共查询到20条相似文献,搜索用时 109 毫秒
1.
The effects of mast cells (MCs) isolated from rat peritoneal cavity on rat hepatoma cell line (CBRH7919)in vitro were studied with phase contrast microscope, scanning and transmission electron microscope. The results showed that different
degrees of degeneration were presented in all CBRH7919 cells and a few of them exhibited necrosis or disruption when CBRH7919
cells were cocultured with MCs for 24 h.In situ hybridization demonstrated that the expression of c-myc mRNA in CBRH7919 cells was markedly reduced by MCs. These results suggest that MCs had an antitumor effect.
This subject was supported by grant from National Natural Scientific Foundation of China (No. 39170335). 相似文献
2.
Jianyong Xiao Xiaolan Wang Yingya Wu Qing Zhao Xiaodong Liu Guangxian Zhang 《Cancer biology & therapy》2019,20(2):183-191
Despite its low transfer efficiency, suicide gene therapy with HSV-TK is known for its bystander killing effect. The connexin-based gap junction is believed to mediate the bystander effect. Recently, we found that resveratrol, a polyphenol compound, increased the expression of Cx26 and Cx43, which are connexins and important constituents of gap junctions, in murine hepatoma cells. Hypothetically, the resveratrol-induced upregulation of gap junctions may improve the bystander effect that HSV-TK/GCV has on hepatoma cells. Our present investigation revealed that resveratrol could enhance intercellular communication at the gap junctions in CBRH7919 hepatoma cells and thereby enhance the bystander killing effect of GCV on CBRH7919TK cells. However, inhibition of gap junction using its long-term inhibitor alpha-glycyrrhetinic acid had a negative influence on the bystander effect of gene therapy with HSV-TK/GCV. In addition, combined resveratrol and GCV treatment in tumor-bearing mice with CBRH7919TK and CBRH7919WT cells at a ratio of 2:3 resulted in a significant decrease in the volume and weight of the tumor in comparison to GCV or only resveratrol. The present results demonstrate that resveratrol can enhance the bystander effect exerted by the HSV-TK/GCV system by enhancing connexin-mediated gap junctional communication. 相似文献
3.
4-1BBL基因真核表达载体构建及在肝癌细胞中表达的研究 总被引:3,自引:1,他引:2
目的 研究含鼠源性4-lBBL真核表达载体体系的构建及其在大鼠肝细胞癌(HCC)细胞系CBRH7919中获得稳定、高效表达的方法。方法 将4-lBBL全长cDNA亚克隆到真核表达载体PCI-neo中,获得4-1BBL定向插入重组子PCI-neo-4-lBBL,采用酶切法和测序法鉴定。用阳离子脂质体将PCI-neo-4-1BBL转染CBRH7919,经G418筛选,获得阳性克隆,命名为PCI-neo-4-lBBL-CBRH7919 细胞。逆转录-聚合酶链反应(RT-PCR)检测4-1BBL在CBRH7919中的表达。结果 PCI-neo-4-1BBL经限制性内切酶切,电泳后显示有980bp的4-lBBL目的基因片段和5.4kb的线性化PCI-neo载体片段;重组子测序结果与Genbank中4-lBBL cDNA序列相符,证实构建成功。RT-PCR检测到4-lBBL在PCI-neo-4-1 BBL-CBRH7919 细胞中获得稳定表达。结论 重组4-1BBL真核表达载体构建正确,并在PCI-neo-4.1 BBL-CBRH7919 细胞中获得稳定、高效表达。 相似文献
4.
Jiang H Meng Q Tan H Pan S Sun B Xu R Sun X 《International journal of cancer. Journal international du cancer》2007,121(2):416-424
Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers. 相似文献
5.
背景与目的:研究三氯化镧(LaCl3)对大鼠肝癌细胞CyclinD1和CDK4蛋白表达的影响.材料与方法:采用体外培养大鼠肝癌细胞株CBRH-7919,分别加入0.01、0.10、1.00 mmol/L LaCl3培养1、3、5 d后观察CBRH-7919细胞生长变化;运用流式细胞术、MTF实验和免疫细胞化学检测与G1期调控有关的CyclinD1和CDK4的变化情况,以培养液中不加LaCl3体外培养CBRH-7919作为对照.结果:0.10、1.00 mmol/L LaCl3组培养后3、5 d对细胞的生长均具有抑制作用,与对照组比差异具有统计学意义(P<0.01);G0/G1期细胞百分数均有显著性增加,与对照组比差异均具有统计学意义(P<0.01);CyclinD1、CDK4阳性表达均显著减弱,与对照组比差异具有统计学意义(P<0.01).结论:LaCl3可通过下调CyclinD1和CDK4,使肿瘤细胞从G1期进入S期受阻,从而抑制CBRH-7919细胞的生长. 相似文献
6.
Ribatti D Vacca A Marzullo A Nico B Ria R Roncali L Dammacco F 《International journal of cancer. Journal international du cancer》2000,85(2):171-175
Node biopsies of 16 benign lymphadenopathies and 72 B-cell non-Hodgkin's lymphomas (B-NHLs) were investigated for counts of microvessels, total metachromatic mast cells (MCs) and MCs expressing tryptase, an angiogenesis-inducing molecule. Counts were higher in B-NHLs. When grouped according to the Working Formulation (WF) malignancy grades, they were significantly higher in low-grade B-NHLs vs. lymphadenopathies and intermediate-grade vs. low-grade tumors and there was a further increase in the high-grade tumors. A high correlation was demonstrated in all groups of tissues between microvessel counts and both total metachromatic and tryptase-reactive MCs. These results suggest that angiogenesis in B-NHLs increases with their progression, and that MCs cooperate in its induction via the tryptase contained in their secretory granules. 相似文献
7.
Min-Jie Ju Shuang-Jian Qiu Qiang Gao Jia Fan Ming-Yan Cai Yi-Wei Li Zhao-You Tang 《Cancer science》2009,100(7):1267-1274
The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase+ MCs in addition to Foxp3+ T-regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence (54.1% vs 39.2%, P = 0.026). High-dense MCs were especially related to increased probability of early recurrence (within 2 years) ( P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density ( r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC]survival = 0.629 vs 0.589, AUCrecurrence = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker ( P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response–related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis. ( Cancer Sci 2009; 100: 1267–1274) 相似文献
8.
Ribatti D Vacca A Ria R Marzullo A Nico B Filotico R Roncali L Dammacco F 《European journal of cancer (Oxford, England : 1990)》2003,39(5):666-674
Tissues from 92 proliferative lesions of the melanocytic lineage defining distinct steps in tumour progression were investigated immunohistochemically for changes in angiogenesis, expression of fibroblast growth factor-2 (FGF-2) and density of total mast cells (MCs) and MCs expressing tryptase, an angiogenic-inducing molecule. Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed 'nevi with ADMA'), and these changes persisted during tumour development. Progression of primary melanomas was accompanied by a high microvessel number, and the progression to metastases by another significant increase in the microvessel counts. Expression of FGF-2, evaluated as percentages of positive lesions and positive cells per lesion was upregulated in the course of progression. Changes in expression were associated with nevi with ADMA, tumour changeover, penetration of the tumour into the dermis and metastases. A high correlation was demonstrated in all groups of tissues between the microvessel counts, percentages of FGF-2-positive tumour cells, and both total metachromatic and tryptase-reactive MCs. These results suggest that angiogenesis in human melanoma increases with tumour progression and that FGF-2 secreted by tumour cells and tryptase secreted by host MCs cooperate in its induction. 相似文献
9.
Diego Guidolin Beatrice Nico Enrico Crivellato Andrea Marzullo Angelo Vacca Domenico Ribatti 《Cancer letters》2009
Mast cells (MCs) accumulate in the stroma surrounding tumors and take part in the inflammatory reaction occurring at the margin of the neoplasia. Moreover, MC secretes angiogenic cytokines and matrix metalloproteinases. The aim of this study was to investigate the pattern of distribution of MCs in biopsy samples obtained from four different human tumors, utilizing an image analysis system and a mathematical model to make a quantitative approach to characterizing their spatial distribution. Results showed a similar spatial arrangement of MCs in all the neoplastic tissues examined, despite histological and/or pathologic differences. In all these tissues MCs demonstrated a virtually random spatial distribution, albeit with varying densities. These results suggest that MC–MC interactions could play a minor role in the formation of the MC pattern in neoplastic tissues. The random distribution of the cells in the tissues could be accounted for by a random walk-migration under the influence of cell-matrix interactions or chemotactic fields potentially generated by tumor or endothelial cells. 相似文献
10.
Eva Rietk?tter Annalen Bleckmann Michaela Bayerlová Kerstin Menck Han-Ning Chuang Britta Wenske Hila Schwartz Neta Erez Claudia Binder Uwe-Karsten Hanisch Tobias Pukrop 《Oncotarget》2015,6(17):15482-15493
The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown.Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression.Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis. 相似文献
11.
Pittoni P Tripodo C Piconese S Mauri G Parenza M Rigoni A Sangaletti S Colombo MP 《Cancer research》2011,71(18):5987-5997
Mast cells (MC) are c-Kit-expressing cells, best known for their primary involvement in allergic reactions, but recently reappraised as important players in either cancer promotion or inhibition. Here, we assessed the role of MCs in prostate tumor development. In prostate tumors from both tumor-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and human patients, MCs are specifically enriched and degranulated in areas of well-differentiated (WD) adenocarcinoma but not around poorly differentiated (PD) foci that coexist in the same tumors. We derived novel TRAMP tumor cell lines, representative of WD and PD variants, and through pharmacologic stabilization or genetic ablation of MCs in recipients mice, we showed that MCs promote WD adenocarcinoma growth but are dispensable for PD tumors. WD tumors rely on MCs for matrix metalloprotease 9 (MMP-9) provision, as reconstitution of MC-deficient mice with wild-type but not MMP-9(-/-) MCs was sufficient to promote their growth. In contrast, PD tumors are MMP-9 self-competent, consistently with epithelial-to-mesenchymal transition. Such a dual source of MMP-9 was confirmed in human tumors, suggesting that MCs could be a good target for early-stage prostate cancer. Interestingly, in testing whether MC targeting could block or delay tumorigenesis in tumor-prone TRAMP mice, we observed a high incidence of early and aggressive tumors, characterized by a neuroendocrine (NE) signature and c-Kit expression. Taken together, these data underscore the contribution of MCs in tumor progression and uncover a new, opposite role of MCs in protecting against the occurrence of aggressive NE variants in prostate cancer. 相似文献
12.
Masato Yoshihara Hiroaki Kajiyama Akira Yokoi Mai Sugiyama Yoshihiro Koya Yoshihiko Yamakita Wenting Liu Kae Nakamura Yoshinori Moriyama Hiroaki Yasui Shiro Suzuki Yusuke Yamamoto Carmela Ricciardelli Akihiro Nawa Kiyosumi Shibata Fumitaka Kikkawa 《International journal of cancer. Journal international du cancer》2020,146(8):2268-2280
Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell-to-cell crosstalk or phenotypic alterations including the acquisition of platinum-resistance in OvCa cells. Herein, we report how OvCa-associated mesothelial cells (OCAMs) induce platinum-resistance in OvCa cells through direct cell-to-cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF-β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum-sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell-to-cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF-β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell-to-cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum-resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination. 相似文献
13.
Fujiwara S Nawa A Luo C Kamakura M Goshima F Kondo C Kiyono T Kikkawa F Nishiyama Y 《Cancer gene therapy》2011,18(2):77-86
Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. We have developed replication-competent attenuated herpes simplex virus type 1 (HSV-1) mutants, named HF10 and Hh101, which have been evaluated for their oncolytic activities. However, the host immune system remains a significant obstacle to effective intraperitoneal administration of these viruses in the clinical setting. In this study, we investigated the use of these HSV-1 mutants as oncolytic agents against ovarian cancer and the use of human peritoneal mesothelial cells (MCs) as carrier cells for intraperitoneal therapy. MCs were efficiently infected with HSV-1 mutants, and MCs loaded with HSV-1 mutants caused cell killing adequately when cocultured with cancer cells in the presence or absence of HSV antibodies. In a mouse xenograft model of ovarian cancer, the injection of infected carrier cells led to a significant reduction of tumor volume and prolonged survival in comparison with the injection of virus alone. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on ovarian cancer, which may be further enhanced by the utilization of a carrier cell delivery system, based on amplification of viral load and possibly on avoidance of neutralizing antibodies. 相似文献
14.
15.
Ananya Roy Antoine Coum Voichita D. Marinescu Jelena P?lajeva Anja Smits Sven Nelander Lene Uhrbom Bengt Westermark Karin Forsberg-Nilsson Fredrik Pontén Elena Tchougounova 《Oncotarget》2015,6(27):23647-23661
Glioblastoma (GBM) is a high-grade glioma with a complex microenvironment, including various inflammatory cells and mast cells (MCs) as one of them. Previously we had identified glioma grade-dependent MC recruitment. In the present study we investigated the role of plasminogen activator inhibitor 1 (PAI-1) in MC recruitment.PAI-1, a primary regulator in the fibrinolytic cascade is capable of forming a complex with fibrinolytic system proteins together with low-density lipoprotein receptor-related protein 1 (LRP1). We found that neutralizing PAI-1 attenuated infiltration of MCs. To address the potential implication of LRP1 in this process, we used a LRP1 antagonist, receptor-associated protein (RAP), and demonstrated the attenuation of MC migration. Moreover, a positive correlation between the number of MCs and the level of PAI-1 in a large cohort of human glioma samples was observed. Our study demonstrated the expression of LRP1 in human MC line LAD2 and in MCs in human high-grade glioma. The activation of potential PAI-1/LRP1 axis with purified PAI-1 promoted increased phosphorylation of STAT3 and subsequently exocytosis in MCs.These findings indicate the influence of the PAI-1/LRP1 axis on the recruitment of MCs in glioma. The connection between high-grade glioma and MC infiltration could contribute to patient tailored therapy and improve patient stratification in future therapeutic trials. 相似文献
16.
17.
Tumor cells are surrounded by an infiltrate of inflammatory cells, namely lymphocytes, neutrophils, macrophages and mast cells (MCs). Increasing evidence indicates that MCs play a role in tumor growth and tumor-related angiogenesis in both solid and haematological tumors. In this review article, we discuss the involvement of MCs in angiogenesis in haematological malignancies and suggest that MCs might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis. 相似文献
18.
C. A. Pappa G. Tsirakis M. Devetzoglou M. Zafeiri R. Vyzoukaki A. Androvitsanea A. Xekalou K. Sfiridaki M. G. Alexandrakis 《Tumour biology》2014,35(6):5647-5651
Angiogenesis is a crucial process in growth and progression of multiple myeloma (MM). Mast cells (MCs) play an important role in MM angiogenesis. Various angiogenic mediators secreted by MCs regulate endothelial cell proliferation and function. Among them, ELR+ CXC chemokines, such as growth-related oncogen-alpha (GRO-α) and epithelial neutrophil activating protein-78 (ENA-78), have been described as potential mediators in regulation of angiogenesis. The purpose of the study was to quantify MCs in bone marrow (BM) biopsies of MM patients, expressed as MC density (MCD), and correlate it with serum concentrations of vascular endothelial factor (VEGF), GRO-α, ENA-78. Fifty-four newly diagnosed MM patients and 22 healthy controls were studied. Tryptase was used for the immunohistochemical stain of MCs. VEGF, GRO-α, and ENA-78 were measured in sera by ELISA. MCD and serum levels of GRO-α, ENA-78, and VEGF were significantly higher in MM patients compared to controls (p?<?0.001 in all cases). MCD was significantly increasing with increased stage of the disease (p?<?0.001). Furthermore, significant correlations were found between MCD with VEGF, GRO-α, and ENA-78. These findings support that MCs participate in the pathophysiology of MM and is implicated in the angiogenic process and disease progression. 相似文献
19.
Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma 总被引:8,自引:0,他引:8
Ribatti D Vacca A Nico B Quondamatteo F Ria R Minischetti M Marzullo A Herken R Roncali L Dammacco F 《British journal of cancer》1999,79(3-4):451-455
Immunohistochemical, cytochemical and ultrastructural data showing vivid angiogenesis and numerous mast cells (MCs) in the bone marrow of 24 patients with active multiple myeloma (MM) compared with 34 patients with non-active MM and 22 patients with monoclonal gammopathy of undetermined significance (MGUS) led us to hypothesize that angiogenesis parallels progression of MM, and that MCs participate in its induction via angiogenic factors in their secretory granules. 相似文献
20.
G Al�� L Boldrini M Lucchi A Picchi M Dell'Omodarme M C Prati A Mussi V Corsi G Fontanini 《British journal of cancer》2009,101(11):1869-1875