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1.
《Pathology, research and practice》2020,216(6):152991
Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion. 相似文献
2.
Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma
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Georgia Levidou Dimitrios Theodorou Nikolaos V. Michalopoulos Efstratios Patsouris Angelica A. Saetta 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(8):639-647
Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings. 相似文献
3.
Moussa Ndong Machiko Kazami Tsukasa Suzuki Mariko Uehara Shin-ichi Katsumata Hirohumi Inoue Ken-Ichi Kobayashi Tadahiro Tadokoro Kazuharu Suzuki Yuji Yamamoto 《Nutrition Research》2009,29(9):640-647
Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity. 相似文献
4.
L. Elghazi L. Rachdi A. J. Weiss C. Cras-Méneur E. Bernal-Mizrachi 《Diabetes, obesity & metabolism》2007,9(S2):147-157
The insulin receptor substrate-2/phosphoinositide 3-kinase (PI3K) pathway plays a critical role in the regulation of β-cell mass and function, demonstrated both in vitro and in vivo . The serine threonine kinase Akt is one of the promising downstream molecules of this pathway that has been identified as a potential target to regulate function and induce proliferation and survival of β cells. Here we summarize some of the molecular mechanisms, downstream signalling pathways and critical components involved in the regulation of β-cell mass and function by Akt. 相似文献
5.
目的: 研究PI3K/PTEN/AKT/mTOR信号转导通路中mTOR和PTEN蛋白在胆管癌中的表达及其在胆管癌发生、发展中的作用。方法:用免疫组织化学方法和RT-PCR法,检测胆管癌中mTOR 和PTEN 的表达。结果:与正常组织相比,免疫组化法和RT-PCR两种方法结果均显示,胆管癌中的mTOR表达明显增加,而PTEN的表达明显下降;两者呈负相关(r=-0.862,P<0.01)。结论:PI3K/PTEN/AKT/mTOR信号转导通路中重要的调节位点和节点PTEN在胆管癌中的表达明显降低,而mTOR的表达明显增高。〖KG(*8〗提示该信号转导通路在介导胆管癌的发生、发展的过程中起重要作用。 相似文献
6.
Differential Cellular Gene Expression in Ganglioglioma 总被引:1,自引:0,他引:1
Uzma Samadani †Alexander R. Judkins ‡Albert Akpalu §Eleonora Aronica ¶Peter B. Crino 《Epilepsia》2007,48(1):646-653
Summary: Purpose: Gangliogliomas (GGs) are neuronal-glial tumors highly associated with epilepsy. We hypothesized that the expression of select gene families including neurotransmitter receptor subunits and growth factors would be distinct in neurons and astrocytes within GG compared with adjacent cortex and that these changes would yield insights into seizure onset and lesion formation.
Methods: Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex.
Results: Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins.
Conclusion: We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth. 相似文献
Methods: Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex.
Results: Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins.
Conclusion: We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth. 相似文献
7.
Tailoring immunosuppressive therapy. 总被引:1,自引:1,他引:0
8.
Chanika Phornphutkul Ke-Ying Wu Valerie Auyeung Qian Chen Philip A Gruppuso 《Developmental dynamics》2008,237(3):702-712
The mammalian Target Of Rapamycin (mTOR) is a nutrient-sensing protein kinase that regulates numerous cellular processes. Fetal rat metatarsal explants were used as a physiological model to study the effect of mTOR inhibition on chondrogenesis. Insulin significantly enhanced their growth. Rapamycin significantly diminished this response to insulin through a selective effect on the hypertrophic zone. Cell proliferation (bromodeoxyuridine incorporation) was unaffected by rapamycin. Similar observations were made when rapamycin was injected to embryonic day (E) 19 fetal rats in situ. In the ATDC5 chondrogenic cell line, rapamycin inhibited proteoglycan accumulation and collagen X expression. Rapamycin decreased content of Indian Hedgehog (Ihh), a regulator of chondrocyte differentiation. Addition of Ihh to culture medium reversed the effect of rapamycin. We conclude that modulation of mTOR signaling contributes to chondrocyte differentiation, perhaps through its ability to regulate Ihh. Our findings support the hypothesis that nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth. 相似文献
9.
[目的] 观察膜肾1号方对膜性肾病大鼠肾脏病理的改善作用及其对自噬通路磷脂肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)相关蛋白表达的影响。[方法] 将大鼠随机分为对照组、模型组、膜肾1号方高剂量组、中剂量组、低剂量组,盐酸贝那普利组。采用大鼠尾静脉注射阳离子化牛血清白蛋白(C-BSA)的方法建立MN大鼠模型,灌胃、取材。苏木精-伊红(HE )染色法观察大鼠肾脏组织病理改变;免疫球蛋白G(IgG)免疫荧光染色观察大鼠IgG沉积;蛋白免疫印迹法(Western Blot)检测PI3K/Akt/mTOR 信号通路相关蛋白及自噬相关蛋白轻链3(LC3)表达。[结果] 药物干预后,膜肾1号方组大鼠24 h尿蛋白、三酰甘油、总胆固醇、低密度脂蛋白下降且低于模型组,并具有统计学差异(P<0.05)。光镜下观察,HE染色示正常组肾组织整体结构基本正常,膜性肾病(MN)模型组肾小球毛细血管丛充血,系膜增生,基底膜出现增厚,部分肾小管细胞空泡变、组织内可见炎症细胞浸润,可见嗜复红蛋白及IgG沉积。经膜肾1号方和盐酸贝那普利干预后,大鼠肾脏病理学改变均有所减轻。各组大鼠IgG沉积显示,与对照组比较模型组IgG沉积明显,IgG荧光表达升高,差异具有统计学意义(P<0.05),盐酸贝那普利组和膜肾1号方组IgG荧光表达下降且低于模型组,具有统计学差异(P<0.05)。Western Blot检测显示,药物干预后,盐酸贝那普利组和膜肾1号方组大鼠PI3K-Akt信号通路相关蛋白表达下降,LC3 表达增加,并具有统计学差异(P<0.05)。[结论] 膜肾1号方可改善大鼠肾脏病理损伤,膜肾1号方干预后PI3K-Akt信号通路相关蛋白磷酸化磷酸肌醇3激酶(p-PI3K),磷酸化Akt蛋白(p-Akt),磷酸化雷帕霉素靶蛋白(p-mTOR)表达明显降低,自噬相关蛋白LC3表达升高,其分子机制与自噬信号通路的调控有关。 相似文献
10.
目的 研究铁皮石斛Dendrobium officinale水提物对4T1乳腺癌荷瘤模型小鼠的抑瘤及免疫调节作用,并进一步探讨其作用机制。方法 采用BALB/c雌性小鼠构建4T1乳腺癌荷瘤小鼠模型后,随机分为模型组、盐酸表柔比星组(8 mL/kg)和铁皮石斛水提物低、中、高剂量(0.5、1.0、1.5 g/kg)组,另选10只正常BALB/c雌性小鼠作为对照组,给予相应药物进行干预,观察小鼠生存状态,每3天测量肿瘤直径与短径,连续给药28 d后处死小鼠,称定肿瘤质量,计算抑瘤率;采用小动物活体成像仪和转移灶计数观察肺部肿瘤转移情况;称定小鼠脾脏、胸腺质量,计算脏器系数;苏木素-伊红(HE)染色观察肿瘤、肺部以及脾脏形态学变化;血液分析仪检测荷瘤小鼠外周血中白细胞数目和淋巴细胞占比;ELISA法检测血清中白细胞介素-2(interleukin-2,IL-2)、γ干扰素(interferon-γ,IFN-γ)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;流式细胞术检测外周血中T淋巴细胞比例;脾淋巴细胞增殖试验检测脾脏中T淋巴细胞、B淋巴细胞增殖能力;... 相似文献