Abstract:
:Classical Hodgkin lymphoma (cHL) tumor cells are surrounded by a protective tumor microenvironment (TME). Trabectedin, an anticancer drug targeting both tumor cells and TME, demonstrated a potent antitumor activity against Hodgkin Reed Sternberg (HRS) cells. It was cytotoxic against cHL cell lines, including the doxorubicin-resistant clones, with subnanomolar IC50 values, and inhibited clonogenic growth and heterospheroid cell viability. It induced necroptosis, caused DNA damage, G2/M cell cycle arrest, and increased reactive oxygen species production. It reduced HRS cell secretion of CCL5, M-CSF, IL-6, IL-13 and TARC, and inhibited migration. Conditioned medium from trabectedin-treated HRS cells was less chemoattractive toward monocytes, mesenchymal stromal cells and lymphocytes, and less effective in educating monocytes to become immunosuppressive macrophages. These monocytes expressed lower levels of indoleamine 2,3-dioxygenase-1, CD206 and PD-L1, secreted lower amounts of IL-10, TARC, and TGF-β, and were less able to inhibit the growth of activated lymphocytes. In vivo, trabectedin inhibited by >75% the growth of cHL murine xenografts with minimal weight loss; tumors of trabectedin-treated mice had fewer TAMs and less angiogenesis. Altogether, this study offers a preclinical rationale for trabectedin use as a new drug candidate in relapsed/refractory cHL patients.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Casagrande N,Borghese C,Favero A,Vicenzetto C,Aldinucci Ddoi
10.1016/j.canlet.2020.12.015subject
Has Abstractpub_date
2021-03-01 00:00:00pages
182-193eissn
0304-3835issn
1872-7980pii
S0304-3835(20)30665-0journal_volume
500pub_type
杂志文章相关文献
CANCER LETTERS文献大全abstract::The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2016.10.040
更新日期:2017-02-01 00:00:00
abstract::The effect of vitamin A (retinyl acetate) on lung tumor development in strain A mice exposed to radiation was assessed. Four groups of 75 mice were utilized. Two groups were fed a low vitamin A diet (less than 100 IU/100 g diet) and the other 2 were fed a high vitamin A diet (800 IU/100 g diet). After 2 weeks one grou...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(84)90051-x
更新日期:1984-02-01 00:00:00
abstract::Potassium bromate (KBrO(3)) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO(3) in F344 rats. Detection of cytoplasmic periodic ac...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(02)00407-x
更新日期:2002-12-10 00:00:00
abstract::V600E being the most common mutation in BRAF, leads to constitutive activation of the MAPK signaling pathway. The majority of V600E BRAF positive melanoma patients treated with the BRAF inhibitor vemurafenib showed initial good clinical responses but relapsed due to acquired resistance to the drug. The aim of the pres...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2015.02.041
更新日期:2015-05-28 00:00:00
abstract::BRCA1 regulates gene transcription as part of its tumor suppressor function. Prior studies on BRCA1 transactivation did not account for the impact of its binding partner, BARD1. Here we tested the effect of BARD1 on BRCA1 transactivation of the p21 and Gadd45 promoters. We show that BARD1 promoted nuclear accumulation...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2008.01.001
更新日期:2008-05-18 00:00:00
abstract::Dibenzoylmethane (DBM), a minor beta-diketone constituent of licorice and sunscreens, has been shown to exhibit anti-neoplastic effects in chemically induced skin and mammary cancers in several animal models. To date, no mechanism for the growth inhibitory effects of DBM on prostate cancer cells has been proposed. In ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(01)00844-8
更新日期:2002-04-25 00:00:00
abstract::Cancer stem-like cells (CSLCs) are potential targets for treatment of glioblastoma multiforme (GBM) due to their role in tumorigenesis and recurrence. In this study, we investigated the inhibitory effect of arsenic trioxide (As(2)O(3)) on CSLCs of GBM in human glioma cell lines (U87MG, U251MG and U373MG) in vivo and i...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2009.11.005
更新日期:2010-06-01 00:00:00
abstract::Methylation of liver and nasal mucosal DNA at the O6 position of guanine (O6-MeG) was measured in intact and castrated male rats after a dose of N-nitrosobis(2-oxopropyl)amine (BOP) (20 mg/kg; i.p.). There were no differences in O6-MeG persistence in liver DNA from either group. In the nasal mucosa more O6-MeG was det...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(90)90008-l
更新日期:1990-08-01 00:00:00
abstract::Nitric oxide synthase (NOS), an important bioregulator of a variety of biological processes, is overexpressed in colonic tumors of humans and rodents. In this study, effects of L-N(G)-nitroarginine methyl ester (L-NAME), a NOS inhibitor, on development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in F344...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(99)00310-9
更新日期:2000-01-01 00:00:00
abstract::Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and me...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2017.02.012
更新日期:2017-05-01 00:00:00
abstract::Starting with an extract derived from the bark of Mundulea sericea Willd. (Leguminosae) that was active in the process of inhibiting 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase activity (ODC) in cultured mouse epidermal ME 308 cells, the isoflavonoid munetone was isolated and identified ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(98)00309-7
更新日期:1999-02-08 00:00:00
abstract::A cell line partially resistant to dimethylsulfoxide (DMSO) was derived from the HL-60 cell line. Cycloleucine, theophylline, sodium butyrate and elevated levels of DMSO were found to induce myeloid differentiation in this cell line while TPA induced monocytic differentiation. The levels of myc RNA and the genomic str...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(84)90043-0
更新日期:1984-02-01 00:00:00
abstract::Cancer cachexia patients experience significant muscle wasting, which impairs the quality of life and treatment efficacy for patients. Skeletal muscle protein turnover is imparted by increased expression of ubiquitin-proteasome pathway components. Mitogen-activated protein kinases p38 and ERK have been shown to augmen...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.07.025
更新日期:2020-10-28 00:00:00
abstract::The rate and extent of metastasis by prostate adenocarcinoma-III cells was enhanced in Lobund-Wistar rats by administration of immune-suppressive cyclosporine A. PA-III cells spread from the subcutaneous PA-III-derived tumor, through ipsilateral lymph nodes, to the lungs in which they developed secondary tumors. Swoll...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(96)04538-7
更新日期:1997-01-01 00:00:00
abstract::Treatment of human epidermoid carcinoma A431 cells with transplatin (trans-DDP) and beta-hydroxyisovalerylshikon (beta-HIVS) together had a strong inhibitory effect on A431 cells. By contrast, trans-DDP and beta-HIVS by themselves, at the same respective concentrations, had practically no effect. The tyrosine kinase a...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(02)00457-3
更新日期:2002-12-15 00:00:00
abstract::Amplification and overexpression of PPM1D (protein phosphatase magnesium-dependent 1 delta) has been observed in various cancer cell lines and primary tumors and has also been associated with cancers of poor prognosis. In addition to the negative feedback regulation of p38-p53 signaling, PPM1D inhibits other tumor sup...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2007.09.019
更新日期:2008-01-18 00:00:00
abstract::As a third-generation platinum drug, oxaliplatin has been widely applied in colorectal cancer (CRC); however, acquired resistance to oxaliplatin has become a major obstacle. In the present study, we found that the nuclear transcription factor Y subunit beta (NFYB) and E2F transcription factor 1 (E2F1) expression level...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2017.11.040
更新日期:2018-02-28 00:00:00
abstract::The notions of inter- and intra-tumour heterogeneity (ITH) have been recognised for many years but recent advances in sequencing technology are allowing the true extent of both forms of heterogeneity to be revealed in detail for the first time. In this review we examine the current evidence for ITH, the possibility of...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2012.10.031
更新日期:2013-11-01 00:00:00
abstract::Gastrin-releasing peptide (GRP) activates phosphatidylinositol 3-kinase (PI3-K)/Akt, an important cell survival signaling pathway, to stimulate growth of various cell types. Transforming growth factor (TGF) superfamily ligands activate intracellular Smad signaling to regulate cell growth, differentiation and apoptosis...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2005.11.007
更新日期:2006-10-28 00:00:00
abstract::The overexpression of the MDM2 oncoprotein frequently occurs in hepatocellular carcinoma (HCC). Small molecules that inhibit MDM2-p53 binding show efficacy against p53 wild-type HCC, but most patients have p53-mutant tumors and intrinsic resistance to such MDM2 inhibitors. We have recently discovered that the NFAT1 tr...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2019.114429
更新日期:2019-09-10 00:00:00
abstract::Sulfasalazine (SSZ) is an anti-inflammatory drug that has been demonstrated to induce apoptosis and tumor regression through inhibition of plasma membrane cystine transporter xc(-). Cysteine is a rate-limiting precursor for intracellular glutathione (GSH) synthesis, which is vital for compound detoxification and maint...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2015.07.031
更新日期:2015-11-01 00:00:00
abstract::Irradiation with 90Sr-90Y beta rays induced ornithine decarboxylase (ODC) activity in mouse skin. Maximum activity appeared after about 17 days, at the time of appearance of skin injuries. These findings suggest the presence of tumor-promoting activity of beta rays. ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(82)90070-2
更新日期:1982-01-01 00:00:00
abstract::Epithelial-to-mesenchymal transition (EMT) is the fundamental process by which an epithelial cell loses its epithelial characteristics including cell polarity and acquires mesenchymal and stemness-related features. Therefore, we investigated whether malignant pleural mesothelioma (MPMs) histologies were associated wit...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2011.01.009
更新日期:2011-03-28 00:00:00
abstract::Cellular phosphoprotein profiles from normal mouse embryonic fibroblast AKR-2B cells were compared to those of their permanently, chemically transformed malignant counterparts AKR-MCA cells, and AKR-2B cells reversibly transformed by transforming growth factor (AKR-TGF). Similar 32P-phosphorylation profiles were obser...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(85)90153-3
更新日期:1985-11-01 00:00:00
abstract::Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-der...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2014.09.016
更新日期:2014-12-01 00:00:00
abstract::In a search for anti-tumor-promoting agents, we carried out a primary screening of ten 4-phenylcoumarins isolated from Calophyllum inophyllum L. (Guttiferae), by examining their possible inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(01)00521-3
更新日期:2001-08-10 00:00:00
abstract::DDX1, a gene mapping to the 2p24 region, has been observed to be co-amplified with MYCN in neuroblastoma. Co-amplification of the DDX1 gene is a consequence of the short physical distance between the two genes. Recently, it has been found that neuroblastoma cells can show a low increase in MYCN gene copy number, defin...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2007.05.010
更新日期:2007-10-18 00:00:00
abstract::New, potentially tumor-specific antigens have been described in Bcr/Abl positive leukemias. Besides the main BCR/ABL hybrid fusion transcripts, a small number of transcripts derived from alternative splicing between BCR exons 1, 13, and 14 with ABL exons 4 and 5 have been identified. These variants are expressed in ch...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2008.10.032
更新日期:2009-04-08 00:00:00
abstract::The relationship between the degree of lymphocytic infiltration into the tumor and the prognosis has not been completely evaluated between Epstein-Barr virus (EBV)-positive and -negative gastric carcinoma (GC). Although the average numbers and the grades of the infiltrating CD8+T cells, natural killer cells, dendritic...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(03)00410-5
更新日期:2003-10-08 00:00:00
abstract::Treatment of glioblastoma remains a challenge in neuro-oncology. We investigated if treatment with neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL) alone or in combination with proteasome inhibitors is a feasible therapeutic approach for experimental glioma. Glioma cells showed resistance to ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2011.06.029
更新日期:2011-11-28 00:00:00