动物肿瘤模型的建立及其标准研讨

白细胞介素2是山T^H细胞在有丝分裂原／抗原及IL-1的双重信号作用下而产生的一种可溶性糖蛋白。其主要功能是维持T细胞持续生长、增殖．表达IL-2受体等。IL-2的产生和／或IL-2R表达异常与多种肿瘤、自身免疫疾病等所致的免疫功能障碍有关。因此，检测T细胞产生IL-2、表达IL-2R和对IL-2的增殖反应水平．可在一定程度上反映机体的免疫应答能力。本文就肿瘤患者PBL对rlL-2增殖反应的水平，与肿瘤术后者及健康者相比较，分析讨论了肿瘤患者免疫调节障碍的具体环节。     

动物肿瘤模型的建立及其标准研讨

动物肿瘤模型，也是人类肿瘤的复制，对肿瘤发生、发展机制的研究及肿瘤预防和治疗等研究具有重要的意义．动物肿瘤模型的建立应注意选择动物的种系和致癌物的类型。动物种系间的差异很大，相同的致癌物对不同种系的动物可诱发不同的肿瘤，因此要诱发出台适的动物肿瘤模型，动物种系的选择极为重要．动物肿瘤模型分为动物自发瘤模型．诱发瘤模型和移植瘤模型．而移植瘤模型为本文讨论的重点。人类肿瘤移植瘤(指移植于免疫缺陷动物)的来源有肿瘤活检组织，手术切除的肿瘤标本和人类肿瘤细胞系。建立移植瘤的基本条件是：肿瘤标本的取材，应在无菌条件下取新鲜、无坏死、无包膜的瘤组织，手术标本的取材应在1—2个小时内完成．移植瘤受体动物(包括免疫缺陷动物)要求在4周龄左右，移植的最常用部位是背侧皮下。移植瘤建成的标准是：传代数应在15—20代(每代传3-4只动物)；最终移植成瘤率为100％；自发消退率减少到虽低限度(不一定完全达到零)；生长速度要稳定；宿主寿命相似(重复性强)；宿主反应性低(已适应受体动物体内生长)；瘤组织的组织学结构仍保持与原发瘤相似．符合以上标准即可称为移植性肿瘤模型。     

肿瘤基因工程纳米疫苗NL(MH)抗肿瘤复发的实验研究

目的：在小鼠体内观察纳米疫苗NL（MH）抗肿瘤复发作用。方法：以PBS、空白脂质体、MH、MH／NL、NL（MH）免疫C57BL／6小鼠3次后，IFN-γ ELISPOT和LDH杀伤实验检测纳米疫苗激活小鼠特异性细胞免疫反应的情况；以肿瘤攻击实验和肿瘤切除后复发实验来评价纳米疫苗预防肿瘤复发作用。结果：与对照组相比，NL（MH）组小鼠脾淋巴细胞中分泌IFN-γ的T细胞数量明显增多（P〈0．05），CTL对B16-MAGE3细胞具有显著的特异性杀伤作用；在肿瘤攻击实验中，NL（MH）组B16-MAGE3肿瘤成瘤时间长、成瘤率低；肿瘤切除后，NL（MH）组B16-MAGE3肿瘤复发时间延迟，复发率明显降低。结论：NL（MH）能够刺激机体产生强烈的MAGE3特异性的细胞免疫反应，对表达MAGE3的肿瘤细胞具有显著的杀伤作用，能有效预防B16-MAGE3切除后复发。     

循环肿瘤细胞自激注入的研究进展

由于缺乏有效的治疗手段,转移仍是癌症病人死亡的首要原因。肿瘤转移的新理论认为循环肿瘤细胞能够回到肿瘤原发灶,从而滋养肿瘤细胞,并产生更具侵袭力的转移株。本文就该现象加以综述,并对其在人类癌症转移研究中的意义进行探讨。     

Prognostic value of tumor thickness in patients with Merkel cell carcinoma

BACKGROUND AND OBJECTIVES: Merkel cell carcinoma is an aggressive skin malignancy that often presents with tumor metastases. We hypothesized that tumor thickness might correlate with both regional and metastatic tumor spread and could, therefore, be used as an independent prognostic variable. The purpose of this study was to see if depth of tumor invasion would predict prognosis independent of tumor stage. METHODS: Data pertaining to clinical presentation, pathology, treatment, and survival were collected for patients diagnosed with Merkel cell carcinoma from 1972 to 2005. Patients were staged according to AJCC guidelines. Pathologic specimens were evaluated for tumor thickness. The relationship between tumor thickness and disease-free survival or overall survival was analyzed using Kaplan-Meier survival analyses. RESULTS: Sixty patients were identified. Five-year disease-free survivals for Stages 1, 2, and 3 patients were 20%, 33%, and 0%, respectively. Five-year overall survivals for Stages 1, 2, and 3 patients were 33.3%, 60%, and 16.7%, respectively. There was no correlation between tumor thickness and either disease-free survival or overall survival. CONCLUSIONS: This study suggests that tumor thickness is not an independent risk factor for survival. Mean tumor thickness did increase with the AJCC stages, but this most likely represents more advanced stage of disease.     

循环肿瘤细胞自激注入的研究进展

由于缺乏有效的治疗手段,转移仍是癌症病人死亡的首要原因。肿瘤转移的新理论认为循环肿瘤细胞能够回到肿瘤原发灶,从而滋养肿瘤细胞,并产生更具侵袭力的转移株。本文就该现象加以综述,并对其在人类癌症转移研究中的意义进行探讨。     

Bilateral malignant Brenner tumor of the ovary

The clinicopathologic features of a case of malignant Brenner tumor with bilateral ovarian involvement are described. The tumor was apparently confined within the ovaries at initial laparotomy. However, multiple skeletal metastases developed 4 months later and the patient died of the disease 6 months after diagnosis.     

Chordoma: natural history and treatment results in 33 cases

Thirty-three chordomas were observed at the Istituto Nazionale Tumori of Milan from 1933 to 1983: 27 sacrococcygeal, 3 spheno-occipital, and 3 vertebral. The male:female ratio was 2.7, and the median age was 63 yr for patients with sacrococcygeal and 35.2 yr for those with nonsacral chordomas. After pathologic reassessment, distinct cytologic patterns were found: physaliphorous, syncytial, and mixed subtypes, with variable degrees of cytologic atypia. However, no evident difference in survival was documented in relation to these cytohistologic features. Four cases had a prior traumatic fracture, and the pathogenetic role of trauma is stressed. Eight cases were operated with adequate surgery and only three recurred, whereas of 11 inadequate operations, 10 developed local relapse. However, follow-up for recent adequate operations is short. Radiation therapy seemed to be effective with adjuvant or palliative aims. No chemotherapeutic regimen achieved any result; one case had a short complete remission after cis-dichlorodiammineplatinum + vinblastine + bleomycin (PVB). This analysis confirms the possibility of achieving radicality with high resection of the sacrum for lesions confined below the second sacral vertebra. Nonsacral chordomas were all unresectable. The best treatment for unresectable lesions seems to be palliative surgery plus radiotherapy.     

肿瘤免疫生物治疗新途径——载药肿瘤囊泡

正常细胞及肿瘤细胞在发生凋亡或受到某些信号刺激时均可释放出直径为0.1~1 μm的膜状囊泡。肿瘤细胞受到信号刺激后骨架改变，导致细胞质膜包裹细胞内容物并向膜外侧起泡形成囊状小体，称为肿瘤囊泡，其不仅影响肿瘤细胞的生物学特性，对肿瘤免疫微环境也产生深刻的影响。除生物学效应外肿瘤囊泡还可作为一种天然的药物载体将治疗药物递送到肿瘤细胞，发挥抗肿瘤作用。研究证实，载药的肿瘤囊泡在天然免疫和获得性免疫反应中均体现良好的抗肿瘤激活效应，目前载药肿瘤囊泡已经进入临床应用阶段，在胆管癌、恶性胸腔积液的治疗中展现了良好的应用前景。     

Plasma thromboxane A2 and prostacyclin concentrations in squamous cell carcinoma of the head and neck

Circulating prostaglandins, including thromboxane A2 and prostacyclin, have been implicated as possible facilitative agents in the growth and dissemination of squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the relationship of plasma concentrations of these compounds to tumor stage and the effect of surgical resection on plasma prostaglandin levels. Blood samples were obtained from 40 patients with head and neck cancer. Ten treated patients were clinically disease-free (NED), and 30 patients with active disease were previously untreated at the time of this study. Plasma concentrations of thromboxane A2 and prostacyclin were measured by radioimmunoassay of their stable metabolites thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI). Platelet aggregation was performed with normal donor platelets (PRP) and normal control or patient plasma (PPP). TxB and TxB/PGI ratios were increased in T1N0M0 patients, compared with NED and with T4N0M0 primary lesions versus all other groups. With lymphatic and hematogenous metastases, TxB and TxB/PGI ratios fell to NED levels. ADP-induced platelet aggregation was significantly increased in head and neck cancer patients, compared with normal controls, and with T4N0M0 lesions, compared with NED. There were no significant differences in PGI levels. TxB, PGI, TxB/PGI, and platelet aggregometry did not change significantly with curative surgery. TxB and TxB/PGI interactions are involved in head and neck cancer. Changes in TxB and TxB/PGI may be related to increased platelet aggregation.     

胸壁恶性小细胞性肿瘤：Askin瘤

目的:为提高对胸壁恶性小细胞性肿瘤(Askin瘤)的诊断及治疗水平.方法:通过本院确诊的一例,结合国内文献报告的14例Askin瘤,进行文献复习,对其临床表现、影像学特点、病理特点、鉴别诊断和治疗原则等逐一分析.结果:分析表明,Askin瘤好发于青少年,恶性度高,预后差,鉴别诊断困难.结论:Askin瘤的诊断应以免疫组化和电镜检查为主,治疗上应强调综合治疗.     

Classification of Pediatric Gangliogliomas Based on the Histological Infiltration

Ganglioglioma is a well-circumscribed low-grade glioneuronal tumor with a broad morphological spectrum. Diffuse glioneuronal tumors are used to describe cases with infiltrative growth. Molecular studies of some of these cases are consistent with ganglioglioma. This work aimed to clarify the growth patterns in ganglioglioma. The available slides and clinical and molecular information for 46 patients (50 samples) with a diagnosis of ganglioglioma under the open pediatric brain tumor atlas from the children’s brain tumor network database were reviewed to confirm the integrated diagnosis and to evaluate the growth patterns in these cases. Ten samples from nine patients were excluded as no slides were available, the integrated diagnoses were changed in seven cases (nine samples), ten cases (ten samples) were diagnosed as low-grade glial/glioneuronal tumors, and the diagnosis of ganglioglioma was confirmed in seventeen samples from sixteen patients (nine females and seven males; age ranges from eight months–19 years with a mean of 9.9 years). Infiltration is defined as the presence of neoplastic cells among the nonneoplastic parenchyma. The growth pattern was predominantly circumscribed in six cases, predominantly infiltrative in five cases, and combined growth patterns in five cases. This work confirmed the presence of an infiltrative/diffuse variant of ganglioglioma as a significant pattern. The differential diagnosis in these cases was mainly infiltrative glioma, usually IDH-wild type in this population, which may introduce a high-grade glioma in the differential. Awareness of infiltrative ganglioglioma variants should be helpful in this scenario.     

肿瘤休眠机制与治疗靶点的发现

肿瘤休眠（tumor dormancy）是指肿瘤细胞在人体内长期存在而没有明显生长的一种状态。肿瘤休眠的现象非常普遍,休眠的肿瘤细胞在部分肿瘤患者甚至正常人体内均可检测到。休眠细胞的长期存在是肿瘤复发和远处转移的根源之一,对肿瘤休眠机制和标志物的深入研究将有助于设计靶向治疗。本文中我们主要就肿瘤休眠发生的机制、肿瘤休眠与肿瘤干细胞的关系进行综述。     

Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis.

BACKGROUND: The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether they develop primarily in the retroperitoneum or whether they are metastases of a primary testicular tumor has long been debated. PATIENTS AND METHODS: We retrospectively analyzed 26 patients treated as having primary extragonadal retroperitoneal germ cell tumors based upon the findings of testicular palpation by the referring physician. Testicular evaluation was then extended with ultrasonographical and histological examinations. RESULTS: Biopsy of the extragonadal tumor was performed in 25 patients, confirming diagnosis of extragonadal retroperitoneal germ cell tumor. Prior to treatment patients were clinically evaluated by several physicians and the testes were not considered suspicious for testicular cancer. At urological workup, testes were found to be atrophic and/or indurated in 14 (54%) patients, enlarged in one (4%) and unremarkable in 11 (42%). Ultrasound examination of the testes in 20 patients showed pathological findings in all of them. Histology of the testis was available in 25 of 26 patients and revealed active tumor in three, intratubular germ cell neoplasia in four, scar tissue in 12, sclerosis in three, sclerosis and fibrosis in one, and fibrosis alone in two. CONCLUSIONS: So-called primary extragonadal germ cell tumors in the retroperitoneum are very likely a rare or non-existing entity and should be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All of our patients with histologically examined testes had pathological finding, 76% of which were either viable tumor or scars.     

Tumor microvasculature supports proliferation and expansion of glioma‐propagating cells

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The identification of ‘cancer stem cells’ (CSC) has shed new light on the potential mechanism of therapy resistance of these tumors. Because these cells appear to be more resistant to conventional treatments, they are thought to drive tumor regrowth after therapy. Therefore, novel therapeutic approaches that target these cells are needed. Tumor cells interact with their microenvironment. It has been reported that close contact between CSCs and tumor microvascular endothelium in GBM is important for CSCs to preserve their undifferentiated state and self‐renewal ability. However, our understanding of this interaction is still rudimentary. This is in part due to a lack of suitable in vitro models that accurately represent the in vivo situation. Therefore, we set up a co‐culture system consisting of primary brain tumor microvascular endothelial cells (tMVECs) and glioma propagating cells (GPCs) derived from biopsies of GBM patients. We found that tMVECs support the growth of GPCs resulting in higher proliferation rates comparing to GPCs cultured alone. This effect was dependent on direct contact between the 2 cell types. In contrast to GPCs, the FCS‐cultured cell line U87 was stimulated by culturing on tMVEC‐derived ECM alone, suggesting that both cell types interact different with their microenvironment. Together, these results demonstrate the feasibility and utility of our system to model the interaction of GPCs with their microenvironment. Identification of molecules that mediate this interaction could provide novel targets for directed therapy for GBM. © 2009 UICC     

Extragonadal germ-cell tumors: treatment experience in nine patients

Background We treated nine patients with uncommon and high-risk extragonadal germ-cell tumors (EGCTs) between 1982 and 1991. Methods Anterior mediastinal lesions were located in five patients, retroperitoneal tumors in three patients, and in one patient both mediastinal and retroperitoneal tumors were found. Chemotherapeutic regimens consisted of cisplatin, vincristine, bleomycin and actinomycin D (PVcBA); cisplatin, vinblastine and bleomycin (PVB); vinblastine, actinomycin D, cyclophosphamide, bleomycin and cisplatin (VAB-6); and bleomycin, etoposide and two doses of cisplatin (high-dose BEP). Results Two patients receiving PVcBA and second-line chemotherapy showed partial responses. Six patients; one treated with PVB, two with VAB-6, and three others with high-dose BEP with or without additional chemotherapy, underwent surgical resection of residual tumors. Histologic examinations showed either necrotic debris or necrosis including mature teratoma (complete response). In one patient, whose tumor marker was negative, unresectable residual tumors continued to shrink and disappeared with no maintenance therapy following administration of high-dose BEP. Overall, 7 of 9 patients (77.8%) achieved a complete response to either chemotherapy alone or a combination of chemotherapy and surgery. One patient, who suffered a relapse from an apparent CR, was also treated successfully. These patients remain disease free. Conclusion Patients with EGCTs are curable, even if the tumors in question are in highly advanced stages, as long as appropriate chemotherapy and surgical resection are undertaken in a timely fashion.     

肿瘤免疫微环境在肿瘤常规治疗效应中的作用

机体免疫系统能识别和杀伤恶变的细胞,从而清除肿瘤细胞或控制其生长.在机体免疫选择压力下,肿瘤细胞可以依靠自身的高突变特性,逃避免疫监视,逐步建立起免疫抑制微环境,以抵抗和抑制机体抗肿瘤免疫反应,从而能够突破限制而持续扩增,最终发展成为临床可见的肿瘤.目前肿瘤治疗的策略主要是着眼于直接抑制肿瘤细胞增殖以及杀伤和清除肿瘤细胞,然而越来越多的研究结果表明,常规治疗导致的肿瘤细胞免疫原性死亡,可以激活先天性免疫信号通路,诱发机体内在的抗肿瘤免疫反应,在肿瘤治疗效应中起着关键作用,尤其对防止残存肿瘤细胞的复发具有非常重要的意义.本文概述肿瘤发生、发展和常规治疗过程中,机体抗肿瘤免疫反应与肿瘤免疫抑制微环境的细胞和分子机制,重点讨论两者在肿瘤常规治疗效应中的作用,解析以肿瘤免疫微环境为靶点的治疗策略,讨论该策略对提高目前肿瘤常规治疗疗效和发展新的肿瘤治疗方案的积极意义.     

抑癌基因ARHI与全身各系统肿瘤相关性及机制的研究进展

抑癌基因 ARHI（aplasia ras homologue I）是1999年新发现的母源性印迹基因。最近研究发现ARHI 具有抑制肿瘤细胞增殖、转移、侵袭,调控肿瘤细胞自噬等作用。另外,学者们还发现 ARHI 不仅与卵巢癌、乳腺癌、胰腺癌密切相关,而且还与其他生殖、消化、内分泌等全身各系统肿瘤具有相关性。本文就最近几年国内外对 ARHI 与全身各系统肿瘤的相关性及其机制的最新研究进展进行综述。     

肿瘤疫苗在肿瘤治疗中的研究进展

肿瘤疫苗应用其表达特异性的、具有免疫原性的肿瘤抗原,来激活、恢复或加强机体抗肿瘤的免疫反应,进而杀伤、清除残余和转移的肿瘤细胞.因此,肿瘤疫苗在肿瘤治疗方面有很好的前景.