Infantile (congenital) anaplastic intracranial solitary fibrous tumor/hemangiopericytoma—A case report with brief literature review

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare primary central nervous system (CNS) tumor, included in the World Health Organization (WHO) 2016 classification. Very few cases have been described in the literature so far, especially the infantile type. It is a mesenchymal tumor of the fibroblastic type, characterized by the fusion of NAB 2 and STAT 6 genes. A 10-month-old boy presented to our neurosurgery department with complaints of increasing head circumference since 1 month of age. The magnetic resonance imaging (MRI) showed a space-occupying lesion measuring 8.2 cm × 7 cm × 6.9 cm in the fronto-temporo-parietal region with a clinical diagnosis of glioma/atypical teratoid rhabdoid tumor (ATRT). The microscopy revealed a spindle cell tumor arranged in a patternless pattern with variable cellularity, increased mitosis, and areas of coagulative necrosis. The immunohistochemistry showed vimentin, CD 34, STAT6, CD99 positivity whereas Glial fibrillary acidic protein, Epithelial membrane antigen, and S-100 negativity. Hence, a diagnosis of anaplastic SFT/HPC (grade-III) was rendered. The patient improved after gross total resection (GTR). The primary intracranial congenital SFT/HPC are extremely rare, often a clinico-radiologically misdiagnosed entity. Thus, the immunohistochemistry/molecular study in addition to histology is mandatory for accurate diagnosis.

Tumor fibroso solitario de próstata: informe de caso y revisión de la literatura / Solitary fibrous tumor of the prostate: case report and literature review

El tumor fibroso solitario (TFS) es una neoplasia mesenquimatosa de tipo fibroblástico que, a pesar de ser localizado principalmente en pleura, se ha observado en otros órganos como la próstata. Por su parte, el tumor fibroso solitario de la próstata es una neoplasia de baja incidencia, crecimiento lento y potencial maligno incierto, que generalmente se compone de células fusiformes de apariencia citológicamente benignas, dispuestas en una arquitectura desorganizada, mezcladas con colágeno y pequeños vasos sanguíneos. Establecer su diagnóstico se ha vuelto más reproducible desde la identificación de la fusión de los genes NAB2-STAT6 por biología molecular, que lleva a la sobreexpresión de STAT6 por inmunohistoquímica, el cual es un marcador muy sensible y específico para TFS. Presentamos el caso clínico de un paciente que debutó con síntomas de compresión vesical, en quien se identificó una masa con epicentro en la próstata que infiltraba la vejiga y llegaba a la pared rectal, y que luego de estudios de patología, inmunohistoquímica y pruebas moleculares se clasificó como un TFS de la próstata, finalmente tratado con cistoprostatectomía radical más derivación urinaria

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm of fibroblastic type, which despite being located mainly in the pleura, has been observed in other organs such as the prostate. On the other hand, solitary fibrous tumor of the prostate is a rare neoplasm, slow growing, and of uncertain malignant potential, which is generally composed of spindle cells of cytologically benign appearance, arranged in a disorganized architecture, mixed with collagen and small blood vessels. Establishing its diagnosis has become more reproducible since the identification of the NAB2-STAT6 gene fusion by molecular biology, leading to the overexpression of STAT6 by immunohistochemistry, a very sensitive and specific marker for SFT. We present a clinical report of a patient who consulted with symptoms of bladder compression, in whom a mass was identified with the epicenter in the prostate infiltrating into the bladder and reaching the rectal wall. Following histopathology study, immunohistochemistry and molecular tests it was classified as a SFT of the prostate, finally treated with radical cystoprostatectomy plus urinary shunt

The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Mechanism of sinomenine in regulating M2 macrophage polarization induced by gastric cancer cells / 西安交通大学学报(医学版)

【Objective】 To study the role and mechanism of sinomenine in the macrophage polarization induced by gastric cancer cells. 【Methods】 Sinomenine was added to gastric cancer cells BGC-823 and MKN-45， cell viability was measured by CCK-8， cell proliferation was measured by colony formation experiment， Co-culture and Transwell cell migration experiments were used to evaluate the recruitment and polarization of macrophages by sinomenine， flow cytometry was used to evaluate the polarization of macrophages， and qRT-PCR and Western blot were used to detect the expression of gene RNA and protein levels. 【Results】 Sinomenine could inhibit the proliferation of gastric cancer cells and the recruitment of gastric cancer cells to macrophages， thus promoting macrophage M2 polarization. It simultaneously inhibited the expression of STAT6 as well as the expression and phosphorylation of C/EBPβ. When STAT6 is overexpressed， it could reduce these inhibitory effects of sinomenine on gastric cancer cells. Further research found that STAT6 mediated the secretion of IL-6 by gastric cancer cells， which was the cause of sinomenine-mediated macrophage recruitment and M2 polarization. 【Conclusion】 The natural drug sinomenine has a good tumor-suppressing ability against gastric cancer， directly inhibits the survival and migration of gastric cancer cells， and inhibits the expression of IL-6 and the M2 phenotype in the tumor microenvironment， reshapes the tumor environment， and reduces the risk of M2 type macrophages for gastric cancer tumors.

El análisis inmunohistoquímico para el diagnóstico del tumor fibroso solitario/hemangiopericitoma / Immunohistochemical analysis for the diagnosis of solitary fibrous tumor/hemangiopericytoma

Resumen El tumor fibroso solitario/ hemangiopericitoma (TFS/HP) es un tumor extraaxial de origen mesenquimático de infrecuente observación, que usualmente se confunde con el meningioma, del cual puede ser clínica y radiológicamente indistinguible. El análisis molecular con la detección de la expresión nuclear STAT6 (signal transducer and activator of transcription 6) o la fusión NAB2-STAT6 (NGFI-A binding protein 2) es recomendable para confirmar el diagnóstico. Presentamos 3 casos clínicos, 2 mujeres y 1 varón, con diagnóstico anatomopatológico de meningioma meningotelial en el primer caso; y los casos 2 y 3 con sospecha radiológica de meningioma. La revisión anatomopatológica con estudio molecular permitió certificar el diagnóstico de TFS/ HP. Para el diagnóstico diferencial entre TFS/HP meníngeo y meningioma, se recomienda buscar la expresión de STAT6 como primer paso o la fusión NAB2-STAT6. La revisión de las muestras de biopsia debe estar garantizada en todos los pacientes, inclusive en aquellas que fueron estudiadas en Servicios de Patología Nivel 3.

Abstract The solitary fibrous tumor/ hemangiopericytoma (TFS/HP) is a rare mesenchymal extraaxial tumour. TFS/HP can sometimes be difficult to distinguish from other extra-axial tumors like meningioma, which can be clinically and radiologically indistinguishable. Molecular analysis with STAT6 (signal transducer and activator of transcription 6) nuclear expression or NAB2-STAT6 (NGFI-A binding protein 2) fusion is recommended to confirm the diagnosis. We present 3 cases, 2 women and 1 male, with pathological diagnosis of meningothelial meningioma in the first case; cases 2 and 3 with radiological suspicion of meningioma. The pathological review with molecular study certified the diagnosis of TFS/HP. For differential diagnosis between meningeal TFS/HP and meningioma, it is recommended to look for STAT6 expression as a first step, or NAB2-STAT6 fusion in order to confirm TFS/HP. The review of biopsy samples must be guaranteed in all patients, including those who were studied in Pathology Services Level 3.

Primary solitary fibrous tumour of the prostate: A case report and literature review

@#Introduction: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. Case Report: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. Conclusion: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

Solitary Fibrous Tumor of Breast with Anaplastic Areas (Malignant Solitary Fibrous Tumor): A Case Report with Review of Literature / 한국유방암학회지

Solitary fibrous tumor (SFT) is a rare, soft tissue neoplasm that rarely presents in breast tissue, with only 27 previously reported cases. To our knowledge, only one case of malignant SFT has been reported in the English literature. A 75-year-old Caucasian woman presented to our institution with a 3-month history of a palpable left breast mass. No other symptoms, including nipple discharge or skin changes, were noted. She underwent 3 previous biopsies for right breast masses, all of which were benign, with no evidence of spindle cell neoplasm, atypical hyperplasia, or malignancy. Microscopic examination of the mass demonstrated a classic area of SFT with areas of high-grade anaplastic component. In these areas, the tumor showed atypical epithelioid cells arranged in hypercellular sheets with diminished branching vasculature, nuclear pleomorphism, and increased mitotic count (up to 9/10 high-power fields). This case represents the second case of malignant SFT in the breast.

Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathological analysis of 60 cases / 中华病理学杂志

Objective@#To investigate the clinical manifestations, imaging features, clinicopathologic features, and differential diagnosis of solitary fibrous tumors/anginoblastomas (SFT/HPCs) originating in the central nervous system.@*Methods@#Sixty cases of SFT/HPCs originating in the central nervous system were collected at Nanjing Jinling Hospital, from January 1, 2008 to December 31, 2016. The clinical data, imaging data, histomorphologic changes and immunohistochemical finding were analyzed in the sixty cases.@*Results@#The 60 cases included 26 males and 34 females, aged 14 to 85 (median 49) years. The main clinical manifestations were headache, dizziness with nausea and vomiting. Radiologically, the tumors were large, enhancing, solid and cystic masses attached to the dura. Histopathologically, the neoplasms were composed of spindle cells with oval nuclei, inconspicuous nucleoli and moderate amount of eosinophilic cytoplasm arranged in fascicles with areas of hyalinized stroma, myxoid changes and a staghorn vascular pattern. Immunohistochemically, tumor cells of all cases were positive for vimentin (100.0%, 60/60), STAT6 (98.3%, 59/60), CD34 (61.7%, 37/60), and the tumor cells were typically positive for CD99, bcl-2, EMA and SSTR2 as well.Negative for S-100 protein, SOX10, E-cadherin, GFAP. Ki-67 index ranged from 1% to 50%. Forty cases were followed up for 6 to 82 months with average of 40 months, 30 patients were alive and 10 patients died.@*Conclusions@#Central nervous system SFT/HPCs can be aggressive and relapses may occur several years after diagnosis. STAT6 is highly sensitive and specific for the diagnosis. Complete tumor resection is optional treatment followed by radiotherapy and chemotherapy. There is a correlation between the prognosis and the location of the disease, the histological grade, Ki-67 index, and fusion gene variants.

Extrapleural solitary fibrous tumor with uncommon histology: a clinicopathologic analysis of 7 cases / 中华病理学杂志

Objective@#To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology.@*Methods@#Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People′s Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers.@*Results@#There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6.@*Conclusions@#Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite(HDM),and to explore its possible mechanism.Methods:The human bronchial epithelial cells(16 HBE)were divided into PBS group and HDM group(1 μg·L-1HDM).The cells were transfected by liposome.The luciferase report gene of MUC5AC promoter was constructed.The relative luciferase unit(RLU)was detected by double luciferase report gene assay.The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope.The expression level of STAT6 in the 16HBE cells was detected by Western blotting method.Results:The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group(P<0.05).The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention(P<0.05).The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group(P<0.05),and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention(P<0.05).The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA(P<0.05). Conclusion:Deficiencyof Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells,and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite (HDM), and to explore its possible mechanism. Methods: The human bronchial epithelial cells 16HBE) were divided into PBS group and HDM group 1 μg · L-1 HDM). The cells were transfected by liposome. The luciferase report gene of MUC5AC promoter was constructed. The relative luciferase unit (RLU) was detected by double luciferase report gene assay. The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope. The expression level of STAT6 in the 16HBE cells was detected by Western blotting method. Results: The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group (P<0.05). The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention (P<0.05). The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group (P<0.05), and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention (P<0.05). The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA (P<0.05). Conclusion: Deficiency of Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells, and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Intracranial malignant solitary fibrous tumor/hemangiopericytoma:a clinicopathologic analyses of 16 cases / 临床与实验病理学杂志

Purpose To investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of malignant solitary fibrous tumor/hemangiopericytoma ( SFT/HPC). Methods Sixteen cases of intracranial malignant SFT/HPC were retrospectively studied. The clinical data, imaging features, histopathological and immunohistochemical characteris-tics were analyzed. Results The 8 male and 8 female patients were between 31 and 71 years of age ( mean 51). The median age was 51 years (range, 31-71 years). 16 malignant SFT/HPC cases were originated from intracalvarium. The imaging features showed intracranial neoplasms with relatively clear surrounding boundaries. Microscopically spindle shaped cells were hypercel-lular, and exhibited≥5 mitoses per 10 HPF. Cytological atypia was mild. The clinicopathologic characteristics included pattern-less growth pattern, storiform or fascicular growth pattern, solita-ry fibrous tumor-like regions and hemangiopericytoma-like re-gions. Tnere were 2 cases with abundant papillary structure and 2 with sarcomatous structure, 2 with focal necrosis, 2 with inva-ded cerebral tissues, and 10 with invaded meninges. Immuno-histochemically, 93. 75% ( 15/16 ) cases were positive for STAT6, with 15/16 showing diffuse staining. 87. 5% (14/16) cases were positive for CD34, with 37. 5% (6/16) showing dif-fuse staining. 81. 25% (13/16) cases were positive for BCL-2. 68. 75% (11/16) cases were positive for CD99. The Ki-67 in-dex ranged from 5% to 40% . Sixteen patients were followed up for 1-64 months, and 7 patients ( 43. 75% ) had recurrences. Conclusion Malignant SFT/HPC shares malignant behaviours. STAT6 is a specific marker for the diagnosis of this tumor. The prognosis of malignant SFT/HPC is related to the extent of tumor excision and long-term follow-up.

Expression and significance of STAT6 in solitary fibrous tumor / 中华病理学杂志

Objective@#To study the clinicopathologic features, the differential diagnosis and the expression of STAT6 in solitary fibrous tumor (SFT).@*Methods@#Eighty cases of SFT were evaluated. The expression of STAT6, CD34, CD99 and bcl-2 protein was studied in these cases and in other groups of soft tissue tumors by immunohistochemical EnVision method. The results were analyzed and relevant literature were reviewed.@*Results@#The expression rate of STAT6 in SFT was 97.5% (78/80) and that in other soft tissue tumors was 3.3% (3/90). The difference was significant (P<0.05). The expression rates of CD34, CD99 and bcl-2 were 88.8% (71/80), 76.3% (61/80) and 75.0% (60/80) in SFT, respectively, which were significantly different from STAT6 expression rate (P<0.05).@*Conclusions@#The expression of STAT6 in SFT has high sensitivity (97.5%) and specificity (96.7%). The expression of STAT6 in SFT is higher than that of CD34, CD99 and bcl-2. STAT6 may be a useful marker for clinical diagnosis of SFT.

Schistosoma japonicum infection in obese mouse insulin resistance / 安徽医科大学学报

Objective To investigate Schistosoma japonicum infection on mice high-fat diet of insulin resistance. Methods 36 male C57 BL/6 J mice were randomly assigned into three equal groups: normal control group ( NC group) , high-fat diet group ( HF group) and high-fat diet with Schistosoma japonicum infected group ( HSJ group) . Specimen was collected 6 and 12 weeks after high-fat diet, separately. The levels of fasting blood glucose ( FBG) , fasting plasma insulin resistance index ( FINS) and insulin ( HOMA-IR) were detected. Interferon-γ( IFN-γ) ,in-terleukin-4 ( IL-4 ) and singal transductor and activator of transcription-4 ( STAT4 ) singal transductor and activator of transcription-6 (STAT6)were detected by ELISA and immunohistochemical method. Results The mice from HF group showed higher levels of HOMA-IR than those from NC groups by the end of 6 and 12 weeks after infection( P<0. 01 );the levels of HOMA-IR in mice from HSJ group were lower than NC group and HF group by the end of 12 weeks(P<0. 05);the levels of IL-4 in mice from HSJ group were higher than NC group and HSJ group by the end of 6 and 12 weeks after infection ( P<0. 05 ); the levels of STAT6 in mice from HSJ group were higher than HF group by the end of 12 weeks after infection ( P<0. 05 );the levels of STAT4 in mice from HF group were higher than NC group by the end of 6 and 12 weeks after infection. Conclusion Schistosome japonicum chronic infection may improve insulin resistance in obese mice with induced STAT6 protein expressed in liver tissue and secrete IL-4,providing new ideas for the prevention and treatment of diabetes.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of β-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of WNT/β-catenin and STAT signaling.

Afatinib Reduces STAT6 Signaling of Host ARPE-19 Cells Infected with Toxoplasma gondii

Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked IFN-γ. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, 5 µM) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine (5 µM) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, 20 µM) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, 10 µM) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis

BACKGROUND: The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. METHODS: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. RESULTS: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. CONCLUSIONS: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.

Effects of triptolide on airway remodeling as well as on STAT6 and eotaxin in asthmatic mice / 实用医学杂志

Objective To investigate the effect of triptolide on asthmatic airway remodeling and signal transducer and activator of transcription 6 (STAT6), acid neutrophil chemokines (eotaxin) impact. Methods The total of 30 mice with ovalbumin (OVA) model of asthma were randomly divided into three groups, control group, asthma group and triptolide group. After 24 hours of the last shot, lung tissue was stained Bronchial inflammatory cell infiltration was determined by using semi-quantitative method and calculate the proportion of goblet cells in airway epithelial cells. Hydroxyproline was determined by McMillan airway mucus score. The mRNA level and protein level of STAT6 and eotaxin in airway epithelium were determined by RT-PCR and immunohistochemistry. Results Compared with asthma group, peribronchial inflammatory cells infiltration of triptolide group were reduced, which mucus index is (1.31 ± 0.23) and hydroxyproline is (284 ± 13) μmg/100 mg. it had a significant in asthma group (P < 0.05). Besides, the protein level and mRNA level of STAT6 and eotaxin were significantly decreased (P < 0.05). Moreover, it was a positive correlation between STAT6 and eotaxin level in airway epithelial (r = 0.668, P < 0.05). Conclusion Triptolide can inhibit airway remodeling and might through the down regulation of STAT6 and eotaxin expression.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) Modulates Th2 Immunity through Attenuation of IL-4 Expression

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.

IL-13 induces STAT6 phosphorylation and promotes fibrosis in human hepatic stellate cells / 中华微生物学和免疫学杂志

Objective To investigate the effects of IL-13 on fibrosis in hepatic stellate cells and its molecular mechanism .Methods The effects of IL-13 on the proliferation of hepatic stellate cell line LX-2 were measured by MTT assay .The transcription level of collagen typeⅠ( COLⅠ) in LX-2 cells was detec-ted by RT-PCR.The secretion of COLⅠin LX-2 cells was measured by ELISA assay and hydroxyproline as-say.Western blot assay was used to analyze the effects of IL-13 on the phosphorylation of signal transducer and activator of transcription(STAT6).Results Compared with control group, IL-13 (10 ng/ml, 20 ng/ml and 50 ng/ml ) significantly stimulated the proliferation of LX-2 cells in a dose-dependent manner ( P0.05).The expression of phosphorylated STAT6 protein in LX-2 cells was significantly enhanced upon the stimulation with 50 ng/ml of IL-13 ( P<0.05 ) for60 min or 120 min.C onclusion IL-13 promoted the proliferation of human hepatic stellate cells and up-regulated the expression of COLⅠat mRNA and protein levels .IL-13 might promote the fibrosis in human hepatic stellate cells through activating STAT 6 phosphorylation .