Abstract:
BACKGROUND:Peripheral T-cell lymphomas (PTCLs) are often aggressive tumors and resistant to conventional chemotherapy. Dysregulation of extrinsic apoptosis plays an important role on tumor cell sensitivity to chemotherapeutic agents. Cellular FLICE inhibitory protein (c-FLIP) is a key regulator of extrinsic apoptotic pathway. METHODS:c-FLIP expression was assessed by real-time PCR and compared according to clinical parameters in patients with PTCLs. The relation of c-FLIP to tumor cell apoptosis mediated by histone deacetylases inhibitors (HDACIs) and the possible mechanism were examined in T-lymphoma cell lines and in a murine xenograft model. RESULTS:c-FLIP was overexpressed and associated with decreased tumor TRAIL/DR5 expression, elevated serum lactate dehydrogenase level and high-risk International Prognostic Index of the patients. In vitro, molecular silencing of c-FLIP by specific small-interfering RNA increased TRAIL/DR5 expression, enhanced T-lymphoma cell apoptosis and sensitized cells to chemotherapeutic agents. However, HDACIs valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) could downregulate c-FLIP expression and triggered extrinsic apoptosis of T-lymphoma cells, through inhibiting NF-κB signaling and interrupting P50 interaction with c-FLIP promoter. As Class I HDACIs, both VPA and SAHA inhibited HDAC1, resulting in P50 inactivation and c-FLIP downregulation. In vivo, oral VPA treatment significantly retarded tumor growth and induced in situ apoptosis, consistent with inhibition of HDAC1/P50/c-FLIP axis and increase of TRAIL/DR5 expression. CONCLUSIONS:c-FLIP overexpression in PTCLs protected tumor cells from extrinsic apoptosis and contributed to tumor progression. Although linking to chemoresistance, c-FLIP indicated tumor cell sensitivity to HDACIs, providing a potential biomarker of targeting apoptosis in treating PTCLs.
journal_name
J Hematol Oncoljournal_title
Journal of hematology & oncologyauthors
Zheng Z,Cheng S,Wu W,Wang L,Zhao Y,Shen Y,Janin A,Zhao WLdoi
10.1186/s13045-014-0088-ysubject
Has Abstractpub_date
2014-12-05 00:00:00pages
88issn
1756-8722pii
s13045-014-0088-yjournal_volume
7pub_type
杂志文章abstract:BACKGROUND:Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. CASE ...
journal_title:Journal of hematology & oncology
pub_type: 临床试验,杂志文章
doi:10.1186/s13045-016-0357-z
更新日期:2016-11-25 00:00:00
abstract:BACKGROUND:HTLV-1 is a retrovirus that infects over 20 million people worldwide and is responsible for the hematopoietic malignancy adult T cell leukemia (ATL). We previously demonstrated that Notch is constitutively activated in ATL cells. Activating genetic mutations were found in Notch; however, Notch signaling was ...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-018-0665-6
更新日期:2018-09-19 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1756-8722-5-67
更新日期:2012-10-22 00:00:00
abstract::According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloprolife...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/s13045-014-0093-1
更新日期:2014-12-12 00:00:00
abstract::To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic re...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/s13045-020-01002-0
更新日期:2020-12-02 00:00:00
abstract::The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initiall...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/s13045-017-0403-5
更新日期:2017-01-25 00:00:00
abstract::The current study evaluated the differential expression detected in the proteomic profiles of low risk- and high risk- ALL pediatric patients to characterize candidate biomarkers related to diagnosis, prognosis and patient targeted therapy. Bone marrow and peripheral blood plasma and cell lysates samples were obtained...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/1756-8722-6-52
更新日期:2013-07-12 00:00:00
abstract::MicroRNAs are small RNA molecules that regulate gene expression and play critical roles in B cell development and malignancy. miRNA expression is important globally, as B cell specific knockouts of Dicer show profound defects in B cell development; and is also critical at the level of specific miRNAs. In this review, ...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/1756-8722-5-7
更新日期:2012-03-08 00:00:00
abstract:BACKGROUND:Mounting evidence has demonstrated the vital importance of tumor-associated macrophages (TAMs) and exosomes in the formation of the premetastatic niche. However, the molecular mechanisms by which tumor-derived exosomal miRNAs interact with TAMs underlying premetastatic niche formation and colorectal cancer l...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-020-00991-2
更新日期:2020-11-19 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/1756-8722-6-13
更新日期:2013-02-05 00:00:00
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pub_type: 杂志文章,评审
doi:10.1186/s13045-020-00901-6
更新日期:2020-05-26 00:00:00
abstract:BACKGROUND:Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient o...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-018-0596-2
更新日期:2018-04-07 00:00:00
abstract:BACKGROUND:MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated. METHODS:We found direct downstream target of miR-612, hadha by RNA immunop...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-019-0841-3
更新日期:2020-02-07 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 信件
doi:10.1186/s13045-014-0102-4
更新日期:2015-02-06 00:00:00
abstract:BACKGROUND:Chemoresistance remains a major treatment obstacle in multiple myeloma (MM). Novel new therapies are thus in need. Transient Receptor Potential Vanilloid type 1 (TRPV1) is a calcium-permeable ion channel that has been demonstrated to be expressed in solid tumors. Calcium channels have been shown to be involv...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-020-00993-0
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of ...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/1756-8722-1-2
更新日期:2008-05-28 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous disease caused by several gene mutations and cytogenetic abnormalities affecting differentiation and proliferation of myeloid lineage cells. FLT3 is a receptor tyrosine kinase commonly overexpressed or mutated, and its mutations are associated with poor prognosis in AML....
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/s13045-020-00992-1
更新日期:2020-11-19 00:00:00
abstract:BACKGROUND:Minimal residual disease detection in the bone marrow is usually performed in patients with acute myeloid leukemia undergoing one course of induction chemotherapy. To optimize the chemotherapy strategies, more practical and sensitive markers are needed to monitor the early treatment response during induction...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-015-0145-1
更新日期:2015-05-10 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 杂志文章,多中心研究
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journal_title:Journal of hematology & oncology
pub_type: 信件
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更新日期:2018-08-16 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-017-0532-x
更新日期:2017-10-06 00:00:00
abstract::P-type ATPase inhibitors are among the most successful and widely prescribed therapeutics in modern pharmacology. Clinical transition has been safely achieved for H+/K+ ATPase inhibitors such as omeprazole and Na+/K+-ATPase inhibitors like digoxin. However, this is more challenging for Ca2+-ATPase modulators due to th...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/s13045-020-01015-9
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS:Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, ...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,多中心研究
doi:10.1186/1756-8722-5-49
更新日期:2012-08-13 00:00:00
abstract::Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolit...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
doi:10.1186/1756-8722-6-79
更新日期:2013-10-22 00:00:00
abstract::To validate its efficacy in the context of the human immune system, a novel therapeutic vaccine of hGM-CSF/hTNFα surface-modified PC-3 cells against human prostate cancer was evaluated in the human peripheral blood lymphocytes-severe combined immunodeficiency (huPBL-SCID) chimeric mouse model. The hGM-CSF or/and hTNFα...
journal_title:Journal of hematology & oncology
pub_type: 信件
doi:10.1186/s13045-015-0175-8
更新日期:2015-06-25 00:00:00
abstract:BACKGROUND:Long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to non-small-cell lung cancer (NSCLC) metastasis remain poorly understood. Our previous and other studies have revealed the involvement of upregulated LINC01234 in regulating gastric cancer and c...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-019-0842-2
更新日期:2020-01-20 00:00:00
abstract::Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CAR-T therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experie...
journal_title:Journal of hematology & oncology
pub_type: 杂志文章,评审
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更新日期:2020-07-02 00:00:00
abstract:BACKGROUND:Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from hapl...
journal_title:Journal of hematology & oncology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2020-05-04 00:00:00
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journal_title:Journal of hematology & oncology
pub_type: 杂志文章
doi:10.1186/s13045-016-0371-1
更新日期:2017-01-06 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2020-03-30 00:00:00