体外实验中巨噬细胞对肿瘤细胞的作用

利用小鼠肺腺癌细胞母系与巨噬细胞混合培养，通过扫描电镜及３Ｈ－ＴｄＲ掺入，观察巨噬细胞对肿瘤细胞的作用。结果显示：在共培养１２小时时，巨噬细胞呈活跃状态包绕瘤细胞，瘤细胞的细胞溶解率在共培养１２及２４小时时分别为７２．５％和９３．８％，表明，巨噬细胞对肿瘤细胞有抑制和细胞毒作用。     

肥大细胞反应与直肠癌关系的探讨

本文复习１９８０～１９８３年外检标本，通过对５７例直肠癌肥大细胞反应的观察、计数及综合分析认为：肥大细胞是一组多形性细胞。直肠癌间质肥大细胞数量与患者生存率关系密切，肥大细胞多病人预后好。肥大细胞与淋巴细胞、嗜酸性白细胞及其他免疫细胞协同参与抗肿瘤免疫反应，故可能是机体抗肿瘤的细胞之一。在综合分析中证实，生物学行为好，病期早的肿瘤机体反应能力强的个体中，肿瘤间质肥大细胞数量多，揭示直肠癌中肥大细胞反应为机体与肿瘤相互作用的结果。     

可溶性喉鳞癌抗原和抗CD3单抗及rlL-2共同诱导的杀瘤细胞-TAK细胞的杀瘤机制的研究

作在前期研究工作的基础上，进一步探讨喉鳞癌抗原诱导的TAK细胞的杀瘤机理。结果表明：TAK细胞除直接杀伤靶细胞外，还通过分泌肿瘤坏死因子间接杀伤靶细胞。电镜观察表明，靶细胞的死亡形式有两种：溶解坏死和凋亡。     

嗜酸性细胞胃炎中的肥大细胞

研究嗜酸性细胞胃炎中的肥大细胞的分布及其意义。方法：２７例嗜酸性细胞胃炎常规切片，分别做ｐＨ６．４０．５％甲苯胺蓝染色显示肥大细胞和２硫堇染色大细胞异梁颗粒，光镜观察。结果：在胃粘膜，粘膜下层及溃疡的肉芽组织 ，均可见未释放型和释放型两种肥大的细胞分布。不同部位不同类型的肥大细胞，被激活后均参与相应部位炎性反应，引起粘膜溃疡的肉芽肿形成。     

嗜酸性细胞胃炎中的肥大细胞

目的研究嗜酸性细胞胃炎中的肥大细胞的分布及其意义。方法27例嗜酸性细胞胃炎常规切片．分别做pH6.40.5％甲苯胺蓝染色显示肥大细胞和2％硫染色人细胞异染颗粒，此镜观察。结果：在胃粘膜、粘膜下层及溃疡的肉芽组织中．均可见未释放型和释放型两种肥大细胞分布。不同部位不同类型的肥大细胞，被激活后均参与相应部位的炎性反应、引起粘膜溃疡和肉芽肿形成。结论本病的发生．主要与肥大细胞的分布和激活有着重要的关系。肥大细胞释放的各种介质、虽然双本病的发生起到重要作用，同时也具有一定的抗癌作用，这种病变属于一种迟发性免疫反应性疾病.     

金黄色葡萄球菌对S180小鼠腹腔巨噬细胞超微结构的影响

作者以肉瘤Ｓ１８０小鼠为模型，经皮下注射金黄色葡萄球菌ＣｏｗａｎＩ（ＳｔａｐｈｙｌｏｃｏｃｕｓａｕｒｅｕｓＣｏｗａｎＩ，ＳＡＣ），在扫描电镜和透射电镜下，观察了ＳＡＣ体内治疗对带瘤小鼠腹腔巨噬细胞超微结构的影响。结果显示，与对照组相比，ＳＡＣ治疗后巨噬细胞体积明显增大，表面皱褶增多，有许多粗大的伪足，胞质丰富，胞质内充满大小不一的噬体，肥大细胞增多。结果提示，ＳＡＣ能使带瘤小鼠腹腔巨噬细胞明显活化，吞噬功能加强，这与其抗肿瘤机制可能有关，肥大细胞增多与其过敏反应可能有关。     

可溶性喉鳞癌抗原和抗CD_3单抗及r1L-2共同诱导的杀瘤细胞—TAK细胞的杀瘤机制的研究

作者在前期研究工作的基础上,进一步探讨喉鳞癌抗原诱导的TAK细胞的杀瘤机理。结果表明:TAK细胞除直接杀伤靶细胞外,还通过分泌肿瘤坏死因子间接杀伤靶细胞。电镜观察表明,靶细胞的死亡形式有两种:溶解坏死和凋亡。     

外阴血管肌纤维母细胞瘤1例并文献复习

目的：分析外阴血管肌纤维母细胞瘤（Angiomyofibroblastoma，AMFB）的临床病理特征。方法：结合文献复习，对1例罕见的AFMB进行临床特点、病理形态及免疫组化研究，并探讨其鉴别诊断。结果：AMFB在肉眼上表现为境界清楚的结节；显微镜下，该瘤呈现为在富于水肿和富于薄壁血管的背景中见细胞密集区和细胞稀疏区交替存在，瘤细胞梭形、胖梭形或上皮样，围绕血管排列，间质中见散在肥大细胞和淋巴细胞浸润。免疫组化瘤细胞表达Vimentin、CD34、CD99、bcl-2和PR，不表达Desmin、S-100、ER、EMA、AE1／AE3以及SMA。结论：AMFB是一种罕见的良性肿瘤，手术切除后未见局部复发，罕见恶变，可经外科完全切除而治愈。主要应与外阴侵袭性血管粘液瘤鉴别。     

细胞瘤苗对红白血病荷瘤小鼠抗瘤作用的研究

目的：观察三种瘤苗抗肿瘤作用。方法：用不同佐剂的三种瘤苗，免疫预防及治疗红白血病荷瘤小鼠。观察肿瘤生长情况，小鼠寿命，局部肿瘤、全身脏器反应及病理变化。结果：由灭活细胞、不完全福氏佐剂及细胞因子组成的瘤苗，预防后小鼠成瘤率低，预防及治疗后肿瘤生长速度减慢，存活期延长，与灭活细胞，灭活细胞加不完全福氏佐剂瘤苗相比，有显著性差异；病理可见瘤组织坏死及以单个核细胞为主的炎细胞浸润，各脏器无异常，结论：包含细胞因子的瘤苗是安全，方便，经济、有效的瘤苗。     

胃间质瘤的临床病理改变

目的：了解胃间质瘤的特殊临床病理改变。方法：收集37例胃间质瘤的临床病理资料，常规光镜切片观察，免疫组化SMA，S100，CD34，CD117，CKp标记。2例恶性胃间质瘤新鲜组织常规电镜切片，观察超微结构。结果：胃间质瘤临床症状以上腹痛、肿块和呕血为主。良性间质瘤直径〈4．5cm，无出血坏死，瘤细胞以梭形细胞为主，核分裂0—2个／50HPF。多数恶性间质瘤直径〉5cm（20／25），有出血坏死，瘤细胞多形性，核分裂6—564／HPF。免疫组化标记：肿瘤细胞以CD34和CD117阳性为主。电镜观察2例恶性间质瘤的瘤细胞中细胞器稀少，无密体密斑、神经内分泌颗粒和细胞外基板。结论：胃间质瘤临床症状与胃癌相似，良性和恶性胃间质瘤的病理诊断依据组织学改变和免疫组化染色。免疫组化和电镜观察示胃间质瘤以未分化型为主。     

Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis

Background. Increased numbers of mast cells are found in various solid tumors. To investigate the role of mast cells in the vicinity of gastric cancer cells, we used special staining and an immunohistochemical technique. Methods. Specimens were surgically obtained from 102 patients with gastric cancer. Mast cells around the tumor edge of gastric cancer nests were counted by staining with 0.05% toluidine blue solution. Blood vessels in these areas were also counted, by immunohistochemical staining of endothelial cells for factor VIII. Results. The average number of mast cells and blood vessels in gastric cancer specimens was significantly higher than that in normal gastric tissue. Specimens from patients with advanced disease with metastases to lymph nodes had more mast cells than specimens from patients with early-stage disease. Mast cells in specimens from patients with metastatic lymph nodes were significantly increased in comparison with numbers in specimens from those without nodal metastases. Mast cell numbers in the specimens of patients with lymphatic or blood vessel invasion were significantly higher than numbers in specimens from patients without such invasion. Mast cells were localized near the new vessels around gastric cancer cells. Mast cell numbers increased as the number of blood vessels increased (correlation coefficient, 0.783). Postoperative survival curves revealed that patients with increased numbers of mast cells had a poor prognosis. Conclusions. All these results suggest that mast cell accumulation at the tumor site may lead to increased rates of tumor vascularization and, consequently, increased rates of tumor growth and metastasis. Received for publication on Oct. 9, 1998; accepted on Feb. 1, 1999     

Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer

BACKGROUND.: The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients. METHOD.: The authors performed an immunohistochemical study to identify and count the number of CD68(+) macrophages, c-kit(+) mast cells, and CD8(+) T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis. RESULTS.: There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests < stroma cases median survival time (MST 440 days vs 199 days; P < .0001). Patients with more tumor-infiltrating CD8(+) T cells in cancer nests than in cancer stroma (CD8(+) T cells: nests > stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8(+) T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome. CONCLUSIONS.: Evaluation of the numbers of macrophages and CD8(+) T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response. Cancer 2008. (c) 2008 American Cancer Society.     

THE PHENOTYPE OF MAST CELL IN PRIMARY ADENOID LIVER TUMOR OF RAT AND ITS RELATION TO TUMOR CELL

Mast cells in adenoid liver tumors of 32 rats induced with nitrosomorpholine were observed ultrastructurally, and among them, some were studied immunocytochemically via immunogold techniques. Data indicating that mast cells which located in tumor tissues presented positive expression of rat mast cell protein (RMCP) Ⅰ, Indicating origination from the mucosa mast cells, while those in the connective tissues around tumors were largely stained negatively with either RMCP Ⅰor RMCP Ⅰ antisera, with the exception of only a few cells showing positive RMCP Ⅰ staining. Ultrastructural observation showed that mast cells in tumon contacted closely with the tumor cells. Membranes of the intracytoplasmic granules in these mast cells were fusing together. The content inside the granules were discharged and spread along the intercellular space between the tumor cells. There was not any lesion observed uitrasructrually in the tumor cells contacting with the mast cells. The significance of mucosa mast cells in adenoi     

Potential role of mast cells in hamster cheek pouch carcinogenesis

During the process of activation, mast cells release products stored in their granules. Tryptase, a protease released from mast cell granules after activation, induces tumor cell proliferation through the activation of PAR-2 (protease activated receptor 2) on the plasma membrane of carcinoma cells. Chemical cancerization (DMBA) of the hamster cheek pouch is the most accepted model of oral cancer. However, there are no reports on the activation of mast cells during experimental carcinogenesis or on the correlation between mast cell activation and cell proliferation. The aim of the present study was to evaluate the potential effect of mast cells on the proliferation of epithelial cells at different times during the cancerization process. Paraffin serial sections of cancerized, tumor-bearing pouches were stained with Alcian Blue-Safranin to identify the different degrees of mast cell activation. Immunohistochemistry was performed to identify BrdU-positive cells to study tumor cell proliferation. Mast cells were counted and grouped into two categories: inactive mast cells AB-S+++ (red) and active mast cells AB+++S- (blue). Mast cell counts were performed in tumor stroma, base of the tumor (connective tissue immediately below the exophytic tumor), connective and muscle tissue underlying the cancerized epithelium (pouch wall) and adventitious tissue underlying the pouch wall. There was a significant increase in the number of mast cells at the base of tumors (p<0.001) compared to the number of mast cells in the wall of the pouch and in tumor stroma. In normal non-cancerized pouches, inactive mast cells were prevalent both in the wall (AB:S=1:2.15; p<0.001) and in the adventitious tissue (AB:S=1:1.6; p<0.004) of the hamster cheek pouch. At most of the experimental times examined, the ratio of active/inactive mast cells (AB/S) in the wall approximated unity and even reverted. The ratio of mast cells was AB:S 1:1.05 at the base of the tumor and 1:0.24 in tumor stroma (p<0.001). The evaluation of epithelial nuclei labeled for BrdU revealed a statistically significant increase in cells undergoing DNA synthesis in the epithelium of the wall of the cancerized pouch compared to control (p<0.017). Tumor parenchyma exhibited a highly statistically significant increase in DNA synthesis compared to control (p<0.001) and compared to the epithelium of the wall of the cancerized pouch (p<0.036). We conclude that mast cell activation in this model is associated to the increase in tumor cell proliferation, conceivably mediated by the release of tryptase.     

Distribution of mast cells in benign odontogenic tumors

The aim of this study was to investigate the presence of mast cells in a series of odontogenic tumors. Forty-five cases of odontogenic tumors were investigated using immunohistochemistry for mast cell triptase, and differences between groups were statistically evaluated. Mast cells were present in 96% of odontogenic tumors. Mast cells present in solid ameloblastoma were observed in the tumor stroma surrounding more solid and follicular epithelial islands, with or without squamous metaplasia. The odontogenic mixoma showed few mast cells. In odontogenic tumors with a cystic structure, the mast cells were distributed throughout all areas of the lesions, mainly in keratocystic odontogenic tumor. In addition, the total density of mast cells between all odontogenic tumors showed no significant difference (p > 0.05). A greater mast cells distribution was found in keratocystic odontogenic tumor in relation to adenomatoid odontogenic tumor (p < 0.01), and when the unicystic ameloblastoma and keratocistic odontogenic tumor were compared to the odontogenic myxoma (p < 0.05). Syndrome keratocystic odontogenic tumor showed a higher mean of mast cells when compared with the other tumors of the sample. Mast cells values presented by syndrome keratocystic odontogenic tumor were significantly greater than those of the sporadic keratocystic odontogenic tumor that were not associated with the syndrome (p = 0.03). Mast cells are probably one of the major components of the stromal scaffold in odontogenic tumors. We found significant differences of mast cells between syndrome nonsyndrome keratocystic odontogenic tumors, although their distribution did not seem to have any influence on the biologic behavior of benign odontogenic tumors.     

Fas ligand expressed in colon cancer is not associated with increased apoptosis of tumor cells in vivo

Expression of Fas ligand (FasL/CD95L) may help to maintain colon cancers in a state of immune privilege by inducing apoptosis of antitumor immune effector cells. Colon tumor-derived cell lines appear to be relatively insensitive to apoptosis mediated by their own or exogenous FasL in vitro, despite expression of cell surface Fas. In our present study, we sought to investigate if FasL upregulated in human colon cancers leads to any increase in apoptosis of the tumor cells in vivo. FasL and Fas receptor (APO-1/CD95) expression by tumor cells were detected immunohistochemically. Apoptotic tumor cell death was detected by immunohistochemistry for caspase-cleaved cytokeratin-18. FasL expression did not correlate with the extent of apoptosis of tumor cells. There was no significant local difference in the frequency of apoptosis of tumor cells between tumor nests that expressed FasL (mean = 2.4%) relative to those that did not (mean = 2.6%) (p = 0.625, n = 10; Wilcoxon signed rank). FasL expressed by the tumor cells appeared to be functional, since FasL expression in tumor nests correlated with diminished infiltration of tumor-infiltrating lymphocytes (TILs). TILs were detected using immunohistochemistry for CD45. Expression of FasL by tumor nests was associated with a mean 4-fold fewer TILs relative to FasL-negative nests (range 2.4-33-fold, n = 10, p < 0.003). Together, our results indicate that colon tumors are insensitive to FasL-mediated apoptosis in vivo.     

Mast cell kinetics during tumor growth

The behavior of mast cells was studied during tumor growth. Sarcoma 13, and normal syngeneic kidney, as control, were implanted subcutaneously in BALBc mice. The number of mast cells in the hypodermis and peritumoral tissue increased 3-fold, 20 days after implantation. In the peritumoral tissue, mast cell degranulation increased together with tumor growth, while in the dermis and hypodermis, it first decreased and only became evident on day 20. Mitosis and mast cell degranulation, more conspicuous in tissues near the tumor, seem to indicate the existence of tumoral factors which spread slowly from the tumor to distant zones. The role of mast cells in peritumoral tissues will be evaluated in the near future.     

Mast cell: insight into remodeling a tumor microenvironment

Mast cells are of paramount importance to allergies, pathogen immune responses during infections, and angiogenesis, as well as innate and adaptive immune regulations. Beyond all these roles, mast cells are now more and more being recognized as modulators of tumor microenvironment. Notwithstanding mounting evidences of mast cell accumulation in tumors, their exact role in tumor microenvironment is still incompletely understood. In this review, we discuss the significant role of mast cells in the remodeling of tumor microenvironment by either releasing various factors after activation or interacting with other cells within tumor and, as a result, the possible role of mast cell in cancer invasion and metastasis. We also discuss recent findings that mast cells actively release microparticles, which account for the transfer of membrane-type receptor signal and regulatory molecules such as microRNAs to tumor cells and immune cells. These findings on mast cells provide further insights into the complexity of tumor microenvironment remodeling.     

Inverse correlation between tumor incidence and tissue histamine levels in W/WV, WV/+, and +/+ mice

The influence of mast cells on tumor incidence and growth rate was studied in 2 grafted tumor models (fibrosarcoma MC-B6-1 and the Lewis lung carcinoma 3LL). Three kinds of WBB6F1 mice (a cross between WB/ReJ-W/+ and C57BL/6J-WV/+ mice) were used: W/WV (deeply mast cell depleted), WV/+ (partially mast cell depleted), and +/+ (normal mast cell number). The presumed resistance of F1 hybrids to tumor cells of parental origin was observed in 12 of 13 +/+ mice, but only in 11 of 22 WV/+ mice and in none of 39 W/WV mice. Tumor incidence and metastasis incidence were inversely correlated with tissue histamine levels and mast cell number. Growth rates of tumors were similar in W/WV and WV/+ mice, but the tumor growth rate was much slower in the only +/+ mouse in which the tumor grew. These results confirm the protective role of mast cells against tumors.     

Prolactin binding and localization in rat mammary tumor mast cells

We found that prolactin is taken up by mast cells residing in prolactin-dependent, 7,12-dimethylbenzanthracene-induced rat mammary tumors. Light and electron microscopic immunocytochemistry showed that mast cells concentrate prolactin in their cytoplasmic granules. No prolactin was found on mast cell surface membranes or in their nuclei. In primary cultures of tumor cells, mast cells were found mainly in the periphery of dome structures and these cells concentrated prolactin. When purified rat peritoneal mast cells were incubated with 125I-labeled prolactin, uptake was time, energy, and temperature dependent. Seventy % of accumulated prolactin was released intact from cytoplasmic granules by C48/80-induced degranulation. A mouse mastocytoma cell line also took up and released prolactin. These cells contained prolactin receptors (Kd = 4.5 nM) as determined in whole cells (approximately 3150 sites/cell) and in crude membranes (approximately 180 fmol/mg protein). We conclude that mast cells might significantly influence mammary tumor growth by accumulating and releasing prolactin within tumor tissue.