211,813 research outputs found
Trastuzumab (Herceptin (R)): Monoclonal antibody in the treatment of HER2/neu-overexpressing breast cancer in the metastatic and (neo)adjuvant situation
No full textTrastuzumab (Herceptin (R)) is a humanized monoclonal antibody that specifically targets HER2/neu (human epidermal growth factor receptor-2) breast cancer cells, which are overexpressed in about 25-30% of breast carcinomas. After phase I and II trials, several phase III studies of trastuzumab alone or in combination with various chemotherapies were conducted. Patients with HER2/neu overexpression levels of 3+ determined by immunohistochemical assay or gene amplification (fluorescence in situ hybridization) derive most clinical benefit from trastuzumab. Taking into consideration efficacy and side effect profile, the combination of trastuzumab and paclitaxel showed an improvement of all clinical parameters, including overall survival, for the first time in the history of palliative breast cancer therapy. The application of trastuzumab has meanwhile become an established part of systemic therapy of metastastic breast cancer, and excellent data of its application in the adjuvant setting now exist (NSABP-B31, NCCTG-N9831, HERA), with significantly better relapse-free survival in the treatment arms with trastuzumab. Ongoing trials investigate the role of trastuzumab in the neoadjuvant setting. Trastuzumab is generally well tolerated. Cardiotoxicity is the main concern, thus monitoring of cardiac function is recommended
Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis
No full textBackground: P53, egfr and her-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. Methods: Published studies that investigated the association between p53, egfr and her-2/neu status and survival were identified. Meta-analysis was performed using a dersimonian-laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. Results: A total of 62 studies were included for p53, 15 for egfr and 20 for her-2/neu. P53, egfr and her-2/neu status had a modest effect on overall survival (Pooled hr 1.47, 95% Ci 1.33-1.61 For p53; Hr 1.65, 95% Ci 1.25-2.19 For egfr and hr 1.67, 95% Ci 1.34-2.08 For her-2/neu). Meta-regression analysis for p53 showed that figo stage distribution influenced study outcome. For egfr and her-2/neu, considerable publication bias was present. Conclusions: Although p53, egfr and her-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies. British journal of cancer ( 2009) 101, 149-159. Doi: 10.1038/Sj.Bjc.6605112 Www.Bjcancer.Com published online 9 june 2009 (C) 2009 Cancer research uk
The anticancer effect of baicalein on p185HER2/neu overexpressing ovarian cancer cells
No full text碩士神經膠原致癌基因 (HER2/neu) 的穿膜醣蛋白產物分子量約為185仟道爾吞，因此 HER2/neu 也稱為 p185HER2/neu。p185HER2/neu 蛋白屬於上皮生長因子受體 (EGFR) 家族的其中一員，其過度表現常與許多癌症發生有關。黃芩素 (baicalein) 為傳統中草藥上應用廣泛的黃芩根部中一種類黃酮素物質，根據已發表的研究文獻指出，黃芩素可當作抗氧化及抗發炎試劑。此外，黃芩素也有抗癌的效果，但是黃芩素在 p185HER2/neu 過度表現細胞中的抗癌分子機轉值得進一步去探討研究。本論文研究結果顯示，黃芩素可抑制神經膠原致癌基因的表現。此外也深入探討黃芩素在p185HER2/neu 過度表現的 SKOV-3 卵巢癌細胞及中的抗癌效果。實驗結果指出黃芩素在 p185HER2/neu 過度表現的細胞中可以抑制經由神經膠原致癌基因所誘發的轉形能力 (transforming ability)。HER2, also known as p185HER2/neu, is a transmembrane receptor tyrosine kinase that belongs to the epidermal growth factor receptor (EGFR) family. Overexpression of the HER2/neu is associated with a wide range of human cancers. HER2 downstream signal transductions are related to cell proliferation, growth, survival, angiogenesis and metastasis. Baicalein, a flavonoid, is derived from the root of Scutellaria baicalensis Georgi, a plant traditionally used in Chinese herbal medicine. According to the literature, baicalein is known as an antioxidant and anti-inflammatory agent. Besides, it also has other activities such as anticancer effect, but the molecular mechanism of this effect in p185HER2/neu overexpressing cells is still unclear. Our results showed that baicalein could suppress HER2 gene expression. In addition, We also evaluated the anticancer effects of baicalein on p185HER2/neu overexpressing SKOV-3 ovarian cancer cells. Together, these finding suggest that the inhibition of the expression of p185HER2/neu by baicalein is capable of supperssing the HER2/neu-mediated transforming ability in p185HER2/neu overexpressing ovarian cancer cells.摘要.......................I
中文摘要.................I
英文摘要................II
縮寫表....................IV
第一章 緒論................1
第一節 神經膠原致癌基因..1
第二節 黃芩素...........15
第三節 實驗動機與目的...26
第二章 材料與方法.........27
第三章 結果...............34
第一節 實驗結果.........34
第二節 實驗圖表.........38
第四章 討論...............46
第五章 參考文獻...........51
附錄一....................61
附錄二....................63學號: 696180180, 學年度: 9
EBNA1 may prolong G2/M phase and sensitizes HER2/neu-overexpressing ovarian cells to both topoisomerase II-targeting and paclitaxel drugs
No full textWe have shown previously that the Epstein-Barr virus nuclear antigen-1 (EBNA1) can act as a transforming suppressor in the HER2/neu-overexpressing ovarian cancer cells. In the present study, by using flow cytometric analysis, we demonstrate that EBNA1 could prolong G(2)/M phase and sensitize to Taxol-induced apoptosis in the EBNA1-expressing ovarian cancer cell stable transfectants. In addition, EBNA1 could also significantly increase topoisomerase IIalpha protein expression, indicating that the up-regulation of topoisomerase IIalpha may be one of the mechanisms by which EBNA1 enhances the sensitivity of ovarian cancer cells to topoisomerase II-targeting anticancer drugs, such as VP-16 and Adriamycin. These data suggest that EBNA1 not only prolongs cell cycle at G(2)/M phase and up-regulates topoisomerase IIalpha expression in HER2/neu-overexpressing ovarian cancer cells, but also increases cellular apoptosis through sensitization of cancer cells to topoisomerase II-directing anticancer drugs.國外SCI紙本US
Die kollisionsrechtliche Behandlung von Persönlichkeitsrechtsverletzungen im Internet
No full textNeu M. Die kollisionsrechtliche Behandlung von Persönlichkeitsrechtsverletzungen im Internet. Bielefeld; 2001
Suppression of HER2/Neu-Overexpressing Cancers by siRNA against HER2/Neu Proto-Oncogene
No full textHER2/neu proto-oncogene是epidermal growth factor receptor(EGFR)家族成員之一。在許多癌症如卵巢癌、乳癌、肺癌、腎癌、結腸癌、胃癌等等，常有HER2/neu大量表現的現象。HER2/neu大量表現的癌症常伴隨著較強的轉移能力、血管新生能力、抗藥性及較差治癒率等特性，因此HER2/neu成為癌症治療上一個重要的標的。目前已有許多抑制HER2/neu表現及活性的方法，經由抑制HER2/neu，這些方法皆能有效抑制HER2/neu-overexpressing癌症。siRNA是抑制基因表現的有力工具，我們實驗室已篩選到可以抑制HER2/neu的siRNA。為了提高攜帶siRNA進入細胞的效率，本實驗室利用重組腺病毒作為攜帶針對HER2/neu的 siRNA的載體(rAdv-siHER2)，並想探討rAdv-siHER2是否可作為HER2/neu-overexpressing癌症的基因療法。結果發現rAdv-siHER2可以抑制HER2/neu-overexpressing癌細胞株BT-474、MDA-MB-453、SK-OV-3-sub1及SK-OK-3-ip1中HER2/neu的表現量。rAdv-siHER2感染HER2/neu-overexpressing癌細胞株後，發現細胞週期中sub-G1比例增加及PARP出現被切割的小片段，但是在HER2/neu low-expressing癌細胞株MDA-MB-231、MCF-7、HeLa及NPC-TW04及正常細胞株ECV304並沒有這些現象。代表rAdv-siHER2可專一性地促進HER2/neu-overexpressing癌細胞走向凋亡。此外，rAdv-siHER2能有效抑制HER2/neu-overexpressing癌細胞在柔軟瓊脂中形成的聚落數，而對HER2/neu low-expressing癌細胞影響不大。rAdv-siHER2感染BT-474後，也能減少HER2/neu下游訊息傳遞分子ERK1/2及Akt被活化的現象。此外，將rAdv-siHER2注射入腫瘤中，可以抑制SK-OV-3-ip1腫瘤在NOD/SCID小鼠皮下的生長。最後，rAdv-siHER2加上抗癌藥物CDDP (cisplatin)複合處理後，更能促進 CDDP誘發HER2/neu-overexpressing癌細胞凋亡的能力。綜合以上結果， rAdv-siHER2未來有潛力開發作為治療HER2/neu-overexpressing癌細胞的基因療法之一。HER2/neu proto-oncogene is a member of epidermal growth factor receptor family. Overexpression and amplification of HER2/neu is found in many types of human cancers, including ovary, breast, lung, kindey, colon and gastrointestinal cancers. Overexpression of HER2/neu in cancers is correlated with enhanced metastasis, angiogenesis, and chemo-resistance, and poor prognosis, therefore treatment of HER2/neu-overexpressing cancers has become an urgent issue in cancer therapy. Inhibition of HER2/neu expression has been shown to be able to suppress HER2/neu-overexpressing cancers. Many strategies have been developed to inhibit HER2/neu in hope to cure this devastating disease. In this study, we chose to use siRNA against HER2/neu to suppress HER2/neu-overexpressing cancer cells. We have constructed a recombinant adenovirus expressing HER2/neu siRNA (named rAdv-siHER2). We demonstrated that rAdv-siHER2 could effectively inhibit HER2/neu expression in various HER2/neu-overexpressing cancer cell lines. This inhibition of HER2/neu expression by rAdv-siHER2 can lead to inhibition of ERK and AKT activities, both of which are downstream signaling molecules of HER2/neu and are required for cell proliferation and survival.
In accordance with its ability to inhibit HER2/neu expression, rAdv-siHER2 was shown, by sub-G1 analysis and PARP cleavage assay, to be able to specifically induce apoptosis in HER2/neu-overexpressing cancer cell lines (BT-474, MDA-MB-453, SK-OV-3-sub1 and SK-OV-3-ip1), but not in HER2/neu low-expressing cancer cell lines (MDA-MB-231, MCF-7, HeLa and NPC-TW04) and non-transformed cell line (ECV304). We also found that rAdv-siHER2 could specifically inhibit the soft-agar colony-forming ability of the HER2/neu-overexpressing cancer cell lines, but not that of the HER2/neu low-expressing cancer cell lines. Moreover, intratumoral injection of rAdv-siHER2 could effciently suppress the growth of established subcutaneous SK-OV-3-ip1 tumor on NOD/SCID mice. Finally, we demonstrated that rAdv-siHER2 could sensitize HER2/neu-overexpressing cancer cell lines, but not HER2/neu low-expressing cancer cell lines, to chemotherapeutic agent, cisplatin (CDDP). Taken together, these data suggest that rAdv-siHER2 has the potential to be developed into a gene therapy agent specifically against HER2/neu-overexpressing cancers.中文摘要……………………………………………………………… 1
英文摘要……………………………………………………………… 3
序言…………………………………………………………………… 5
研究目標………………………………………………………………17
材料與方法……………………………………………………………18
結果……………………………………………………………………30
討論……………………………………………………………………38
附圖……………………………………………………………………47
參考資料………………………………………………………………6
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
sj-pdf-1-neu-10.1177_19714009211049713 - Supplemental material for Heterogeneity between proximal and distal aspects of occlusive thrombi on pretreatment imaging in acute ischemic stroke
No full textSupplemental material, sj-pdf-1-neu-10.1177_19714009211049713 for Heterogeneity between proximal and distal aspects of occlusive thrombi on pretreatment imaging in acute ischemic stroke by Tetsuya Hashimoto, Takenobu Kunieda, Tristan Honda, Fabien Scalzo, Latisha K Sharma, Jason D Hinman, Neal M Rao, May Nour, Mersedeh Bahr-Hosseini, Jeffrey L Saver, Radoslav Raychev and David S Liebeskind in The Neuroradiology Journal</p
Demokratie neu denken
No full textHeinrich M, Minsch J, Tschapka J. Demokratie neu denken. Umwelt und Bildung. 2004;(4):24-25
- …
