Top 9 Biorxiv Papers Today in Cancer Biology


2.058 Mikeys
#1. Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines
Kathryn M Appleton, Charuta C Palsuledesai, Sean A Misek, Maja Blake, Joseph Zagorski, Thomas S Dexheimer, Richard R Neubig
The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (~50% BRAFV600 mutations and ~30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells which have a high level of trametinib resistance. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib...
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biorxivpreprint: Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines https://t.co/wUU89EX2QA #bioRxiv
biorxiv_cancer: Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines https://t.co/NsYTlM0EfZ #biorxiv_cancer
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Authors: 7
Total Words: 9170
Unqiue Words: 2680

2.024 Mikeys
#2. Mutation distribution density in tumors reconstructs human's lost diversity
Jose Maria Heredia-Genestar, Tomas Marques-Bonet, David Juan, Arcadi Navarro
Mutations do not accumulate uniformly across the genome. Human germline and tumor mutation density correlate poorly, and each is associated with different genomic features. Here, we analyze the genome-wide distribution of mutation densities in human and non-human Great Ape (NHGA) germlines as well as human tumors. Strikingly, non-human Great Ape germlines present higher correlation with tumors than the human germline does. This situation is mediated by a different distribution in the human germline of mutations at non-CpG sites, but not of CpG>T transitions. We propose that the impact of ancestral and historical human demographic events on human mutation density leads to this specific disruption in its expected genome-wide distribution. Tumors partially recover this distribution by the accumulation of pre-neoplastic-like somatic mutations. Our results highlight the potential utility of using Great Ape population data, rather than human controls, to establish the expected mutational background of healthy somatic cells.
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biorxivpreprint: Mutation distribution density in tumors reconstructs human's lost diversity https://t.co/EnQXkWnFod #bioRxiv
biorxiv_cancer: Mutation distribution density in tumors reconstructs human's lost diversity https://t.co/EfKIcHD1Zb #biorxiv_cancer
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Authors: 4
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2.024 Mikeys
#3. RELA is Sufficient to Mediate Interleukin-1 (IL-1) Repression of Androgen Receptor Expression and Activity in LNCaP Disease Progression Model
Shayna Thomas-Jardin, Haley Dahl, Mohammed Kanchwala, Freedom Ha, Joan Jacob, Reshma Soundharrajan, Monica Bautista, Afshan Nawas, Dexter Robichaux, Ragini Mistry, Vanessa Anunobi, Chao Xing, Nikki Delk
Background: The Androgen Receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR mRNA levels and activity in AR-positive (AR+) PCa cell lines concomitant with the upregulation of pro-survival biomolecules. Thus, we contend that IL-1 can select for AR-independent, treatment-resistant PCa cells. Methods: To begin to explore how IL-1 signaling leads to the repression of AR mRNA levels, we performed comprehensive pathway analysis on our RNA sequencing data from IL-1-treated LNCaP PCa cells. Our pathway analysis predicted Nuclear Factor Kappa B (NF-κB) p65 subunit (RELA), a canonical IL-1 signal transducer, to be significantly active...
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biorxivpreprint: RELA is Sufficient to Mediate Interleukin-1 (IL-1) Repression of Androgen Receptor Expression and Activity in LNCaP Disease Progression Model https://t.co/I3p76ddWrt #bioRxiv
biorxiv_cancer: RELA is Sufficient to Mediate Interleukin-1 (IL-1) Repression of Androgen Receptor Expression and Activity in LNCaP Disease ... https://t.co/istTzQhj97 #biorxiv_cancer
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Authors: 13
Total Words: 0
Unqiue Words: 0

2.001 Mikeys
#4. Personalized Cancer Therapy Prioritization Based on Driver Alteration Co-occurrence Patterns
Lidia Mateo, Miquel Duran-Frigola, Albert Gris-Oliver, Marta Palafox, Maurizio Scaltriti, Pedram Razavi, Sarat Chandarlapaty, Joaquin Arribas, Meritxell Bellet, Violeta Serra, Patrick Aloy
Molecular profiling of personal cancer genomes, and the identification of actionable vulnerabilities and drug-response biomarkers, are the basis of precision oncology. Tumors often present several driver alterations that might be connected by cross-talk and feedback mechanisms, making it difficult to mark single oncogenic variations as reliable predictors of therapeutic outcome. In the current work, we uncover and exploit driver alteration co-occurrence patterns from a recently published in vivo screening in patient-derived xenografts (PDXs), including 187 tumors and 53 drugs. For each treatment, we compare the mutational profiles of sensitive and resistant PDXs to statistically define Driver Co-Occurrence (DCO) networks, which capture both genomic structure and putative oncogenic synergy. We then use the DCO networks to train classifiers that can prioritize, among the available options, the best possible treatment for each tumor based on its oncogenomic profile. In a cross-validation setting, our drug-response models are able to...
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MrsLaviniaG: RT @biorxiv_cancer: Personalized Cancer Therapy Prioritization Based on Driver Alteration Co-occurrence Patterns https://t.co/XFL3yKLLnD #…
mduranfrigola: RT @biorxivpreprint: Personalized Cancer Therapy Prioritization Based on Driver Alteration Co-occurrence Patterns https://t.co/000HtXTTBi…
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Sample Sizes : [23, 9, 7, 5, 2, 3, 2, 2, 2, 38, 32, 51, 27, 38, 15212, 2021, 15, 14, 7, 5, 5, 5, 2, 2]
Authors: 11
Total Words: 20618
Unqiue Words: 4980

1.994 Mikeys
#5. Lesions of canine prostate underwent laser ablation, radiofrequency ablation, and microwave ablation: Lesions’ shapes and clinical significances
Ruiqing Liu, Lianzhong Zhang, Shaobo Duan, Huicun Cao, Guangshao Cao, Zhiyang Chang, Ye Zhang, Yaqiong Li, Yuejin Wu, Luwen Liu
Objective To explore the shapes and clinical significances of the lesions of canine prostate underwent laser ablation (LA), radiofrequency ablation (RFA), and microwave ablation (MWA). Methods Here, 6 male Beagle dogs were randomly assigned to LA, RFA, and MWA groups, respectively. The ablations were conducted with the doses commonly applied in clinical practice (LA: 3 W/1200 J; RFA and MWA: 30 W/120 s) for one region in the left and right lobes of the prostate, which totally resulted in 12 lesions. An energy transmitter was inserted via the perineum under the guidance of transrectal ultrasound (TRUS) and the ablation process was observed dynamically. After ablation, the efficacy was assessed by contrast-enhanced ultrasonography (CEUS),and transverse diameter (TRD), anteroposterior diameter (APD), and longitudinal diameter (TRD) were measured. Then, the volume (V) was calculated according to the following formulae, V = 1/6 × π × (MLD × APD × LD), and ratio (R) R =[(MLD + APD)/2 × LD], which was used to show the shape of the lesion...
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Authors: 10
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1.98 Mikeys
#6. STAT3-dependent systems-level analysis reveals PDK4 as an independent predictor of biochemical recurrence in prostate cancer
Monika Oberhuber, Matteo Pecoraro, Mate Rusz, Georg Oberhuber, Maritta Wieselberg, Peter Haslinger, Elisabeth Gurnhofer, Jan Pencik, Robert Wiebringhaus, Michaela Schlederer, Theresa Weiss, Margit Schmeidl, Andrea Haitel, Marc J Brehme, Wolfgang Wadsak, Johannes Griss, Thomas Mohr, Alexandra Hofer, Anton Jäger, Gerda Egger, Jügen Pollheimer, Gunda Koellensperger, Matthias Mann, Brigitte Hantusch, Lukas Kenner
Prostate cancer (PCa) has a broad spectrum of clinical behaviour, hence biomarkers are urgently needed for risk stratification. We previously described the protective effect of STAT3 in a prostate cancer mouse model. By utilizing a gene co-expression network in addition to laser microdissected proteomics from human and murine prostate FFPE samples, we describe STAT3-induced downregulation of the TCA cycle/OXPHOS in PCa on transcriptomic and proteomic level. We identify pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging and PSA level. Furthermore, PDK4 expression is causally linked to type 2 diabetes mellitus, which is known to have a protective effect on PCa. We conclude that this effect is related to PDK4 expression and that PDK4 loss could serve as a biomarker for PCa with dismal prognosis.
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Authors: 25
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1.98 Mikeys
#7. OTULIN prevents liver inflammation and hepatocellular carcinoma by inhibiting FADD- and RIPK1 kinase-mediated hepatocyte apoptosis
Lien Verboom, Arne Martens, Dario Priem, Esther Hoste, Mozes Sze, Hanna Vikkula, Sofie Voet, Laura Bongiovanni, Alain de Bruin, Charlotte L Scott, Manolis Pasparakis, Mathieu JM Bertrand, Geert van Loo
Inflammatory signaling pathways are tightly regulated to avoid chronic inflammation and the development of inflammatory pathologies. OTULIN is a deubiquitinating enzyme that specifically cleaves linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC), and OTULIN deficiency causes OTULIN-related autoinflammatory syndrome (ORAS) in humans. OTULIN was shown to negatively control NF-kB signaling in response to various stimuli, but also to protect cells from tumor necrosis factor (TNF)-induced apoptosis. To investigate the importance of OTULIN in liver homeostasis and pathology, we developed a novel mouse line specifically lacking OTULIN in liver parenchymal cells. These mice spontaneously develop a severe liver disease, characterized by liver inflammation, hepatocyte apoptosis and compensatory hepatocyte proliferation, leading to steatohepatitis, fibrosis and hepatocellular carcinoma (HCC). Genetic ablation of Fas-associated death domain (FADD) completely rescues the severe liver pathology, and...
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Authors: 13
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1.978 Mikeys
#8. Light-Activated Nanoscale Gas Vesicles Selectively Kill Tumor Cells
Jean Gariepy, Ann Fernando
Protein-based nanobubbles such as halophilic archaeabacterial gas vesicles (GVs) represent a new class of stable, homogeneous nanoparticles with acoustic properties that allow them to be visualized by ultrasound (US) waves. To design GVs as theranostic agents, we modified them to respond to light, with a view to locally generate reactive oxygen species that can kill cancer cells. Specifically, up to 60,000 photoreactive chlorin e6 (Ce6) molecules were chemically attached to lysine ε-amino groups present on the surface of each purified Halobacterium sp. NRC-1 GV. The resulting fluorescent NRC-1 Ce6-GVs have dimensions comparable to that of native GVs and were efficiently taken up by human breast [MCF-7] and human hypopharyngeal [FaDu-GFP] cancer cells as monitored by confocal microscopy and flow cytometry. When exposed to light, internalized Ce6-GVs were 200-fold more effective on a molar basis than free Ce6 at killing cells. These results demonstrate the potential of Ce6-GVs as novel and promising nanomaterials for image-guided...
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Authors: 2
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1.975 Mikeys
#9. IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival
Afshan Nawas, Mohammed Kanchwala, Shayna Thomas-Jardin, Haley Dahl, Kelly Daescu, Monica Bautista, Vanessa Anunobi, Ally Wong, Rachel Meade, Ragini Mistry, Nisha Ghatwai, Felix Bayerl, Chao Xing, Nikki Delk
Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity. Methods: We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and...
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Authors: 14
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