Patterns of Transcription Factor Programs and Immune Pathway Activation Define Four Major Subtypes of SCLC with Distinct Therapeutic Vulnerabilities

Using tumor expression data and non-negative matrix factorization, scientists identified four small cell lung cancer (SCLC) subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed gene signature.
[Cancer Cell]
Gay, C. M., Stewart, C. A., Park, E. M., Diao, L., Groves, S. M., Heeke, S., Nabet, B. Y., Fujimoto, J., Solis, L. M., Lu, W., Xi, Y., Cardnell, R. J., Wang, Q., Fabbri, G., Cargill, K. R., Vokes, N. I., Ramkumar, K., Zhang, B., Corte, C. M. D., … Byers, L. A. (2021). Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2020.12.014 Cite
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Enhancer of Zeste Homolog 2-Mediated Paired Box 8 Methylation Promotes Gastrointestinal Stromal Tumor Progression through Wnt4 Downregulation

The authors explored whether enhancer of zeste homolog 2-mediated paired box 8 methylation affects gastrointestinal stromal tumor (GIST) development through regulation of Wnt4. A total of 50 cases of GIST tissues were collected and the human GIST cell lines were cultured.
[Cancer Gene Therapy]
Miao, Z., Wu, F., Wei, H., Luo, Z., Wu, K., & Zhang, J. (2021). Enhancer of zeste homolog 2-mediated paired box 8 methylation promotes gastrointestinal stromal tumor progression through Wnt4 downregulation. Cancer Gene Therapy, 1–13. https://doi.org/10.1038/s41417-020-00266-5 Cite
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Inhibition of Histone Methyltransferase G9a Attenuates Liver Cancer Initiation by Sensitizing DNA-Damaged Hepatocytes to p53-Induced Apoptosis

Using liver-specific G9a-deficient mice, scientists revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine.
[Cell Death & Disease]
Nakatsuka, T., Tateishi, K., Kato, H., Fujiwara, H., Yamamoto, K., Kudo, Y., Nakagawa, H., Tanaka, Y., Ijichi, H., Ikenoue, T., Ishizawa, T., Hasegawa, K., Tachibana, M., Shinkai, Y., & Koike, K. (2021). Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis. Cell Death & Disease, 12(1), 1–13. https://doi.org/10.1038/s41419-020-03381-1 Cite
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Prediction and Verification of Target of Helenalin against Hepatic Stellate Cell Activation Based on miR-200a-Mediated PI3K/Akt and NF-κB Pathways

Hepatic stellate cell (HSC)‐T6 cells were activated by interleukin-1 beta and then treated with helenalin. HSC‐T6 cells were transfected with miR-200a mimic or inhibitor, and the effect of helenalin on the miR-200a-mediated PI3K/Akt and NF-κB signaling pathways was investigated.
[International Immunopharmacology]
Fang, B., Wen, S., Li, Y., Bai, F., Wei, Y., Xiong, Y., Huang, Q., & Lin, X. (2021). Prediction and verification of target of helenalin against hepatic stellate cell activation based on miR-200a-mediated PI3K/Akt and NF-κB pathways. International Immunopharmacology, 92, 107208. https://doi.org/10.1016/j.intimp.2020.107208 Cite
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Suppressing BCL-XL Increased the High Dose Androgens Therapeutic Effect to Better Induce the Enzalutamide-Resistant Prostate Cancer Autophagic Cell Death

Scientists found that the antiandrogen Enzalutamide-resistant prostate cancer cells can be suppressed by hyper-physiological doses of the androgen DHT.
[Cell Death & Disease]
Xiang, Z., Sun, Y., You, B., Zhang, M., Huang, C., Yu, J., You, X., Wu, D., & Chang, C. (2021). Suppressing BCL-XL increased the high dose androgens therapeutic effect to better induce the Enzalutamide-resistant prostate cancer autophagic cell death. Cell Death & Disease, 12(1), 1–14. https://doi.org/10.1038/s41419-020-03321-z Cite
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Cyclophilin A Inhibits A549 Cell Oxidative Stress and Apoptosis by Modulating the PI3K/Akt/mTOR Signaling Pathway

Researchers showed the protective effect of human recombinant CypA on hydrogen peroxide-induced oxidative damage in A549 cells, which play crucial roles in lung cancer.
[Bioscience Reports]
Ma, Z., Zhang, W., Wu, Y., Zhang, M., Wang, L., Wang, Y., Wang, Y., & Liu, W. (2021). Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway. Bioscience Reports, BSR20203219. https://doi.org/10.1042/BSR20203219 Cite
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MicroRNA-520d-3p Alleviates Hypoxia/Reoxygenation-Induced Damage in Human Cardiomyocytes by Targeting ATG-12

Researchers investigated the in vitro role of microRNA-520d-3p in human myocardial cell myocardial H/R injury.
[Journal of Thrombosis and Thrombolysis]
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Age-Related Injury Responses of Human Oligodendrocytes to Metabolic Insults: Link to BCL-2 and Autophagy Pathways

Using cells derived from surgically resected tissue, investigators demonstrated that young pediatric-aged sample oligodendrocytes (OLs) were more resistant to in-vitro metabolic injury than fetal O4+ progenitor cells, but more susceptible to cell death and apoptosis than adult-derived OLs.
[Communications Biology]
Fernandes, M. G. F., Luo, J. X. X., Cui, Q.-L., Perlman, K., Pernin, F., Yaqubi, M., Hall, J. A., Dudley, R., Srour, M., Couturier, C. P., Petrecca, K., Larochelle, C., Healy, L. M., Stratton, J. A., Kennedy, T. E., & Antel, J. P. (2021). Age-related injury responses of human oligodendrocytes to metabolic insults: link to BCL-2 and autophagy pathways. Communications Biology, 4(1), 1–10. https://doi.org/10.1038/s42003-020-01557-1 Cite
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Albanol B from Mulberries Exerts Anti-Cancer Effect through Mitochondria ROS Production in Lung Cancer Cells and Suppresses In Vivo Tumor Growth

Scientists showed that albanol B inhibited the proliferation of four human lung cancer cell lines and induced apoptosis, based on the cleavage of caspase-7 and PARP, as well as the downregulation of Bcl-2.
[International Journal of Molecular Sciences]
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The Flavonol Isoquercitrin Promotes Mitochondrial-Dependent Apoptosis in SK-Mel-2 Melanoma Cell via the PI3K/AKT/mTOR Pathway

The anti-cancer mechanism of Isoquercitrin (IQ) against human melanoma, particularly its effect on the mitochondria-mediated apoptosis, was investigated. Treatment with IQ at 25 μM concentration effectively inhibited the proliferation of SK-MEL-2 skin cancer cells while the same concentration did not exhibit cytotoxicity against human keratinocytes HaCaT.
[Nutrients]
Won, Y.-S., Kim, J.-H., Lizardo, R. C. M., Min, H.-J., Cho, H.-D., Hong, S.-M., & Seo, K.-I. (2020). The Flavonol Isoquercitrin Promotes Mitochondrial-Dependent Apoptosis in SK-Mel-2 Melanoma Cell via the PI3K/AKT/mTOR Pathway. Nutrients, 12(12), 3683. https://doi.org/10.3390/nu12123683 Cite
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BH3 Mimetics Potentiate Pro-Apoptotic Activity of Encorafenib in BRAFV600E Melanoma Cells

Researchers investigated five BRAFV600E melanoma cell lines derived from drug-naïve tumor specimens to assess cell death response to encorafenib, a recently FDA-approved BRAFV600E inhibitor.
[Cancer Letters]
Hartman, M. L., Gajos-Michniewicz, A., Talaj, J. A., Mielczarek-Lewandowska, A., & Czyz, M. (2020). BH3 mimetics potentiate pro-apoptotic activity of encorafenib in BRAFV600E melanoma cells. Cancer Letters. https://doi.org/10.1016/j.canlet.2020.11.036 Cite
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