肿瘤患者抗坏血酸水平的初步研究

为探讨恶性肿瘤患者抗坏血酸水平的变化，对１０６例肿瘤病人及５０例健康人做了血浆抗坏血酸浓度的检测。实验结果，健康人血浆抗坏血酸均值为（７．６±１．４）ｍｇ／Ｌ（ｘ±ｓ）；肝癌、肺癌、乳腺癌、鼻咽癌患者抗坏血酸水平均低于健康人（Ｐ＜０．０５）；而胃癌、直结肠癌、恶性淋巴瘤及多发性骨髓瘤患者与健康人比较，则无明显差异（Ｐ＞０．０５）。提示在某些肿瘤的发生、发展过程中，癌细胞的代谢和浸润，使机体抗氧化能力下降，血浆中抗坏血酸消耗增加。还对肿瘤患者放疗前后抗坏血酸的变化作了探讨和研究     

三氧化二砷联合抗坏血酸在肿瘤治疗中的研究进展

自20世纪70年代初,哈尔滨医科大学第一附属医院开始尝试用砷剂(As2O3)治疗急性早幼粒细胞白血病(APL),并取得良好效果,自此As2O3的抗肿瘤效应成为了研究热点.近年来,不断有研究表明GSH在决定肿瘤细胞对化疗药物敏感性方面起着重要作用,对As2O3敏感的肿瘤细胞比耐药肿瘤细胞的GSH含量低,而抗坏血酸(AA)可降低细胞内GSH水平.据此,一些学者为了提高As2O3的抗肿瘤疗效,减少其应用剂量,提出了以AA与As2O3联合应用为基础的新型治疗方案,并在一些肿瘤的基础实验和临床研究中取得了一定成效.因此,本文中我们主要就该方案在不同肿瘤中应用的最新研究进展加以综述,并展望As2O3联合AA在抗肿瘤治疗中的应用价值和前景,为进一步研究和探寻更合理的化疗方案提供参考.     

抗坏血酸对血卟啉衍生物渗入肿瘤组织及其光敏作用的影响

目的了解肿瘤组织在血卟啉衍生物及抗坏血酸溶液中浸泡一定时间后,血卟啉衍生物渗入瘤组织的深度、在瘤组织中的含量及抗坏血酸对其渗入和光敏作用的影响。方法以小鼠Ｓ１８０实体瘤和光敏剂癌光啉（ＰｓＤ－００７）为材料,将肿瘤组织分别浸泡在ＰｓＤ－００７（浸Ⅰ组）及ＰｓＤ－００７－抗坏血酸（浸Ⅱ组）溶液中１小时,并以静脉注入ＰｓＤ－００７２４小时的肿瘤为对照（静注组）。通过紫外光照射,观察肿瘤组织中ＰｓＤ－００７红色荧光,测定肿瘤组织中ＰｓＤ－００７和丙二醛含量。结果（１）肿瘤横剖面及肿瘤组织冰冻切片在紫外光照射下所显示的ＰｓＤ－００７红色荧光,浸Ⅰ组和浸Ⅱ组均强,且外周强于中心部位;而静注组则弱,但分布均匀。（２）肿瘤中心部组织匀浆中,ＰｓＤ－００７和丙二醛含量均为浸Ⅱ组＞浸Ⅰ组＞静注组（Ｐ＜０．０５）。结论ＰｓＤ－００７及抗坏血酸均能通过浸泡渗入肿瘤组织,抗坏血酸有促进ＰｓＤ－００７渗入肿瘤组织和增强ＰｓＤ－００７光敏反应的作用。     

肝癌患者腹水心钠素水平的初步研究

心钠素(Cardionatrin,CN)亦称心房利钠肽(ANP),是由心房肌细胞产生的具有广泛生物活性的多肽类激素.临床研究已证实肝硬化患者血浆CN水平显著增高.本文报告肝癌患者腹水CN水平的研究结果,并探讨其发生机理与临床意义.对象和方法 受检者为30例中晚期原发性肝细胞癌(PHC),男23例,女7例,年龄27岁～70岁,平均58岁.对照组为30例失代偿期肝硬化(LC),男27例,女3例,年龄24岁～62岁,平均47岁.于同一日上午采集受检者空腹静脉血和腹水各3ml,经放射免疫法(RIA)检测标本CN含量.     

抗坏血酸抗肿瘤作用机制的研究进展

 抗坏血酸（VitC）在国外作为一种辅助抗肿瘤治疗药物,已经使用多年。尽管一直未被主流医学所接纳,但在最近的10年,越来越多的体外试验和动物实验得出相同的结论,一致认为药理浓度的VitC能选择性杀灭肿瘤细胞。就不同途径、不同剂量下的VitC对肿瘤细胞的影响作一综述。     

膀胱内灌注血卟啉衍生物加抗坏血酸全膀胱激光照射预防膀胱癌…

目的 探讨预防膀胱癌术后复发的新疗法,评价经膀胱内灌注血卟啉衍生物加抗坏血酸行激光全膀胱照射的光动力疗法预防复发的疗效。方法 采用经膀胱内灌注血卟啉衍生物癌光啉（ＰｓＤ－００７）加抗坏血酸行全膀胱激光照射方法,治疗３０例膀胱癌术后患者。结果 ３０例患者随诊３０个月,其肿瘤复发率为２３．３％（７／３０）。无一例发生膀胱挛缩以及皮肤光毒副反应。结论 用膀胱内灌注血卟啉衍生物加抗坏血酸全膀胱照射能有效地     

急性白血病患者体内肿瘤坏死因子水平和临床关系的初步探讨

采用ＴＮＦ生物活性检测法，测定了３０例正常健康人和３２例急性白血病患者体内ＴＮＦ浓度，急性白血病患者体内ＴＮＦ浓度明显增高，血浆ＴＮＦ浓度（９．４３±６．２２ｕ／ｍｌ），初治患者血浆ＴＮＦ浓度增高尤为显著（１３．１４±５．３９ｕ／ｍｌ），急性白血病患者体内ＴＮＦ浓度与白血病类型有一定联系，部分类型白血病细胞可自发分泌ＴＮＦ，其意义有待深入研究。     

恶性肿瘤患者血浆孤啡肽水平的初步观察

孤啡肽（ＯｒｐｈａｎｉｎＦＱ,ＯＦＱ）是新近发现的一种神经肽,由１７个氨基酸组成,分子量１８１０道尔顿。最初的动物实验发现侧脑室注射及鞘内注射ＯＦＱ,使小鼠运动减少,对伤害性刺激的反应性增高,即有痛敏作用,故又称痛敏肽（Ｎｏｃｉｃｅｐｔｉｎ）。ＯＦＱ...     

124例肿瘤患者眩晕病因初步分析

目的:研究恶性肿瘤患者中眩晕疾病的分布特征及规律,探讨并分析肿瘤患者眩晕的常见病因,减少临床误诊及漏诊,为进一步提高肿瘤患者临床治疗效果和患者生存质量提供理论参考。方法:本研究采用横断面研究,采用普查方法,调查2020年3月至2020年9月就诊于我院肿瘤科的1 273例患者,共收集124例眩晕的肿瘤患者,根据病史、临床症状及体征、辅助检查分析明确眩晕病因,并分析疾病特征及规律。结果:肿瘤患者的眩晕患病率为9.7%,高于一般人群中眩晕的患病率,且在各个年龄段均可能发生,女性略多于男性,周围性眩晕占25.8%,其中良性阵发性位置性眩晕（benign paroxysmal positional vertigo,BPPV）占16.9%,中枢性眩晕占32.3%（其中脑转移所致眩晕占29%）,精神性眩晕占21.8%,与接受抗肿瘤治疗相关眩晕占18.5%,其他少见病因占1.6%。结论:肿瘤患者的眩晕患病率高于一般人群,在肿瘤患者中,眩晕最常见病因是脑转移,其后依次是精神性眩晕、肿瘤治疗相关性眩晕及BPPV。     

A prospective study of plasma ascorbic acid concentrations and breast cancer (United States)

Objectives:To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case–control study. Methods:Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n=115) and controls (n=115) were matched by age, menopausal status at donation, and date and hour of blood donation. Results:Median ascorbic acid concentrations were similar between cases and controls (1.44mg/dl vs. 1.39mg/dl, p=0.78). There was no evidence for a dose–response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: OR_adjusted=0.90, p _trend=0.98). Conclusions:Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5years of follow-up.     

Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study

Arsenic trioxide (As(2)O(3)) has established clinical activity in acute promyelocytic leukaemia and has pre-clinical data suggesting activity in lymphoid malignancies. Cell death from As(2)O(3) may be the result of oxidative stress. Agents which deplete intracellular glutathione, such as ascorbic acid (AA), may potentiate arsenic-mediated apoptosis. This multi-institution phase II study investigated a novel dosing schedule of As(2)O(3) and AA in patients with relapsed or refractory lymphoid malignancies. Patients received As(2)O(3) 0.25 mg/kg iv and AA 1000 mg iv for five consecutive days during the first week of each cycle followed by twice weekly infusions during weeks 2-6. Cycles were repeated every 8 weeks. The primary end point was objective response. In a subset of patients, sequential levels of intracellular glutathione and measures of Bcl-2 and Bax gene expression were evaluated in peripheral blood mononuclear cells during treatment. Seventeen patients were enrolled between March 2002 and February 2004. The median age was 71, and the majority of enrolled patients had non-Hodgkin's lymphoma (12/17). Sixteen patients were evaluable, and one patient with mantle cell lymphoma achieved an unconfirmed complete response after five cycles of therapy for an overall response rate of 6%. The trial, which had been designed as a two-stage study, was closed after the first stage analysis due to lack of activity. Haematologic toxicities were the most commonly reported events in this heavily pre-treated population, and comprised the majority of grade 3 and 4 toxicities. Intracellular depletion of glutathione was not consistently observed during treatment. As(2)O(3) and AA in this novel dosing strategy was generally well tolerated but had limited activity in patients with relapsed and refractory lymphoid malignancies.     

The effects of ascorbic acid and butylated hydroxyanisole in the chemoprevention of 1,2-dimethylhydrazine-induced large bowel neoplasms

Human large bowel neoplasia seems to be caused by environmental carcinogens. The experimental carcinogen, 1,2-dimethylhydrazine (DMH), must be oxidized in the body to have effect. The antioxidants, butylated hydroxyanisole (BHA) and ascorbic acid, were tested for efficacy in prevention of experimental large bowel neoplasia. Carcinogenesis was induced in female CF-1 mice by administering DMH, 20 mg/kg, sq for 24 weekly doses. Test animals received varying doses of ascorbic acid, BHA, or both agents together. Animals were sacrificed when moribund or at 35 weeks. All colons were totally embedded and analyzed histologically. Ascorbic acid demonstrated no effects on incidence or density of large bowel tumors. Ascorbic acid did increase the ratio of adenomas to adenocarcinomas. BHA decreased the incidence and density of large bowel tumors. The lowest incidence was obtained in the group receiving both agents combined. It is concluded that BHA is effective in the chemoprevention of DMH-induced large bowel neoplasms. Ascorbic acid demonstrates only modest effect. The greatest effect on tumor incidence is seen when ascorbic acid and BHA are administered together.     

唑来膦酸联合放疗治疗骨转移癌的临床疗效

目的：观察唑来膦酸联合放疗治疗骨转移癌的疗效。方法：将60例骨转移癌患者随机分为观察组（30例）和对照组（30例）。观察组静滴唑来膦酸4mg加局部放疗30Gy／10f/2w，对照组单纯行放疗。结果：观察组与对照组止痛有效率分别为93．3％和73．3％，有显著性差异（P〈0．05）。观察组和对照组活动能力改善有效率分别为86．7％和63．3％，两组差异有统计学意义（P〈0．05）。结论：唑来膦酸联合放疗是目前治疗骨转移癌的优选方案。     

Effect of ascorbic acid, lysine, proline and green tea extract on human osteosarcoma cell line MNNG-HOS xenografts in nude mice

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling MMPs, VEGF, Ki-67 (proliferative protein), and constitutents of ECM play a critical role in angiogenecontaining lysine, proline, arginine, ascorbic acid, and green tea extract (NM) on the growth of tumors induced by implanting human osteosarcoma MNNG in athymic nude mice and the expression of MMPs, VEGF, Ki-67 and fibroenectin in these tumors, as well as the production of mucin (by PAS staining). We also investigated the effect of the supplemented diet on serum ascorbic acid, total protein content, alkaline phosphatase activity, and liver enzymes Athymic male nude mice (n=12) were inoculated with 3×10⁶ osteosarcoma cells MNNG-HOS and randomy divided into group A (fed a regular diet) and group B (fed a regular diet supplemented with 0.5% NM). Four weeks later, the mice were sacrificed. Results showed that NM inhibited the growth and reduced the size of tumors in nude mice. Histological evaluation revealed increased mitotic index, MMP-9, and VEGF secretion in the control group tissues. Results demonstrate that the nutrient mixture of lysine, proline, arginine, ascorbic acid, and green tea extract tested strongly suppressed the growth of tumors without adverse effects in nude mice, suggesting potential as an anticancer agent.     

Antimetastatic effect of a lipophilic ascorbic acid derivative with antioxidation through inhibition of tumor invasion

Purpose: Ascorbic acid (AA), the natural antioxidant, has been demonstrated to exert an antimetastatic action; however, AA is quite unstable in physiological condition. The aim of the present study is to investigate the stability, the antioxidation and the antimetastatic effects of three lipophilic AA derivatives in vitro as well as in vivo. Methods: The 95D cells were treated with ascorbic acid-2-O-phosphate-6-O-laureate (AA2P6L), ascorbic acid-2-O-phosphate-6-O-myristate (AA2P6M) and ascorbic acid-2-O-phosphate-6-O-stearate (AA2P6S). AA derivatives’ stability in medium under cell culture condition, in the presence and in the absence of 95D cells, was assessed by high-performance liquid chromatography assay. Cell viability and intracellular oxidative stress were measured by MTT assay and CDCFH assay, respectively. Wound healing assay and cell adhesion assay were used to investigate the antimetastatic activities against 95D cells in vitro, and the C57BL/6 mice model was used to evaluate the antimetastatic action in vivo. Results: All the three AA derivatives exhibited excellent stability, significantly different from AA. Results of MTT assay showed that IC₅₀ values of the cytotoxicity of those AA derivatives, namely AA2P6L, AA2P6M and AA2P6S, were 38.46, 28 and 22.97 μg/ml, while the CDCFH assay indicated that EC₅₀ values of antioxidant effects on 95D cells were 31.12, 33.51 and 38.31 μg/ml, respectively. Through the ratio of IC₅₀ vs EC₅₀ for AA derivatives, AA2P6L was demonstrated to be the most effective AA derivative, which retained the antioxidant ability as well as low cytotoxicity. AA2P6L dose-dependently inhibited 95D cells’ migration and adhesion, by 50% at the concentration of 20 and 57 μg/ml, respectively. In the animal experiment, intraperitoneal administration of 75 mg/kg AA2P6L decreased the number of metastatic nodules by 62% and elevated the survival rate of C57BL/6 mice about onefold compared to the control group. Conclusion: AA2P6L, a lipophilic AA derivative with antioxidation, is shown to be a potent antimetastatic agent through the inhibition of tumor invasion. These results support future investigations on the feasibility of cancer chemotherapy with AA2P6L.     

单纯放疗与放疗联合唑来膦酸治疗骨转移瘤临床观察

目的：观察单纯放疗与放疗联合唑来膦酸治疗骨转移瘤的疗效与不良反应。方法：82例骨转移瘤患者随机分成A、B两组各例。A组采用^60Coγ射线或直线加速器6MVX射线单纯放疗，B组给静滴唑来膦酸4mg，后局部放疗，放疗结束后每4周静滴唑来膦酸1次，连用12周期。结果：两组效果比较差异有显著性（P〈0．01）。结论：唑来膦酸联合放疗治疗骨转移瘤效果较好。