造血生长因子在肿瘤化疗中应用的研究进展

众多特异的造血生长因子调控着人体造血,给肿瘤患者的化、放疗提供了有力的支持.重组人粒细胞集落刺激因子(rhG-CSF)的应用减少了化疗导致的持续而严重的中性粒细胞减少症和相关感染的发生,使外周血干细胞动员高效安全,加速干细胞移植后的造血功能重建.聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)半衰期长,每周期1次给药可有效防治发热性中性粒细胞减少引起的感染和非血液系统恶性肿瘤化疗导致的中性粒细胞减少症.干细胞因子在临床中单独使用,并无体外实验的动员效果,只能与rhG-CSF联合使用.防治化疗引起的口腔粘膜已经成为粒/巨噬细胞集落刺激因子的一种新的临床用途.白细胞介素-11是目前惟一被美国FDA批准上市的防治血小板减少的药物.血小板生长因子由于临床效果不确切,并可导致中和抗体的产生,已停止临床研究.促红细胞生成素被广泛用于治疗慢性肾衰引起的贫血,但在肿瘤患者贫血中的应用仍缺乏足够的研究.     

造血生长因子在肿瘤化疗中应用的研究进展

众多特异的造血生长因子调控着人体造血,给肿瘤患者的化、放疗提供了有力的支持.重组人粒细胞集落刺激因子(rhG-CSF)的应用减少了化疗导致的持续而严重的中性粒细胞减少症和相关感染的发生,使外周血干细胞动员高效安全,加速干细胞移植后的造血功能重建.聚乙二醇重组人粒细胞集落刺激因子(PEG-rhG-CSF)半衰期长,每周期1次给药可有效防治发热性中性粒细胞减少引起的感染和非血液系统恶性肿瘤化疗导致的中性粒细胞减少症.干细胞因子在临床中单独使用,并无体外实验的动员效果,只能与rhG-CSF联合使用.防治化疗引起的口腔粘膜已经成为粒/巨噬细胞集落刺激因子的一种新的临床用途.白细胞介素-11是目前惟一被美国FDA批准上市的防治血小板减少的药物.血小板生长因子由于临床效果不确切,并可导致中和抗体的产生,已停止临床研究.促红细胞生成素被广泛用于治疗慢性肾衰引起的贫血,但在肿瘤患者贫血中的应用仍缺乏足够的研究.     

造血生长因子受体超家族

细胞因子受体是细胞因子展现其生物学功能的关键结构。造血生长因子受体超家族的发现对于解释众多细胞因子的功能多样性和交叉反应具有十分重要的意义。造血生长因子受体可分为３个亚类，各自针对一系列细胞因子发生反应，其核心为各亚类受体所具备的共用受体链。     

造血生长因子的生物效应与临床应用

集落形成试验中发现的造血生长因子,是一族能刺激和促进粒细胞。单核细胞增殖的糖蛋白,称之为集落刺激因子(Colony-stimulating factots,CSF)。目前,人类4种CSF的基因均已被克隆,并且获得了重组的CSF蛋白。这4种CSF是粒细胞集落刺激因子(G-CSF)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、巨噬细胞集落刺激因子(M-CSF或CSF-1)和白细胞介素-3(IL-3或multi-CSF)。这些CSF的分子与生化特征以及主要的靶细胞见表1。除CSF外的其他造血生长因子包括红细胞生成素(EPO)和白细胞介素均能促进血细胞的增殖分化。一、造血生长因子的细胞来源与生物效应体内多种细胞可以产生一种或多种造血生长因子。虽然体内产生CSF的生理调节机制还不太清     

造血生长因子及其受体与急性白血病的关系

本文综述了急性髓性白血病（ＡＭＬ）和急性淋巴细胞白血病（ＡＬＬ）祖细胞对造血生长因子（ＨＧＦｓ）的依赖性以及多种调控因子对它们的生长调节作用，并介绍了ＡＭＬ，ＡＬＬ细胞表面ＨＧＦｓ受体的特征和白血病细胞能长期存活的机制，展望了ＨＧＦｓ用于治疗急性白血的前景。     

介入热灌注化疗栓塞对肝癌患者血管内皮生长因子的影响

[目的]探讨介入热灌注化疗栓塞对肝癌患者血管内皮生长因子(VEGF)的影响.[方法]采用ELISA方法检测60例原发性肝癌患者(介入热疗组30例和常规介入组30例)治疗前后VEGF的变化,并对两组数据进行对比分析.[结果]治疗前介入热疗组血清VEGF中位值为256.42pg/ml,常规介入组为255.16pg/ml;治疗后1周介入热疗组为179.37pg/ml,较前下降;常规介入组343.58pg/ml,较治疗前升高,两组比较均有显著性差异(P＜0.05).介入热疗组2年生存率(70％)明显高于常规介入组(50％).[结论]介入热灌注化疗栓塞可抑制VEGF的产生,对减少肿瘤新生血管的形成、防止或降低肿瘤的复发起到积极的作用,其疗效优于常规介入疗法,是治疗中晚期肝癌的一种安全有效的方法.     

高剂量化疗合并造血干细胞移植治疗卵巢癌

在卵巢癌的综合治疗中，化疗已成为其根治性治疗的重要组成部分。由于传统剂量化疗的局限性以及存在着剂量强度的量效关系，造血干细胞支持下的高剂量化疗治疗卵巢癌已取得一定疗效。在提高缓解率及降低毒副反应的同是，亦改善了患者的生活质量，因而具有广阔的临床应用前景。     

表皮生长因子及其受体在胃癌患者中的表达

采用放射免疫法测定２６例胃癌病人血清、尿液ＥＧＦ水平，同时采用免疫组化ＳＡＢＣ法检测胃粘膜组织切片中ＥＧＦＲ染色的阳性率，并与正常对照进行比较分析。结果表明：胃癌患者血清和尿ＥＧＦ水平均显著高于正常对照（３．７２±１．８３μｇ／Ｌ与１．７７±０．６０μｇ／Ｌ，Ｐ＜０．０１；１８．４４±１７．８８ｎｇ／ｍｇ与５．１９±６．３７ｎｇ／ｍｇ，Ｐ＜０．０１），胃粘膜组织切片ＥＧＦＲ染色阳性率也明显高于正常对照（７３％与１１％，Ｐ＜０．０１）。胃癌病人中，ＥＧＦＲ染色阳性者血清ＥＧＦ水平显著高于ＥＧＦＲ阴性者（Ｐ＜０．０５），但两者尿ＥＧＦ水平无显著性差异。胃癌患者血清、尿ＥＧＦ水平与胃癌大小、分化程度及淋巴结转移无显著性相关。     

联合化疗加粒细胞集落刺激因素动员外周造血干细胞的作用

目的研究大剂量联合化疗(HDCT)加粒细胞集落刺激因子(G-CSF)对外周血造血干细胞的动员作用。方法8例非霍奇金淋巴瘤(NHL)多周期诱导化疗达完全缓解后,采用大剂量联合化疗,联合应用小剂量G-CSF进行外周造血干细胞的动员。结果动员后外周血WBC及MNC总数明显增加,与动员前比较,差异有显著性。冷冻前后,MNC计数、GFU-G集落总数无明显差异。预处理后,病人中性粒细胞、血小板恢复时间分别平均为(10.5±4)天及(11.5±6)天。结论大剂量联合化疗加小剂量G-CSF联合动员方案是安全有效的,值得推广。     

肿瘤患者化疗后严重不良反应相关因素分析

目的 探讨实体肿瘤患者化疗后严重不良反应的影响因素.方法 纳入145例实体肿瘤患者,记录患者化疗前的年龄、性别、体重指数、体能状态评分(ECOG-PS)、肿瘤类型、临床分期、根据MAX2判定的化疗方案级别、剂量强度等因素及化疗后不良反应,采用单因素及多因素分析研究严重不良反应的影响因素.结果单因素分析结果显示,肿瘤类型、MAX2化疗方案级别、血红蛋白水平对3~4级血液学毒性的发生率有影响(P﹤0.05);多因素分析结果显示,非消化道肿瘤和血红蛋白水平下降是3~4级血液学毒性发生的独立危险因素(P﹤0.05).对于非血液学毒性而言,年龄、ECOG-PS评分、肿瘤类型、体质指数(BMI)、白蛋白水平、血红蛋白水平、肌酐清除率、MAX2化疗方案级别、剂量强度对3~4级非血液学毒性的发生率均无影响(P﹥0.05).结论 实体肿瘤患者化疗前需评估耐受性,对于肺癌、肉瘤或头颈部肿瘤等非消化道肿瘤、MAX2化疗方案级别2级、存在贫血的患者,应警惕严重血液学不良反应的发生,并给予预防治疗.     

Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia

Nineteen adults with primary refractory or relapsed acute leukemia (12 ALL and 7 ANLL) were treated with an intensive salvage chemotherapy (intermediate-dose ara-C, intermediate-dose methotrexate, vindesine, cyclophosphamide, mitoxantrone and prednisolone) followed by a hematopoietic growth factor (HGF), either granulocyte colony-stimulating factor (5 μg/kg) or granulocyte-macrophage colony-stimulating factor (10 μg/kg). Both were given from the day after chemotherapy ended and until the neutrophil count rose above 1 × 10⁹/l for three consecutive days. Eleven patients (58%. 95% CI 33% to 82%) achieved complete remission, and 15 courses of salvage therapy were given to these complete responders. In a historical control group that did not receive HGF, 23 out of 38 patients (60%, 95% CI 44% to 77%) achieved complete remission, and 27 courses of therapy were delivered to complete responders. Treatment with a HGF accelerated the recovery of neutrophils to 0.5 × 10⁹/l significantly, shortening it from a mean of 28 to 22 days (p = .0002), with no effect on platelet recovery. There were no differences in the rates of documented and fatal infections, which were relatively high in both groups. In the patients with ANLL, there was no evidence that HGF accelerated leukemic regrowth. We conclude that HGF accelerates neutrophilic recovery following intensive salvage chemotherapy for acute leukemia, although no reduction in documented infections was found. Many factors, including the small patient sample, may have contributed to this latter finding.     

化疗序贯自体造血干细胞移植治疗淋巴瘤的疗效评价及影响因素分析

目的:探讨化疗序贯自体造血干细胞移植(auto-HSCT)对淋巴瘤患者的疗效及影响因素.方法:回顾性分析2015年09月至2020年12月于我科接受大剂量化疗(HDC)序贯自体外周血造血干细胞移植治疗的患者,并进行疗效及不良反应评价.结果:40例患者,其中非霍奇金淋巴瘤34例,霍奇金淋巴瘤6例;男性27例,女性13例,...     

The effect of surgery and pretreatment or posttreatment adjuvant chemotherapy on primary tumor growth in an animal model.

The Ca755 solid tumor in the C57B1 mouse has been used as a model to study the interrelationship of surgery and adjuvant chemotherapy on primary tumor growth. Surgery was performed on various days after tumor implantation. Surgical mortality increased with delay in surgery. The mean survival time (MST) was significantly increased by surgery. An increased cure rate in mice with late surgery may be due to immunological factors. Pretreatment cytoxan chemotherapy prior to a number of surgical days on the most effect schedule increased MST in the later surgical days primarily due to shrinkage of tumor and a diminished surgical mortality. Posttreatment chemotherapy significantly increased MST primarily on the basis of reducing tumor cell population after surgery and increasing both the cure rate and the time until death of those mice dying of regrowth of tumor. Optimal chemotherapy alone significantly increased MST compared to untreated controls. Optimal postsurgery chemotherapy increased survival longer than the additive increase of chemotherapy alone and surgery alone. This paper illustrates relationships between day of surgery dose and schedule of chemotherapy and effect on various measurable parameters. The results can best be understood in relationship to each other. It is suggested that adjuvant chemotherapy has specific definable benefits. It is apparent from human studies that carefully devised designs which consider these interrelationships are necessary if optimal therapeutic results are to be achieved.     

Chemotherapy in carcinomas of unknown primary site: A high-dose intensity policy

Background: Unknown primary tumors are highly malignant diseases which portend a dire prognosis. We designed a prospective high dose-intensity policy with the aim of improving the results obtained with conventional chemotherapy.Patients and methods: Chemotherapy regimens were determined according to clinical features. In patients younger than 61 years with an ECOG performance status of 0 or 1, poorly differentied adenocarcinoma or poorly differentiated carcinoma, and no evidence of brain or bone marrow involvement (group A), the treatment plan included four sequential high-dose courses with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 µg/kg/d) was given until engraftment. It was planned that cycles would be delivered every three weeks. The remaining patients (group B) received alternative cycles of AC (doxorubicin 50 mg/m2, cyclophosphamide 1000 mg/m2) and EP (etoposide 300 mg/m2, cisplatin 100 mg/m2). Cycles were given at two-week intervals with GM-CSF support (5 µg/kg/d) from day 4 to day 10. Patients without measurable lesions were included, since the major endpoint was survival.Results: Sixty patients entered the study. Twenty patients were assigned to group A and 40 patients to group B. In group A, 5 of 12 patients with measurable lesions (42%; 95% confidence interval (95% CI): 22%–62%) achieved major responses to chemotherapy, including one complete response. The duration of the overall median survival was 11 months. In group B, a major response was observed in 12 (39%; 95% CI: 28%–50%) of 31 patients with measurable lesions, including three complete responses. The overall median survival was 8 months. Hematological toxicities were noteworthy in both groups. Two toxic deaths occurred in group B.Conclusion: Using these doses and schedules of chemotherapy, a high-dose intensity policy does not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with new drugs are required.     

介入化疗对直肠癌血管内皮生长因子及微血管的影响

目的　探讨介入化疗对直肠癌血管内皮生长因子表达 (VEGF)及微血管计数 (MVD)的影响。方法　对 3 4例直肠癌患者介入化疗前后的肿瘤组织 ,用CD3 4对VEGF表达进行测定 ,并进行MVD计数。结果　本组患者介入化疗前及后 4至 5周VEGF阳性表达率分别为 61.7% (2 1/3 4)、3 2 .4% (11/3 4) ,MVD计数明显降低 ,差异均有显著性意义(P <0 .0 1)。结论　介入化疗能降低直肠癌组织VEGF的表达 ,减少MVD计数 ,提示介入化疗可能调节直肠癌的分化程度 ,减少术后转移。     

实体瘤化疗患者植入式静脉输液港治疗的相关感染并发症及危险因素分析

目的:对实体瘤化疗患者行植入式静脉输液港治疗的临床感染并发症及感染率进行分析,探究引起患者相关感染并发症的危险因素.方法:纳入2016年1月至2018年6月在我院介入科接受数字减影血管造影(DSA)引导植入式静脉输液港(IVAP)治疗的实体瘤化疗患者495例进行研究,对患者植入IVAP治疗期的病情进展情况、相关感染并发...     

ABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factors.

BACKGROUND: We investigated whether administration of full-dose ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy without growth factors, and irrespective of the granulocyte count, caused treatment delays or increased the number of infective episodes, in patients with Hodgkin's lymphoma (HL). PATIENTS AND METHODS: Thirty-eight patients with confirmed predominantly early-stage HL were treated with ABVD outside clinical trial protocols over a 5-year period on an outpatient basis. RESULTS: Ninety-five per cent of patients completed their scheduled ABVD regimen without adverse effects despite the development of neutropenia. Anaemia and thrombocytopenia did not present problems. Febrile neutropenia complicated 0.57% of combination chemotherapy injections. No growth factors were used and no dose modifications were carried out apart from the omission of bleomycin in one patient for the last two cycles of treatment due to the development of lung toxicity. All patients are currently disease-free, although three (7.8%) required salvage high-dose therapy (one relapsed and two with refractory disease). CONCLUSIONS: ABVD administration irrespective of granulocyte counts allowed the treatment to be given at full dose without delays or significant number of infective episodes. There was no need for growth factor support, minimising treatment costs. The use of full-dose ABVD irrespective of granulocyte count should be evaluated in future protocols for HL.