放射治疗下实体肿瘤演变的数学模型和数值模拟

目的数值模拟研究放射治疗下放射敏感性系数、治疗频率、肿瘤细胞成熟年龄等因素对实体肿瘤放射治疗效果的影响。方法建立放射治疗下实体肿瘤演变的连续-离散混合数学模型,模型考虑肿瘤的微环境(氧、细胞外基质、基质降解酶)以及自身行为(增殖、凋亡、黏附)对肿瘤演变的影响,并引入线性二次模型描述肿瘤对放射治疗的响应,采用数值模拟方法模拟不同条件下肿瘤演变的过程,评价放射治疗的疗效。结果肿瘤的放射治疗效果与放射敏感性系数、肿瘤细胞成熟年龄正相关,而在放射剂量总量不变的情况下,高频治疗和低频治疗效果并没有特别明显的区别。结论模拟结果与临床结果相吻合,可为肿瘤放射治疗的理论及临床研究提供一种新的方法。     

Treatment of multiple brain metastases with a divide-and-conquer spatial fractionation radiosurgery approach

Brain metastases are a common problem, managed with surgery, stereotactic radiosurgery (SRS), whole brain irradiation (WBI), or a combination. SRS targets individual tumors with large dosages of radiation. There is a trend toward using more SRS and less WBI, due to a reduction in cognitive damage, shorter treatment course, and improved tumor control. In conventional radiation a total dose of radiation is frequently divided over time into several smaller “fractions”, which helps spare normal tissues such as the brain. Two doses of 10 Gy each given on separate days will result in 45% less damage to normal brain tissue than a single dose of 20 Gy, according to the linear quadratic model for biologically effective dose (BED). Unfortunately, standard fractionation also reduces the effective dose to the tumor. It would therefore be highly beneficial to be able to fractionate the dose to the normal brain, but not fractionate the tumor dose. When a tumor is irradiated, there are dozens of beams that pass through the skull and converge on the tumor, also irradiating healthy brain tissue in the beam paths. If multiple tumors are irradiated, there are areas of brain that are overlapped by beams that are targeting separate tumors. If these tumors were treated on separate days, then on any given day portions of normal brain may only see the radiation beams for one tumor instead of 2 or more. That is how spatial fractionation of multiple metastases works. By treating groups of tumors on separate days the beams are spread out over time, reducing areas of beam overlap, and effectively fractionating the dose to healthy brain. Yet, each tumor still receives a single treatment. The hypothesis is that an array of metastases may be divided into 2–5 different groups that are treated on different days such that the BED to normal brain tissue is minimized. This should benefit patients by reducing side effects, allowing greater numbers of tumors to be treated, and making retreatment safer. An algorithm is discussed, which places the largest tumors and tumors situated close together into different groups. Modifications for axial beam delivery systems such as helical tomotherapy are discussed.     

Radiation treatment of brain tumors: concepts and strategies

Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.     

Dual role of the mitochondrial protein frataxin in astrocytic tumors

The mitochondrial protein frataxin (FXN) is known to be involved in mitochondrial iron homeostasis and iron-sulfur cluster biogenesis. It is discussed to modulate function of the electron transport chain and production of reactive oxygen species (ROS). FXN loss in neurons and heart muscle cells causes an autosomal-dominant mitochondrial disorder, Friedreich's ataxia. Recently, tumor induction after targeted FXN deletion in liver and reversal of the tumorigenic phenotype of colonic carcinoma cells following FXN overexpression were described in the literature, suggesting a tumor suppressor function. We hypothesized that a partial reversal of the malignant phenotype of glioma cells should occur after FXN transfection, if the mitochondrial protein has tumor suppressor functions in these brain tumors. In astrocytic brain tumors and tumor cell lines, we observed reduced FXN levels compared with non-neoplastic astrocytes. Mitochondrial content (citrate synthase activity) was not significantly altered in U87MG glioblastoma cells stably overexpressing FXN (U87-FXN). Surprisingly, U87-FXN cells exhibited increased cytoplasmic ROS levels, although mitochondrial ROS release was attenuated by FXN, as expected. Higher cytoplasmic ROS levels corresponded to reduced activities of glutathione peroxidase and catalase, and lower glutathione content. The defect of antioxidative capacity resulted in increased susceptibility of U87-FXN cells against oxidative stress induced by H(2)O(2) or buthionine sulfoximine. These characteristics may explain a higher sensitivity toward staurosporine and alkylating drugs, at least in part. On the other hand, U87-FXN cells exhibited enhanced growth rates in vitro under growth factor-restricted and hypoxic conditions and in vivo using tumor xenografts in nude mice. These data contrast to a general tumor suppressor function of FXN but suggest a dual, pro-proliferative but chemosensitizing role in astrocytic tumors.     

Clinically relevant biomarkers in targeted radiotherapy

Three classic parameters have been recognized as predictors or biomarkers of radiation response: intrinsic radiosensitivity, degree of hypoxia and repopulation capacity of clonogenic cells during a course of fractionated radiation therapy. Although good functional assays exist to measure these tumor parameters, and their use has led to the understanding of factors affecting outcome after radiotherapy, their application in clinical practice is hampered by technical difficulties, the length of time needed to obtain results and the lack of prospective randomized clinical trials. Recently, with the progress in molecular biology, genome-wide screening methods have been used to look for genetic signatures that can distinguish between good and bad outcome after radiotherapy. One of the most promising candidates is the epidermal growth factor receptor which is overexpressed or mutated in a variety of malignancies, such lung and head and neck cancer. Inhibition of this receptor has led to radio-sensitization with the prolongation of median survival in several cancers. Since there is significant variability in the response of patients with the same disease to radiotherapy, it would be very valuable to be able to predict which patients would benefit from a molecularly targeted therapy administered with concomitant radiation in order to increase the response rate (and cure rate) of those patients with radioresistant tumors. Optimally, this assay should be able to provide results in an efficient and reproducible manner and detect tumor genetic mutations that would provide specificity to the intervention. One approach currently in clinical practice to overcome intrinsic radioresistance and repopulation is stereotactic body radiotherapy coupled with image-guided radiation, a highly precise and powerful form of radiation, allowing radiation oncologist to treat tumors with more aggressive biological doses of radiation without causing serious normal tissues injury.     

RETROVIRUS PARTICLES IN SPONTANEOUSLY OCCURRING AND RADIATION-INDUCED TUMORS IN ddY MICE

Among spontaneously occurring tumors, pulmonary tumor, malignant lymphoma, mammary tumor, and ovarian tumor were the major ones in 232 ddY female mice. The former three tumors appeared significantly earlier and the latter one increased in incidence in 229 mice given 600 R whole or 800 R partial body (tunk) x-irradiation at the age of 10 weeks. Five tumors were examined electronmicroscopically from each tumor type of both the spontaneously occurring and radiation-induced tumors. G type virus particles were present only in the malignant lymphoma and B particles in the mammary, ovarian and pulmonary tumors, which are all of epithelial character. Thus, as far as we were concerned in this mouse strain, B particles were produced preferentially in epithelial cells and C particles in non-epithelial cells. The retrovirus particles were found in the same frequency, namely, 10 of 20 tumors examined in both the tumor groups. From our results, the intervention of virus in radiation carcinogenesis still remains in question.     

Primary malignant giant cell tumor of bone: "dedifferentiated" giant cell tumor

Well documented examples of primary malignant giant cell tumor of bone (giant cell tumor and concurrent sarcoma arising de novo) are exceedingly rare in the literature. We report a case arising in the left ischium of a 44-yr-old man. He had no previous history of radiation therapy or multiple resections. Histologically, the tumor was a typical giant cell tumor of bone juxtaposed to a malignant fibrous histiocytoma (MFH). The juxtaposition of a high grade sarcoma (MFH) and a locally aggressive nonmalignant neoplasm such as giant cell tumor is analogous to several other tumors of bone and soft tissue in which a low grade malignant or locally aggressive tumor can be associated with MFH or fibrosarcoma de novo, namely chondrosarcoma, chordoma, liposarcoma, and well differentiated intraosseous and parosteal osteosarcoma. The presence of a high grade malignant component in each of the aforementioned neoplasms generally portends a more ominous prognosis, although this is not invariably true. Recognition of the phenomenon of "dedifferentiation" (or tumor progression) in some bone tumors and sarcomas is important to ensure appropriate treatment. Distinction from secondary malignant giant cell tumors which are usually radiation induced is also important, since the latter have a much worse prognosis than those with dedifferentiation occurring de novo.     

Neural Stem Cell-based Gene Therapy for Brain Tumors

Advances in gene-based medicine since 1990s have ushered in new therapeutic strategy of gene therapy for inborn error genetic diseases and cancer. Malignant brain tumors such as glioblastoma multiforme and medulloblastoma remain virtually untreatable and lethal. Currently available treatment for brain tumors including radical surgical resection followed by radiation and chemotherapy, have substantially improved the survival rate in patients suffering from these brain tumors; however, it remains incurable in large proportion of patients. Therefore, there is substantial need for effective, low-toxicity therapies for patients with malignant brain tumors, and gene therapy targeting brain tumors should fulfill this requirement. Gene therapy for brain tumors includes many therapeutic strategies and these strategies can be grouped in two major categories: molecular and immunologic. The widely used molecular gene therapy approach is suicide gene therapy based on the conversion of non-toxic prodrugs into active anticancer agents via introduction of enzymes and genetic immunotherapy involves the gene transfer of immune-stimulating cytokines including IL-4, IL-12 and TRAIL. For both molecular and immune gene therapy, neural stem cells (NSCs) can be used as delivery vehicle of therapeutic genes. NSCs possess an inherent tumor tropism that supports their use as a reliable delivery vehicle to target therapeutic gene products to primary brain tumors and metastatic cancers throughout the brain. Significance of the NSC-based gene therapy for brain tumor is that it is possible to exploit the tumor-tropic property of NSCs to mediate effective, tumor-selective therapy for primary and metastatic cancers in the brain and outside, for which no tolerated curative treatments are currently available.     

MR-visible lipids and the tumor microenvironment

MR-visible lipids or mobile lipids are defined as lipids that are observable using proton MRS in cells and tissues. These MR-visible lipids are composed of triglycerides and cholesterol esters that accumulate in neutral lipid droplets, where their MR visibility is conferred as a result of the increased molecular motion available in this unique physical environment. This review discusses the factors that lead to the biogenesis of MR-visible lipids in cancer cells and in other cell types, such as immune cells and fibroblasts. We focus on the accumulations of mobile lipids that are inducible in cultured cells by a number of stresses, including culture conditions, and in response to activating stimuli or apoptotic cell death induced by anticancer drugs. This is compared with animal tumor models, where increases in mobile lipids are observed in response to chemo- and radiotherapy, and to human tumors, where mobile lipids are observed predominantly in high-grade brain tumors and in regions of necrosis. Conducive conditions for mobile lipid formation in the tumor microenvironment are discussed, including low pH, oxygen availability and the presence of inflammatory cells. It is concluded that MR-visible lipids appear in cancer cells and human tumors as a stress response. Mobile lipids stored as neutral lipid droplets may play a role in the detoxification of the cell or act as an alternative energy source, especially in cancer cells, which often grow in ischemic/hypoxic environments. The role of MR-visible lipids in cancer diagnosis and the assessment of the treatment response in both animal models of cancer and human brain tumors is also discussed. Although technical limitations exist in the accurate detection of intratumoral mobile lipids, early increases in mobile lipids after therapeutic interventions may be useful as a potential biomarker for the assessment of treatment response in cancer.     

Glioblastomatous transformation of ganglioglioma: case report with reference to molecular genetic and flow cytometric analysis

Gangliogliomas generally behave as benign indolent tumors. However, gangliogliomas undergoing malignant transformation have also been reported. The molecular basis for the malignant transformation of gangliogliomas remains unclear. We describe a case of ganglioglioma, which had transformed to glioblastoma after the gross total resection of the original tumor, in a 4-year-old girl. The present case is unusual in four aspects: (i) it arose from a low-grade ganglioglioma in the absence of previous radiation or chemotherapy, which is the fourth reported case; (ii) the original tumor showed a high proliferative index on flow cytometry but a low Ki-67 labeling index, implying that the application of flow cytometry might play a certain role in predicting biological and clinical behavior of low grade gangliogliomas; (iii) p53 mutation and deletion appeared in the secondary glioblastoma, which was not shown in the original well-differentiated ganglioglioma; and (iv) the transformed glioblastoma showed p16 inactivation detected by methylation and deletion, which are relatively uncommon genetic events in secondary glioblastomas. This is the first report of a genetic alteration in glioblastoma arising from a well differentiated ganglioglioma prior to radiation or chemotherapy. Based on the above findings, irrespective of radiotherapy or chemotherapy, rare recurrence of malignant evolution, especially tumors of high S-phase fraction on flow cytometry, warrants long-term follow-up, even in a well-differentiated ganglioglioma.     

脑肿瘤干细胞的研究现状

背景：在脑肿瘤中存在一种具有自我更新、无限增殖与多向分化能力的细胞,即脑肿瘤干细胞。脑肿瘤干细胞被认为是脑肿瘤发生、发展、转移与复发的根源。 目的：总结和探讨脑肿瘤干细胞的研究现状。 方法：以“脑肿瘤、脑肿瘤干细胞”为检索词,应该计算机检索Pubmed 数据库1977-01/2011-07的相关文章,并查阅与干细胞及脑肿瘤干细胞实验有关的书籍,对资料进行初审,选取符合要求的有关文章共32 篇。 结果与结论：在恶性脑肿瘤中存在脑肿瘤干细胞。脑肿瘤干细胞是恶性脑肿瘤发生、发展、转移及复发的根源,其表达特异性的CD133、Nestin蛋白和ABC转运体。目前已经获得了分离脑肿瘤干细胞的简便方法。CD133阳性的肿瘤干细胞所占的比例与脑肿瘤的恶性程度呈正相关,可作为预后诊断指标之一。      

Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI

Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis. CD133 has been considered a putative marker of cancer stem cells (CSCs) in malignant cancers, including GBMs. MicroRNAs (miRNAs), highly conserved small RNA molecules, may target oncogenes and have potential as a therapeutic strategy against cancer. However, the role of miRNAs in GBM-associated CSCs remains mostly unclear. In this study, our miRNA/mRNA-microarray and RT-PCR analysis showed that the expression of miR145 (a tumor-suppressive miRNA) is inversely correlated with the levels of Oct4 and Sox2 in GBM-CD133⁺ cells and malignant glioma specimens. We demonstrated that miR145 negatively regulates GBM tumorigenesis by targeting Oct4 and Sox2 in GBM-CD133⁺. Using polyurethane-short branch polyethylenimine (PU-PEI) as a therapeutic-delivery vehicle, PU-PEI-mediated miR145 delivery to GBM-CD133⁺ significantly inhibited their tumorigenic and CSC-like abilities and facilitated their differentiation into CD133⁻-non-CSCs. Furthermore, PU-PEI-miR145-treated GBM-CD133⁺ effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation and temozolomide. Finally, the in vivo delivery of PU-PEI-miR145 alone significantly suppressed tumorigenesis with stemness, and synergistically improved the survival rate when used in combination with radiotherapy and temozolomide in orthotopic GBM-CD133⁺-transplanted immunocompromised mice. Therefore, PU-PEI-miR145 is a novel therapeutic approach for malignant brain tumors.     

Preliminary experiences with intraoperative radiation therapy (IORT) for the treatment of brain tumors.

Ten brain tumor patients underwent wide resection of the tumor followed by Intraoperative Radiation Therapy (IORT) at the first surgery or at the second salvage surgery after failure of conventional external beam irradiation. Two patients(1 meningioma, 1 glioblastoma multiforme) were treated at the first surgery and 8 patients(3 anaplastic astrocytoma, 3 glioblastoma multiforme, 1 meningioma, 1 gliosarcoma) were treated after salvage surgery. The IORT doses were ranged from 15-25 Gy depending on the tumor volume and previous radiation therapy. The neurological status(Karnofsky performance status) was improved in 4 cases, not changed in 6 cases after IORT. There were several complications after IORT; radiation necrosis, communicating hydrocephalus, wound infection, and abnormal CT findings such as diffuse low density area in an around operation site. The radiation necrosis was confirmed by operation in a recurrent meningioma patient 12 months after IORT. At follow-up, ranging from 1 to 16 months, there was no deaths. Based on our limited experiences, the IORT might be one of the adjuvant therapeutic modalities especially for the malignant brain tumors and unresectable huge meningioma.     

Hyalinizing Trabecular Tumor of the Thyroid: An Update

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. This tumor is known to share morphological and architectural similarities with paraganglioma and medullary thyroid carcinoma, as well as the nuclear features and RET/PTC1 translocations of papillary thyroid carcinoma. These tumors are not associated with RAS or BRAF mutations. Whether the presence of RET alterations in HTT are sufficient molecular proof of its relationship with papillary thyroid carcinoma (PTC) is still to be defined. Of great interest is the characteristic strong peripheral cytoplasmic and membranous staining of the tumor cells with MIB1 immunostain, not seen in any other thyroid neoplasm. Although cases of malignant HTT have been recorded, HTT should be considered a benign neoplasm or, at most, a neoplasm of extremely low malignant potential.     

基于FDK算法的数字合成X线体层成像

目的:放射治疗是恶性肿瘤病人的主要治疗手段之一。放疗的基本目标是最大限度地将放射线的剂量集中到病变(靶区)内,杀灭肿瘤细胞,而使周围正常组织和器官少受或免受不必要的照射。放疗过程中的一些不确定性因素,可以影响到靶区的几何形态,进而影响肿瘤实际照射剂量的分布,造成肿瘤脱靶和(或)危及器官损伤增加。因此,放射治疗中摆位的准确性和重复性成为影响肿瘤放疗疗效的关键性因素之一,特别是当高剂量梯度存在的时候。提高放疗摆位精度核心就是要及时获取并修正摆位误差。方法:测量摆位误差,需要比较治疗位置图像与模拟定位时的图像。研究成像剂量低,图像质量好的成像模式可以更好的提高放射治疗的摆位精度。数字合成X线体层成像(Digital Tomosynthesis,DTS)是一种基于有限角度的二维投影图像获取三维图像的重建方法。本文提出利用与FDK(Feldkamp-Davis-Kress)相似的算法重建治疗位置DTS图像,并对DTS图像质量的影响因素进行研究。结果:DTS图像比传统千伏射野验证片显示更多的解剖信息,骨结构和软组织清晰度明显提高。结论:DTS可以替代传统射野验证片和CBCT,作为放疗摆位校正的另一种方法。     

Small cell malignant tumors of the thyroid: A light and electron microscopic study

Three small cell malignant tumors involving the thyroid gland were examined by light and electron microscopy. In each, numerous similarities were presented on light microscopic analysis rendering interpretation difficult. In the first patient the small cells were identified on electron microscopy as moderately well differentiated lymphocytes. This tumor occurred in an elderly woman as a locally invasive thyroid tumor, subsequently involving distant sites, including the liver, spleen, lymph nodes, and soft tissue. The tumor repeatedly regressed following radiotherapy. The patients eventually died with disseminated lymphocytic lymphoma. In the second patient the thyroid tumor, also locally invasive, was composed principally of neoplastic epithelial cells when studied on electron microscopy. This patient responded poorly to radiation and died within a year after diagnosis. The third patient presented with an enlarging thyroid mass, which ultrastructurally was found to be composed principally of well differentiated lymphocytes. Subsequent clinical evaluation established a diagnosis of chronic lymphocytic leukemia. Small cell malignant tumors of the thyroid represent a difficult diagnosis problem for surgical pathologists. Ultrastructural study, we believe, is a useful adjunct in the differentiation of these tumors.     

侧群细胞及其在干细胞研究中的应用

肿瘤干细胞学说的提出为肿瘤的治疗提供了新的靶点和方向。尽管已经从白血病、乳腺癌、脑肿瘤等肿瘤中初步分离鉴定出肿瘤干细胞，但是还有许多恶性肿瘤由于肿瘤干细胞表面标记尚不清楚而无法鉴定，通过侧群细胞(side population cells，SP) 分选来初筛肿瘤干细胞，方法简便、有效，正被越来越多地应用。     

Dormant tumor cells in liver and brain. An autopsy study on metastasizing tumors

In 96 of 100 autopsy cases with metastasizing tumor diseases single disseminated tumor cells were detected in liver or brain tissues. These tumor cells appear to be in a resting state. Most of the resting or dormant tumor cells (dtc) are distinguishable from tumor cells within metastasis (mtc) by morphological criteria such as cell size or density, shape and size of the nucleus. These observations suggest that disseminated cells from many primary tumors might pass through a resting (Go) state before they eventually initiate malignant cell growth and give rise to metastatic colonies. Most likely the dtc are not affected by systemic chemotherapy.     

MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumors.

The expression of human MDR1 P-glycoprotein (Pgp) in the capillary endothelial cells of the central nervous system has been demonstrated. The brain capillary endothelial cells maintain the structure and function of the blood-brain barrier. Recently, the human MDR1 Pgp (and its mouse homologue MDR1a Pgp) has been shown to function as an important part of this barrier, pumping out xenobiotics from endothelial cells into the lumen of capillaries resulting in the protection of the brain parenchyma. To examine whether the endothelial cells of the newly formed capillaries during neoangiogenesis within malignant human brain tumors express MDR1 Pgp, 35 adult surgical brain tumor specimens (29 gliomas and 6 tumors metastatic to the brain) were obtained from previously untreated patients and studied by a new immunohistochemical sandwich method developed in our laboratory using the JSB-1 monoclonal antibody. JSB-1 is specific for the Pgp product of the human MDR1 (and not MDR3) gene. This sensitive method allows the detection of Pgp in capillary endothelial cells of normal brain in conventional paraffin sections after formalin fixation. The endothelial cells of the newly formed capillaries in 25 of 29 gliomas (86%) and 3 of 6 metastatic tumors, immunostained positive for MDR1 Pgp. The tumor cells in 7 of 35 cases were also positive for Pgp. In the 35 brain tumor cases investigated, the endothelial cells were Pgp positive in the tumor-brain border and in the brain further from the tumor. Capillary endothelial cells of neovasculature in 137 malignant tumors (non-brain) obtained from previously untreated patients showed no MDR1 Pgp expression. These results demonstrated that MDR1 Pgp is expressed not only in the capillaries of normal brain but also in the majority of the newly formed capillaries of brain tumors. Multidrug resistance of brain tumors may result not only from the expression of resistance markers in neoplastic cells but also from the MDR1 Pgp expression in endothelial cells of tumor capillaries. Pgp in this special localization can exclude chemotherapeutic agents from tumor cells that are located around the capillaries. The therapeutic benefit and selectivity of chemotherapeutic agents in combination with a Pgp-reversing agent should be evaluated.     

脐血造血干细胞对原发性肝细胞癌的抑制作用

背景：原发性肝细胞癌是一种临床常见的恶性肿瘤,虽然近年来各种治疗方式如外科手术、射频消融以及选择性动脉栓塞等治疗方式均取得了进展,但对于某些进展期肝癌患者,这些治疗方法具有一定的局限性。在这样的背景下,干细胞对恶性肿瘤的治疗或抑制作用正逐渐成为人们关注的焦点。 目的：对原发性肝细胞癌的发病情况、肿瘤免疫编辑过程、肿瘤微环境以及脐血造血干细胞对原发性肝细胞癌和其他实体肿瘤的抑制作用进行综述。 方法：检索万方医药网及外文生物医学期刊数据库2000-01/2010-09有关原发性肝细胞癌发病情况、免疫微环境以及造血干细胞对包括肝细胞癌在内的实体肿瘤抑制作用的文章,中文检索词为“肝癌,造血干细胞,免疫微环境”,英文检索词为“hepatocellular carcinoma, hematopoietic stem cell, microenvironment”。最终筛选出33篇文献作进一步分析。 结果与结论：肿瘤的发生及发展与机体免疫系统的变化密切相关,在已发生肿瘤的机体内,免疫系统处于抑制状态,对于恶性肿瘤细胞无反应或者低反应。脐血造血干细胞具有免疫原性低、分裂能力强、分化谱系广等特点,在接受移植的机体内能够分化为多种谱系的细胞,其中包括多种免疫细胞,从而弥补机体原有免疫系统的缺陷,起到杀伤肿瘤细胞、抑制肿瘤生长的作用。然而其作用机制、适应证及不良反应等仍需进一步深入研究。