scholarly journals Senescence marker protein 30 inhibits tumor growth by reducing HDAC4 expression in non-small cell lung cancer

2021 ◽  
Vol 10 (12) ◽  
pp. 4558-4573
Author(s):  
Changjian Shao ◽  
Kai Guo ◽  
Liqun Xu ◽  
Yimeng Zhang ◽  
Hongtao Duan ◽  
...  
2021 ◽  
Author(s):  
Benjamin J Solomon ◽  
Todd M Bauer ◽  
Filippo de Marinis ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  

This is a summary of a research study (known as a clinical trial) called CROWN. The study tested two medicines called lorlatinib and crizotinib in participants with untreated non-small cell lung cancer that had spread to other parts of their body. All those who took part had changes in a gene called ALK, which is involved in cell growth. In total, 296 participants from 23 countries took part. Half the participants took lorlatinib and half took crizotinib. After participants started taking lorlatinib or crizotinib, they were checked regularly to see if their tumors had grown or spread to other parts of their body (known as tumor progression) and to monitor any side effects. After 1 year of treatment, the participants who took lorlatinib were twice as likely to be alive with no tumor growth as the participants who took crizotinib. More participants who took lorlatinib had cancer that shrank (76%) compared with the participants who took crizotinib (58%). This was also true of the participants whose cancer had spread to their brain. The most common side effects in participants who took lorlatinib were increases in the amount of cholesterol and triglycerides (a type of fat) in their blood, swelling, weight gain, nerve damage, unclear thoughts, and diarrhea. Among the participants who took crizotinib, the most common side effects were diarrhea, feeling like you want to throw up, sight problems, swelling, vomiting, changes in liver function, and feeling tired. Overall, the CROWN study showed that fewer participants with advanced ALK+ non-small cell lung cancer died or had tumor growth with lorlatinib compared with crizotinib treatment. ClinicalTrials.gov NCT number: NCT03052608 .


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Xue Yang ◽  
Gaopei Meng

Abstract In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.


2019 ◽  
Vol 51 (8) ◽  
pp. 1-13 ◽  
Author(s):  
Dong Ha Kim ◽  
HyeongRyul Kim ◽  
Yun Jung Choi ◽  
Seon Ye Kim ◽  
Jung-Eun Lee ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 705 ◽  
Author(s):  
Cédric Zeltz ◽  
Elena Pasko ◽  
Thomas R. Cox ◽  
Roya Navab ◽  
Ming-Sound Tsao

Integrin α11, a stromal collagen receptor, promotes tumor growth and metastasis of non-small cell lung cancer (NSCLC) and is associated with the regulation of collagen stiffness in the tumor stroma. We have previously reported that lysyl oxidase like-1 (LOXL1), a matrix cross-linking enzyme, is down-regulated in integrin α11-deficient mice. In the present study, we investigated the relationship between LOXL1 and integrin α11, and the role of LOXL1 in NSCLC tumorigenicity. Our results show that the expression of LOXL1 and integrin α11 was correlated in three lung adenocarcinoma patient datasets and that integrin α11 indeed regulated LOXL1 expression in stromal cells. Using cancer-associated fibroblast (CAF) with either a knockdown or overexpression of LOXL1, we demonstrated a role for LOXL1 in collagen matrix remodeling and collagen fiber alignment in vitro and in vivo in a NSCLC xenograft model. As a consequence of collagen reorganization in NSCLC tumor stroma, we showed that LOXL1 supported tumor growth and progression. Our findings demonstrate that stromal LOXL1, under regulation of integrin α11, is a determinant factor of NSCLC tumorigenesis and may be an interesting target in this disease.


PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0214610 ◽  
Author(s):  
Linda O’Flaherty ◽  
Steven D. Shnyder ◽  
Patricia A. Cooper ◽  
Stephen J. Cross ◽  
James G. Wakefield ◽  
...  

2011 ◽  
Vol 6 (12) ◽  
pp. 1984-1992 ◽  
Author(s):  
Lars Henning Schmidt ◽  
Tilmann Spieker ◽  
Steffen Koschmieder ◽  
Julia Humberg ◽  
Dominik Jungen ◽  
...  

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