Effect of low dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via VEGF and mTOR

Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in vivo.Methods Human cisplatin-resistant ovarian carcinoma cells(SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation(LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and m TOR, and Western blots detected the expression of corresponding proteins.Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different(P < 0.05). The rate of tumor inhibition in the LDFRT group(37.5603%) was lower than in the conventionaldose group(47.4446%), but there was no significant difference(P 0.05). Compared with the other two groups, the m RNA expression of VEGF was significantly lower in the LDFRT group(P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the m RNA expression of m TOR among the three groups, but the expression of the protein p-m TOR was lower in the LDFRT group(P < 0.05), as confirmed by Western blotting.Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-m TOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.

Low-dose fractionated radiation reverses cisplatin resistance in ovarian cancer cells via PI3K/AKT/GSK-3β signaling

Objective To investigate whether low-dose fractionated radiation(LDFRT) could enhance cisplatin sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying mechanism.Methods SKOV3/DDP ovarian cancer cells were divided into three groups as follows: control, LDFRT, and conventional-dose radiation groups. Cells from all three groups were treated with different concentrations of cisplatin(0, 1.25, 2.5, 5, 10, and 20 μg/m L) for 48 h. The proliferation inhibition rate was investigated using the cell counting kit 8(CCK8). The rate of apoptosis was determined by flow cytometry(FCM). Protein levels of AKT, P-AKT, GSK-3β, P-GSK-3β, P21, cyclin D1, and P27 were examined by Western blotting. Results As expected, LDFRT significantly reduced the half-maximal inhibitory concentration(IC50) of cisplatin and promoted apoptosis in SKOV3/DDP cells. Moreover, in the LDFRT group, protein levels of P-AKT, P-GSK-3β, and cyclin D1 were markedly decreased, those of P21 and P27 were greatly increased, and total AKT and GSK-3β levels showed no significant difference compared to those in both the control and conventional-dose radiation groups.Conclusion LDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation of PI3 K/AKT/GSK-3β signaling.

EFFECT OF IRRADIATION TEMPERATURE ON GENERAL EQUATION OF SOL FRACTION-DOSE RELATIONSHIP FOR FLUOROPOLYMERS

In this paper, the effect of irradiation temperature on sol fraction-dose relationship of tluoropolymers was studied. It was found that the increasing of irradiation temperature can result in the decreasing of β value of fluoropolymer, which increases the crosslinking probability of fluoropolymer. The relationship between crosslinking parameter β and irradiation temperature (T_i)of fluoropolymer is established as follows:β=2.2×10^(-3) T_g+4×10^(-4)(T_g-T_i)+0.206.values of some tluoropolymers calculated from the above expression are in agreement with the experimental values.

How Safe Are Reduced Doses per Fraction in Target Volumes of 2^ndto 4^thOrder in the Simultaneous Integrated Boost Irradiation Technique in Head and Neck Carcinoma Patients?

Aim: The simultaneous irradiation of target volumes of different total dose levels using intensity modulated radiotherapy leads to reduced doses per fraction and longer treatment times in target volumes of 2nd?to 4th?order. Does the thereby caused reduced biological effectiveness induce an increased recurrence risk? The current work deals with the problem of recurrences of patients with head and neck carcinomas treated either with an intensitiy (IMRT) or with a volumetric modulated (VMAT) irradiation technique. Methods: From October 2002 to September 2014, 699 patients with carcinomas of the head and neck were irradiated using IMRT or VMAT. The median follow up of the patients was 21.9 months (2 to 145 months). Primary tumor regions (1st?order target volume) of 565 patients were treated with doses per fraction of 2 Gy. Accordingly, further 133 target volumes of the primary tumor received reduced doses per fraction. In 1 patient, the lymphatic drainage was treated solely without irradiation of the primary region. For the lympatic drainage, 854 1st?order target volumes were treated with a dose per fraction of 2 Gy. Reduced doses per fraction were applied to further 1780 target volumes. Results: 54 of 699 patients developed a recurrence in the primary tumor region after radio-(chemo) therapy, 4 patients developed a recurrence of the primary tumor and a unilateral recurrence of the lymphatic drainage, 2 patients a recurrence of the primary tumor and a bilateral lymph node recurrence. 18 patients showed an isolated unilateral recurrence and additionally 2 patients a bilateral recurrence of the lymphatic drainage. 619 patients stayed recurrence free. In primary tumor regions, receiving a dose per fraction of 2 Gy 55 patients (9.7%) developed a recurrence, whereas in target volumes receiving a reduced dose per fraction 5 patients (3.8%) developed a recurrence (p < 0.001). In lympatic drainage target volumes receiving a dose per fraction of 2 Gy, 25 target volumes (2.9%) developed a recurrence, whereas in target volumes receiving a reduced dose per fraction, 5 patients (0.3%) developed a recurrence (p = 0.001). Conclusion: The recurrence risk in target volumes of 2nd?to 4th?order was not increased due to reduced doses per fraction deposited by means of a simultaneous integrated boost technique. Therefore, the simultaneous irradiation of target volumes with different dose levels is safely applicable within one treatment plan.

Radiobiological effect of abdominal X-ray hypo-fraction irradiation on Wistar rats liver

Objective: The aim of our study was to investigate the impact of abdominal hypo-fraction irradiation on liver damage in rats so as to provide a reference for its clinical application. Methods: A total of 100 Wistar rats were equally randomized to five groups as control, 4 Gy, 6 Gy, 8 Gy and 12 Gy group, and the corresponding fractionated doses were offered. Liver functions were examined at the 2nd, 4th, 6th, 8th and 10th week after irradiation. Morphological changes were observed by HE staining. Expressions of Bcl-2 and Bax were examined by immunohistochemical technique. Results: In all irradiation groups, hepatocellular swell, degeneration, necrosis and even hepatic fibrosis could be seen. The differences of the liver coefficient, Glutamyl pyruvic transaminase (GPT), Glutamyl oxaloacetic transaminase (GOT) were significant among the groups and different time points (F = 11.833-781.972, F = 20.857-264.692, P < 0.001). Expressions of Bcl-2 and Bax were significantly different between each group (F = 211.607, 116.577; P < 0. 001), and between each time point (F = 54.083, 68.749; P < 0. 001). Conclusion: Compare with conventional fraction, abdominal hypo-fraction irradiation may cause radiation damage to rat liver, being dose-and-time dependent. Up-regulation of activating apoptosis protein Bax and down-regulation of inhibiting apoptosis protein Bcl-2 may involve in the process.

IMRT Optimization with Both Fractionation and Cumulative Constraints

Radiation therapy plans are optimized as a single treatment plan, but delivered over 30 - 50 treatment sessions (known as fractions). This paper proposes a new mixed-integer linear programming model to simultaneously incorporate fractionation and cumulative constraints in Intensity Modulated Radiation Therapy (IMRT) planning optimization used in cancer treatment. The method is compared against a standard practice of posing only cumulative limits in the optimization. In a prostate case, incorporating both forms of limits into planning converted an undeliverable plan obtained by considering only the cumulative limits into a deliverable one within 3% of the value obtained by ignoring the fraction size limits. A two-phase boosting strategy is studied as well, where the first phase aims to radiate primary and secondary targets simultaneously, and the second phase aims to escalate the tumor dose. Using of the simultaneous strategy on both phases, the dose difference between the primary and secondary targets was enhanced, with better sparing of the rectum and bladder.

小剂量分次放疗增敏化疗在转移性结直肠癌治疗中的临床研究

目的:探究小剂量分次放疗增敏化疗在转移性结直肠癌(mCRC)治疗中的疗效及安全性。方法:根据治疗方式不同将72例一线化疗失败的mCRC患者分为观察组(n=37)和对照组(n=35)。对照组采用贝伐珠单抗^(+)化疗二线治疗。随访两年,比较两组患者的临床疗效、不良反应发生情况(白细胞、血小板)、治疗前后的血清肿瘤标志物水平[癌胚抗原(CEA)、糖类抗原199(CA199)]、免疫功能(CD3^(+)、CD4^(+)、CD8^(+))和生存情况[总生存期(OS)、无进展生存期(PFS)]。结果:观察组治疗后总有效率高于对照组(20.00%vs.43.24%,P<0.05);治疗后,两组CEA、CA199水平低于治疗前,且观察组低于对照组(P<0.05);两组CD3^(+)、CD4^(+)水平上升,且观察组高于对照组(P<0.05);CD8^(+)下降,且观察组低于对照组(P<0.05);两组白细胞下降、血小板减少等不良反应发生情况比较,差异无统计学意义(P>0.05);观察组两年OS、PFS分别为62.16%、40.54%,均高于对照组的37.14%、17.14%(P<0.05)。结论:小剂量分次放疗增敏化疗联合贝伐珠单抗^(+)化疗二线治疗mCRC具有较好的临床疗效,能改善患者的血清肿瘤标志物水平,提高其免疫功能,延长患者生存期,且具有一定安全性。

Radiological characterization of building materials used in Malaysia and assessment of external and internal doses

In this study, the activity concentrations of ^(226)Ra,^(232)Th,^(222)Rn, and ^(40)K, emanation fractions(P),equilibrium equivalent concentration(EEC), and mass exhalation rates(E_m) of radon released from building materials used in Malaysia were studied using gamma-ray spectrometer with HPGe detector. Radiological parameters[activity concentration index(ACI), indoor air-absorbed dose rate(D_(in)), annual effective dose(AED_(in)) from external and internal(E_(Rn)), soft tissues(H_(ST)) and lung(H_L), and effective dose equivalent(H_(eff))] were estimated to evaluate radiological hazards due to the use of these building materials: sand, cement, gravel, bricks, tiles, fly ash, white cement, and ceramic raw materials. The measured P, EEC,and E_m vary from 10 to 30%, 0.9 to 22 Bq m^(-3), and 33 to 674 mBq h^(-1) kg^(-1), respectively, while the calculated ACI and AED_(in) vary from 0.1 ± 0.01 to 2.1 ± 0.1 and 0.1 ± 0.01 to 2.4 ± 0.6 mSv y^(-1), respectively. On the other hand, the internal annual effective dose ranges from 0.1 to 1.4 mSv y^(-1). The estimated radiological risk parameters were below the recommended maximum values, and radiological hazards associated with building materials under investigation are therefore negligible.

放射性矿山氡及氡子体浓度特征的氡暴露有效剂量估算

氡及氡子体暴露剂量是地下放射性矿山工作人员辐射剂量的主要来源。为了掌握氡及氡子体浓度分布并估算氡暴露剂量,对某放射性矿山井下6个典型场所的氡、结合态和未结合态氡子体浓度和通风情况进行了监测,并确定平衡因子和氡子体未结合态份额,依据氡及氡子体浓度特征参数估算该矿井的典型场所的氡暴露有效剂量;基于估算得到的氡暴露有效剂量、生产要求和通风现状,提出了通风降氡的管理措施以确保矿井生产安全。结果显示:(1)该放射性矿山井下典型场所的平衡因子在0.02~0.29,氡子体未结合态份额在0.034~0.098,平衡因子与氡子体未结合态份额之间存在负相关性。(2)正常生产场所的氡暴露年有效剂量E_(Rn1)和E_(Rn2)分别为0.17~19.70 mSv和0.11~16.52 mSv,均低于20 mSv。

基于体素的射波刀肺追踪剂量覆盖率体积直方图研究

目的:基于体素计算分次间射波刀肺追踪的剂量覆盖率体积直方图(CVH),并探讨肿瘤体积、解剖位置与CVH鲁棒性之间的相关性。方法:回顾性分析外周型肺癌患者55例(上肺26例,中肺22例,下肺7例),共339分次。所有患者均采用射波刀(VSI型)Xsight Lung追踪(2-view)方式进行治疗,拍片时间间隔为60 s。在射波刀的动态追踪系统(MTS)中记录的呼吸追踪数据均转化为患者坐标系。以射波刀治疗时产生的log文件为基础,基于体素利用MATLAB科学计算软件计算不同外扩范围下的CVH,并讨论肿瘤体积、解剖位置与CVH鲁棒性之间的相关性。结果:采用95%靶区覆盖率(C95)大于95%即C95>95%作为是否满足临床要求的评价指标,满足临床要求的计划在整个治疗疗程内并非所有治疗分次都能达到评价指标。对于同一外扩范围,其CVH由大到小依次为:上肺>中肺>下肺。另外,对于中、下肺而言,肿瘤外扩5 mm并不能满足临床评价指标即C95>95%。肿瘤体积和治疗过程中CVH的鲁棒性之间呈负相关。肿瘤体积越大治疗过程中的CVH波动越小,反之,肿瘤体积越小,治疗期间覆盖率的不确定度越大,鲁棒性越差。对于下肺肿瘤,上述现象更加明显。另外,随着外扩范围的增加,CVH的鲁棒性也逐渐上升。结论:对于小体积和下肺肿瘤的治疗,平均覆盖率小于大体积和上肺肿瘤,治疗过程中应根据患者肿瘤体积、位置等因素综合考虑外放范围,以进一步提高临床疗效。

建筑火灾与人员疏散耦合模拟研究

为研究火灾环境下烟气对人员的影响,将火灾发展与人员疏散过程进行耦合。以某商场为研究对象,引入当量速度系数和有效剂量分数模型对商场火灾场景下的人员疏散速度进行修正,利用Pyrosim与Pathfinder建立更贴近真实火场的商场火灾与人员疏散耦合模型,得到火灾发展过程中的烟气浓度、温度、能见度与人员疏散过程的耦合时空分布图和烟气毒性对人员伤害的累积作用。模拟结果表明:通过对火灾发展与人员疏散的时空动态分析,在火灾发生380s后,商场剩余77人由于能见度下降不能完成疏散。相比于比较建筑内人员可用安全疏散时间(ASET)和必需安全疏散时间(RSET)的大小的传统判定方式,耦合模型更能直观准确地表现建筑物内火灾烟气对被疏散人员的实时影响。

事故吸入^(241)Am后RBE加权吸收剂量系数计算

当已经发生或即将发生放射性核素急性大量摄入时,对于确定效应(或组织反应)剂量范围,需要一个能够快速估计敏感靶器官或组织在短时间内吸收辐射能量的技术手段或工具,从而能够基于国际原子能机构(IAEA)安全导则GSG-2进行核与辐射应急响应和其他响应行动决策,尽可能地减少受照射人员的急性大剂量照射、保护人员的生命健康。本文在系统研究国际放射防护委员会(ICRP)呼吸道模型、系统模型、消化道模型设计原理和参数建立依据基础上,编写^(241)Am为代表的超铀核素吸入后的滞留排泄份额m(t)计算程序,计算事故吸入^(241)Am后敏感靶器官的短期相对生物效应(RBE)加权吸收剂量AD(30)_(T)系数,并经验证确保计算结果正确。

Low dose effects on cultured mammalian cells...

The low dose effects induced by carbon ions on Chinese hamster V79 cells and murine melanoma B16 cells were investigated in this paper. Both cell lines were divided into four groups for irradiation: (1) control, (2) 0.02 Gy or 0.05 Gy(D1), (3) 1 Gy(D2), (4) D1+D2. The survivors and micronuclei were studied as biological endpoints. The results of group (1) and group (2) showed that there were no obvious differences on micronucleus frequency but there were significant increases when irradiation dose was 0.02Gy on colony formation efficiency. Although low dose ion irradiation could not contribute to DNA damages, it could enhance the colony formation efficiency. In the study of group (3) and (4), when the ion dose was 0.02 Gy, there were evident increases on surviving fraction and decreases on micronucleus frequency, but there were no statistical changes on these endpoints when the ion dose was 0.05Gy. This meant that high LET radiation could induce the adaptive response of cultured cells, furthermore, in the range of inducing ion dose , low dose irradiation was more profitable than high dose one.

分割剂量射线照射富集宫颈癌肿瘤干细胞的研究

【目的】研究分割剂量射线照射的宫颈癌Hela细胞表达肿瘤干细胞相关蛋白情况及裸鼠体内成瘤能力,探讨经此法富集宫颈癌肿瘤干细胞的可行性。【方法】Hela细胞分组接受分割剂量分别为2、4、6、8、10及12 Gy的射线照射,总照射剂量24～42 Gy。流式细胞术检测各照射组及对照组细胞的ABCG2、CD44及CD133表达率;各组细胞接种裸鼠皮下,检测其体内成瘤能力。【结果】各照射组细胞的ABCG2表达率均明显上调,以Hela-R2组(4 Gy×10次)细胞的表达率最高[(46.89±1.20)%],且随着照射次数的增加而升高(P<0.05);各组细胞的CD44及CD133表达率变化均无明显趋势;Hela-R2组细胞的裸鼠体内成瘤能力最高,其次为Hela-R5组(10 Gy×3次)。【结论】分割剂量射线照射可在体外富集宫颈癌肿瘤干细胞,以分割剂量为4 Gy组富集效果最好,诱导Hela细胞株表达ABCG2显著上调,及提高其裸鼠体内成瘤能力。

现场环境氡子体未结合态份额测量及剂量评价

氡子体未结合态份额直接影响环境中氡暴露剂量。为了弄清楚现场环境氡子体未结合态份额,准确评价氡暴露剂量,利用累积式氡子体未结合态份额测量装置对环境中氡子体未结合态份额进行了现场测量,对不同环境氡暴露剂量和未结合态氡子体的影响进行了评价。研究表明,尽管不同环境氡子体浓度有较大差别,室内外氡子体未结合态份额差别不是太明显,室内外环境氡子体未结合态份额变化范围9.27%～16.87%,未结合态氡子体对氡子体暴露有效剂量贡献的份额在30.22%～46.24%变化,矿山环境氡子体未结合态份额和剂量贡献份额明显高于室内环境。

107例瘢痕疙瘩术后两种分割剂量放疗疗效分析

目的:分析两种放疗分割方式对预防瘢痕疙瘩术后复发的疗效,探讨瘢痕疙瘩术后放疗的最佳方式。方法:北京大学第一医院放射治疗科自2011年8月至2012年10月对瘢痕疙瘩患者术后24 h内开始放疗,并采取两种放疗分割方式治疗:每天1次5 Gy照射,连续4 d(5 Gy组);每天1次4 Gy照射,连续5 d(4 Gy组)。共治疗107例患者的139个病变,为使材料更具可比性,在同患者同部位出现多个病变时,仅取一个最大病变进行疗效分析,最终纳入114个病变。参考Darzi的瘢痕疙瘩疗效标准将疗效分为治愈、好转、无效,有效为治愈与好转之和,复发指放疗无效患者。采用SPSS 14.0软件进行统计学处理和分析。结果:总有效率5 Gy组为90.7%(49/54),4 Gy组为66.7%(40/60),两组差异有统计学意义(P=0.001)。将病变部位按皮肤张力大小分为耳部面颈区、前胸肩背区、其他部位进一步分析,5 Gy组及4 Gy组的疗效分别为94.1%和85.0%(P=0.609)、89.7%和60.0%(P=0.009)、87.5%和50.0%(P=0.152),前胸肩背区5 Gy组疗效明显优于4 Gy组。两组的放疗副作用均不明显。结论:瘢痕疙瘩术后24 h内开始放疗,每天治疗1次,每次给予5 Gy(连续4 d)或4 Gy(连续5 d)均是有效的,特别是每次5 Gy(连续4 d)的放疗效果更好,提示大分割短疗程的放疗效果更好,对患者也更加经济方便,值得进一步探讨。

老年Ⅳ期胰腺癌高剂量少分次放疗的效果观察

目的评估高剂量少分次放疗模式治疗老年Ⅳ期胰腺癌的疗效及毒副反应。方法收集2011年9月-2015年5月于中国人民解放军空军总医院肿瘤放疗科就诊的胰腺癌伴远处转移患者的临床资料,所有患者接受螺旋断层放疗高剂量少分次模式治疗。通过随访获取疗效及毒副反应,依据NCI-CTCAE 4.02标准行不良反应评价。生存分析采用Kaplan-Meier法。结果共33例65岁以上患者接受高剂量少分次模式放疗,30例获得随访,获访率91.0%,其中位生存时间9个月,1年生存率为24.0%,疼痛缓解率80.0%(20/25)。17例患者可评价胰腺病灶治疗效果,其中部分缓解4例(23.5%),稳定12例(70.6%),进展1例(5.9%)。毒副反应中血液学反应3级占6.7%(2/30),无2级以上消化道反应。结论采用高剂量少分次模式治疗老年Ⅳ期胰腺癌,副反应可接受,可缓解患者癌痛,有延长生存时间的趋势。

地肤子皂苷抗过敏活性部位及量效关系的研究

分别采用4-AP致小鼠过敏性皮肤瘙痒模型和组胺致小鼠足肿胀试验，探索地肤子总皂苷硅胶柱层析的活性部位和量效关系。结果表明，地肤子抗过敏活性成分主要集中在氯仿一甲醇为9：1的2、3BV，8：2的1—3BV，7：3的1—3BV洗脱液中；地肤子总皂苷抗过敏作用的有效阈剂量为32mg／kg，良效剂量为150mg／kg，且抗过敏性瘙痒作用比抗过敏介质的致炎作用强。

2Gy多分割不同顺序照射对鼻咽癌CNE-2细胞生物效应的研究

目的探讨总剂量为2 Gy时部分分割和顺序照射对鼻咽癌CNE-2细胞的杀伤效应的差异。方法采用克隆形成法和四唑盐(MTT)比色法,检测2 Gy剂量照射后鼻咽癌CNE-2细胞的细胞生存率和具有代谢活性细胞比例。结果在多个等分割照射中,较小分割(≤0.5 Gy)多次照射的细胞存活率均明显低于单次照射组(2 Gy),差异有统计学意义(P<0.05),而较大分割(1 Gy)照射与单次照射组细胞生存率差异无统计学意义;在2个部分分割和3个部分分割照射中,随着S分割剂量的增大,各S-L和S-S-L照射组细胞生存率呈逐渐下降趋势,至S分割为0.4 Gy(S-L)或者0.5Gy(S-S-L)组时细胞生存率最低;大部分S-L照射组细胞生存率明显低于L-S照射组,大部分S-S-L照射组细胞生存率和相对细胞生存率明显低于L-S-S照射组,差异有统计学意义(P<0.05)。结论总剂量为2 Gy照射时,分割剂量大小和照射顺序是影响鼻咽癌CNE-2细胞放射治疗生物效应的重要因素。

射波刀-低分割单次大剂量立体定向放射治疗的最佳执行者

常规放疗模式沿用多年，肿瘤治愈率难以得到大的突破。放疗总剂量与肿瘤预后直接相关，按照放射生物学推断的肿瘤治疗剂量明显高于目前常规放疗模式的放射总剂量。生物有效剂量与局控率和生存率有显著相关性，其提高依赖于单次剂量的提高。短疗程高分次剂量的放射治疗模式主要通过立体定向适形放疗实现。目前立体定向放射治疗装置单次放射剂量提高至4—8Gy，但是治疗精度无法进一步提高。射渡刀在固定方式、实时位置验证、影像引导及动态追踪病灶等方面具有明显的技术优势，单次放射剂量能够提高至15～30Gy，成为短疗程单次高剂量放疗模式的最佳执行者，治疗效果更好。射波刀高分次剂量短疗程放疗模式本身在很多方面有待完善发展。