Danova M, Aglietta M
Internal Medicine and Medical Oncology, University and IRCCS San Matteo, Pavia, Italy.
Haematologica. 1997 Sep-Oct;82(5):622-9.
An increasing number of growth factors have been shown to be responsible for the proliferation, survival and enhanced function of many cell types within the hemopoietic system. The action of these hemopoietic growth factors in stimulating cell growth and survival applies both to cells within the progenitor compartment and mature cells. Whether a specific cytokine influences in vivo hematopoietic progenitor cell proliferation or survival depends on cytokine-mediated modulation or target cell cytokine receptors, cell proliferation, and cell death regulator genes and other pathways. To address these issues, particularly in view of the current and future clinical use of hemopoietic growth factors, the Italian Society of Experimental Hematology organized a Meeting in Florence on July 4th, 1996.
The material examined in the present review includes full papers and abstracts published in journals covered by the Science Citation Index and Medline. All the participants to the Meeting in Florence have been actively working in the field of biology and clinical application of hemopoietic growth factors. Summaries of their oral presentations at the Florence Meeting are reported in the Appendix to this article.
Myelopoietic growth factors particularly granulocyte (G-) colony-stimulating factor (CSF) and granulocyte-macrophage (GM)-CSF, have been available for clinical use for only a few years but they have already markedly changed the management of chemotherapy-induced neutropenia, the use of dose-intensive chemotherapy regimens and the practice and safety of autologous stem cell transplantation. While these growth factors have been rapidly introduced as routine agents in the management of cancer patients, they have continued to generate a considerable amount of fundamental research into the biology of hematopoiesis as well as the growth regulation of normal and cancer cells. For instance, one goal of cancer treatment is to protect hematopoietic stem and progenitor cells from the damaging effects of chemotherapy, while maintaining their anticancer action. Any means of preferentially and reversibly suppressing the proliferation of normal hematopoietic stem and progenitor cells while leaving the proliferation of tumor cells and their susceptibility to chemotherapy unmodified, could potentially optimize treatment efficacy. In this field, the possibility of using colony-stimulating factors as myeloprotective agents in dose-intensive chemotherapy to enhance anticancer activity could be an attractive goal of current anti-cancer treatment modalities.
越来越多的生长因子已被证明与造血系统中多种细胞类型的增殖、存活及功能增强有关。这些造血生长因子刺激细胞生长和存活的作用既适用于祖细胞区室中的细胞，也适用于成熟细胞。特定细胞因子是否会影响体内造血祖细胞的增殖或存活，取决于细胞因子介导的调节作用或靶细胞细胞因子受体、细胞增殖、细胞死亡调节基因及其他途径。为解决这些问题，特别是考虑到造血生长因子当前及未来的临床应用，意大利实验血液学协会于1996年7月4日在佛罗伦萨组织了一次会议。
本综述所研究的材料包括发表在《科学引文索引》和《医学索引》收录期刊上的全文及摘要。参加佛罗伦萨会议的所有人员均在造血生长因子的生物学及临床应用领域积极开展研究工作。他们在佛罗伦萨会议上的口头报告摘要刊载于本文附录。
骨髓造血生长因子，尤其是粒细胞（G-）集落刺激因子（CSF）和粒细胞-巨噬细胞（GM）-CSF，临床应用至今不过数年，但已显著改变了化疗所致中性粒细胞减少症的治疗、剂量密集化疗方案的应用以及自体干细胞移植的实践与安全性。虽然这些生长因子已迅速成为癌症患者治疗中的常规用药，但它们仍不断激发人们对造血生物学以及正常细胞和癌细胞生长调节进行大量的基础研究。例如，癌症治疗的一个目标是保护造血干细胞和祖细胞免受化疗的损伤，同时维持其抗癌作用。任何能够优先且可逆地抑制正常造血干细胞和祖细胞的增殖，而不改变肿瘤细胞的增殖及其对化疗的敏感性的方法，都有可能优化治疗效果。在这一领域，在剂量密集化疗中使用集落刺激因子作为骨髓保护剂以增强抗癌活性，可能是当前抗癌治疗模式的一个有吸引力的目标。
