1.Prevalence of Foxp3 Positive T Regulatory Cells is Increased during Progression of Cutaneous Squamous Tumors.
Yonsei Medical Journal 2008;49(6):942-948
PURPOSE: Forkhead box p3 (Foxp3) positive T regulatory cells (Tregs) have a functionally immunosuppressive property that prevents effector cells from acting against self in autoimmune diseases or a tumor. It is known that Tregs may be highly relevant in cancer progression. Dendritic cells (DCs) induce cutaneous immune response, however several studies have suggested that DCs are involved in immunosuppression. The aim of this study is to evaluate the prevalence of Tregs and DCs infiltration in cutaneous premalignant and malignant squamous lesions. MATERIALS AND METHODS: We evaluated Tregs and DCs in skin tissue samples obtained from 83 patients with actinic keratosis, Bowen's disease or squamous cell carcinoma by immunohistochemistry. RESULTS: The prevalence of Tregs and DCs was significantly higher in squamous cell carcinoma and Bowen's disease than in actinic keratosis. In addition, the number of DCs was closely correlated with the prevalence of Tregs, and DCs were also located in direct proximity to Tregs. CONCLUSION: Tregs is related to cutaneous squamous tumor progression.
Bowen's Disease/immunology/metabolism/pathology
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Carcinoma, Squamous Cell/immunology/metabolism/pathology
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Dendritic Cells/immunology/metabolism/pathology
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Forkhead Transcription Factors/immunology/*metabolism
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Humans
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Immune Tolerance
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Keratosis, Actinic/immunology/metabolism/pathology
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Skin Neoplasms/*immunology/metabolism/pathology
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T-Lymphocytes, Regulatory/*immunology/metabolism/pathology
2.Inflammasomes in cancer: a double-edged sword.
Ryan KOLB ; Guang-Hui LIU ; Ann M JANOWSKI ; Fayyaz S SUTTERWALA ; Weizhou ZHANG
Protein & Cell 2014;5(1):12-20
Chronic inflammatory responses have long been observed to be associated with various types of cancer and play decisive roles at different stages of cancer development. Inflammasomes, which are potent inducers of interleukin (IL)-1β and IL-18 during inflammation, are large protein complexes typically consisting of a Nod-like receptor (NLR), the adapter protein ASC, and Caspase-1. During malignant transformation or cancer therapy, the inflammasomes are postulated to become activated in response to danger signals arising from the tumors or from therapy-induced damage to the tumor or healthy tissue. The activation of inflammasomes plays diverse and sometimes contrasting roles in cancer promotion and therapy depending on the specific context. Here we summarize the role of different inflammasome complexes in cancer progression and therapy. Inflammasome components and pathways may provide novel targets to treat certain types of cancer; however, using such agents should be cautiously evaluated due to the complex roles that inflammasomes and pro-inflammatory cytokines play in immunity.
Animals
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Carcinoma
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immunology
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pathology
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therapy
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Gastrointestinal Neoplasms
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immunology
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pathology
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therapy
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Humans
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Inflammasomes
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metabolism
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Melanoma
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immunology
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pathology
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therapy
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Neoplasms
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immunology
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pathology
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therapy
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Skin Neoplasms
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immunology
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pathology
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therapy
3.Changes of fibroblast immunophenotype and their clinical significance in stromal remodeling of breast tumors.
Xing HUA ; Xiaoxiao HUANG ; Zexiao LIAO ; Qi XIAN ; Lina YU
Chinese Journal of Oncology 2014;36(11):834-838
OBJECTIVETo evaluate the immunophenotype conversion of fibroblasts and its clinical significance in the process of breast tumor stromal remodeling.
METHODSCD34, FAP-α, p63 and a-SMA were detected by immunohistochemistry in 273 breast biopsies, including 60 normal breast tissues, 46 atypical ductal hyperplasia (ADH), 60 ductal carcinoma in situ (DCIS), 47 DCIS microinvasive carcinoma (DCIS-MI) and 60 invasive ductal carcinoma (IDC).
RESULTSThe positive expression rates of CD34, FAP-α and α-SMA in the stromal fibroblasts of normal breast tissues were 93.3%, 6.7% and 18.3%, respectively. Those in the stromal fibroblasts of ADH tissues were 95.7%, 4.3% and 10.9%, respectively. Those in the stromal fibroblasts of DCIS tissues were 95.0%, 8.3% and 15.0%, respectively. Those in the IDC tissues were 35.0%, 85.0% and 93.3%, respectively. The expressions of CD34, α-SMA and FAP-α in the stromal fibroblasts of normal, ASH and DCIS breast tissues did not show significant differences (χ(2) = 1.142, P = 0.896). The main immunophenotype of stromal fibroblasts in the tumor-host interface at the invasive front of ADH and DCIS lesions was CD34(+)α-SMA(+)FAP-α(+). There were statistically significant differences in the expression of CD34, α-SMA and FAP-α between IDC and ADH, DCIS and normal breast tissues (χ(2) = 8.351, P < 0.001). The immunophenotype of stromal fibroblasts in the IDC and DCIS-MI breast tissues was CD34(-) α-SMA(+) FAP-α(+).
CONCLUSIONSImmunophenotype conversion from CD34(+) α-SMA(-) FAP-α(-) to CD34(-) α-SMA(+)FAP-α(+) may be a sensitive indicator to judge whether DCIS has microinvasion. Detection of the immunophenotype conversion of stromal fibroblasts may be helpful to determine the presence of microinvasion, and to improve the diagnostic accuracy rate of DCIS.
Breast ; Breast Neoplasms ; immunology ; pathology ; Carcinoma in Situ ; Carcinoma, Ductal, Breast ; Carcinoma, Intraductal, Noninfiltrating ; Fibroblasts ; immunology ; Gelatinases ; metabolism ; Humans ; Hyperplasia ; Immunohistochemistry ; Immunophenotyping ; Membrane Proteins ; metabolism ; Serine Endopeptidases ; metabolism
4.Expression of a plant associated human cancer antigen in breast cancer.
Jun FU ; Hai-mei TIAN ; Ping QU ; Mo LI ; Xin-wen ZHENG ; Zhen-hai ZHENG ; Wei ZHANG
Chinese Journal of Oncology 2004;26(7):403-405
OBJECTIVETo study the expression of a glycoprotein of plant origin in normal, benign and malignant breast tissues.
METHODSExpression of a plant glycoprotein was examined in 5 samples of normal breast tissues, 20 fibro-adenoma and 136 breast cancer by SABC immunohistochemical staining and the results were analyzed by SPSS statistics software.
RESULTSNo positive staining was detected in normal breast tissues (0/5). Weak staining was observed in 4 of 20 (20.0%) breast fibro-adenoma. Positive staining was demonstrated in 116 out of 136 (85.3%) breast cancer specimens. The differences were statistically significant. The expression of plant-associated human cancer antigen was related to pathological grade (P < 0.05), tissue invasiveness (P < 0.01) and recurrence (P < 0.05), but not to patients' age, tumor size and c-erbB-2 expression.
CONCLUSIONThe plant glycoprotein studied may be a human cancer-associated antigen which might be a potential marker of breast cancer.
Adenocarcinoma, Mucinous ; immunology ; pathology ; Adult ; Aged ; Antigens, Neoplasm ; metabolism ; Biomarkers, Tumor ; metabolism ; Breast ; immunology ; Breast Neoplasms ; immunology ; pathology ; Carcinoma, Ductal, Breast ; immunology ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; immunology ; pathology ; Female ; Fibroadenoma ; immunology ; pathology ; Humans ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; metabolism ; Plants ; immunology ; Receptor, ErbB-2 ; metabolism
5.Inhibitory effect of anti-type IV collagenase intrabody on invasiveness of human pulmonary giant cell carcinoma PG cells in vitro.
En-yun SHEN ; Wei-gang WANG ; Sheng-hua ZHANG ; Yong-su ZHEN
Chinese Journal of Oncology 2006;28(4):265-270
OBJECTIVETo explore the inhibitory effects of endoplasmic reticulum-retained intrabody on the secretion of type IV collagenase and the invasion of human pulmonary giant cell carcinoma PG cells in vitro.
METHODSTwo expression plasmids were constructed, pcDNA3.1-CP.scFv and pcDNA3.1-ER.scFv encoding cytoplasm-retained and endoplasmic reticulum-retained single chain antibodies against the type IV collagenase, respectively. The intracellular antibody genes were transfected into the human pulmonary giant cell carcinoma PG cells. Western blot was performed to detect the expression of pcDNA3.1-CP.scFv and pcDNA3.1-ER.scFv. Gelatin zymography was performed to detect seretion of type IV collagenase in PG cells and Matrigel assay was employed for determination of the cell invasiveness.
RESULTSBoth of cytoplasm-retained and endoplasmic reticulum-retained introbodies, CP.scFv and ER.scFv, were expressed in PG cells. ER.scFv, significantly inhibited the secretion of type IV collegenase. As shown, matrix metalloproteinase 9 and matrix metalloproteinase 2 were inhibited by 85.7% and by 51.2%, respectively. However, CP.scFv did not show such inhibitory effect. The ER.scFv encoding gene-transfected PG cells were much less invasive than parental or vector control cells, the inhibition rate was 76.3% (P < 0.05), whereas CP.scFv encoding gene-transfected PG cells showed no reduction in invasiveness.
CONCLUSIONThose findings demonstrate that endoplasmic reticulum (ER)-retained intracellular antibody technology may selectively abrogate the activity of type IV collagenase in the protein trafficking and secretory pathway and effectively inhibit tumor cell invasion in vitro. Anti-type IV collagenase intrabody may be further used in cancer gene therapy.
Carcinoma, Giant Cell ; metabolism ; pathology ; Cell Line, Tumor ; Cytoplasm ; immunology ; Endoplasmic Reticulum ; immunology ; Genetic Vectors ; Humans ; Immunoglobulin Variable Region ; metabolism ; physiology ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; immunology ; metabolism ; Matrix Metalloproteinase 9 ; immunology ; metabolism ; Neoplasm Invasiveness ; Plasmids ; Transfection
7.Integrin beta1 mediates hepatocellular carcinoma cells chemotaxis to laminin.
Bian-hong FU ; Ze-zhi WU ; Hai-yan ZHANG ; Jian QIN ; Shao-xi CAI ; Yun-peng WU ; Cheng DONG
Chinese Journal of Hepatology 2003;11(10):605-608
OBJECTIVETo study the effects of integrin beta1 on the chemotaxis of hepatocellular carcinoma (HCC) cells to laminin (LN).
METHODSA micropipette technique was adopted to investigate the effect of integrin beta1 blockade on pseudopod protrusion of HCC cells in response to LN stimulation. Chemotactic pseudopod protrusion of a HCC cell was evaluated using a dual-pipette set-up, in which two pipettes filled with LN solution were positional in close contact with the same cell, and pseudopod protrusion into each pipette was viewed dynamically and recorded with a tape recorder. The lengths of pseudopods were measured, then plotted against time to obtain a pseudopod growth curve. The integrin beta1 subunit on the surfaces of HCC cells was analyzed by flow cytometry.
RESULTSIn dual pipette chemotaxis experiment, when the two pipettes were filled with LN (50microg/ml, 200microg/ml), pseudopods extended from the HCC cells into each of the pipettes nearly symmetrically. Upon addition of anti-CD29 (20microg/ml) to one of the pipettes, the pseudopod protrusion was blocked almost completely, while the pseudopod protrusion into the opposite pipette became more evidently, with larger maximum length. The expression rate of integrin beta1 on the cells was up to 95.78%.
CONCLUSIONIntegrin beta1 subunit is the important receptor for mediating HCC cells chemotaxis to laminin.
Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Chemotaxis ; Humans ; Integrin beta1 ; immunology ; metabolism ; physiology ; Laminin ; metabolism ; Liver Neoplasms ; pathology
8.Renal collecting duct carcinoma associated with tumor embolus in the inferior vena cava.
Ling-Ling GUO ; Mei-Qing WANG ; Yi-Ran CAI ; Yan WANG
Chinese Journal of Pathology 2005;34(2):123-124
Carcinoma, Renal Cell
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immunology
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pathology
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surgery
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Humans
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Keratin-19
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metabolism
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Kidney Neoplasms
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immunology
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pathology
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surgery
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Male
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Middle Aged
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Neoplastic Cells, Circulating
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pathology
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Nephrectomy
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Vena Cava, Inferior
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pathology
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surgery
9.Apoptosis and expression of Fas/FasL in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma.
Jian-jun JIA ; Zi-neng WANG ; Ge-xiu LIU ; Zhi-xin WANG
Journal of Southern Medical University 2011;31(10):1693-1696
OBJECTIVETo investigate apoptosis of tumor infiltrating dendritic cells (TIDC) and their expression of Fas/FasL (CD95/CD95L) in human endometrioid adenocarcinoma.
METHODSThe apoptotic rate of TIDC was measured in 45 cases of endometrioid adenocarcinoma and 20 cases of normal endometrium tissues (control) by double-label immunohistochemistry using the monoclonal antibody S-100 protein and TUNEL technique. The expressions of Fas and FasL in TIDCs were detected using double-label immunohistochemistry and imaging analysis.
RESULTSThe apoptotic rate of TIDCs in endometrioid adenocarcinoma were significantly higher than that in normal endormetrium [(13.02∓0.64)% vs (6.82∓0.53)%, P<0.05]. The expression levels of Fas in the TIDCs were significantly lower, whereas FasL expression significantly higher in endometrioid adenocarcinoma than in normal endormetrium (7.88∓1.05 vs 19.25∓3.03, P<0.05; 12.95∓2.25 vs 7.51∓1.14, P<0.05).
CONCLUSIONIncreased apoptosis of the TIDCs and abnormal expression of Fas/FasL in TIDCs in endometrioid adenocarcinoma may lead to tumor immune escape.
Apoptosis ; physiology ; Carcinoma, Endometrioid ; immunology ; metabolism ; pathology ; Case-Control Studies ; Dendritic Cells ; immunology ; Endometrial Neoplasms ; immunology ; metabolism ; pathology ; Fas Ligand Protein ; genetics ; metabolism ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating ; immunology ; Tumor Escape ; fas Receptor ; genetics ; metabolism
10.Mechanism of spontaneous rupture of hepatocellular carcinoma.
Li-xin ZHU ; Xiao-ping GENG ; Shang-da FAN
Chinese Journal of Surgery 2004;42(17):1036-1039
OBJECTIVETo study the mechanism of spontaneous rupture of hepatocellular carcinoma (HCC).
METHODSThe specimens of 30 patients with ruptured HCC and 30 patients with non-ruptured HCC were collected. Immunofluorescence, immunohistochemical and flow cytometry techniques were used to detect the phagocytosis of macrophages and the deposition of immune complex (IC) on vascular wall.
RESULTSIn this study, the poor function of macrophage phagocytosis was found in patients with ruptured HCC, which could results in the cumulating of IC and deposition on vascular wall. The IC, which composed of hepatitis B virus e1 antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the elastic membrane of arteries. Likely as a result of IC deposition, vascular injury occurs mainly in the small arteries where the deposition of IC was present. As the small arteries were the blood vessels with predominant injury, they would likely to be the ones to split and cause hemorrhage and rupture of HCC during vascular load increase.
CONCLUSIONSWe would conclude that the poor function of macrophage phagocytosis, which lead to the IC deposition and vascular injury may be the factors involved in the pathogenesis of ruptured HCC.
Adult ; Antigen-Antibody Complex ; metabolism ; Carcinoma, Hepatocellular ; immunology ; pathology ; Complement C1q ; metabolism ; Female ; Flow Cytometry ; Hepatitis B e Antigens ; metabolism ; Humans ; Immunoglobulins ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; immunology ; pathology ; Macrophages ; immunology ; Male ; Middle Aged ; Rupture, Spontaneous ; immunology