常见骨原发肿瘤研究新进展

正原发性骨肿瘤发病率相对较低,其中常见的恶性骨肿瘤包含骨肉瘤、尤文肉瘤及软骨肉瘤。骨巨细胞瘤(giant cell tumor,GCT)属中间性肿瘤。恶性骨肿瘤易复发和转移,恶性程度较高,并可影响患者运动功能。骨肿瘤的发病机制尚不清楚,临床治疗上仍有很大提高空间,许多方面需要更多深入研究。笔者旨在对常见原发性骨肿瘤:骨肉瘤、尤文肉瘤、软骨肉瘤以及GCT的近年的亮点研究进行系统综述。     

377例双向分化恶性肿瘤血管生成拟态临床意义分析

目的:探讨双向分化恶性肿瘤组织中血管生成拟态的临床意义.方法:收集1955～2000年间我院病理科石蜡包埋双向分化恶性肿瘤样本887例,其中临床和病理资料完整的377例作为研究对象,分为有血管生成拟态组和无血管生成拟态组,分析具有血管生成拟态肿瘤的临床意义.结果:除滑膜肉瘤外(P=0.759),恶性黑色素瘤(P=0.038 2)、间皮肉瘤(P=0.035 6)、横纹肌肉瘤(P=0.028 2)中具有血管生成拟态的肿瘤患者生存时间明显低于无血管生成拟态肿瘤患者,两者比较差异有显著性.结论:具有血管生成拟态的双向分化恶性肿瘤恶性度高、血道转移早、临床预后差.     

晚期原发性脾血管肉瘤1例

<正>血管肉瘤(angiosarcoma,AS)是一种高度恶性血管源性肿瘤,由血管内皮细胞分化的间叶细胞、血管内皮细胞或淋巴管内皮细胞直接发生而来,占软组织肉瘤的1%～2%^[1]。AS在软组织肉瘤中恶性程度较高、复发和转移较快,预后较差,转移性血管肉瘤患者的中位生存仅6.6个月^[2]。     

胶皮质瘤血管发生发展机制研究

恶性胶质瘤是人体血管化程度最高的肿瘤，血管生成和增长在胶质瘤生长和侵袭过程中起重要作用，并与其恶性进展相关、内皮细胞在血管生成中起重要作用，内皮细胞与肿瘤细胞的相互作用是肿瘤血管生成的关键因素，血管生成因子以及微环境的改变主要调控胶质瘤的血管生成。组织重构的研究方法有助于对正常和病理性的血管生成分子机制进一步了解，胶质瘤血管生成机制将得以明确。     

肿瘤血管生成与乳腺癌研究进展

肿瘤新生血管生成在肿瘤的生长和转移过程中起着重要作用，抗血管生成治疗可能成为肿瘤治疗的新方法。本文综述了乳腺癌的血管生成机制及乳腺癌抗血管生成治疗的研究进展。     

血管内皮生长因子C、D与肿瘤淋巴转移的关系

肿瘤侵袭转移是恶性肿瘤危及患者生命最主要的恶性行为特征，也是导致肿瘤患者死亡的主要原因之一。肿瘤诱导血管生成对肿瘤转移的影响已为研究者重视，而肿瘤转移主要方式之一的淋巴转移分子机制却长期未被重视。由于淋巴管较脆，在解剖中不易得到，以及病理上对淋巴管内皮细胞的识别与分离技术方面存在困难，因此淋巴管生成及调控机制的研究迟缓。肿瘤相关的淋巴管生成是如何调控的至今尚不清楚，仍不知肿瘤细胞是如何逃离原发肿瘤进入淋巴管的。[第一段]     

一种新型肿瘤血管生成抑制因子——血管稳定素的研究进展

为了研究原发性肿瘤抑制其转移瘤生长的分子机制，Ｏ’Ｒｅｉｌｌｙ等从一个原发性肺肿瘤抑制其转移瘤的小鼠模型上，分离纯化到一个由原发瘤产生的抑制肿瘤血管生成和转移瘤生长的多肽，并命名为血管稳定素。     

血管生成抑制剂联合放射线治疗肿瘤的机制及现状

20世纪初，Goldman观察到血管围绕肿瘤生成（angiogenesis）现象。1971年，Folkman提出肿瘤生长和转移是血管依赖性的，阻断血管生成是遏止肿瘤生长的有效策略这一学说。近十年来，对肿瘤血管形成机制进行了深人的研究，     

肿瘤血管生成及抗血管生成基因治疗

肿瘤的侵袭和转移明显影响患者的预后,而肿瘤的血管生成是肿瘤生长、侵袭、转移的基本条件。因而抑制肿瘤血管生成是治疗肿瘤的关键。本文就肿瘤血管生成的调控及抗肿瘤血管生成基因治疗的研究进展作一综述。     

新冠肺炎疫情期间对骨肿瘤患者的建议

在这个疫情肆虐的特殊时期,提倡减少外出、避免人群聚集的原则下,针对属于新型冠状病毒感染高危人群的肿瘤患者,给出几点建议,供大家参考。一、初诊疑似为恶性骨肿瘤的患者1.警惕何种情况可能疑似为恶性骨肿瘤恶性骨肿瘤占骨肿瘤的40%,以骨肉瘤、软骨肉瘤、纤维肉瘤为多见。恶性骨肿瘤多发生在10~20岁,尤其是骨肉瘤患者。     

Cancer vascularization: implications in radiotherapy?

PURPOSE: Although hypoxia is considered a major cause of failure of radiotherapy, the mechanisms of tumor hypoxia are unclear, and effective ways for its correction or targeting are missing. Tumoral vasculature is the vehicle for the hemoglobin to reach the tumoral stroma. Although anemia has long been focused on as an important parameter related to tumor hypoxia, differences in vascular density may also affect the intratumoral access of hemoglobin. METHODS AND MATERIALS: In the present study, we examined the vascular density in 1459 human carcinomas. The distribution of the vascular density within tumors was studied in 436 non-small-cell lung carcinomas and 298 breast carcinomas. RESULTS: The vascular density was found to vary up to 22-fold even among tumors of the same histology. Overall, the vascular density was significantly higher in the tumor periphery as compared to inner areas. Three different patterns of vascularization were identified in both lung and breast cancer specimens; (1) tumors with low or (2) tumors with high vessel density throughout the tissue section, and (3) tumors with high vessel density in the tumor periphery and low in inner areas. The death rate following surgery showed a direct association with the vascular density in lung, breast, colon, and endometrial cancer. In inoperable gastric cancer patients treated with chemotherapy, and in head and neck cancer patients treated with radical chemoradiotherapy there was a 'U-like' association of the death rate with the vascular density suggesting that very low (poor oxygen and drug availability) and very high (intensified angiogenic pathways) vascularization are both linked to poor outcome. CONCLUSION: The present study stresses the importance of the vascular density as a putative variable that may have affected the results of large clinical trials that investigated the role of anemia, hyperbaric oxygen, hypoxic sensitizers, or even of combined chemoradiotherapy in the outcome of radiation treatment.     

Liver resection in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma is a leading cause of cancer death worldwide. Liver resection and liver transplantation remain the only options for cure. Since the indications for orthotopic liver transplantation are limited, partial liver resection is the more common treatment. Recently, indications for liver resection have been expanded and there have been advances in the associated surgical techniques. This review describes the state-of-the-art of liver resection for hepatocellular carcinoma. Topics covered include: new indications, such as treatment of large tumors, bilobar tumors and those associated with vascular invasion; preoperative assessment of liver function; and surgical strategies. An overview of the most common staging systems, which are useful in predicting prognosis after liver resection for hepatocellular carcinoma, is given.     

Liver resection in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma is a leading cause of cancer death worldwide. Liver resection and liver transplantation remain the only options for cure. Since the indications for orthotopic liver transplantation are limited, partial liver resection is the more common treatment. Recently, indications for liver resection have been expanded and there have been advances in the associated surgical techniques. This review describes the state-of-the-art of liver resection for hepatocellular carcinoma. Topics covered include: new indications, such as treatment of large tumors, bilobar tumors and those associated with vascular invasion; preoperative assessment of liver function; and surgical strategies. An overview of the most common staging systems, which are useful in predicting prognosis after liver resection for hepatocellular carcinoma, is given.     

Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment

In many past clinical studies in which hyperthermia enhanced the efficacy of radiotherapy, the tumor temperatures could be raised only to 40–42°C range in most cases. The heat-induced cell death, cellular radiosensitization, and vascular damage induced by such mild temperature hyperthermia (MTH) are likely to be insignificant despite the increased response of tumors to radiotherapy. Heating rodent tumors at 40–42°C was found to cause an enduring increase in blood flow and oxygenation in the tumors. Recent studies with canine soft tissue sarcoma and human tumor clinical studies also demonstrated that MTH improves tumor oxygenation, and enhances response of the tumors to radiotherapy or chemoradiotherapy. The increased blood flow and vascular permeability caused by MTH may also improve the delivery of various therapeutic agents such as chemotherapy drugs, immunotherapeutic agents and genetic constructs for gene therapy to tumor cells. MTH as a means to potentiate the efficacy of radiotherapy and others warrants further investigation.     

Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment.

In many past clinical studies in which hyperthermia enhanced the efficacy of radiotherapy, the tumor temperatures could be raised only to 40-42 degrees C range in most cases. The heat-induced cell death, cellular radiosensitization, and vascular damage induced by such mild temperature hyperthermia (MTH) are likely to be insignificant despite the increased response of tumors to radiotherapy. Heating rodent tumors at 40-42 degrees C was found to cause an enduring increase in blood flow and oxygenation in the tumors. Recent studies with canine soft tissue sarcoma and human tumor clinical studies also demonstrated that MTH improves tumor oxygenation, and enhances response of the tumors to radiotherapy or chemoradiotherapy. The increased blood flow and vascular permeability caused by MTH may also improve the delivery of various therapeutic agents such as chemotherapy drugs, immunotherapeutic agents and genetic constructs for gene therapy to tumor cells. MTH as a means to potentiate the efficacy of radiotherapy and others warrants further investigation.     

Catalase-overexpressing thymocytes are resistant to glucocorticoid-induced apoptosis and exhibit increased net tumor growth

Glucocorticoids are used for the treatment of lymphoid neoplasms, taking advantage of the well-known ability of these compounds to cause apoptosis in lymphoid tissues. Previously, we have shown that dexamethasone, a synthetic glucocorticoid, causes a down-regulation of several antioxidant defense enzymes and proteins, including catalase and thioredoxin, concomitant with the induction of apoptosis in WEHI7.2 mouse thymoma cells. To test whether this down-regulation plays a critical role in the mechanism of steroid-induced apoptosis, WEHI7.2 cells were transfected with rat catalase. Two clones, expressing 1.4-fold and 2.0-fold higher catalase specific activity, respectively, when compared with vectoronly transfectants were selected for further study. An increase to 1.4-fold parental cell catalase activity delayed cell loss after dexamethasone treatment, whereas a 2.0-fold parental catalase activity prevented dexamethasone-induced cell loss for 48 h after treatment. Dexamethasone treatment of the WEHI7.2 cells stimulated a release of cytochrome c into the cytosol. Catalase-overexpressing cells showed a delay or lack of cytochrome c release from the mitochondria, which correlated temporally with the delay or prevention of cell loss in the culture after dexamethasone treatment. A decreased amount of cell death from WEHI7.2 cells overexpressing catalase was also seen in tumor xenografts in severe combined immunodeficient mice when compared with tumors from vector-only transfected cells. Similarly, thioredoxin-overexpressing WEHI7.2 cells, shown previously to be apoptosis resistant, showed decreased cell death in tumor xenografts. This resulted in larger tumors from cells overexpressing these proteins. Cell death in control transfectant tumor xenografts was primarily attributable to apoptosis. In contrast, the cell death we observed in tumors from thioredoxin- or catalase-overexpressing cells had a higher frequency of a nonapoptotic, nonnecrotic type of cell death termed para-apoptosis. These data suggest that: (a) oxidative stress plays a critical role in steroid-induced apoptosis prior to the commitment of the cells to undergo apoptosis; and (b) resistance to oxidative stress can contribute to tumor growth.     

Vascular targeting agents as cancer therapeutics.

Vascular targeting agents (VTAs) for the treatment of cancer are designed to cause a rapid and selective shutdown of the blood vessels of tumors. Unlike antiangiogenic drugs that inhibit the formation of new vessels, VTAs occlude the pre-existing blood vessels of tumors to cause tumor cell death from ischemia and extensive hemorrhagic necrosis. Tumor selectivity is conferred by differences in the pathophysiology of tumor versus normal tissue vessels (e.g., increased proliferation and fragility, and up-regulated proteins). VTAs can kill indirectly the tumor cells that are resistant to conventional antiproliferative cancer therapies, i.e., cells in areas distant from blood vessels where drug penetration is poor, and hypoxia can lead to radiation and drug resistance. VTAs are expected to show the greatest therapeutic benefit as part of combined modality regimens. Preclinical studies have shown VTA-induced enhancement of the effects of conventional chemotherapeutic agents, radiation, hyperthermia, radioimmunotherapy, and antiangiogenic agents. There are broadly two types of VTAs, small molecules and ligand-based, which are grouped together, because they both cause acute vascular shutdown in tumors leading to massive necrosis. The small molecules include the microtubulin destabilizing drugs, combretastatin A-4 disodium phosphate, ZD6126, AVE8062, and Oxi 4503, and the flavonoid, DMXAA. Ligand-based VTAs use antibodies, peptides, or growth factors that bind selectively to tumor versus normal vessels to target tumors with agents that occlude blood vessels. The ligand-based VTAs include fusion proteins (e.g., vascular endothelial growth factor linked to the plant toxin gelonin), immunotoxins (e.g., monoclonal antibodies to endoglin conjugated to ricin A), antibodies linked to cytokines, liposomally encapsulated drugs, and gene therapy approaches. Combretastatin A-4 disodium phosphate, ZD6126, AVE8062, and DMXAA are undergoing clinical evaluation. Phase I monotherapy studies have shown that the agents are tolerated with some demonstration of single agent efficacy. Because efficacy is expected when the agents are used with conventional chemotherapeutic drugs or radiation, the results of Phase II combination studies are eagerly awaited.     

血管内皮生长因子、Ki-67、Bcl-2和Bax在小儿恶性实体瘤的表达及意义

背景与目的:随着先天性畸形及感染性疾病死亡率的不断下降,恶性实体瘤逐渐成为儿童的主要死亡原因.本研究旨在探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)、Ki-67、Bcl-2和Bax在小儿恶性实体瘤的表达及意义,以期为小儿恶性实体瘤的诊断及预后判断提供理论依据.方法:应用免疫组织化学方法检测69例小儿恶性实体瘤患者VEGF、Ki-67、Bcl-2和Bax的表达,并用原位杂交方法检测VEGF mRNA、Bcl-2 mRNA的表达.结果:VEGF、Ki-67、Bcl-2和Bax在小儿恶性实体瘤中表达率分别为58.0％、69.6％、69.6％和30.9％.Bcl-2 mRNA及VEGF mRNA在小儿恶性实体瘤的表达率均为82.0％.VEGF、Ki-67和Bcl-2在小儿恶性实体瘤中高表达,Bax表达较低,与正常组织相比,差异有统计学意义(P＜0.05).经相关分析显示,VEGF与Ki-67、Bcl-2呈显著正相关(P＜0.01).结论:VEGF、Ki-67、Bcl-2和Bax与小儿恶性实体瘤的发生、发展密切相关,可为小儿恶性实体瘤的诊断及预测预后提供依据.     

TNF-alpha levels in patients with malignant tumors after hyperthermic isolated regional perfusion

Hyperthermic isolated regional perfusion is an alternative method for the treatment of malignancies especially sited in the pelvic region and extremities. The perfusion is performed via the extracorporeal system with a pump flow and chemotherapeutic agents and some cytokines, like tumor necrosis factor, may be added. It's well known that in the ischemia-reperfusion injury, hemorrhagic necrosis and cell death occurs and these cytokines are produced endogenously. In this study the endogenous TNF-alpha levels before, during and after hyperthermic isolated regional perfusion were compared in 16 patients with malignant tumors. The TNF-alpha levels were determined from the blood samples taken systemically before and after perfusion, and from perfusate at the 15th, 30th, 45th minute. The 15th minute samples were the ones where vascular clamps were applied to the vessels before starting the perfusion. TNF-alpha levels between the 15th minute samples and the blood samples that were taken systemically before and after perfusion were found statistically significant. The cause of this was suggested to be the ischemia-reperfusion injury in this period. It was shown in this study that high endogenous TNF-alpha levels and good clinical results could be achieved with hyperthermic isolated regional perfusion in the treatment of malignant tumors.     

Abdominal desmoid tumors

Desmoid tumors are rare, benign, fibromatous lesions that are the result of abnormal proliferation of myofibroblasts. Desmoid tumors can be classified as extra-abdominal and abdominal. Abdominal desmoid tumors are either superficial or intraabdominal. These tumors are associated with a high recurrence rates, even if their microscopic characters indicate a benign disease; their biologic behavior often indicates rather a "malignant" disease, which can cause even the death. Intraabdominal desmoid tumors can engulf surrounding viscera and vessels, thereby greatly complicating their surgical treatment. Management is multidisciplinary. Simple observation is a reasonable management option for asymptomatic patients; spontaneous regression of these tumors may be observed. Complete excision is the treatment of choice for tumors causing symptoms or complications. Surgery should be minimized as much as feasible, while at the same time achieving free margins. Adjuvant therapy should be considered in selected cases; the role of other management options (including gene transfer therapy) is currently under intensive investigation.