人基因重组红细胞生成素治疗75例癌症贫血的临床分析

本文对用人基因重组红细胞生成素（ｒＨｕＥＰＯ）治疗７５例癌症血的临结果进行了分析，观察不同的给药剂量，给药途径对疗效的影响，发现治疗有效组的血红蛋白（Ｈｂ）、网织红细胞计数（Ｒｃ）、血细胞比容（Ｈｃｔ）、血清铁蛋白（Ｆｅｒｒｉｔｉｎ）变化显著，而无效组的则不显著。合理使用ｒＨｕＥＰＯ有减轻贫血症状，减少输血依赖性，提高生活质量并降低治疗费用。     

红细胞生成素在妇科恶性肿瘤治疗中的应用

红细胞生成素(ＥＰＯ)也称红细胞生长因子,是人体内由肾皮质内及肝脏的成纤维细胞样间质细胞和肝脏的肝细胞产生分泌的一种糖蛋白[1,2],其作用类似于激素的作用,主要作为一种促细胞分裂剂,作用于骨髓的造血细胞的前体细胞,具有促细胞分裂及使细胞成熟和分化的功能。近年来由于分子生物学技术的进展,红细胞生长因子———红细胞生成素(ＥＰＯ)克隆成功,进而重组人红细胞生成素(ｒＨｕＥＰＯ)也广泛地用于了临床。临床应用已证明,ＥＰＯ及ｒＨｕＥＰＯ能提高肿瘤病人血红蛋白水平,增加氧携带能力,改善伴有贫血的肿瘤病人的生活质量[3,4],其在…     

重组人促红细胞生成素治疗肿瘤相关性贫血的疗效影响因素

目的　分析重组人促红细胞生成素（ｒｈＥＰＯ）治疗肿瘤相关性贫血疗效的影响因素。方法　回顾性分析ｒｈＥＰＯ治疗晚期恶性肿瘤合并贫血１７９例患者的临床资料,探讨年龄、性别、骨转移、感染、活动性出血、接受化疗周期数、放疗史、血清转铁蛋白饱和度、铁蛋白、叶酸及维生素Ｂ１２等对疗效的影响。结果　性别、接受化疗周期数、有无放疗史、血清叶酸、维生素Ｂ１２等对疗效无影响（Ｐ＞０.０５）,年龄、骨转移、感染、活动性出血、血清转铁蛋白饱和度及铁蛋白等对疗效有影响（Ｐ＜０.０５）。经两分类Ｌｏｇｉｓｔｉｃ回归模型分析,年龄、骨转移、感染及血清转铁蛋白饱和度均为预测ｒｈＥＰＯ疗效的独立因素。结论 ｒｈＥＰＯ的疗效与肿瘤相关性贫血患者的年龄、骨转移、感染、血清转铁蛋白饱和度等因素有关。     

癌性贫血患者内源性促红细胞生成素水平的研究

 目的 研究癌性贫血患者血清促红细胞生成素（ＥＰＯ）水平及其与血红蛋白（Ｈｂ）含量之间的关系。方法 用放射免疫分析检测血清ＥＰＯ含量，以直线相关分析ＥＰＯ水平与Ｈｂ含量之间的关系。结果癌性贫血患者血清ＥＰＯ含量为２．６２±０．９５μｇ／Ｌ（ｎ＝４３），显著高于不伴有贫血的癌症患者（１．７０±０．４１μｇ／Ｌ，ｎ＝３９）和正常对照组（１．５９±０．６９μｇ／Ｌ，ｎ＝９４）。癌性贫血患者血清 ＥＰＯ含量与 Ｈｂ水平存在明显的负相关关系（ｒ＝－０．６８２９３，Ｐ＜０．０１）。结论 癌性贫血患者血清内源性 ＥＰＯ水平增高，提示对此类患者检测血清 ＥＰＯ水平有助于指导临床治疗。     

大刺猴头（88）多糖抗突变,抗氧化及对免疫功能影响的研究

本实验观察了大刺猴头多糖（Ｈｅｒｉｃｌｉｕｍｐｏｌｙｓａｃｃｈａｒｉｄｅ（ＨＥＰＳ）对大肠杆菌ＳＯＳ应答的抑制作用；径口给大鼠ＨＥＰＳ（３０ｄ）测定大鼠血液和肝组织中超氧化物歧化酶（ｓｕｐｅｒｏｘｘｉｄｅｄｉｓｕｍｕｔａｓｅＳＯＤ），脂质过氧化物丙三醛（Ｍａｌｏｎｙｌｄｉａｌｄｅｇｙｄｅ（ＭＤＡ）含量的变化；经口给小鼠（ＨＥＰＳ）（３０ｄ），其对小鼠腹腔吞噬率、吞噬指数，脏器指数的影响。结果表明：ＨＥＰＳ可以抑制由（ＭｉｔｏｍｙｃｉｎｃＭＭＣ）诱导的ＳＯＳ应答，其抑制率大肠杆菌ＰＱ３５为６４％，ＰＱ３７为５６％；经口给大鼠ＨＥＰＳ其血液及肝匀浆中ＳＯＤ含量均高于对照组。ＭＤＡ的含量均低于对照组，各自２组比较分别有非常显著性差异及显著性差异（Ｐ＜０．０１，ｐ＜０．０５）。ＨＥＰＳ组小鼠的腹腔吞噬细胞吞噬率、吞噬指数，胸腺指数，腺指数与对照组比较也有非常显著性差异（ｐ＜０．０１）。结果提示：大刺猴头（８８）（ＨＥＰＳ）在本实验体系表现有抗突变，抗氧化及增强免疫功能的作用。     

白血病患者红细胞超氧化物歧化酶活性,血清过氧化脂质,维生素E…

本文观察了４４例白血病患者红细胞中铜、锌超氧化物歧化酶（ＲＢＣ·ＣｕＺｎ－ＳＯＤ）的活性、血清过氧化脂质（ＬＰＯ）和维生素Ｅ（ＶＥ）的水平，结果表明ＲＢＣ·ＣｕＺｎ－ＳＯＤ活性和ＬＰＯ水平在白血病患者中显著增高（Ｐ值均小于０．０１），而ＶＥ水平则明显降低（Ｐ〈０．０１）。对其中１５例急性白血病（ＡＬ）患者进行动态观察，在治疗获完全缓解后，其三者水平恢复到基本正常。反应了白血病患者体内存在着自由基产     

白血病患者红细胞超氧化物歧化酶活性、血清过氧化脂质、维生素E的检测与分析

本文观察了４４例白血病患者红细胞中铜、锌超氧化物歧化酶（ＲＢＣ·ＣｕＺｎ－ＳＯＤ）的活性、血清过氧化脂质（ＬＰＯ）和维生素Ｅ（ＶＥ）的水平，结果表明ＲＢＣ·ＣｕＺｎ－ＳＯＤ活性和ＬＰＯ水平在白血病患者中显著增高（Ｐ值均小于０．０１），而ＶＥ水平则明显降低（Ｐ＜０．０１）。对其中１５例急性白血病（ＡＬ）患者进行动态观察，在治疗获完全缓解后，其三者水平恢复到基本正常。反应了白血病患者体内存在着自由基产生和清除的平衡遭到破坏，而治疗缓解后这种失衡状态可望得到部分恢复。     

榄香烯乳高压氧联合治疗中晚期肺癌患者的临床研究

应用国产抗癌新药榄香烯乳与高压氧（ＨＢＯ）联合应用，治疗经病理确诊的中晚期肺癌患者２０例。观察治疗前后瘤体变化和红细胞免疫功能的改变。结果显示：治疗组（榄香烯乳＋ＨＢＯ）、对肺癌瘤体缩小的显效率达３５％，明显地高于对照组（榄香烯乳）１５％。经过ＨＢＯ、榄香烯乳联合治疗的患者，红细胞免疫功能（Ｅ－Ｃ３ｂＲＲ）明显地高于对照组，两组相比有非常显著性差异（Ｐ＜０．０１）。     

老年晚期非小细胞肺癌患者免疫治疗的疗效和安全性

目的：评价老年晚期非小细胞肺癌（ｎｏｎ ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＮＳＣＬＣ）患者接受免疫检查点抑制剂治疗的 疗效和安全性,探索疗效和预后相关生物标志物。方法：回顾性收集 ２０１８年 ３月至 ２０２１年 １０月于中国 ３家医院接 受免疫治疗的老年晚期 ＮＳＣＬＣ患者资料,对免疫治疗的疗效和安全性进行评估,应用 Ｋａｐｌａｎ Ｍｅｉｅｒ法和 Ｌｏｇ ｒａｎｋ检 验进行生存分析,并采用单因素及多因素 Ｃｏｘ风险比例回归模型、ｔ ｔｅｓｔ来检验各项临床特征和实验室指标与生存的 相关性。结果：研究共纳入 １０２例患者,客观缓解率为 ４１．０２％,疾病控制率为 ８８．４６％,中位无进展生存时间（ｐｒｏ ｇｒｅｓｓｉｏｎ ｆｒｅｅｓｕｒｖｉｖａｌ,ＰＦＳ）为 ７．５个月,中位总生存时间（ｏｖｅｒａｌｌｓｕｒｖｉｖａｌ,ＯＳ）为 ２２．０个月。单因素分析显示,ＥＣＯＧ ＰＳ评分 ０～１分（Ｐ＝０．０４１）、无肝转移（Ｐ＝０．０４８）和一线治疗（Ｐ＝０．０４７）与更长的 ＰＦＳ显著相关,吸烟史（Ｐ＝ ００１０）、无脑转移（Ｐ＜０．００１）与更长的 ＯＳ显著相关。多因素分析显示,ＥＣＯＧＰＳ评分≥２分患者的 ＰＦＳ（Ｐ＝ ０００１）和 ＯＳ（Ｐ＜０．００１）明显短于 ０～１分者,联合治疗组的 ＰＦＳ明显长于单药治疗组（Ｐ＝０．０３１）,脑转移患者的 ＯＳ明显短于不伴脑转移者（Ｐ＝０．０１７）。４８例（４７．０６％）患者在接受免疫治疗时出现不良事件,其中 ２１例 （２０５９％）患者出现≥３级不良事件。预后不佳组患者的基线期血红蛋白（Ｐ＝０．０２６）、白蛋白（Ｐ＝００２５）水平较预 后良好组显著降低。结论：老年晚期 ＮＳＣＬＣ患者接受免疫检查点抑制剂治疗的疗效和安全性良好,ＥＣＯＧＰＳ评分 ０～１分、有吸烟史、一线及联合治疗的患者可能是免疫治疗的潜在优势人群,基线期白蛋白、血红蛋白水平降低可能 预示着免疫治疗效果不佳。     

^153Sm—EDTMP治疗多发性骨转移癌

用１５３Ｓｍ－ＥＤＴＭＰ（ｅｔｈｙｌｅｎｅｄｉａｍｉｎｅｔｅｔｒａｍｅｔｈｙｌｅｎｅＰｈｏｓｐｈｏｎｉｃａｃｉｄ）治疗多发性骨转移癌６０例，其原发灶均经病理及细胞学证实。静脉一次给予量为１４．８～２９．６ＭＢｑ／ｋｇ体重，多数病人（５０／６０）按１８．５ＭＢｑ／ｋｇ体重计算治疗剂量，一般病人治疗１～４次，两次治疗间隔为４～８周。止痛有效率为８１．７％（４９／６０），给药前２周内９９ｍＴｃ－ＭＤＰ与给药后１５３Ｓｍ－ＥＤＴＭＰ全身骨显像进行观察比较。随访１～１２个月，认为１５３Ｓｍ－ＥＤＴＭＰ治疗多发性骨转移癌疗效好、副反应小，使用安全     

Anemia in head and neck cancers

Anemia is very common in head and neck cancer patients, and seems to be correlated with intratumoral hypoxia. Anemia is one of the main prognostic factors of locoregional recurrence and, in some studies, of poor survival. Blood transfusions and human recombinant erythropoietin (rHuEPO) are the two main methods used in clinical practice to correct hemoglobin level during curative treatment. Blood transfusions were rarely evaluated, and did not influence locoregional control of patients treated with radiotherapy with or without chemotherapy. Retrospective studies evaluating combined treatment of rHuEPO and radiotherapy reported positive impact on locoregional recurrence and actuarial survival. Since the end of 2003, this approach is a matter for debate after the negative results of a prospective randomized study on progression-free survival concerning head and neck cancer patients treated with definitive or postoperative external radiotherapy with or without rHuEPO. Although many biases were reported against this publication, several questions are to be answered in the near future. Among them, erythropoietin receptor expression and activation on tumour cell seem to be the more appropriate explanation of these negative results. In October 2004, preliminary results of the RTOG 99-03 study have been presented at the Astro annual meeting in Atlanta. This prospective randomized trial was designed to determine if concurrent rHuEPO administration (40,000 units) with radiotherapy (with or without chemotherapy) could improve locoregional control in non-operative head and neck cancers. In the rHuEPO arm, haemoglobin level was significantly increased compared with control arm. However, the addition of concurrent rHuEPO to definitive radiotherapy did not improve locoregional control or survival for mildly/moderately anemic patients with head and neck squamous cell carcinoma. Future clinical trials using biological markers are thus imperative to target which patients could benefit from these molecules.     

Cost-effectiveness of recombinant human erythropoietin in the prevention of chemotherapy-induced anaemia.

Recombinant human erythropoietin (rHuEPO) has been advocated for the treatment of anaemia in patients submitted to cancer chemotherapy. We used decision analysis to compare the cost-effectiveness of rHuEPO supplemented with red blood cell (RBC) transfusions with conventional treatment with RBC transfusions alone. At baseline, we analysed the use of rHuEPO as secondary prophylaxis according to effectiveness estimates from a community-based oncology study. In order to reduce the probability of transfusions from 21.9% to 10.4%, and the number of RBC units per patient per month from 0.55 to 0.29, 150 units kg(-1) s.c. rHuEPO three times per week for 4 months resulted in an incremental cost of $189,652 per quality-adjusted life year (QALY). In patients treated with cisplatin-containing chemotherapy, rHuEPO added $190,142 per QALY. In a hypothetical scenario of a transfusion pattern that maintained the same haemoglobin level of rHuEPO-responsive patients, the marginal cost of rHuEPO was always greater than $100,000 per QALY. Results were stable with regard to variations in the probability of blood-borne infections, quality of life of responding patients and cancer-related mortality. The additional cost could be lowered to less than $100,000 per QALY by saving 4.5 RBC units over 4 months for any patient treated. In conclusion, according to current use, rHuEPO is not cost-effective in the treatment of chemotherapy-induced anaemia. More tailored utilization of the drug and better consideration of predictive response indicators may lead to an effective, blood-sparing alternative.     

Comparison of clinical outcomes of different erythropoietin usage strategies

AIM: There is no comprehensive study that compares the different usage strategies of recombinant human erythropoietin (rHuEPO) in platinum-induced anemia. In order to clarify this issue, we conducted a prospective clinical study. MATERIAL AND METHODS: Seventy-seven patients were studied in three main groups. Group 1 (n = 17) consisted of cancer patients without anemia. These patients received rHuEPO starting from the first chemotherapy cycle. Group 2 (n = 26) consisted of patients whose hemoglobin (Hb) values decreased by at least 1 g/dL after the first cycle of chemotherapy. Group 3 (n = 34) consisted of patients whose Hb values dropped below 10.5 g/dL after the second chemotherapy cycle. Groups 2 and 3 were each divided into two subgroups. In groups 1, 2A and 3A rHuEPO (5000 U/day subcutaneously three times a week) treatment was continued until three weeks after the completion of chemotherapy. In groups 2B and 3B, rHuEPO was given for 12 weeks only. RESULTS: There were no prominent differences between the Hb values of these groups throughout the chemotherapy cycles. Transfusion rates and the number of patients who became anemic were also not different between groups. CONCLUSION: No rHuEPO usage strategies are superior to others in terms of Hb levels and transfusion requirements. The decision as to when rHuEPO is to be added to platinum-containing therapy should be tailored to the health conditions of individual patients.     

促红细胞生成素及其受体在卵巢癌细胞的表达及相关作用的实验研究

 目的　检测卵巢癌细胞中的促红细胞生成素（EPO）及其受体（EPOR）表达，以及重组人EPO（rhEPO）对卵巢癌细胞增生的影响，探讨rhEPO在癌性贫血治疗中的意义。方法　RT-PCR方法检测人类卵巢癌细胞株 HO-8910 EPOR mRNA的表达。用流式细胞仪检测rhEPO对卵巢癌细胞凋亡及增生影响。结果　卵巢癌细胞表面有EPOR的表达，rhEPO干预后卵巢癌细胞增生受到抑制（P＜0.01）。结论　EPOR在卵巢癌细胞株HO-8910有表达，rhEPO可抑制卵巢癌细胞的增生。rhEPO可用于卵巢癌伴发的贫血的治疗。     

Human recombinant erythropoietic agents do not induce changes in circulating levels of endoglin and vascular endothelial growth factor in anemic cancer patients

The correlation of erythropoietin (EPO) receptor levels with angiogenesis and progression in some cancers has suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic (rHuEPO) agents in cancer patients with chemotherapy-induced anaemia on endoglin and vascular endothelial growth factor (VEGF) circulating levels as a possible marker of angiogenesis. Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anemia before and after 3-4 weeks of treatment with rHuEPO. A group of 28 healthy voluntaries was used as control. VEGF serum levels were significantly higher in cancer patients than in controls. For endoglin, higher levels were observed without reaching statistical significance. No statistically significant differences in endoglin and VEGF serum levels were found between samples obtained before and after treatment with rHuEPO agents. In conclusion, our result do not support that rHuEpo treatment in anaemic cancer patients induce angiogenesis.     

Role of iron in optimizing responses of anemic cancer patients to erythropoietin

Approximately 50% of cancer patients develop anemia. In the past, the only available treatment option for these patients was transfusion. Since the late 1980s, recombinant human erythropoietin (rHuEPO, epoetin alfa [Epogen, Procrit]) has provided a treatment alternative. Controlled clinical trials have shown that rHuEPO increases hemoglobin and hematocrit levels and reduces the need for transfusions in patients with cancer-related anemia. These controlled trials have suggested (as larger, uncontrolled studies) that the improvements in hemoglobin are associated with increases in energy level, functional status, and overall quality of life. However, only about 50% of patients respond adequately to usual doses of rHuEPO. In the chronic renal failure population, functional iron deficiency is the most common cause of inadequate response to rHuEPO. It has been hypothesized that functional iron deficiency may also occur in cancer patients receiving rHuEPO and may account for the lack of response in up to half of those patients. Studies in renal failure patients have shown that administration of intravenous iron can correct functional iron deficiency more effectively than oral iron and may improve response to rHuEPO. Intravenous iron also reduces the total amount of rHuEPO needed to normalize hematocrit and hemoglobin levels, thereby reducing treatment costs. Ongoing clinical trials are evaluating whether IV iron can also improve rHuEPO responsiveness in patients with cancer-related anemia.     

Erythropoietin-induced reduction of hypoxia before and during fractionated irradiation contributes to improvement of radioresponse in human glioma xenografts

PURPOSE: Our study investigated the influence of recombinant human erythropoietin (rHuEPO) treatment, inducing raised hemoglobin levels in nonanemic mice, on intratumor oxygenation before and during fractionated irradiation. Furthermore, the consequences of rHuEPO administration on tumor response to fractionated radiotherapy (RT) were evaluated. METHODS AND MATERIALS: Experiments were performed on two human malignant glioma (GBM Nan1 and U87) xenografted in nude mice. RHuEPO was daily delivered (0.3 IU/g/day, 5 days/week). Tumor hypoxia was assessed before (T1) and during (T6) fractionated irradiation using (1) pO(2)-Histograph (Eppendorf, Hamburg, Germany) and (2) the EF5-binding assay. Vascular density was determined using type IV collagen immunostaining. To assess RT efficacy, the irradiation schedule was 20 fractions of 2 Gy, once daily, 5 days/week over 4 weeks. RESULTS: At T1, hemoglobin levels in rHuEPO-treated mice were significantly increased. Percentage of pO(2) values <2.5 mm Hg was reduced in rHuEPO-treated tumors as compared with control groups (37.1 +/- 19.1% vs. 58.5 +/- 27.0%; p = 0.009 for GBM Nan1; 81.6 +/- 13.4% vs. 91.5 +/- 8.3%; p = 0.035 for U87). The decrease of viable hypoxic tumor cells fraction after rHuEPO was confirmed by the EF5-binding assay. Vascular density was not altered after rHuEPO treatment. At T6, rHuEPO reduced the hypoxic fraction by about 20% (p = 0.036 and p = 0.171) in GBM Nan1 and U87 irradiated tumors. RHuEPO did not influence tumor growth by itself. RT alone or combined with rHuEPO induced a significant tumor growth delay. Finally, rHuEPO significantly enhanced RT efficacy (p = 0.012 in GBM Nan1 and p = 0.037 in U87), resulting in radiopotentiation ratios of 1.21 and 1.54 for respective models. CONCLUSIONS: Our results indicate that rHuEPO, by enhancing blood oxygen-carrying capacity, decreases intrinsic tumor hypoxia and maintains its effect during fractionated irradiation in malignant glioma xenografts. Therefore, rHuEPO contributes to radiosensitize these tumors.     

Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors

The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg/kg i.v.) resulting in a long-lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU/kg) administered s.c. three times/week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg/kg i.p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13.3 days versus 8.6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13.3 days). These results suggest that chemotherapy-induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue.     

The Value of Erythropoietin Therapy in Cancer Patients

Fatigue is an extremely common symptom in cancer patients, often producing a deleterious effect on quality of life. It is most commonly the consequence of anemia, which results from the cancer itself or therapy. Considerable interest exists as to whether the use of recombinant human erythropoietin (rHuEPO) or a newer analog, darbepoetin alfa, is able to correct or prevent anemia in cancer patients, reduce or abolish transfusion requirements, and improve quality of life. Studies have explored the use of erythropoietin in several settings, including patients receiving (or not) cytostatic therapy. Fifty to sixty percent of patients respond to erythropoietin but the expense of this drug prompts concern about its cost effectiveness and as a result, consideration of how best to target its use. The prolonged duration of action of darbepoetin alfa allows less frequent administration (typically once a week) compared with rHuEPO, but the optimal dose and regimen are less well defined. However, it is clear that in randomized placebo-controlled trials and in large open-label community based programs of cancer patients rHuEPO is clinically effective in reducing transfusion requirements and preserving quality of life, whether or not anticancer treatments are being used. The major unresolved dilemma is whether rHuEPO is a cost-effective replacement of transfusion services, a question that has not been well studied in cancer patients.