trial of radiosensitizing effect and safety of sodium glycididazole in thoracic esophegeal squamous carcinoma / 中华放射肿瘤学杂志

ObjectiveTo evaluate the efficacy and clinical safety of sodium glycididazole (CMNa)in thoracic esophageal squamous carcinoma.Methods From June 1,2008 to October 13,2009,66pathologically proved thoracic esophageal squamous carcinoma (stage Ⅱa-Ⅲ,stage Ⅳ with metastases only in supraclavicular lymph nodes,by AJCC 6th ed) were randomized into radiotherapy plus CMNa (A) or radiotherapy plus placebo (B) group.Radiotherapy was given by conventional schedule:1.8-2.0 Gy per fraction,5 times per week to a total dose of 66 Gy/6.6-7.2w.CMNa was given intravenously 800 mg/m2 3 times a week in solution of 100 ml saline within 30 minutes.Radiotherapy was started 30-60 minutes after completion of infusion.Patients of Group B received placebo in saline solution.A total of 66 patients were enrolled ( Group A:32 ; Group B:34 ),and four patients were unanalyzable,remaining 31 patients in each Group.Baseline factors were balanced.ResultsFollow-up rate was 97％.Group A vs.Group B:the overall response rate was 93.5％ vs.67.7％ ( x2 =6.61,P =0.01 ),2-year overall survival was 39.9％ vs.29.9％ ( x2 =0.62,P =0.433 ),2-year cancer specific survival was 43.1％ vs.26.8％ ( x2 =0.30,P =0.878),and 2-year progression-free survival was 30.1％ vs.27.9％ ( x2 =0.02,P =0.586).No severe side effects observed.All patients tolerated CMNa infusion well.Conclusions CMNa is tolerable and effective as a hypoxic radiosensitizer,and its combination with radiotherapy can improve short term effect.However,survival is not improved within our follow-up period.

Gefitinib at different administration time in radiosensitizing lung adenocarcinoma cells in vitro / 中华放射肿瘤学杂志

Objective To investigate the radiosensitizing effects of gefitinib at different administration time. Methods Gefitinib was administered to A549 lung cancer cells in three different ways (method 1, 24 h before irradiation ;method 2, upon irradiation and method 3, 24 h after irradiation). Cell-surviving rates were evaluated by the colony-forming assays. Cell apoptnsis and cell-cycle distributions were detected by the flow cytometry (FCM). Protein expression of p21, Cdc25c, Bcl-2, Bax, Rad51 and phosphorylated DNA - PKcs (phnspho - DNA - PK) were measured with the Western blot analysis. Results The sensitizing effect ratio (ratio of D_0 value) was 2.23, 1.51 and 1.30 with method 1, 2 and 3, respectively. A higher apoptosis rate and more G_2/M phase arrest were observed with method 1 when compare with method 2 or 3. With the similar tendency, the protein level of p21, Cdc25c, Bcl-2, Bax, RadSl and phospho-DNA-PK changed distinctly. Conclusions Radiosensitizing effects are obtained in all three methods, with gefitinib delivered before irradiation being the best.

Radiation sensitization by CAPE on human HeLa cells of cervical cancer / 中华放射医学与防护杂志

Objective To study the radiosensitizing effect of caffic acid phenethyl ester(CAPE)on human cervical cancer HeLa cells.Methods MTT assay was used to measure the relation between the inhibition effect and CAPE concentrations by CAPE with different concentrations on HeLa cells for 24 hours.HeLa cells were divided into the control and experimental groups,both of which were given 0,2,4,6 and 8 Gy of 60Co γ-irradiation,respectively.The cell clones were counted.Meanwhile HeLa cells were divided into the control,CAPE,irradiation and combination groups.Flow cytometric analysis was adopted to detect the changes of cell cycle distribution induced by CAPE.Results The inhibition rate of CAPE acting on Hela cells increased with concentrations(F=126.49～3654.88,P＜0.01).HeLa cells cloning survival decreased with the increase of radiation dose(F=174.42～9422.81,P＜0.01).At the game radiation dose,HeLa cells cloning survival was less in experimental group than conlrol group(F=120.14～251.91,P＜0.01).The mean lethal dose(D0)(1.45 and 1.82 Gy)and the quasi-threshold dose(Dq)(1.89 and 3.21 Gy)of HeLa cells in experimental group decreased comparing with control group,SER was 1.26.Compared with the sole irradiation group,cells in G2/M phase of the CAPE group and the sole irradiation group increased(P＜0.01)while the combination group decreased(P＜0.01).Conclusions CAPE could increase the radiation sensitivity of HeLa cells by G2/M arrest and may be related to the inhibition of the sub-lethal damage repair.

Radiation sensitization by dihydroartemisinin on human HeLa cells of cervical cancer / 中华放射医学与防护杂志

Objective To investigate the radiosensitizing effects of dihydroartemisinin(DHA)on human HeLa cells of cervical cancer irradiated by X rays.Methods Cell growth kinetics was determined using MTF assay.Cell survival was analyzed by elonogenic assay.The change of cell cycle and apeptosis was measured by flow cytometry.Results Dihydroartemisinin inhibited the growth of HeLa cells of human cervical cancer and showed a dose-dependent and time-dependent manner.Dihydroartemisinin(20 μmol/L)showed the radiosensitizing effects on HeLa cells,and the sensitizing enhancement ratio(SER)was 1.47.Dihydroartemisinin abrogated radiation-induced G2 arrest of the tested HeLa cells,the G2 ratio of medicine + radiation group dechned from 73.58% to 48.31%.Dihydroartemisinin enhanced the apoptosis of HeLa cells by X-irradiation,the apoptosis rates of medicine + radiation group significantly increased from 29.46%,48.04%,70.21% to 45.79%,66.36% and 79.58%,respectively for 2,4 and 6 Gy.Conclusions Dihydroartemisinin could increase the radiesensitivity of HeLa cells of human cervical cancer.Abrogation of radiation-induced C2 arrest could be part of the mechanism.

Estudo fase I/II com capecitabina e radioterapia neoadjuvante em / pacientes com câncer de mama localmente avançado resistentes as / antraciclinas

De acordo com dados do Instituto Nacional de Câncer do Brasil, quase 30% dos pacientes novos com câncer de mama apresentam no momento do diagnóstico, tumor localmente avançado, inoperável, sendo necessário tratamento primário com quimioterapia. Usualmente esquemas baseados em antraciclinas são efetivos, porém cerca de 30% dos tumores não responderão. Para estes pacientes ainda não existe uma segunda linha de tratamento estabelecida. Objetivo: Avaliar eficácia e toxicidade de radioterapia e capecitabina como segunda linha neo-adjuvante. Pacientes e Métodos: Vinte e oito pacientes com câncer de mama localmente avançados, refratários à quimioterapia primária com antraciclinas, foram estudados entre janeiro de 2003 e maio de 2004. Os pacientes receberam radioterapia (50Gy) e capecitabina (850mg/m2) duas vezes ao dia por 14 dias cada 3 semanas. Resultados: Vinte três de 28 pacientes (82%) tornaram se operáveis. Cinco pacientes não realizaram a cirurgia por progressão de doença. A mediana do tamanho do tumor por avaliação clínica reduziu de 80 cm² para 49cm². Doença residual microscópica foi observada em 3 pacientes (13%) e resposta patológica completa em um paciente. A mediana de linfonodos acometidos foi de dois. O tratamento foi bem tolerado, sem eventos grau 3 ou 4. Conclusão: Nossos resultados indicam que o tratamento de segunda linha neo-adjuvante com radioterapia e capecitabina em pacientes com câncer de mama localmente avançado e refratários a quimioterapia primária com antraciclinas, foi eficaz e bem tolerado. Estudo randomizado e prospectivo comparando radioterapia isolada e capecitabina combinada com radioterapia deverá ser realizado

According to data from Brazil’s National Cancer Institute, nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable, and tumor reduction is usually attempted with chemotherapy. Firstline anthracyclin-based neoadjuvant chemotherapy is often effective, but about 30% of the patients fail. For those, there is yet no established second-line treatment. Objectives: We have studied the concomitant use of radiation therapy and capecitabine in this setting, in order to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment. Methods: Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (50Gy) and concomitant capecitabine (850mg/m²) for 14 days every 3 weeks. Results: This treatment rendered 23 of the 28 patients (82%) operable. The five remaining patients did not undergo surgery due to disease progression. The median clinical tumor size decreased from 80 cm2 to 49 cm2. Microscopic residual disease was observed in 3 patients (13%), and another patient achieved a complete pathologic response. The median number of involved lymph nodes was two. Treatment was well tolerated, with no grade 3 or 4 events. Conclusion: Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy

The Cytotoxic and Radiosensitizing Effects of Taxol in Uterine Sarcoma Cell Lines / 대한산부인과학회잡지

OBJECTIVE: The cytotoxic and radiosensitizing effects of Taxol in uterine sarcoma cell lines were investigated. METHODS: Two uterine sarcoma cell lines with different Taxol responses were used, namely, Taxol- sensitive and MDR gene negative MES-SA, and Taxol-resistant and MDR gene positive MES-SA/MX2 cells. These cells were treated with Taxol, radiation, or both, and cytotoxicities were compared by XTT assay and TUNEL staining. The cytotoxic mechanism was also studied by flow cytometry and by RT-PCR of the MDR gene expression. RESULTS: In Taxol-sensitive MES-SA cell lines, Taxol showed highly cytotoxic activity than radiation or the Taxol-radiation combined treatment. On the contrary, in Taxol-resistant MDR positive MES-SA/MX2 cell lines, Taxol significantly increased the sensitivity to radiation therapy, and increased cytotoxicity and apoptosis. Flow cytometry showed that treatment with Taxol alone produced the highest rate of cell cycle shifting to the G0/G1 phase in the MES-SA cell line. However, in the MES-SA/MX2 cell line, Taxol only treatment did not show significant cell cycle shifting compared to the control group. However, in cases of combined Taxolradiation treatment, the rate of cell cycle shifting was higher than for radiation treatment only. CONCLUSION: Taxol has cytotoxic and radiosensitizing effects on uterine sarcoma cell lines.

The Cytotoxic and Radiosensitizing Effects of Taxol in Uterine Sarcoma Cell Lines / 대한산부인과학회잡지

OBJECTIVE: The cytotoxic and radiosensitizing effects of Taxol in uterine sarcoma cell lines were investigated. METHODS: Two uterine sarcoma cell lines with different Taxol responses were used, namely, Taxol- sensitive and MDR gene negative MES-SA, and Taxol-resistant and MDR gene positive MES-SA/MX2 cells. These cells were treated with Taxol, radiation, or both, and cytotoxicities were compared by XTT assay and TUNEL staining. The cytotoxic mechanism was also studied by flow cytometry and by RT-PCR of the MDR gene expression. RESULTS: In Taxol-sensitive MES-SA cell lines, Taxol showed highly cytotoxic activity than radiation or the Taxol-radiation combined treatment. On the contrary, in Taxol-resistant MDR positive MES-SA/MX2 cell lines, Taxol significantly increased the sensitivity to radiation therapy, and increased cytotoxicity and apoptosis. Flow cytometry showed that treatment with Taxol alone produced the highest rate of cell cycle shifting to the G0/G1 phase in the MES-SA cell line. However, in the MES-SA/MX2 cell line, Taxol only treatment did not show significant cell cycle shifting compared to the control group. However, in cases of combined Taxolradiation treatment, the rate of cell cycle shifting was higher than for radiation treatment only. CONCLUSION: Taxol has cytotoxic and radiosensitizing effects on uterine sarcoma cell lines.

THE CONCURENT TREATMENT OF ADVANCED ESOPHAGEAL CANCER BY REDIOTHERAPY AND CIS-PLATINUM / 中国癌症杂志

PURPOSETo evaluate the radiosensitizing effect of cisplatin combined with radiotherapy for esophageal carcinoma. METHODS From 1989 to 1990. 60 patients with esophageal were treated. It was divided into two groups. Radiotherapy group (R) and radiotherapy plus cisplatin (20mg iv. twice a week) (R + C). A total dose of 66-70 Gy/6-7 wk was used in (R) and (R+C) group. RESULTS The 1 year. 3 year. 5 year survival rats were R : R+C = 46. 7%、20%、10% : 60%、30%、23%. CONCLUSION This study may imply that rational administration of cisplatin in the radiotherapy could improve the radiotherapy result of the esophageal carcinoma.

A COMPARISON OF RADIOSENSITIZING EFFECT ON SOLID TU- MOR IN MICE BETWEEN METRONIDAZOlE AND ITS DERIVA-TIVE / 第二军医大学学报

This paper compares the radiosensitizing effect of metronidazole(M) with that of its derivatives(CM)on sarcoma 180 (S180).After i.p injection S180 bearing mice were either irradiated with y-ray 17Gy or unirradiated under aerated or tumor acute local hypoxic conditions.Results indicate that under hypoxic condition tumor growth Was inhibited within 10 d after a single i.p injection of drugs, but under aerated condition inhibition of tumor growth did not occur.CM was found to be stronger than M in tumor inhibiting effect.After aerated irradiation the drug groups demonstrated an apparent slowing down of tumor growth.But the difference between groups was not obvious.Hypoxic irradiation produced a very strong inhibiting effect in the drug groups.CM, especially when it was chelated with Ca++to form CMCa, was strongest in tumor growth inhibition.Its tumor inhibiting ratio was 77.4%, enhancement ratio(ER)2.46 and sensitizing enhancement ratio(SER)1.89.Its tumor inhibiting effect was stronger than irradiation without drug administration and irradiation after the administration of M.Its radiossnsitizng effect was found to be twice stronger than that of the original compound(M), but its toxic side effect was slighter than M.