| Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and parasellar region. According to the tumor classification of WHO, Craniopharyngioma can be divided into adamantinomatous craniopharyngioma and squamous papillary craniopharyngioma in pathology with low-grade histological malignancy..Craniopharyngs represent approximately4.7%～6.9%of intracranial tumors and1.2%-4.0%of pediatric brain tumors. In pediatric patients, craniopharyngiomas represent the most common intracranial tumor of nonglial origin and account for approximately50%of all sellar and prechiasmatic tumors. Craniopharyngiomas are dysontogenic tumors with benign histology and malignant behavior, as they have a tendency to affect the surroundings important structures greatly and recur after a neurosurgery.Craniopharyngiomas closely adhere to the optic nerve,optic chiasma, pituitary stalk and hypothalamus, basilar artery rings and other important neurovascular structures. Our preliminary study have showed that there was a complex inflammation in craniopharyngiomas. Many inflammation factors such as CD45, NF-κB, ICAM-1, OPN of express in craniopharyngiomas. Inflammation is a important reason of adhesion of Craniopharyngioma.Interferon alpha and transforming growth factor beta1are inflammatory cytokines, which play an important role in the inflammatory process.Many studies have confirmed Interferon alpha was closely related to NF-kappa B and OPN. In the central nervous system Interferon alpha can induce the expression of nitric oxide synthase/nitric oxide synthesis, and suppress the expression of heme oxygenase1(HO-1) synthesis to promote inflammation through the JAK-STAT signaling pathways. TGF-beta1can inhibit inflammation.It can be used to inhibit the proliferation of T lymphocyte and B lymphocyte and hinder the production of the cell factors of Th2cell. There will be infiltration of mononuclear cells of body organs, more severe inflammatory symptoms and death in mice that be knocked out TGF-beta1gene; TGF-beta1also inhibit the production of IL-6, TNF-alpha, IL-1and IFN-gamma.Interferons alpha can promote apoptosis,inhibit tumor angiogenesis and regulate immune.It has been used in a variety of tumor therapy, but its antitumor mechanism has not be completely cleared yet. Interferons alpha may have direct effects on tumor cells by inhibiting the expression of proto-oncogenes, inducing the expression of tumor suppressor genes. On the other hand it can regulate the body’s immune, including macrophages, NK cells, CD4+T cells and CD8++T cells and Th1, dendritic cells (DCS), and other immune cells to attack tumor cells. Interferons alpha has a strong resistance of blood vessel formation by inhibiting VEGF. Literature shows that craniopharyngioma volume is significantly reduced or even disappear through craniopharyngioma cystic or systemic injection of interferons alpha.TGF-beta1is a multifunctional polypeptide factor, involved in a many diseases such as tumor and the development of organ fibrosis. In the early stage of tumor TGF-beta1can inhibit tumor growth, but then promote cell proliferation and invasive ability, help cancer cells evade immune response in the in late stage of tumor.Fas is an important member of the tumor necrosis factor receptor superfamily.lt is a kind of cell surface receptor, when Fas/FasL combination,it can activated caspase-3and induced apoptosis. Ilerardi find soluble Fas Ligand (Fas Ligand, FasL) increased significantly in the cystic fluid of craniopharyngioma after injection of interferons alpha.Interferons alpha may induce tumor cell apoptosis through the Fas/FasL signal pathways. TGF-beta1also can regulate the expression of FAS/FASL in tumors.The aim of this research is to study the inflammation in craniopharyngioma, and discuss its role in regulating ellular proliferation by detect the expressions of interferons alpha, TGF-beta1and Fas in craniopharyngiomas.Materials and methods1. subjectPatients with craniopharyngioma aged2～61, male (n=42) and female (n=16), were studied from May2010to May in2012. Cases acceptance standard.①Patients with craniopharyngioma who accepted first neurosurgery in our department in the period of study;②The craniopharyngioma were confirmed by the postsurgery-pathology;③excluded patients who received chemotherapy or radiotherapy before the operation.2. Trial managementThis study was consisting by two parts:1. To study the relationship between interferons alpha, TGF-beta1and inflammation of craniopharyngioma by HE staining,immunohistochemistry and Western Blot;2. To study the relationship between inflammation and proliferation of craniopharyngiomas by immunohistochemistry, Western Blot.3. Statistics treatment:All data were analyzed by SPSS10.Results1. Accroding to the2007WHO classification of tumours of the central nervous system, Samples were from the58patients whose craniopharyngiomas had been surgically removed in our hospital from May2010to May2012, followed by postoperative pathological diagnosis to find44cases of adamantinomatous craniopharyngiomas and14cases of papillary craniopharyngiomas. Blood vessels could be found in craniopharyngioma tissue, and abundant inflammatory cells such as neutrophils infiltrated.In adamantinomatous craniopharyngiomas a large number of inflammatory cells gathered around the calcified plaques. While there was not calcified plaques in papillary craniopharyngiomas.2. Immunohistochemistry showed that interferon alpha expressed obviously in craniopharyngioma cell nucleus.The positive rate of interferon alpha was90.91%(40/44)in the adamantinomatous craniopharyngiomas.There were12of the14cases in squamous papillary craniopharyngiomas that expressed interferon alpha positively. The expression rate of interferon alpha was higher in adamantinomatous craniopharyngiomas (Z=2.003, p<0.05),and And it was higher in recurrent craniopharyngiomas than primary group (Z=2.085, p<0.05);3.TGF-beta1expressed obviously in the squamous papillary craniopharyngioma cells, but absent or little expressed in the admantinomatous types (Z=2.129, p<0.05). The expression rate of TGF-beta1was higher in primary craniopharyngiomas than recurrent group (Z=2.685, P<0.05). It was negatively correlated with IFN-a by Spearman correlation analysis in all craniopharyngiomas.(rs=0.273, p<0.05).4. Western Blot showed that the protein expression quantity of interferon alpha was higher in admantinomatous craniopharyngiomas; And the protein expression quantity of TGF-beta1was higher in squamous craniopharyngiomas.5. Fas stain grade was significantly in the admantinomatous craniopharyngioma (Z=5.142, P<0.05). The expression of Fas was positively correlated with IFN-a by Spearman correlation analysis in all craniopharyngiomas.(rs=0.328, P<0.05), And it was negatively correlated with TGF-beta1(rs=0.263, p<0.05).6. Western Blot showed that the protein expression quantity of Fas was higher in admantinomatous craniopharyngiomas.Conclusions1. This research shows that the expressions of interferon alpha and TGF-beta1are different in the two pathological types of craniopharyngioma. Interferon alpha may be a inflammatory chemokine that can promote inflammation, and TGF-beta1is a inflammation inhibiting factor. Craniopharyngioma has a complex inflammation which may be the important reason of calcification, closely adhesion with the surrounding structures and cystic fluid formation in craniopharyngioma.Inflammation makes it hard to complete tumor resection which would lead to tumor recurrence.2. The inflammation factor interferons alpha, TGF-beta1can regulate the expression of Fas, which regulates the apoptosis of tumor cells, interferons alpha could upregulate the expression of Fas to promote apoptosis of tumor cells, and TGF-β1can inhibit the expression of Fas to promote tumor proliferation.There may be a antagonistic effect between interferons alpha, TGF-beta1. Inflanamation has inhibitory effect on cell proliferation of craniopharyngioma as the body’s defense mechanism... |
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