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61.
Zheyuan Wang Zhiheng Shi Lu Zhang Huihan Zhang Yawu Zhang 《Pathology, research and practice》2019,215(3):499-505
Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients. 相似文献
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Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment. 相似文献
65.
To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic β-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-γ, IL-1β,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE (20 μM) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose. 相似文献
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Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献68.
《European journal of medical genetics》2020,63(6):103919
Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been involved in neuronal growth and connectivity. Genetic variants, in or near the NEGR1 locus, have been associated with obesity and, more recently, with learning difficulties, intellectual disability, and psychiatric disorders.Here, we described the only second report of NEGR1 gene disruption in 1p31.1 microdeletion in two patients. Patient 1 is a 14-year-old female with neurological and psychiatric features present also in her family. Patient 2 is a 5-month-old infant showing global hypotonia as unique neurological features till now. This patient also carries 7p22.1 duplication, of paternal origin, that could be responsible for some malformations present in the child.We hypothesize a role of NEGR1 in producing the phenotype of our patients and compare them with other cases previously reported in the literature and DECIPHER database to better identify a possible genotype-phenotype correlation. 相似文献
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《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents. 相似文献