Top 6 Biorxiv Papers Today in Cancer Biology


1.998 Mikeys
#1. DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status
Yuki Kataoka, Makoto Iimori, Ryo Fujisawa, Tomomi Morikawa-Ichinose, Shinichiro Niimi, Takeshi Wakasa, Hiroshi Saeki, Eiji Oki, Daisuke Miura, Toshiki Tsurimoto, Yoshihiko Maehara, Hiroyuki Kitao
DNA replication stress is a predominant cause of genome instability, a driver of tumorigenesis and malignant progression. Nucleoside analog-type chemotherapeutic drugs introduce DNA damage and exacerbate DNA replication stress in tumor cells. However, the mechanisms underlying tumor cytotoxicity triggered by the drugs are not fully understood. Here, we show that the fluorinated thymidine analog trifluridine (FTD), an active component of the chemotherapeutic drug trifluridine/tipiracil, delayed DNA synthesis by human replicative DNA polymerases. FTD acted as an inefficient deoxyribonucleotide triphosphate source (FTD triphosphate) and as an obstacle base (trifluorothymine) in the template DNA strand. At the cellular level, FTD decreased thymidine triphosphate in the dNTP pool and induced FTD triphosphate accumulation, resulting in replication fork stalling caused by FTD incorporation into DNA. DNA lesions involving single-stranded DNA were generated as a result of replication fork stalling, and the p53-p21 pathway was activated....
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biorxivpreprint: DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status https://t.co/cuSRXfwRMV #bioRxiv
biorxiv_cancer: DNA replication stress induced by trifluridine determines tumor cell fate according to p53 status https://t.co/3WdueMi1dX #biorxiv_cancer
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Authors: 12
Total Words: 9547
Unqiue Words: 2802

1.997 Mikeys
#2. LncRNA MIR4435-2HG mediates cisplatin resistance in HCT116 cells by regulating Nrf2 and HO-1
XiaoMing Zhong, Ping Luo, ShuGui Wu, ChaoMing Zhou, Xia Yuan, HongMi Li, JinPing Chen, YunFei Tian, Yang Qiu, Ping Luo,ShuGui Wu,ChaoMing Zhou,Xia Yuan,HongMi Li,JinPing Chen,YunFei Tian,Yang Qiu,XiaoMing Zhong
PURPOSE Cisplatin resistance is still a serious problem in clinic. However, the underlying mechanism remains unclear. In this study investigated the drug resistance of cisplatin by the cisplatin resistance cell line HCT116R.RESULTS In this study, we found that LncRNA MIR4435-2HG level dramatically increased in the cisplatin resistance cell line HCT116R. Knockdown of MIR4435-2HG in HCR116R significantly restored the sensitivity to cisplatin, inhibited cell proliferation and promoted cell apoptosis. Furthermore, Nrf2 and HO-1 mRNA level, as the critical molecular of the oxidative stress pathway, was inhibited by the siRNA targeting to MIR4435-2HG, displaying MIR4435-2HG-mediated cisplatin resistance through the Nrf2/HO-1 pathway.CONCLUSION Our findings demonstrated that LncRNA MIR4435-2HG as a main factor could drive the cisplatin resistance of HCT116.
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Authors: 10
Total Words: 2764
Unqiue Words: 1177

1.997 Mikeys
#3. A framework for transcriptome-wide association studies in breast cancer in diverse study populations
Arjun Bhattacharya, Montserrat Garcia-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester, Michael I. Love
Background : The relationship between germline genetic variation and breast cancer survival is largely unknown, especially in understudied minority populations who often have poorer survival. Genome-wide association studies (GWAS) have interrogated breast cancer survival but often are underpowered due to subtype heterogeneity and many clinical covariates and detect loci in non-coding regions that are difficult to interpret. Transcriptome-wide association studies (TWAS) show increased power in detecting functionally-relevant loci by leveraging expression quantitative trait loci (eQTLs) from external reference panels in relevant tissues. However, ancestry- or race-specific reference panels may be needed to draw correct inference in ancestrally-diverse cohorts. Such panels for breast cancer are lacking. Results : We provide a framework for TWAS for breast cancer in diverse populations, using data from the Carolina Breast Cancer Study (CBCS), a North Carolina population-based cohort that oversampled black women. We perform eQTL...
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biorxivpreprint: A framework for transcriptome-wide association studies in breast cancer in diverse study populations https://t.co/OBmnP9DVux #bioRxiv
biorxiv_cancer: A framework for transcriptome-wide association studies in breast cancer in diverse study populations https://t.co/OnBRPnqQrA #biorxiv_cancer
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Authors: 6
Total Words: 0
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1.997 Mikeys
#4. Defining and targeting adaptations to oncogenic KRASG12C inhibition using quantitative temporal proteomics
Naiara Santana-Codina, Amrita Singh Chandhoke, Qijia Yu, Beata Małachowska, Miljan Kuljanin, Ajami Gikandi, Marcin Stańczak, Sebastian Gableske, Mark P. Jedrychowski, David A. Scott, Andrew J. Aguirre, Wojciech Fendler, Nathanael S. Gray, Joseph D. Mancias
Covalent inhibitors of the KRASG12C oncoprotein have recently been developed and are being evaluated in clinical trials. Resistance to targeted therapies is common and likely to limit long-term efficacy of KRAS inhibitors (KRASi). To identify pathways of adaptation to KRASi and to predict drug combinations that circumvent resistance, we used a mass spectrometry-based quantitative temporal proteomics and bioinformatics workflow to profile the temporal proteomic response to KRASG12C inhibition in pancreatic and lung cancer 2D and 3D cellular models. We quantified 10,805 proteins across our datasets, representing the most comprehensive KRASi proteomics effort to date. Our data reveal common mechanisms of acute and long-term response between KRASG12C-driven tumors. To facilitate discovery in the cancer biology community, we generated an interactive KRASi proteome website (https://manciaslab.shinyapps.io/KRASi/). Based on these proteomic data, we identified potent combinations of KRASi with PI3K, HSP90, CDK4/6, and SHP2 inhibitors, in...
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biorxivpreprint: Defining and targeting adaptations to oncogenic KRASG12C inhibition using quantitative temporal proteomics https://t.co/A0WxbU75J5 #bioRxiv
biorxiv_cancer: Defining and targeting adaptations to oncogenic KRASG12C inhibition using quantitative temporal proteomics https://t.co/5nvz7BfYa3 #biorxiv_cancer
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Authors: 14
Total Words: 0
Unqiue Words: 0

1.997 Mikeys
#5. Tumor cell-derived lymphotoxin alpha triggers metastatic extravasation through TNFRs/cIAP1
Lazaros Vasilikos, Kay Haenggi, Lisanne M Spilgies, Wendy Wei-Lynn Wong
Metastasis involves the interaction of the tumor, immune and endothelial cells. Cell death proteins, such as inhibitors of apoptosis proteins (IAPs), are critical players in survival, inflammation and permeability. Whether the use of Smac mimetics, which target cIAP1/2 for degradation would affect metastasis is unknown. We show Smac mimetics reduced metastasis due to the loss of cIAP1 but not cIAP2 in experimental metastasis models. The endothelial compartment rather than the immune cells was responsible for reduction of extravasation upon loss of cIAP1. Loss of cIAP1 in primary endothelial cells did not lead to cell death but resulted in an unresponsive endothelium barrier to permeability factors causing a reduction in tumor cell extravasation. Unexpectedly, the co-loss of TNFR1 and cIAP1 restored the tumor load. We were surprised to find lymphotoxin alpha (LTA), and not TNF, secreted by the tumor cells was critical for the extravasation. Using TCGA data, we found high levels of LTA mRNA expression correlated with decreased...
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1.997 Mikeys
#6. Comparative Anatomical Limits of CART-Cell Delivery to Tumours in Mice and Men
Liam V Brown, Eamonn A Gaffney, Ann Ager, Jonathan Wagg, Mark C Coles
CART (Chimeric Antigen Receptor T)-cells are approved for treatment of several leukaemia and lymphoma indications. However, this therapeutic modality has not delivered comparable clinical efficacy for solid tumour indications despite promising preclinical outcomes in mouse solid tumour models. Lower rates of effective CART-cell delivery to solid tumours in humans as compared to human haematological malignancies and/or solid tumours in mice might partially explain these divergent outcomes. As the initial delivery of CART-cells to tumour tissue is mediated by the circulatory system, we developed in silico models of the human, rat and mouse circulatory systems. Model structure and parameterisation were informed by an extensive body of published comparative anatomical and physiological studies and associated experimental data. Models were used to estimate the species-dependent upper limit and variation of delivery rates of blood borne immune cells, such as T- and NK cells, to tumour tissue across different organs and species. Large...
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biorxivpreprint: Comparative Anatomical Limits of CART-Cell Delivery to Tumours in Mice and Men https://t.co/0o277u7lri #bioRxiv
biorxiv_cancer: Comparative Anatomical Limits of CART-Cell Delivery to Tumours in Mice and Men https://t.co/HdwzKmZnfL #biorxiv_cancer
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Authors: 5
Total Words: 9258
Unqiue Words: 2943

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