一、論文分享
- 題目：
EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1)
- 作者：Tzyh-Chyuan Hour, Shiu-Dong Chung, Wang-Yi Kang, Ying-Chu Lin, Shu-Ju Chuang, A-Mei Huang, Wen-Jeng Wu, Shu-Pin Huang, Chao-Yuan Huang, Yeong-Shiau Pu. Archives of Toxicology. April 2015, Volume 89, Issue 4, pp 591-605
- 摘要：
Recent studies have shown that docetaxel-based chemotherapy confers a survival benefit in patients with castration-resistant prostate cancer (PC). Also epidermal growth factor receptor (EGFR) was found to have multiple roles in prostatic tumorigenesis. However, the EGFR-mediated chemoresistance mechanism in human PC was not well delineated. In this study, we explored the mechanism of EGFR-mediated docetaxel resistance in PC. A series of stable docetaxel-resistant PC/DX sublines were established at our laboratory. The docetaxel IC50s of PC3 and PC/DX25 cells were 0.01 and 1.33 μM, respectively. Cellular resistance to docetaxel was significantly associated with increased EGFR and EGFR activation in PC/DX25. There was a dose-dependent increase in EGFR expression associated with the magnitude of docetaxel resistance. Expression of EGFR in PC/DX25 was higher than that in PC3, RWPE-1 and LNCaP cells. Similar results were also found in human PC tissues by immunohistochemical staining. We showed that docetaxel sensitivity can be stored in PC/DX25 cells by knockdown and inactivation of EGFR expression through EGFR siRNA and specific inhibitors, respectively. Contrarily, overexpression of EGFR or recombinant EGF protein treatment could rescue PC3 cells from docetaxel-mediated cytotoxicity. Gefitninb (ZD1839) significantly inhibited the growth of PC/DX25 cells by MTT in vitro and on xenografted nude mice in vivo. Moreover, EGFR-mediated docetaxel resistance occurred through the Akt-dependent ABCB1 expression in PC cells. These findings demonstrated EGFR played an important role in docetaxel-resistant PC and EGFR inhibition may enhance the therapeutic efficacy of docetaxel-based treatment.
- 題目：
Prognostic Significance of Lymphovascular Invasion in Upper Urinary Tract Urothelial Carcinoma is Influenced by Tumor Location.
- 作者：Hsiang-Ying Lee MD, MS,Ching-Chia Li MD,Chun-Nung Huang MD, PhD,Hung-Lung Ke MD, MS,Wei-Ming Li MD, MS,Peir-In Liang MD,Sheau-Fang Yang MD,Hung-Pin Tu PhD,Wen-Jeng Wu MD, PhD,Hsin-Chih Yeh MD, MS.Annals of Surgical Oncology. April 2015, Volume 22, Issue 4, pp 1392-1400 , Date: 20 Sep 2014.
- 摘要：
Background
To examine the prognostic value of lymphovascular invasion (LVI) in different tumor locations (i.e., renal pelvis and ureter) of upper urinary tract urothelial carcinoma (UTUC).Methods
Data from a total of 250 patients with nonmetastatic UTUC who received radical nephroureterectomy between 2004 and 2010 at our institution were analyzed retrospectively. The significance of LVI and other relevant factors on cancer-specific survival (CSS), metastasis-free survival (MFS), and intraluminal recurrence-free survival (IRFS) were evaluated.Results
Lymphovascular invasion was present in 60 patients (24 %) and was related to advanced pathological T stage (P < 0.001), higher tumor grade (P < 0.001), lymph node metastasis (P = 0.005), and pyelocaliceal tumor location (P = 0.002). By Kaplan–Meier analysis, LVI was found to be significantly correlated with worse CSS and MFS but not with IRFS. Multivariate analysis showed that high pathological T stage and regional lymph node involvement were significant prognostic factors for CSS and MFS, and LVI was an independent predictor for MFS (hazard ratio 1.71, 95 % confidence interval 1.00–2.93, P = 0.049). In patients with ureteral tumors, LVI represented the only significant prognosticator for both CSS and MFS in multivariate analysis. The prognostic value of LVI was not observed in pyelocaliceal tumors.Conclusions
The implication of LVI on prognosis, particularly in ureteral tumors but not in pyelocaliceal tumors, may imply diverse disease characteristics between different tumor locations among UTUC. LVI is essential to identify patients at high risk for metastasis/mortality and can facilitate treatment planning and surveillance strategies, especially in patients with ureteral tumors..