Application of Gold Nanoparticles as Radiosensitizer for Metastatic Prostate Cancer Cell Lines.

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.

The radiosensitizing effect of platinum nanoparticles in proton irradiations is not caused by an enhanced proton energy deposition at the macroscopic scale.

Objective.Due to the radiosensitizing effect of biocompatible noble metal nanoparticles (NPs), their administration is considered to potentially increase tumor control in radiotherapy. The underlying physical, chemical and biological mechanisms of the NPs' radiosensitivity especially when interacting with proton radiation is not conclusive. In the following work, the energy deposition of protons in matter containing platinum nanoparticles (PtNPs) is experimentally investigated.Approach.Surfactant-free monomodal PtNPs with a mean diameter of (40 ± 10) nm and a concentration of 300 µg ml-1, demonstrably leading to a substantial production of reactive oxygen species (ROS), were homogeneously dispersed into cubic gelatin samples serving as tissue-like phantoms. Gelatin samples without PtNPs were used as control. The samples' dimensions and contrast of the PtNPs were verified in a clinical computed tomography scanner. Fields from a clinical proton machine were used for depth dose and stopping power measurements downstream of both samples types. These experiments were performed with a variety of detectors at a pencil beam scanning beam line as well as a passive beam line with proton energies from about 56-200 MeV.Main results.The samples' water equivalent ratios in terms of proton stopping as well as the mean proton energy deposition downstream of the samples with ROS-producing PtNPs compared to the samples without PtNPs showed no differences within the experimental uncertainties of about 2%.Significance.This study serves as experimental proof that the radiosensitizing effect of biocompatible PtNPs is not due to a macroscopically increased proton energy deposition, but is more likely caused by a catalytic effect of the PtNPs. Thus, these experiments provide a contribution to the highly discussed radiobiological question of the proton therapy efficiency with noble metal NPs and facilitate initial evidence that the dose calculation in treatment planning is straightforward and not affected by the presence of sensitizing PtNPs.

Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition.

Recent reports have shown that bromelain (BL), a pineapple extract, acts as an adjuvant therapy in cancer treatment and prevention of carcinogenesis. The present study was designed to investigate the possible mechanisms by which BL could radiosensitize tumor cells in vitro and in a mouse tumor model. BL has shown a significant reduction in the viability of the radioresistant human breast carcinoma (MCF-7) cell line using cell proliferation assay. The in vivo study was designed using the Ehrlich model in female albino mice, treated with BL (6 mg/kg b. wt., intraperitoneal, once daily for 10 days) 1 hour before exposure to a fractionated dose of gamma radiation (5 Gy, 1 Gy for 5 subsequent days). The radiosensitizing effect of BL was evident in terms of a significant reduction in tumor volume, poly ADP ribose polymerase-1 (PARP-1), the proliferation marker Ki-67 and nuclear factor kappa activated B cells (NF-κB) with a significant elevation in the reactive oxygen species (ROS) content and lipid peroxidation (LPO) in tumor cells. The present findings offer a novel insight into the radiosensitizing effect of BL and its potential application in the radiotherapy course.

Celecoxib Blocks Vasculogenic Mimicry via an Off-Target Effect to Radiosensitize Lung Cancer Cells: An Experimental Study.

The resistance to radiotherapy in lung cancer can be attributed to vasculogenic mimicry (VM) to some extent. Celecoxib (CXB), a selective inhibitor of cyclooxygenase-2 (COX-2), is reported as a radiosensitizer in non-small cell lung cancer (NSCLC). However, whether CXB can regulate VM formation via an off-target effect to radiosensitize NSCLC remains unclear. This study aimed to elucidate the mechanism underlying the radiosensitizing effect of CXB on NSCLC, i.e., whether CXB can inhibit VM formation via binding to newly identified targets other than COX-2. CXB radiosensitivity assay was performed in BALB/c mice bearing H460 xenografts and C57 mice bearing Lewis lung cancer (LLC) xenografts, which were divided into the control, CXB, irradiation (IR) treatment, and IR plus CXB groups. VM formation was observed using 3D Matrigel, periodic acid solution (PAS) staining, and immunofluorescence staining. The potential off-targets of CXB were screened using Protein Data Bank (PDB) database, MGLTools 1.5.6, and AutoDock Vina 1.1.2 and confirmed by Western blotting, enzyme activity assay, and RNA interference in vitro experiments and by immunohistochemistry in vivo experiments. CXB treatment almost eliminated the enhancement of VM formation by IR in vitro and in vivo, partially due to COX-2 inhibition. Four potential off-targets were predicted by molecular docking. Among them, aminopeptidase N (APN) and integrin alpha-V (ITAV) were remarkably inhibited in protein expression and enzyme activity in vitro or in vivo, consistent with the remarkable reduction of VM formation in H460 xenografts in BALB/c mice. In conclusion, CXB dramatically blocked VM through inhibiting newly identified off-targets APN and ITAV, other than COX-2, then radiosensitizing NSCLC.

Antitumor and Radiosensitizing Effects of Zinc Oxide-Caffeic Acid Nanoparticles against Solid Ehrlich Carcinoma in Female Mice.

This study aimed to evaluate the anticancer and radio-sensitizing efficacy of Zinc Oxide-Caffeic Acid Nanoparticles (ZnO-CA NPs). ZnO-CA NPs were formulated by the conjugation of Zinc Oxide nanoparticles (ZnO NPs) with caffeic acid (CA) that were characterized by Fourier Transform Infrared Spectra (FT-IR), X-ray Diffractometer (XRD), and Transmission Electron Microscopy (TEM). In vitro anticancer potential of ZnO-CA NPs was evaluated by assessing cell viability in the human breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines. In vivo anticancer and radio-sensitizing effects of ZnO-CA NPs in solid Ehrlich carcinoma-bearing mice (EC mice) were also assessed. Treatment of EC mice with ZnO-CA NPs resulted in a considerable decline in tumor size and weight, down-regulation of B-cell lymphoma 2 (BCL2) and nuclear factor kappa B (NF-κB) gene expressions, decreased vascular cell adhesion molecule 1 (VCAM-1) level, downregulation of phosphorylated-extracellular-regulated kinase 1 and 2 (p-ERK1/2) protein expression, DNA fragmentation and a recognizable peak at sub-G0/G1 indicating dead cells' population in cancer tissues. Combined treatment of ZnO-CA NPs with γ-irradiation improved these effects. In conclusion: ZnO-CA NPs exhibit in-vitro as well as in-vivo antitumor activity, which is augmented by exposure of mice to γ-irradiation. Further explorations are warranted previous to clinical application of ZnO-CA NPs.

Therapeutic Efficacy and Inhibitory Mechanism of Regorafenib Combined With Radiation in Colorectal Cancer.

BACKGROUND: Although both chemotherapy and radiotherapy (RT) can sufficiently maintain tumor suppression of colorectal cancer (CRC), these treatments may trigger the expression of nuclear factor kappa B (NF-κB) and compromise patients' survival. Regorafenib suppresses NF-κB activity in various tumor types. However, whether regorafenib may act as a suitable radiosensitizer to enhance therapeutic efficacy of RT remains unknown. MATERIALS AND METHODS: Here, we established a CRC-bearing animal model to investigate the therapeutic efficacy of regorafenib in combination with RT, through measurement of tumor growth, body weight, whole-body computed tomography (CT) scan and immunohisto-chemistry staining. RESULTS: Smallest tumor size and weight were found in the combination treatment group. In addition, RT-induced up-regulation of NF-κB and downstream proteins were diminished by regorafenib. Moreover, the body weight and liver pathology in the treated group were similar to those of the non-treated control group. CONCLUSION: Regorafenib may enhance the anti-CRC efficacy of RT.

Differences in Linear Energy Transfer Affect Cell-killing and Radiosensitizing Effects of Spread-out Carbon-ion Beams.

BACKGROUND/AIM: The cell-killing and radiosensitizing effects of carbon-ion (C-ion) beams with low linear energy transfer (LET) are underexplored. We aimed to demonstrate the cell-killing effects of 60Co gamma rays and C-ion beams at various LET values and the radiosensitizing effect of C-ion beams at various LET and cisplatin levels. MATERIALS AND METHODS: Human uterine cervical cancer cells were irradiated with 60Co gamma rays and C-ion beams at different levels of LET, with and without cisplatin treatment. RESULTS: Low-LET C-ion beams had a superior cell-killing effect compared to 60Co gamma rays. Survival curves under low-LET C-ion beams were more similar to that of 60Co gamma rays than that of high-LET C-ion beams. Cisplatin significantly reduced cell survival after 1, 2, and 3 Gy C-ion beam irradiations at LET values of 13/30/70 keV/µm, 13/30 keV/µm, and 13 keV/µm, respectively. CONCLUSION: Low-LET C-ion beams combined with cisplatin have higher radiosensitizing effects than high-LET C-ion beams.

Radiosensitizing Effect of Gadolinium Oxide Nanocrystals in NSCLC Cells Under Carbon Ion Irradiation.

Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC.

Radiosensitizing effect of 5-aminolevulinic acid in colorectal cancer in vitro and in vivo.

The radiosensitizing effect of 5-aminolevulinic acid (5-ALA) has been demonstrated in glioma and melanoma in a number of studies. Enhancing the radiosensitivity of colorectal cancer may improve survival rates and lessen adverse effects. The present study assessed the radiosensitizing effect of 5-ALA in colorectal cancer using the human colon cancer cell line HT29 in vitro and in vivo. In vitro, cells were pretreated with 5-ALA and exposed to ionizing radiation. Cells pretreated with or without 5-ALA were compared using a colony formation assay. In vivo, HT29 cells were implanted into mice subcutaneously and subsequently exposed to ionizing radiation. 5-ALA was administrated by intraperitoneal injection. Subcutaneous tumors treated with or without 5-ALA were compared. Single-dose and multi-dose irradiations were applied both in vitro and in vivo. Cells exposed to multi-dose irradiation and pretreated with 5-ALA in vitro had a significantly lower surviving fraction compared with cells without 5-ALA pretreatment. Following multi-dose irradiation in vivo, the volume of the subcutaneous tumors treated with 5-ALA was significantly lower compared with that of tumors without treatment. These results suggest that radiotherapy with 5-ALA may enhance the therapeutic effect in colon cancer.

Fucoidans from brown algae Laminaria longipes and Saccharina cichorioides: Structural characteristics, anticancer and radiosensitizing activity in vitro.

The sulfated α-l-fucans ScF and LlF were obtained from brown algae of the Laminariaceae family (Saccharina cichorioides and Laminaria longipes). According to spectroscopy NMR, the LlF fucan predominantly contained the →3)-α-l-Fucp-(2SO3-)-(1→4)-α-l-Fucp-(1→2)-α-l-Fucp-(4SO3-)-(1→ repeating units, with small amounts of disaccharide 1,4-linked fragments and 3-sulfated fucose residues. Mass spectrometric analysis revealed the presence of the following fragments in the fucan structure: α-l-Fucp-(2SO3-)-(1→4)-α-l-Fucp-(2SO3-)-(1→3)-α-l-Fucp-(4SO3-); α-l-Fucp-(2,4SO3-)-(1→3)-α-l-Fucp-(1→3)-α-l-Fucp-(4SO3-); α-l-Fucp-(2SO3-)-(1→2)-α-l-Fucp; α-l-Fucp-(2SO3-)-(1→2)-α-l-Fucp-(4SO3-); α-l-Fucp-(2SO3-)-(1→3)-α-l-Fucp; α-l-Fucp-(2,4SO3-)-(1→3)-α-l-Fucp; α-l-Fucp-(4SO3-)-(1→4)-α-l-Fucp; and α-l-Fucp-(4SO3-)-(1→4)-α-l-Fucp-(2SO3-). Both ScF and LlF fucoidans inhibited colony formation and growth of melanoma and colon cancer cells and sensitize-tested cancer cells to X-ray radiation to a comparable degree.

Interstitial Brachytherapy in Combination With Previous Transarterial Embolization in Patients With Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: Treatment of patients with large hepatocellular carcinoma (HCC) remains challenging and survival in advanced tumor stages is limited. This study was conducted to investigate the efficacy of embolization followed by computed tomography (CT)-guided interstitial high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable HCC. PATIENTS AND METHODS: A total of 47 patients undergoing CT-HDRBT were divided into 2 groups: i) patients previously treated with transarterial chemoembolization (TACE) and ii) patients treated with bland transarterial embolization (TAE). The primary endpoint was overall survival (OS), while secondary endpoints were the time to progression (TTP) and the local progression rate. RESULTS: A total of 78 lesions were treated. The mean size of the main tumors was 58.3 mm. The median OS in TACE and TAE groups was 28.9 months and 32.3 months, respectively (p=NS). The median OS of patients classified as BCLC stage A using the Barcelona Clinic Liver Cancer classification system (BCLC) was 32.3 months, while the median OS of patients in BCLC stage B and C was 36.9 and 17.7 months, respectively. The local progression rate was 7.7% (6/78), with no statistically significant difference between TACE and TAE. The median TTP was significantly longer in the TACE group compared to the TAE group (11.7 months and 10.3 months, respectively). CONCLUSION: Treatment with transarterial embolization and subsequent CT-HDRBT leads to a very promising survival rate for patients with unresectable HCC.

Single Intense Microsecond Electric Pulse Induces Radiosensitization to Ionizing Radiation: Effects of Time Intervals Between Electric Pulse and Ionizing Irradiation.

Background and Objective: Recent studies have shown the potential of electroporation (EP) as a physical radiosensitizer for ionizing radiation (IR). The amount of sensitizing effect depends on some factors the most important of them is the time interval between the EP and IR. This experimental in vitro study aims to investigate the radiosensitizing effect of EP exposure prior to IR and also evaluate the effects of EP-IR time intervals on the amount of radiosensitizing effects. Methods: Chinese hamster ovary (CHO) cell lines were cultured in vitro. The cells were divided into 10 groups including one untreated or control group, IR, and EP treatment alone groups, and seven combined EP-IR groups with 10, 20, 30, 40, 50, 60, and 70 min intervals. The dose enhancement factors (DEFs) for 6 MV X-rays IR were comparatively investigated between the groups using MTT assay. Results: The EP significantly induced radiosensitizing effect and its amount depends on the time intervals. The viability rate of the cells in the combined EP-IR treatment groups for intervals of 10, 20, 30, 40, and 50 min was significantly lower than the IR alone group. The highest DEF (1.18) was observed 10 min time interval between EP and IR. Conclusion: The radiosensitizing effects of EP persist long enough, 10-50 min, which allows safe application of EP as a radiosensitizer before IR in clinical setting.

Shape-Dependent Radiosensitization Effect of Gold Nanostructures in Cancer Radiotherapy: Comparison of Gold Nanoparticles, Nanospikes, and Nanorods.

The shape effect of gold (Au) nanomaterials on the efficiency of cancer radiotherapy has not been fully elucidated. To address this issue, Au nanomaterials with different shapes but similar average size (∼50 nm) including spherical gold nanoparticles (GNPs), gold nanospikes (GNSs), and gold nanorods (GNRs) were synthesized and functionalized with poly(ethylene glycol) (PEG) molecules. Although all of these Au nanostructures were coated with the same PEG molecules, their cellular uptake behavior differed significantly. The GNPs showed the highest cellular responses as compared to the GNSs and the GNRs (based on the same gold mass) after incubation with KB cancer cells for 24 h. The cellular uptake in cells increased in the order of GNPs > GNSs > GNRs. Our comparative studies indicated that all of these PEGylated Au nanostructures could induce enhanced cancer cell-killing rates more or less upon X-ray irradiation. The sensitization enhancement ratios (SERs) calculated by a multitarget single-hit model were 1.62, 1.37, and 1.21 corresponding to the treatments of GNPs, GNSs, and GNRs, respectively, demonstrating that the GNPs showed a higher anticancer efficiency than both GNSs and GNRs upon X-ray irradiation. Almost the same values were obtained by dividing the SERs of the three types of Au nanomaterials by their corresponding cellular uptake amounts, indicating that the higher SER of GNPs was due to their much higher cellular uptake efficiency. The above results indicated that the radiation enhancement effects were determined by the amount of the internalized gold atoms. Therefore, to achieve a strong radiosensitization effect in cancer radiotherapy, it is necessary to use Au-based nanomaterials with a high cellular internalization. Further studies on the radiosensitization mechanisms demonstrated that ROS generation and cell cycle redistribution induced by Au nanostructures played essential roles in enhancing radiosensitization. Taken together, our results indicated that the shape of Au-based nanomaterials had a significant influence on cancer radiotherapy. The present work may provide important guidance for the design and use of Au nanostructures in cancer radiotherapy.

The radiosensitizing effect of fluorocyclopentenyl-cytosine (RX-3117) in ovarian and lung cancer cell lines.

RX-3117 (fluorocyclopentenyl-cytosine) is a novel cytidine analog currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The radiosensitizing effect of RX-3117 was studied in A2780 ovarian cancer cells and non-small cell lung cancer cell lines and related to cell survival and the effect on cell cycle and cell cycle proteins. RX-3117 has a schedule-dependent radiosensitizing effect, but only at pre-incubation (dose modifying factors: 1.4-1.8), observed at pulse and fractionated irradiation. Radiosensitizion was also seen in a three-dimensional spheroid model. At the low radiosensitizing concentration, RX-3117 in combination with radiation led to an accumulation of cells in S-phase, which was accompanied with an increase of cell cycle proteins such as p-Chk2 and p-cdc25C. In addition, RX-3117 caused DNA damage and increased apoptosis. In conclusion, our in vitro experiments showed a radiosensitizing effect of RX-3117.

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.

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.