Top 7 Biorxiv Papers Today in Cancer Biology


2.01 Mikeys
#1. Multicellular tumor spheroids- an effective in vitro model for understanding drug resistance in head and neck cancer
Mohammad Azharuddin, Karin Roberg, Mayur Vilas Jain, Padraig D' arcy, Jorma Hinkula, Ashis Kumar Dhara, Nigel K H Slater, Hirak K Patra
One of the hallmarks of cancer is the ability of cancer cells to develop resistance to therapy. Therefore, developing effective in vitro strategies for the identification of drug resistant cancers remains with paramount importance for treatment success. A way cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using multicellular tumor spheroids (MCSs) for multidrug resistance (MDR) profile; however, a unified system that uses MCSs to differentiate between MDR and non-MDR cells does not exist. Using MCSs obtained from patient-derived cell lines of head and neck squamous cell cancer that often develops resistance to therapy, we have exploited the drug efflux pump overexpression and function of MDR cancer cells for the identification, characterization, and profiling of multidrug resistance. To achieve this aim, we employed an integrated approach combining clinical drug response and cell cytotoxicity...
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biorxivpreprint: Multicellular tumor spheroids- an effective in vitro model for understanding drug resistance in head and neck cancer https://t.co/xK6Bk7JII6 #bioRxiv
biorxiv_cancer: Multicellular tumor spheroids- an effective in vitro model for understanding drug resistance in head and neck cancer https://t.co/vRB6ab2GnZ #biorxiv_cancer
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Sample Sizes : None.
Authors: 8
Total Words: 9629
Unqiue Words: 2543

1.998 Mikeys
#2. Characters of neoantigens in cancer immunotherapy
Peng Bai, Yongzheng Li, Qiuping Zhou, Jiaqi Xia, Min Wu, Hexiang Deng, John W Kappler, Philippa Marrack, Yu Zhou, Lei Yin
Cancer mutations lead to the production of mutated proteins from which can be processed and presented to CD8+ T cells as neoantigens. Despite the promise of immunotherapy targeting neoantigens, which mutant peptides are likely to induce immune responses remain elusive. Here, we determined two sets of MHCI bound neoantigen structures and performed bioinformatics investigation based on neoantigen data. Structural and bioinformatic analyses reveal that some types of mutations in immunogenic neoantigens are preferentially selected. We also developed a strategy to expand the usage of a known neoantigen by scanning potential MHC alleles. Overall, our results will extend the ability to discover neoantigens that may be useful for cancer immunotherapy.
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lum_lab: RT @biorxivpreprint: Characters of neoantigens in cancer immunotherapy https://t.co/Z0Cx9SL9av #bioRxiv
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Authors: 10
Total Words: 0
Unqiue Words: 0

1.995 Mikeys
#3. Self-assembled primary tumor clusters for precision cancer therapy
Shenyi Yin, Ruibin Xi, Aiwen Wu, Jia-Fu Ji, Jianzhong Xi
Several patient-derived tumor models emerged recently as robust preclinical models. However, their potential to guide clinical therapy remained unclear. We report a novel model for personalized drug testing called patient-derived tumor-like cell clusters (PTC) that enabled us to accomplish personalized drug tests within 10-20 days. Mechanistically, PTCs result from the migration and aggregation of CD8+/CD44+ primary epithelial cells in a mixture of fibroblasts and macrophages, and form spheroid cultures. Phenotypic and genotypic profiling of PTCs showed a high degree of similarity with the original patient tumors, indicating that PTC structurally and functionally recapitulated original tumors. Over 200 PTC models have been established from at least six cancer types and diverse sampling approaches. Given its seamless integration with current clinical sampling approaches, the PTC platform will revolutionize chemotherapy programs for cancer patients.
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Authors: 5
Total Words: 5064
Unqiue Words: 1692

1.995 Mikeys
#4. Mechanistic Elucidation of the Antitumor Properties of a Novel Death Receptor 5 Activator
Mengxiong Wang, Mary Law, Bradley Davis, Elham Yaaghubi, Amanda Franceschini Ghilardi, Renan Ferreira, Chi-Wu Chiang, Olga Guryanova, Daniel Kopinke, Coy Heldermon, Ronald Castellano, Brian Law
Disulfide bond Disrupting Agents (DDAs) are a new chemical class of agents recently shown to have activity against breast tumors in animal models. However, it is unknown how DDAs trigger cancer cell death without affecting nontransformed cells. As demonstrated here, DDAs are the first compounds identified that upregulate the TRAIL receptor DR5 through both transcriptional and posttranscriptional mechanisms. At the protein level, DDAs alter DR5 disulfide bonding to increase steady-state DR5 levels and oligomerization, leading to downstream Caspase 8 and 3 activation. DDAs and TRAIL synergize to kill cancer cells and are cytotoxic to HER2+ cancer cells with acquired resistance to the EGFR/HER2 tyrosine kinase inhibitor. Investigation of the mechanisms responsible for DDA selectivity for cancer cells reveals that DDA-induced upregulation of DR5 is enhanced in the context of EGFR overexpression, and DDA-induced cytotoxicity is strongly amplified by MYC overexpression. Together, the results demonstrate selective DDA lethality against...
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Sample Sizes : [359, 220, 225, 372]
Authors: 12
Total Words: 11921
Unqiue Words: 3522

1.995 Mikeys
#5. Pivotal involvement of the CX3CL1-CX3CR1 axis for the recruitment of M2-TAMs in skin carcinogenesis
Yuko Ishida, Yumi Kuninaka, Yuki Yamamoto, Mizuho Nosaka, Akihiko Kimura, Fukumi Furukawa, Naofumi Mukaida, Toshikazu Kondo
We previously revealed the crucial roles of CX3CL1-CX3CR1 axis in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1+ macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1+ tumor-associated macrophages (TAMs) with M2 phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz-(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). In this mouse skin carcinogenesis process, CX3CR1+ TAMs exhibited M2 phenotypes with the expression of Wnt3a and angiogenic molecules including vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. Compared to wild-type mice, CX3CR1-deficient mice showed fewer numbers of skin tumors with a lower incidence. Concomitantly, M2-macrophage numbers and neovascularization reduced with...
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Authors: 8
Total Words: 0
Unqiue Words: 0

1.995 Mikeys
#6. Tyrosyl-DNA phosphodiesterase 1 and topoisomerase I activities as predictive indicators for Glioblastoma susceptibility to genotoxic agents
Wenjie Wang, Monica Rodriguez-Silva, Arlet M. Acanda de la Rocha, Aizik L. Wolf, Yanhao Lai, Yuan Liu, William C. Reinhold, Yves Pommier, Jeremy W. Chambers, Yuk-Ching Tse-Dinh
Background: Glioblastoma (GBM) patients have an estimated survival of ~15 months with treatment, and the standard of care only modestly enhances patient survival. Identifying biomarkers representing vulnerabilities may allow for selection of efficacious chemotherapy options to address personalized variations in GBM tumors. Irinotecan, currently in clinical trials for GBM, targets topoisomerase I (TOP1) by forming a ternary DNA-TOP1 cleavage complex (TOP1cc) inducing apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that may reduce the effectiveness of irinotecan. Methods: We treated GBM cell lines with increasing concentrations of irinotecan and compared the IC50 values. TOP1 and TDP1 protein levels from each cell type as well as GBM patient tumors were determined by Western blot analysis, while activity levels were ascertained by specific enzymatic assays. Cellular TDP1 was elevated by ectopic expression of wild-type or mutant TDP1. Results: After comparing cellular susceptibility to TDP1 and TOP1...
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Authors: 10
Total Words: 9904
Unqiue Words: 2931

1.99 Mikeys
#7. Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
Hamad Alshetaiwi, Nicholas Pervolarakis, Laura Lynn McIntyre, Dennis Ma, Quy Nguyen, Jan Akara Rath, Kevin Nee, Grace Hernandez, Katrina Evans, Leona Torosian, Anushka Silva, Craig Walsh, Kai Kessenbrock
Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we used single-cell RNAseq to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice to wildtype controls. Our computational analysis of 14,646 single-cell transcriptomes reveals that MDSCs emerge through a previously unrealized aberrant neutrophil maturation trajectory in the spleen giving rise to a unique chemokine-responsive, immunosuppressive cell state that strongly differs from normal myeloid cells. We establish the first MDSC-specific gene signature and identify novel surface markers for improved detection and enrichment of MDSCs in murine and human samples. Our study provides the first single-cell transcriptional map defining the development of MDSCs, which will ultimately enable us to...
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Authors: 13
Total Words: 18707
Unqiue Words: 3920

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