Supramolecular Assembly of Amino Acid Based Cationic Polymer for Efficient Gene Transfection Efficiency in Triple Negative Breast Cancer

2019 ◽  
Vol 2 (12) ◽  
pp. 5349-5365
Author(s):  
Rima Saha ◽  
Sagar Bhayye ◽  
Shuvam Ghosh ◽  
Achintya Saha ◽  
Kishor Sarkar
Epigenomics ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 1247-1268
Author(s):  
Yajie Zhao ◽  
Chunrui Pu ◽  
Dechuang Jiao ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
...  

Aim: To develop an approach to characterize and classify triple-negative breast cancer (TNBC) tumors based upon their essential amino acid (EAA) metabolic activity. Methods: We performed bioinformatic analyses of genomic, transcriptomic and clinical data in an integrated cohort of 740 TNBC patients from public databases. Results: Based on EAA metabolism-related gene expression patterns, two TNBC subtypes were identified with distinct prognoses and genomic alterations. Patients exhibiting an upregulated EAA metabolism phenotype were more prone to chemoresistance but also expressed higher levels of immune checkpoint genes and may be better candidates for immune checkpoint inhibitor therapy. Conclusion: Metabolic classification based upon EAA profiles offers a novel biological insight into previously established TNBC subtypes and advances current understanding of TNBC’s metabolic heterogeneity.


2017 ◽  
Vol 53 (87) ◽  
pp. 11937-11940 ◽  
Author(s):  
Ying Liu ◽  
Ding-Kun Ji ◽  
Lei Dong ◽  
Nicolas Galanos ◽  
Yi Zang ◽  
...  

Supramolecular self-assembly between perylenediimide-based glycoclusters and a red-emitting fluorophore produces structurally uniform and stable glyco-dots amenable to targeted fluorogenic imaging of liver and triple-negative breast cancer cells.


2021 ◽  
Author(s):  
Xianxian Duan ◽  
Xiao Hu ◽  
Zhanzhao Liu ◽  
Ning Li ◽  
Junfang Qin ◽  
...  

Abstract Immune checkpoint blocking therapy targeting the PD-1/PD-L1 axis has shown promising availability for triple-negative breast cancer (TNBC). Nevertheless, in some cases, targeting efficiency is low and efficient gene interaction networks need to be sought, which inspired the exploration that MCT4 and PD-L1 co-expression network analysis and potential regulatory mechanism research. In the paper, bioinformatics, Western blot, qRT-PCR, flow cytometry, biochemical analysis, multiple immunohistochemistry, CRISPR/Cas9 and lentiviral transduction for MCT4 knockout (sgMCT4/231 KO) or overexpression (pEGFP-N1-MCT4/231) were adopted. Analysis of database basis showed MCT4 (SLC16A3) and PD-L1 (CD274) were functionally correlated and highly expressed in TNBC cells, further MCT4 and PD-L1 were co-expressed (more than 50% PD-L1+MCT4+ cells) in tissue section of TNBC patients. The expression of PD-L1 in TNBC cell lines MDA-MB-231, MDA-MB-468 and BT-549 was sensitive to lactate concentration, and lowering MCT4 expression could downregulate PD-L1 expression through affecting the lactate concentration. These data suggests that MCT4 is positively associated with PD-L1 and the co-targeted therapy for TNBC may be a promising clinical treatment strategy.


PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0163138 ◽  
Author(s):  
Vassiliki Kotoula ◽  
Sotiris Lakis ◽  
Ioannis S. Vlachos ◽  
Eleni Giannoulatou ◽  
Flora Zagouri ◽  
...  

2011 ◽  
Vol 103 (2) ◽  
pp. 382-389 ◽  
Author(s):  
Mio Furuya ◽  
Jun Horiguchi ◽  
Hiroki Nakajima ◽  
Yoshikatsu Kanai ◽  
Tetsunari Oyama

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyan Su ◽  
Xiaohong Chen ◽  
Yuanjie Xiao ◽  
Dan Li ◽  
Muxia Li ◽  
...  

Triple-negative breast cancer (TNBC) has been acknowledged as an aggressive disease with worst prognosis, which requires endeavor to develop novel therapeutic agents. Bruceae fructus oil (BO), a vegetable oil derived from the fruit of Brucea javanica (L.) Merr., is an approved marketable drug for the treatment of cancer in China for several decades. Despite that the anti–breast cancer activity of several quassinoids derived from B. javanica has been found, it was the first time that the potential of BO against TNBC was revealed. Although BO had no cytotoxicity on TNBC cell lines in vitro, the oral administration of BO exhibited a gut microbiota–dependent tumor suppression without toxicity on the non-targeted organs in vivo. By metagenomics and untargeted metabolomics, it was found that BO not only altered the composition and amino acid metabolism function of gut microbiota but also regulated the host’s amino acid profile, which was in accordance with the metabolism alternation in gut microbiota. Moreover, the activity of mTOR in tumor was promoted by BO treatment as indicated by the phosphorylation of 4E-binding protein 1 (4E-BP1) and ribosomal protein S6, and hyper-autophagy was consequently restrained. By contrast, the failure of tumor suppression by BO under pseudo germ-free (PGF) condition came with indistinctive changes in autophagy and mTOR activity, implying the critical role of the gut microbiota in BO’s anticancer activity. The present study highlighted a promising application of BO against breast cancer with novel efficacy and safety.


2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Simone Anfossi ◽  
George A. Calin

A new concept is emerging in the non-coding RNA (ncRNA) field: an increasing number of ncRNAs in fact codify for short peptides that have biological activities. In this issue of JEM, Wang et al. (https://doi.org/10.1084/jem.20190950) report the identification of a long ncRNA (lncRNA)–encoded 60–amino acid polypeptide that they name ASRPS, as well as its ability to inhibit angiogenesis in the deadly triple-negative breast cancer (TNBC).


2021 ◽  
Author(s):  
Sabarish Ramachandran ◽  
Souad Sennoune ◽  
Monica Sharma ◽  
Muthusamy Thangaraju ◽  
Varshini Suresh ◽  
...  

Metabolic reprogramming in cancer cells necessitates increased amino acid uptake, which is accomplished by upregulation of specific amino acid transporters. Since amino acid transporters differ in substrate selectivity, mode of transport, and driving forces, not all tumors rely on any single amino acid transporter for this purpose. Here we report on the differential upregulation of the amino acid transporter SLC38A5 in triple-negative breast cancer (TNBC). The upregulation is evident in primary TNBC tumors, conventional TNBC cell lines, patient-derived xenograft TNBC cell lines, and a mouse model of spontaneous mammary tumor representing TNBC. The upregulation is confirmed by functional assays. SLC38A5 is an amino acid-dependent Na+/H+ exchanger which transports Na+ and amino acids into cells coupled with H+ efflux. Since the traditional Na+/H+ exchanger is an established inducer of macropinocytosis, an endocytic process for cellular uptake of bulk fluid and its components, we examined the impact of SLC38A5 on macropinocytosis in TNBC cells. We found that the transport function of SLC38A5 is coupled to induction of macropinocytosis. Surprisingly, the transport function of SLC38A5 is inhibited by amilorides, the well-known inhibitors of Na+/H+ exchanger, possibly related to the amino acid dependent Na+/H+ exchange function of SLC38A5. The Cancer Genome Atlas database corroborates SLC38A5 upregulation in TNBC. This represents the first report on the selective expression of SLC38A5 in TNBC and its role as an inducer of macropinocytosis, thus revealing a novel, hitherto unsuspected, function for an amino acid transporter that goes beyond amino acid delivery but is still relevant to cancer cell nutrition.


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