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101.
Kyung-Min Lee Eun Hye Hwang Seong Eun Kang Cheng Hyun Lee Hyebin Lee Hyeon Jeong Oh Kwangsoo Kim Jiwon Koh Han Suk Ryu 《JOURNAL OF BREAST CANCER》2020,23(6):599
PurposeA relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer.MethodsPre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7).ResultsWARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression.ConclusionOur results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity. 相似文献
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《European journal of surgical oncology》2020,46(5):804-810
IntroductionEstablished preoperative prognostic factors for risk stratification of patients with biliary tract cancer (BTC) are lacking. A prognostic value of the inflammation-based Glasgow Prognostic Score (GPS) and Modified Glasgow Prognostic Score (mGPS) in BTC has been indicated in several Eastern cohorts. We sought to validate and compare the prognostic value of the GPS and the mGPS for overall survival (OS), in a large Western cohort of patients with BTC.Material and methodsWe performed a retrospective single-center study for the period 2009 until 2017. 216 consecutive patients that underwent surgical exploration with a diagnosis of perihilar cholangiocarcinoma (PHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC) were assessed. GPS and mGPS were calculated where both CRP and albumin were measured pre-operatively (n = 168/216). Survival was analyzed by Kaplan-Meier estimate and uni-/multivariate Cox regression.ResultsGPS and mGPS were negatively associated with survival (p < 0.001/p < 0.001), and the association was significant in all three subgroups. GPS, but not the mGPS, identified an intermediate risk group: with GPS = 1 having better OS than GPS = 2 (p = 0.003), but worse OS than GPS = 0 (p = 0.008). In multivariate analyses of resected patients, GPS (p = 0.001) and mGPS (p = 0.03) remained significant predictors of survival, independent of postoperatively available risk factors.ConclusionsPreoperative GPS and mGPS are independent prognostic factors in BTC. The association to OS was shown in all patients undergoing exploration, in resected patients only, and in both cholangiocarcinoma and gallbladder cancer. Furthermore, GPS – which weights hypoalbuminemia higher – could identify an intermediate risk group. 相似文献
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A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury.In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke. 相似文献
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Siavash Rahimi Iolia Akaev Peter A. Brennan Azarel Virgo Carla Marani Ricardo S. Gomez Chit Cheng Yeoh 《Journal of oral pathology & medicine》2020,49(2):110-116
The current three-tier grading system (well, moderate and poorly differentiated) used to morphologically classify head and neck squamous cell carcinoma (HNSCC) is inadequate for categorisation of oropharyngeal squamous cell carcinoma (OPSCC) owing to the lack of prognostic value. The aim of this study was to assess the validity of a classification system for OPSCC based on morphology and human papilloma virus (HPV) infection status. Haematoxylin and eosin slides of 121 patients (100 M, 21 F, age range 40-89 years) with OPSCC were reviewed and categorised as histological types I, II and III. The presence of HPV was assessed by immunohistochemistry with p16 and RNAscope In situ hybridization (ISH). The follow-up period was 36 months. Ninety-six patients were p16+ and clinical stage I. Patient survival with types I, II and III was 93%, 50% and 96%, respectively. Twenty-five patients were p16−: 10 clinical stage I and 15 stage III. Amongst this group, no type I morphology was identified. At follow-up, 65% of type II and 75% of type III patients were alive. All p16+ cases were also positive for E6/E7 mRNA high-risk HPV by ISH, while 23 p16− cases were negative and two were positive. Cox regression identified three predictors of mortality: older age (HR = 1.14, 95% CI = 1.06-1.23, P = .001); female gender (HR = 0.22.95% CI 0.05-0.88, P = .033); and type II morphology (HR = 13.1, 95% CI = 1.09-157.0, P = .043). OPSCC morphological classification in three sub-types, along with HPV infection status, seems to reflect the outcome of patients with OPSCC. 相似文献
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Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. The object of the study was to explore the functions and precise mechanism of miR-142–3p in human keratinocyte HaCaT cells in the presence of M5. Here, the results showed that miR-142–3p expression was heightened in HaCaT cells induced by M5. In addition, inhibition of miR-142–3p dramatically restricted cell proliferation and enhanced apoptosis in HaCaT cells exposed to M5, as exemplified by a decrease in the antiapoptotic Bcl-2 protein, concomitant with an increase in the proapoptotic proteins Bax. Moreover, depleting miR-142–3p effectively ameliorated M5-induced inflammation response, as reflected by the attenuation of multiple inflammatory factors. Importantly, Sema3A was identified as an authentic target of miR-142–3p, and indeed regulated by miR-142–3p. Mechanistically, silencing of Sema3A effectively abolished the anti-proliferative, apoptosis-promoting, and anti-inflammatory effects of miR-142–3p inhibition in keratinocytes. Taken together, these data elucidated that repression of miR-142–3p protect HaCaT cells against M5-induced hyper-proliferation and inflammatory injury by suppressing its target Sema3A, implying that the miR-142–3p/Sema3A axis may be a new target for preventing keratinocyte injury process. These findings provide a new and better understanding of the mediating role of miR-142–3p in psoriasis. 相似文献