高压氧对前列腺癌细胞生长影响的研究及其临床应用价值的探讨
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摘要
一、研究背景
目前随着我国人口老龄化、人民生活水平的提高以及饮食结构的变化,前列腺癌发病率正呈逐年上升趋势,对老年男性健康的影响正逐渐凸现出来。以上海地区为例,前列腺癌发病率在1985年是2.6/10万男性人口,2000年增长到7.7/10万男性人口,2005年已达到10/10万男性人口。
高压氧(hyperbaric oxygen,HBO)是指在海平面位置2-3倍标准大气压的环境下吸入100%的纯氧,它可以使动脉血氧分压超过2000mmHg,组织氧分压接近400mmHg。HBO引起的组织氧分压升高以及氧输送增加不依赖于血红蛋白,如此高浓度的氧可以产生一系列生物化学、细胞学以及生理学方面有益的影响。HBO现已被广泛应用于临床之中,对于恶性肿瘤理论上讲HBO能够消除肿瘤自身缺氧所产生对于放疗、化疗等治疗的抵抗性,从而提高相关治疗的疗效。但是自1966年Johnson和Lauehlan首先报道HBO可能具有促进肿瘤细胞生长的作用之后,陆续有类似的个案报道出现,更加剧了人们的担心,此后很长一段时期恶性肿瘤及其病史被视为HBO治疗的禁忌症。目前HBO对于恶性肿瘤自然进程的确切影响仍不清楚,对于肿瘤细胞的生长是否具有促进生长作用仍存有争论。多数学者认为HBO并不促进肿瘤细胞的生长,但是仍有相当多的研究结果不支持此观点;于此同时,目前普遍认为HBO本身对于肿瘤细胞并没有明确的杀伤作用,单独使用HBO治疗恶性肿瘤并不具有疗效,其治疗作用往往是通过与其它治疗方法的联合应用而得以实现。
通过复习与本研究相关的文献资料发现,目前缺乏HBO对于前列腺癌细胞生长影响的实验性研究;对于HBO在前列腺癌治疗中的应用价值暂无实验研究方面的依据。针对上述现状,设计本课题拟研究以下两方面问题:首先,HBO对于前列腺癌细胞的生长是否具有促进作用,临床上应用HBO治疗前列腺癌患者是否安全?其次,HBO对于前列腺癌细胞是否具有增强其对放疗、化疗等治疗敏感性的实验依据,临床中是否可以将HBO作为前列腺癌的辅助治疗?
二、研究目的
1、研究高压氧对前列腺癌LNCaP细胞株(激素依赖型)、PC-3细胞株(激素非依赖型)生长的影响;
2、探讨高压氧在前列腺癌治疗中的应用价值。
三、研究方法
1、将LNCaP细胞株、PC-3细胞株随机分为对照组常压常氧条件下培养,实验组每日进行1次0.25 MPa(1个标准大气压=0.1 MPa)高压氧暴露,持续70分钟,连续5日;
2、分别应用光学显微镜及透射电子显微镜、CCK—8细胞计数试剂盒、流式细胞仪以及Transwell迁移小室,对所有两组细胞的形态学、增殖能力、细胞周期分布以及迁移能力进行观察比较;
3、构建PC—3细胞株对照组及实验组SCID小鼠移植瘤模型,观察并对比两组移植瘤在生长体积变化、瘤体微血管密度(MVD)、以及瘤细胞增殖(Ki—67蛋白)与凋亡(p53、p27蛋白)方面的差异。
四、结果
1、不同处理组的两类细胞大体及超微形态结构对比均未发现明显改变,细胞增殖及迁移能力均不存在显著性差异(p＞0.05);
2、流式细胞仪检测显示高压氧导致LNCaP、PC—3细胞株在G_2/M期的蓄积;
3、成功建立两组PC-3细胞株移植瘤动物模型,致瘤率为100%,肿瘤接种后第28天,对照组移植瘤体积为(433.6±12.8)mm~3,实验组为(425.8±13.9)mm~3,两组移植瘤生长体积变化差异无显著性(p＞0.05);
4、对照组移植瘤微血管密度及Ki—67、p53、p27蛋白表达的阳性细胞率分别为20.1±2.31、(50.6±7.3)%、(30.5±4.7)%、(85.3±6.4)%,实验组分别为22.4±3.19、(55.2±6.7)%、(31.2±5.3)%、(80.4±5.7)%,病理学特征均无显著性差异(p＞0.05)。
五、结论
1、高压氧不促进前列腺癌细胞的增殖,对前列腺癌中新生血管也无明显影响,高压氧可能不会促进潜伏性前列腺癌的进展,即前列腺癌患者接受高压氧疗可能是安全的;
2、高压氧促使两类前列腺癌细胞在G_2/M期的蓄积,形成细胞周期同步化,可能会增强前列腺癌对其它治疗方法如放疗、化疗等的敏感性,提高治疗效果;
3、由于条件限制和认识不足,目前高压氧在前列腺癌治疗的临床应用尚较少,应用价值有待进一步验证,其合理的病例选择以及最佳的联合应用方案尚需进一步研究。
BACKGROUND
With the development of China and diet changed,the overall incidence of prostate cancer in men increased annually and became a more and more serious healthy problem to the elderly man.Between 1985 and 2005,the incidence of prostate cancer in men increased from 2.6 per 100,000 to 10 per 100,000 in ShangHai territory,an increase of approximately 300%.
Hyperbaric oxygen(HBO)—100 percent oxygen at two to three times the atmospheric pressure at sea level—can result in arterial oxygen tension in excess of 2000 mmHg and oxygen tension in tissue of almost 400 mmHg.HBO increases oxygen tensions and oxygen delivery to tissues independent of hemoglobin.Such doses of oxygen have a number of beneficial biochemical,cellular,and physiologic effects. Over the past 50 years,HBO therapy has been recommended and used in a wide variety of medical conditions.In theory,HBO may remove the hypoxic stimulus;that drives tumour angiogenesis and other adaptations that facilitate tumour growth in a hypoxic environment,thus sensitizing them to radiotherapy,chemotherapy and other therapeutic treatment modalities.Although serious adverse events are rare,HBO cannot be regarded as an entirely benign intervention.In 1966 Johnson and Lauchlan first reported a tumor-stimulatory effect with HBO,demonstrating increased metastases in patients with cervical cancer.The effect of HBO administration on tumour growth has been inconclusive.HBO has been previously contraindicated in the treatment of malignancy due to concern that an increased oxygen pressure may stimulate tumour growth via re-oxygenation of hypoxic tumour cells and increased neovascularization.It has further been suggested that HBO may increase the incidence and/or rate of growth of local recurrence or remote metastatic disease in patients with a history of malignancy.Although most of the experimental and clinical studies suggest that HBO has no direct effect on tumors,there is a considerable amount of conflicting evidence to support the idea that HBO has an effect.The general consensus is that HBO could not kill tumor cells directly and remains ineffective as a stand-alone therapy.However,HBO may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment.
But the exact effect of HBO on the natural history of malignancy is uncertain. Minimal evidence exists regarding the direct effect of HBO on prostate cancer cells. And there are no experimental studies showing treatment with HBO during other therapeutic treatment modalities is to improve the response of prostate cancer.The experimental studies could answer the following questions:
1.Does HBO accelerate the growth of indolent prostate cancer cells(suggesting HBO administration is safe when it is used to manage patients treated by other therapies for prostate cancer)?
2.HBO may improve the ability of other therapies to kill hypoxic prostate cancer cells. As an adjuvant therapy,HBO may result in a reduction in mortality and recurrence?
OBJECTIVE
1.To detect the effects of HBO on human prostate LNCaP and PC-3 cell lines.
2.Assess HBO potential role in therapy for prostate cancer.
METHODS
1.Human prostate LNCaP and PC-3 cell lines were randomized to undergo 5 sessions of either HBO or normobaric air in standardized conditions.Microscope and transmission electron microscope were used to detect the cell morphosis.
2.Detect LNCaP and PC-3 cell lines proliferation in response to HBO by the CCK-8 assay.
3.Observe the effection of HBO on LNCaP and PC-3 cell cycle by FCM.
4.Transwell system were used to assess HBO effect on LNCaP and PC-3 cell migration.
5.Form prostate cancer PC-3 cell xenografts,and analysis of developed tumours' grow up.At the end of the experiment detect xenografts's microvessel density(MVD),apoptosis markers(p53,p27 protein) and proliferative index(Ki-67 protein) by immunohistochemistry.
RESULTS
1.Exposure to HBO at 2.5 atm for 5 treatment sessions comprised a daily 70-min session had no effect on LNCaP and PC-3 cells' proliferation,ultramicro morphosis and cell migration in vitro.
2.HBO induced LNCaP and PC-3 cell lines to enter the cell cycle and accumulated them in G_2/M stage.
3.No differences were observed in volume of prostate cancer PC-3 cell xenografts, tumour microvessel density,proliferative index and apoptosis markers compared to the control group(p＞0.05).
CONCLUSIONS
HBO did not have a tumour stimulatory effect on prostate cancer and may potentially be used safely as an adjuvant therapy.HBO therapy may improve therapeutic efficacy of prostate cancer. Further research may be warranted pending outcomes of the clinical research in evaluating the adjunctive potential of HBO with other therapeutic treatment modalities.
目前随着我国人口老龄化、人民生活水平的提高以及饮食结构的变化,前列腺癌发病率正呈逐年上升趋势,对老年男性健康的影响正逐渐凸现出来。以上海地区为例,前列腺癌发病率在1985年是2.6/10万男性人口,2000年增长到7.7/10万男性人口,2005年已达到10/10万男性人口。
高压氧(hyperbaric oxygen,HBO)是指在海平面位置2-3倍标准大气压的环境下吸入100%的纯氧,它可以使动脉血氧分压超过2000mmHg,组织氧分压接近400mmHg。HBO引起的组织氧分压升高以及氧输送增加不依赖于血红蛋白,如此高浓度的氧可以产生一系列生物化学、细胞学以及生理学方面有益的影响。HBO现已被广泛应用于临床之中,对于恶性肿瘤理论上讲HBO能够消除肿瘤自身缺氧所产生对于放疗、化疗等治疗的抵抗性,从而提高相关治疗的疗效。但是自1966年Johnson和Lauehlan首先报道HBO可能具有促进肿瘤细胞生长的作用之后,陆续有类似的个案报道出现,更加剧了人们的担心,此后很长一段时期恶性肿瘤及其病史被视为HBO治疗的禁忌症。目前HBO对于恶性肿瘤自然进程的确切影响仍不清楚,对于肿瘤细胞的生长是否具有促进生长作用仍存有争论。多数学者认为HBO并不促进肿瘤细胞的生长,但是仍有相当多的研究结果不支持此观点;于此同时,目前普遍认为HBO本身对于肿瘤细胞并没有明确的杀伤作用,单独使用HBO治疗恶性肿瘤并不具有疗效,其治疗作用往往是通过与其它治疗方法的联合应用而得以实现。
通过复习与本研究相关的文献资料发现,目前缺乏HBO对于前列腺癌细胞生长影响的实验性研究;对于HBO在前列腺癌治疗中的应用价值暂无实验研究方面的依据。针对上述现状,设计本课题拟研究以下两方面问题:首先,HBO对于前列腺癌细胞的生长是否具有促进作用,临床上应用HBO治疗前列腺癌患者是否安全?其次,HBO对于前列腺癌细胞是否具有增强其对放疗、化疗等治疗敏感性的实验依据,临床中是否可以将HBO作为前列腺癌的辅助治疗?
二、研究目的
1、研究高压氧对前列腺癌LNCaP细胞株(激素依赖型)、PC-3细胞株(激素非依赖型)生长的影响;
2、探讨高压氧在前列腺癌治疗中的应用价值。
三、研究方法
1、将LNCaP细胞株、PC-3细胞株随机分为对照组常压常氧条件下培养,实验组每日进行1次0.25 MPa(1个标准大气压=0.1 MPa)高压氧暴露,持续70分钟,连续5日;
2、分别应用光学显微镜及透射电子显微镜、CCK—8细胞计数试剂盒、流式细胞仪以及Transwell迁移小室,对所有两组细胞的形态学、增殖能力、细胞周期分布以及迁移能力进行观察比较;
3、构建PC—3细胞株对照组及实验组SCID小鼠移植瘤模型,观察并对比两组移植瘤在生长体积变化、瘤体微血管密度(MVD)、以及瘤细胞增殖(Ki—67蛋白)与凋亡(p53、p27蛋白)方面的差异。
四、结果
1、不同处理组的两类细胞大体及超微形态结构对比均未发现明显改变,细胞增殖及迁移能力均不存在显著性差异(p＞0.05);
2、流式细胞仪检测显示高压氧导致LNCaP、PC—3细胞株在G_2/M期的蓄积;
3、成功建立两组PC-3细胞株移植瘤动物模型,致瘤率为100%,肿瘤接种后第28天,对照组移植瘤体积为(433.6±12.8)mm~3,实验组为(425.8±13.9)mm~3,两组移植瘤生长体积变化差异无显著性(p＞0.05);
4、对照组移植瘤微血管密度及Ki—67、p53、p27蛋白表达的阳性细胞率分别为20.1±2.31、(50.6±7.3)%、(30.5±4.7)%、(85.3±6.4)%,实验组分别为22.4±3.19、(55.2±6.7)%、(31.2±5.3)%、(80.4±5.7)%,病理学特征均无显著性差异(p＞0.05)。
五、结论
1、高压氧不促进前列腺癌细胞的增殖,对前列腺癌中新生血管也无明显影响,高压氧可能不会促进潜伏性前列腺癌的进展,即前列腺癌患者接受高压氧疗可能是安全的;
2、高压氧促使两类前列腺癌细胞在G_2/M期的蓄积,形成细胞周期同步化,可能会增强前列腺癌对其它治疗方法如放疗、化疗等的敏感性,提高治疗效果;
3、由于条件限制和认识不足,目前高压氧在前列腺癌治疗的临床应用尚较少,应用价值有待进一步验证,其合理的病例选择以及最佳的联合应用方案尚需进一步研究。
BACKGROUND
With the development of China and diet changed,the overall incidence of prostate cancer in men increased annually and became a more and more serious healthy problem to the elderly man.Between 1985 and 2005,the incidence of prostate cancer in men increased from 2.6 per 100,000 to 10 per 100,000 in ShangHai territory,an increase of approximately 300%.
Hyperbaric oxygen(HBO)—100 percent oxygen at two to three times the atmospheric pressure at sea level—can result in arterial oxygen tension in excess of 2000 mmHg and oxygen tension in tissue of almost 400 mmHg.HBO increases oxygen tensions and oxygen delivery to tissues independent of hemoglobin.Such doses of oxygen have a number of beneficial biochemical,cellular,and physiologic effects. Over the past 50 years,HBO therapy has been recommended and used in a wide variety of medical conditions.In theory,HBO may remove the hypoxic stimulus;that drives tumour angiogenesis and other adaptations that facilitate tumour growth in a hypoxic environment,thus sensitizing them to radiotherapy,chemotherapy and other therapeutic treatment modalities.Although serious adverse events are rare,HBO cannot be regarded as an entirely benign intervention.In 1966 Johnson and Lauchlan first reported a tumor-stimulatory effect with HBO,demonstrating increased metastases in patients with cervical cancer.The effect of HBO administration on tumour growth has been inconclusive.HBO has been previously contraindicated in the treatment of malignancy due to concern that an increased oxygen pressure may stimulate tumour growth via re-oxygenation of hypoxic tumour cells and increased neovascularization.It has further been suggested that HBO may increase the incidence and/or rate of growth of local recurrence or remote metastatic disease in patients with a history of malignancy.Although most of the experimental and clinical studies suggest that HBO has no direct effect on tumors,there is a considerable amount of conflicting evidence to support the idea that HBO has an effect.The general consensus is that HBO could not kill tumor cells directly and remains ineffective as a stand-alone therapy.However,HBO may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment.
But the exact effect of HBO on the natural history of malignancy is uncertain. Minimal evidence exists regarding the direct effect of HBO on prostate cancer cells. And there are no experimental studies showing treatment with HBO during other therapeutic treatment modalities is to improve the response of prostate cancer.The experimental studies could answer the following questions:
1.Does HBO accelerate the growth of indolent prostate cancer cells(suggesting HBO administration is safe when it is used to manage patients treated by other therapies for prostate cancer)?
2.HBO may improve the ability of other therapies to kill hypoxic prostate cancer cells. As an adjuvant therapy,HBO may result in a reduction in mortality and recurrence?
OBJECTIVE
1.To detect the effects of HBO on human prostate LNCaP and PC-3 cell lines.
2.Assess HBO potential role in therapy for prostate cancer.
METHODS
1.Human prostate LNCaP and PC-3 cell lines were randomized to undergo 5 sessions of either HBO or normobaric air in standardized conditions.Microscope and transmission electron microscope were used to detect the cell morphosis.
2.Detect LNCaP and PC-3 cell lines proliferation in response to HBO by the CCK-8 assay.
3.Observe the effection of HBO on LNCaP and PC-3 cell cycle by FCM.
4.Transwell system were used to assess HBO effect on LNCaP and PC-3 cell migration.
5.Form prostate cancer PC-3 cell xenografts,and analysis of developed tumours' grow up.At the end of the experiment detect xenografts's microvessel density(MVD),apoptosis markers(p53,p27 protein) and proliferative index(Ki-67 protein) by immunohistochemistry.
RESULTS
1.Exposure to HBO at 2.5 atm for 5 treatment sessions comprised a daily 70-min session had no effect on LNCaP and PC-3 cells' proliferation,ultramicro morphosis and cell migration in vitro.
2.HBO induced LNCaP and PC-3 cell lines to enter the cell cycle and accumulated them in G_2/M stage.
3.No differences were observed in volume of prostate cancer PC-3 cell xenografts, tumour microvessel density,proliferative index and apoptosis markers compared to the control group(p＞0.05).
CONCLUSIONS
HBO did not have a tumour stimulatory effect on prostate cancer and may potentially be used safely as an adjuvant therapy.HBO therapy may improve therapeutic efficacy of prostate cancer. Further research may be warranted pending outcomes of the clinical research in evaluating the adjunctive potential of HBO with other therapeutic treatment modalities.
引文
1、前列腺癌流行病学.前列腺癌诊断治疗指南,2007
2.、孙颖浩。我国前列腺癌的研究现状.中华泌尿外科杂志,2004;25(2):77-79.
3、Johnson RJR,Lauchlan SC.Epidermoid carcinoma of the cervix treated by 60Co therapy and hyperbaric oxygen.In:Proceedings of the third international congress on hyperbaric medicine;1966.p.648-52.
4、Lambertsen CJ,Kough RH,Cooper DY,Emmel GL,Loeschcke HH,Schmidt CF.Oxygen toxicity:effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport,cerebral circulation and cerebral metabolism.J Appl Physiol 1953;5:471-86.
5、Mader J,T rBown GL,cGkiuan JCW,ells CH,einRarz AJ.A mechanism of the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits.J Infect Dis 1980;142:915-22.
6、Granowitz EV,et al.Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.Undersea Hyperb Med 2002;29:216-225.
7、Feldmeier J,et al.Hyperbaric oxygen:does it promote growth or recurrence of malignancy? Undersea Hyperb Med 2003;30:1-18.
8、Horoszewicz JS,Leong SS,Kawinski E,et al.LNCaP model of human prostatic carcinoma.Cancer Res,1983,43:1809-1818.
9、Kaighn ME,Shankar N,Ohnuki Y,et al.Establishment and characterization of a human prostatic carcinoma cell line(PC-3).Investigative Urol,1979,17:16-23.
10、Flickinger RA.Induction of tumor cell diferentiation.Diferentiation,2000,65(5): 241-245.
11、细胞培养,司徒镇强主编.西安世界图书出版公司,1996,145.
12、Daruwalla J,Christophi C.Effect of hyperbaric oxygen in the treatment of malignancy:a review.World J Surg30(12):2112-31,2006.
13、Kains JE,Prepmeier EH.Exposure to hyperbaric oxygen induces cell cycle perturbation in prostate cancer cells.In Vitro Cell Dev Biol Anim,1999,35(2):98-101.
14、陈洪雷,彭勇.高压氧与肿瘤放射治疗.国际放射学核医学杂志,2005;29(6),289-291。
15、Cvetkovic D,et al.Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer.Urology 2001;57:821-825.
16、Ziemer LS,et al.Hypoxia and VEGF mRNA expression in human tumors.Neoplasia 2001;3:500-508.
17、Ramnath V,Kuttan G,Kuttan R,et al.Cytotoxic and antitumours activity of Abrin on transplanted tumours in mice.Indian J Physiol Pharmacol 46:69-77,2002.
18、Weidner N,Carroll PR,Flax J,et al.Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.Am J Pathol 143(2):401-409,1993.
19、Bosma M J,Carroll AM.The SCID mouse mutant:definition,characterization,and potential uses.Annu Rev Immunol.1991;9:323-50.Review.
20、Moulder JE,et al.Tumor hypoxia:its impact on cancer therapy.Cancer Metastasis Rev 1987;5:313-341.
21、Horiuchi A,Imai T,Shimizu M,et al.Hypoxia-induced changes in the expression of VEGF,HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells. Anticancer Res 2002; 22:2697-2702.
22、 Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis [J]. J Clin Onco, 2005; 23: 1011 — 1027.
23、 Havrilesky L, Darcy M, Hamdan H,et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2003; 21:3814-3825.
24、 Melillo G. Inhibiting hypoxia-inducible factor 1 for cancer therapy . J Mol Cancer Res, 2006; 4: 601-605.
25、 Lu H, Forbes RA, Verma A,et al. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis: oncogenes in tumor metabolism, tumorigenesis, and poptosis.[J] Biol Chem 2002; 277:23111 —23115.
26、 Cooper R, Sarioglu S, Sokmen S, et al.Glucose transporter-1(GLUT-1): a potential marker of prognosis in rectal carcinoma? Br J Cancer, 2003, 89: 870— 876.
27、 Chung JK, Lee YJ, Kim SK, et al. Comparison of[~(18)F] fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. Nucl Med Commun. 2004. 25: 11 — 17.
28、 Behrend L, Henderson G, Zwacka RM,et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003;31:1441 —1444.
29、 Kalns J, Krock L, Piepmeier E Jr. The effect of hyperbaric oxygen on growth and chemosensitivity of metastatic prostate cancer. Anticancer Res 18:363-7, 1998.
30、 Dettmer CM, Kramer S, Gottlieb SF, et al. The effect of increased oxygen tensions upon animal tumour growth. Am J Roentgenol, Radium Ther Nucl Med 102(4): 804-10, 1968.
31、 Mestrovic J, Kosuta D, Gosovic S, et al. Suppression of rat tumour colonies in the lung by oxygen at high pressure is a local effect. Clin Exp Metasta 8(2): 113-9, 1990.
32、 Daruwalla J, Christophi C. The effect of hyperbaric oxygen therapy on tumour growth in a mouse model of colorectal cancer liver metastases. Eur J Cancer 42(18): 3304-11,2006.
33、 Horiuchi A, et al. Hypoxia-induced changes in the expression of VEGF, HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells. Anticancer Res 2002;22:2697-2702.
34、 Benhar M, et al. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 2002;3:420-425.
35、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 2001;3:323—327.
36、 Talior I, et al. Increased glucose uptake promotes oxidative stress and PKC-delta activation in adipocytes of obese,insulin-resistant mice. Am J Physiol Endocrinol Metab 2003;285:E295-E302.
37、 Arnold RS, et al. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc Natl Acad Sci USA 2001;98:5550-5555.
38、 Jackson AL, et al. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 2001 ;477:7—21.
39、 Behrend L, et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003 ;31:1441-1444.
40、 Hileman EO, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004;53:209-219.
41、 Portakal O, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-284.
42、 Laurent A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res 2005;65:948-956.
43、 Kong Q, et al. A threshold concept for cancer therapy. Med Hypotheses 2000;55:29-35.
44、 Marx RE, Ehler WJ, Tayapongsak P, et al. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surgl60(5):519-24, 1990.
45、 Alagoz T, Buller RE, Anderson B, et al. Evaluation of hyperbaric oxygen as a chemosensitizer in the treatment of epithelial ovarian cancer in xenografts in mice. Cancer 75(9): 2313-22, 1995.
46、Hileman EO, Liu J, AlbitarM, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004; 53:209-219.
47、 Narozny W, Kuczkowski J, Mikaszewski B. Radionecrosis or tumor recurrence after radiation: importance of choice for HBO. Otolaryngol Head Neck Surg ,2007 Jul;137(1):176-7.
48、 Bennett M, Feldmeier J, Smee R, et al. Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD005007.
49、Kohshi K,Yamamoto H,Nakahara A,et al.Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas.J Neurooncol,2007 May;82(3):297-303.
50、林静,王曙光。高压氧下氨甲喋呤透过血脑屏障的观察.中华航海医学杂志,1998;5(4):222.
51、高春锦,杨捷云。实用高压氧学[M].北京:学苑出版社,1997,1.
52、Takiguchi N,Saito N,Nunomura M,et al.Use of 5-FU plus hyperbaric oxygen for treating malignant tumors:evaluation of antitumor effect and measurement of 5-FU in individual organs.Cancer Cheomother Pharmacol,2001,47(1):11-14.
53、Petre PM,Baciewicz FA Jr,Tigan S,et al.Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model.J Thorac Cardiovasc Surg,2003,125(1):85-95.
1、Lambertsen C J,Kough RH,Cooper DY,Emmel GL,Loeschcke HH,Schmidt CF.Oxygen toxicity:effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport,cerebral circulation and cerebral metabolism.J Appl Physiol 1953;5:471-86.
2、Mader J,T rBown GL,cGkiuan JCW,ells CH,einRarz AJ.A mechanisra of the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits.J Infect Dis 1980;142:915-22.
3、Moulder JE,et al.Tumor hypoxia:its impact on cancer therapy.Cancer Metastasis Rev 1987;5:313-341.
4、Kizaka-Kondoh S,et al.Tumor hypoxia:a target for selective cancer therapy.Cancer Sci 2003;94:1021-1028.
5、Cvetkovic D,et al.Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer.Urology 2001;57:821-825.
6、Ziemer LS,et al.Hypoxia and VEGF mRNA expression in human tumors.Neoplasia 2001;3:500-508.
7、Horiuchi A,et al.Hypoxia-induced changes in the expression of VEGF,HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells.Anticancer Res 2002;22:2697-2702.
8、Graeber TG,et al.Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996;379:88-91.
9、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer.Breast Cancer Res 2001;3:323-327.
10、 Havrilesky L, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003;21:3814-3825.
11、 Graeber TG, et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996;379:88-91.
12、 Ravi R, et al. Regulation of tumor angiogenesis by p53 induced degradation of hypoxia-inducible factor lalpha. Genes Dev 2000; 14:34-44.
13、 Warburg O, et al. On growth of cancer cells in media in which glucose is replaced by galactose. Hoppe Seylers Z Physiol Chem 1967;348:1686-1687.
14、 Webster KA, et al. Coordinate reciprocal trends in glycolytic and mitochondrial transcript accumulations during the in vitro differentiation of human myoblasts. J Cell Physiol 1990;142:566-573.
15、 Maxwell PH, et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 1997;94:8104-8109.
16、 Mathupala SP, et al. Glucose catabolism in cancer cells.Isolation, sequence, and activity of the promoter for type II hexokinase. J Biol Chem 1995;270:16918-16925.
17、 Lu H, et al. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis: oncogenes in tumor metabolism, tumorigenesis, and apoptosis. J Biol Chem 2002;277:23111-23115.
18、 Benhar M, et al. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 2002;3:420-425.
19、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 2001;3:323-327.
20、 Talior I, et al. Increased glucose uptake promotes oxidative stress and PKC--delta activation in adipocytes of obese,insulin-resistant mice. Am J Physiol Endocrinol Metab 2003;285:E295-E302.
21、 Arnold RS, et al. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc Natl Acad Sci USA 2001 ;98:5550-5555.
22、 Jackson AL, et al. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 2001;477:7-21.
23、 Behrend L, et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003 ;31:1441-1444.
24、 Hileman EO, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004;53:209-219.
25、 Portakal O, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-284.
26、 Laurent A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res 2005;65:948-956.
27、 Kong Q, et al. A threshold concept for cancer therapy. Med Hypotheses 2000;55:29-35.
28、Granowitz EV,et al.Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.Undersea Hyperb Med 2002;29:216-225.
29、Feldmeier J,et al.Hyperbaric oxygen:does it promote growth or recurrence of malignancy? Undersea Hyperb Med 2003;30:1-18.
30、Marx RE,et al.Relationship of oxygen dose to angiogenesis induction in irradiated tissue.Am J Surg 1990;160:519-524.
31、Phillips SJ..Physiology of wound healing and surgical wound care.ASAIO J 2000;46:S2-S5.
32、Johnson RJR,Lauchlan SC.Epidermoid carcinoma of the cervix treated by 60Co therapy and hyperbaric oxygen.In:Proceedings of the third international congress on hyperbaric medicine;1966.p.648-52.
33、Kains JE,Prepmeier EH.Exposure to hyperbaric oxygen induces cell cycle perturbation in prostate cancer cells.In Vitro Cell Dev Biol Anim,1999,35(2):98-101.
34、陈洪雷,彭勇.高压氧与肿瘤放射治疗.国际放射学核医学杂志,2005,29(6),289-291.
35、Martin DF,et al.Enhancement of tumor radiation response by the combination of a perfluorochemical emulsion and hyperbaric oxygen.Int J Radiat Oncol Biol Phys 1987;747-751.
36、Kmoshita Y,Kohshi K,Kunugita N,et al.Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging.Br J Cancer,2000,82(1):88-92.
37、Van den Brenk HA,et al.An analysis of the progression and development of metastases in patients receiving x-radiation in hyperbaric oxygen.Clin Radiol 1967;18:54-61.
38、Henk JM,et al.Radiotherapy and hyperbaric oxygen in head and neck cancer:final report of first controlled clinical trial.Lancet 1977;2:101-103.
39、林静,王曙光.高压氧下氨甲喋呤透过血脑屏障的观察[J].中华航海医学杂志,1998,5(4):222.
40、高春锦,杨捷云.实用高压氧学[M].北京:学苑出版社,1997.1.
41、Takiguchi N,Saito N,Nunomura M,et al.Use of 5-FU plus hyperbaric oxygen for treating malignant tumors:evaluation of antitumor effect and measurement of 5-FU in individual organs.Cancer Cheomother Pharmacol,2001,47(1):11-14.
42、Petre PM,Baciewicz FA Jr,Tigan S,et al.Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model.J Thorac Cardiovasc Surg,2003,125(1):85-95.
2.、孙颖浩。我国前列腺癌的研究现状.中华泌尿外科杂志,2004;25(2):77-79.
3、Johnson RJR,Lauchlan SC.Epidermoid carcinoma of the cervix treated by 60Co therapy and hyperbaric oxygen.In:Proceedings of the third international congress on hyperbaric medicine;1966.p.648-52.
4、Lambertsen CJ,Kough RH,Cooper DY,Emmel GL,Loeschcke HH,Schmidt CF.Oxygen toxicity:effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport,cerebral circulation and cerebral metabolism.J Appl Physiol 1953;5:471-86.
5、Mader J,T rBown GL,cGkiuan JCW,ells CH,einRarz AJ.A mechanism of the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits.J Infect Dis 1980;142:915-22.
6、Granowitz EV,et al.Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.Undersea Hyperb Med 2002;29:216-225.
7、Feldmeier J,et al.Hyperbaric oxygen:does it promote growth or recurrence of malignancy? Undersea Hyperb Med 2003;30:1-18.
8、Horoszewicz JS,Leong SS,Kawinski E,et al.LNCaP model of human prostatic carcinoma.Cancer Res,1983,43:1809-1818.
9、Kaighn ME,Shankar N,Ohnuki Y,et al.Establishment and characterization of a human prostatic carcinoma cell line(PC-3).Investigative Urol,1979,17:16-23.
10、Flickinger RA.Induction of tumor cell diferentiation.Diferentiation,2000,65(5): 241-245.
11、细胞培养,司徒镇强主编.西安世界图书出版公司,1996,145.
12、Daruwalla J,Christophi C.Effect of hyperbaric oxygen in the treatment of malignancy:a review.World J Surg30(12):2112-31,2006.
13、Kains JE,Prepmeier EH.Exposure to hyperbaric oxygen induces cell cycle perturbation in prostate cancer cells.In Vitro Cell Dev Biol Anim,1999,35(2):98-101.
14、陈洪雷,彭勇.高压氧与肿瘤放射治疗.国际放射学核医学杂志,2005;29(6),289-291。
15、Cvetkovic D,et al.Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer.Urology 2001;57:821-825.
16、Ziemer LS,et al.Hypoxia and VEGF mRNA expression in human tumors.Neoplasia 2001;3:500-508.
17、Ramnath V,Kuttan G,Kuttan R,et al.Cytotoxic and antitumours activity of Abrin on transplanted tumours in mice.Indian J Physiol Pharmacol 46:69-77,2002.
18、Weidner N,Carroll PR,Flax J,et al.Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.Am J Pathol 143(2):401-409,1993.
19、Bosma M J,Carroll AM.The SCID mouse mutant:definition,characterization,and potential uses.Annu Rev Immunol.1991;9:323-50.Review.
20、Moulder JE,et al.Tumor hypoxia:its impact on cancer therapy.Cancer Metastasis Rev 1987;5:313-341.
21、Horiuchi A,Imai T,Shimizu M,et al.Hypoxia-induced changes in the expression of VEGF,HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells. Anticancer Res 2002; 22:2697-2702.
22、 Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis [J]. J Clin Onco, 2005; 23: 1011 — 1027.
23、 Havrilesky L, Darcy M, Hamdan H,et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2003; 21:3814-3825.
24、 Melillo G. Inhibiting hypoxia-inducible factor 1 for cancer therapy . J Mol Cancer Res, 2006; 4: 601-605.
25、 Lu H, Forbes RA, Verma A,et al. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis: oncogenes in tumor metabolism, tumorigenesis, and poptosis.[J] Biol Chem 2002; 277:23111 —23115.
26、 Cooper R, Sarioglu S, Sokmen S, et al.Glucose transporter-1(GLUT-1): a potential marker of prognosis in rectal carcinoma? Br J Cancer, 2003, 89: 870— 876.
27、 Chung JK, Lee YJ, Kim SK, et al. Comparison of[~(18)F] fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. Nucl Med Commun. 2004. 25: 11 — 17.
28、 Behrend L, Henderson G, Zwacka RM,et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003;31:1441 —1444.
29、 Kalns J, Krock L, Piepmeier E Jr. The effect of hyperbaric oxygen on growth and chemosensitivity of metastatic prostate cancer. Anticancer Res 18:363-7, 1998.
30、 Dettmer CM, Kramer S, Gottlieb SF, et al. The effect of increased oxygen tensions upon animal tumour growth. Am J Roentgenol, Radium Ther Nucl Med 102(4): 804-10, 1968.
31、 Mestrovic J, Kosuta D, Gosovic S, et al. Suppression of rat tumour colonies in the lung by oxygen at high pressure is a local effect. Clin Exp Metasta 8(2): 113-9, 1990.
32、 Daruwalla J, Christophi C. The effect of hyperbaric oxygen therapy on tumour growth in a mouse model of colorectal cancer liver metastases. Eur J Cancer 42(18): 3304-11,2006.
33、 Horiuchi A, et al. Hypoxia-induced changes in the expression of VEGF, HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells. Anticancer Res 2002;22:2697-2702.
34、 Benhar M, et al. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 2002;3:420-425.
35、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 2001;3:323—327.
36、 Talior I, et al. Increased glucose uptake promotes oxidative stress and PKC-delta activation in adipocytes of obese,insulin-resistant mice. Am J Physiol Endocrinol Metab 2003;285:E295-E302.
37、 Arnold RS, et al. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc Natl Acad Sci USA 2001;98:5550-5555.
38、 Jackson AL, et al. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 2001 ;477:7—21.
39、 Behrend L, et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003 ;31:1441-1444.
40、 Hileman EO, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004;53:209-219.
41、 Portakal O, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-284.
42、 Laurent A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res 2005;65:948-956.
43、 Kong Q, et al. A threshold concept for cancer therapy. Med Hypotheses 2000;55:29-35.
44、 Marx RE, Ehler WJ, Tayapongsak P, et al. Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am J Surgl60(5):519-24, 1990.
45、 Alagoz T, Buller RE, Anderson B, et al. Evaluation of hyperbaric oxygen as a chemosensitizer in the treatment of epithelial ovarian cancer in xenografts in mice. Cancer 75(9): 2313-22, 1995.
46、Hileman EO, Liu J, AlbitarM, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004; 53:209-219.
47、 Narozny W, Kuczkowski J, Mikaszewski B. Radionecrosis or tumor recurrence after radiation: importance of choice for HBO. Otolaryngol Head Neck Surg ,2007 Jul;137(1):176-7.
48、 Bennett M, Feldmeier J, Smee R, et al. Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD005007.
49、Kohshi K,Yamamoto H,Nakahara A,et al.Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas.J Neurooncol,2007 May;82(3):297-303.
50、林静,王曙光。高压氧下氨甲喋呤透过血脑屏障的观察.中华航海医学杂志,1998;5(4):222.
51、高春锦,杨捷云。实用高压氧学[M].北京:学苑出版社,1997,1.
52、Takiguchi N,Saito N,Nunomura M,et al.Use of 5-FU plus hyperbaric oxygen for treating malignant tumors:evaluation of antitumor effect and measurement of 5-FU in individual organs.Cancer Cheomother Pharmacol,2001,47(1):11-14.
53、Petre PM,Baciewicz FA Jr,Tigan S,et al.Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model.J Thorac Cardiovasc Surg,2003,125(1):85-95.
1、Lambertsen C J,Kough RH,Cooper DY,Emmel GL,Loeschcke HH,Schmidt CF.Oxygen toxicity:effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport,cerebral circulation and cerebral metabolism.J Appl Physiol 1953;5:471-86.
2、Mader J,T rBown GL,cGkiuan JCW,ells CH,einRarz AJ.A mechanisra of the amelioration by hyperbaric oxygen of experimental staphylococcal osteomyelitis in rabbits.J Infect Dis 1980;142:915-22.
3、Moulder JE,et al.Tumor hypoxia:its impact on cancer therapy.Cancer Metastasis Rev 1987;5:313-341.
4、Kizaka-Kondoh S,et al.Tumor hypoxia:a target for selective cancer therapy.Cancer Sci 2003;94:1021-1028.
5、Cvetkovic D,et al.Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer.Urology 2001;57:821-825.
6、Ziemer LS,et al.Hypoxia and VEGF mRNA expression in human tumors.Neoplasia 2001;3:500-508.
7、Horiuchi A,et al.Hypoxia-induced changes in the expression of VEGF,HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells.Anticancer Res 2002;22:2697-2702.
8、Graeber TG,et al.Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996;379:88-91.
9、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer.Breast Cancer Res 2001;3:323-327.
10、 Havrilesky L, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003;21:3814-3825.
11、 Graeber TG, et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996;379:88-91.
12、 Ravi R, et al. Regulation of tumor angiogenesis by p53 induced degradation of hypoxia-inducible factor lalpha. Genes Dev 2000; 14:34-44.
13、 Warburg O, et al. On growth of cancer cells in media in which glucose is replaced by galactose. Hoppe Seylers Z Physiol Chem 1967;348:1686-1687.
14、 Webster KA, et al. Coordinate reciprocal trends in glycolytic and mitochondrial transcript accumulations during the in vitro differentiation of human myoblasts. J Cell Physiol 1990;142:566-573.
15、 Maxwell PH, et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 1997;94:8104-8109.
16、 Mathupala SP, et al. Glucose catabolism in cancer cells.Isolation, sequence, and activity of the promoter for type II hexokinase. J Biol Chem 1995;270:16918-16925.
17、 Lu H, et al. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis: oncogenes in tumor metabolism, tumorigenesis, and apoptosis. J Biol Chem 2002;277:23111-23115.
18、 Benhar M, et al. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep 2002;3:420-425.
19、 Brown NS, et al. Hypoxia and oxidative stress in breast cancer; oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 2001;3:323-327.
20、 Talior I, et al. Increased glucose uptake promotes oxidative stress and PKC--delta activation in adipocytes of obese,insulin-resistant mice. Am J Physiol Endocrinol Metab 2003;285:E295-E302.
21、 Arnold RS, et al. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc Natl Acad Sci USA 2001 ;98:5550-5555.
22、 Jackson AL, et al. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 2001;477:7-21.
23、 Behrend L, et al. Reactive oxygen species in oncogenic transformation. Biochem Soc Trans 2003 ;31:1441-1444.
24、 Hileman EO, et al. Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol, 2004;53:209-219.
25、 Portakal O, et al. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 2000;33:279-284.
26、 Laurent A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res 2005;65:948-956.
27、 Kong Q, et al. A threshold concept for cancer therapy. Med Hypotheses 2000;55:29-35.
28、Granowitz EV,et al.Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.Undersea Hyperb Med 2002;29:216-225.
29、Feldmeier J,et al.Hyperbaric oxygen:does it promote growth or recurrence of malignancy? Undersea Hyperb Med 2003;30:1-18.
30、Marx RE,et al.Relationship of oxygen dose to angiogenesis induction in irradiated tissue.Am J Surg 1990;160:519-524.
31、Phillips SJ..Physiology of wound healing and surgical wound care.ASAIO J 2000;46:S2-S5.
32、Johnson RJR,Lauchlan SC.Epidermoid carcinoma of the cervix treated by 60Co therapy and hyperbaric oxygen.In:Proceedings of the third international congress on hyperbaric medicine;1966.p.648-52.
33、Kains JE,Prepmeier EH.Exposure to hyperbaric oxygen induces cell cycle perturbation in prostate cancer cells.In Vitro Cell Dev Biol Anim,1999,35(2):98-101.
34、陈洪雷,彭勇.高压氧与肿瘤放射治疗.国际放射学核医学杂志,2005,29(6),289-291.
35、Martin DF,et al.Enhancement of tumor radiation response by the combination of a perfluorochemical emulsion and hyperbaric oxygen.Int J Radiat Oncol Biol Phys 1987;747-751.
36、Kmoshita Y,Kohshi K,Kunugita N,et al.Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging.Br J Cancer,2000,82(1):88-92.
37、Van den Brenk HA,et al.An analysis of the progression and development of metastases in patients receiving x-radiation in hyperbaric oxygen.Clin Radiol 1967;18:54-61.
38、Henk JM,et al.Radiotherapy and hyperbaric oxygen in head and neck cancer:final report of first controlled clinical trial.Lancet 1977;2:101-103.
39、林静,王曙光.高压氧下氨甲喋呤透过血脑屏障的观察[J].中华航海医学杂志,1998,5(4):222.
40、高春锦,杨捷云.实用高压氧学[M].北京:学苑出版社,1997.1.
41、Takiguchi N,Saito N,Nunomura M,et al.Use of 5-FU plus hyperbaric oxygen for treating malignant tumors:evaluation of antitumor effect and measurement of 5-FU in individual organs.Cancer Cheomother Pharmacol,2001,47(1):11-14.
42、Petre PM,Baciewicz FA Jr,Tigan S,et al.Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model.J Thorac Cardiovasc Surg,2003,125(1):85-95.