Abstract:
BACKGROUND:Parallel to complex alteration in molecular and cellular events, enrichment of cancer stem cells (CSC) contributes significantly in deliberation and maintenance of cisplatin resistance. Cisplatin mediated CSC enrichment is well established in various cancers, yet the underlying mechanism is largely unknown. Cisplatin also promotes transcriptional upregulation of PIK3CA, hence activating PI3K/AKT signaling in resistant cells. However, such cisplatin-induced transcriptional regulators of PIK3CA and their impact on cancer stem cell population in resistant cells are largely unknown. METHODS:DNA-binding protein pulldown using PIK3CA promoter as bait followed by nLCMS was used to identify, cisplatin-induced potential transcriptional regulators of PIK3CA promoter. PIK3CA promoter activity was estimated by luciferase based reporter assay. ChIP was used to assess interaction of NF-κB with PIK3CA promoter. CSC-enriched side-population was sorted using DCV-dye exclusion methods. All the gene expression levels were assessed using qPCR. RESULTS:Using a transcription factor pull-down assay with PIK3CA promoter, we identified NF-κB as a prime regulator, which escalates both TNFα and PIK3CA expression only in CSC enriched side-population (SP) but not in non side-population (NSP) in platinum resistant ovarian cancer cells upon cisplatin treatment. This SP-specific NF-κB-TNFα-PIK3CA bi-modal loop, on one hand, maintains persistent activation of NF-κB through TNFα- NF-κB autocrine loop, while NF-κB-PIK3CA loop nurture CSC population under cisplatin treatment. Activation of PI3K/AKT signalling drives SP's into an undifferentiated, anti-apoptotic stage through upregulating P21, P27,cFLIP expression. Contrarily, lack of active NF-κB-TNFα-PIK3CA loop makes NSPs vulnerable towards cisplatin and undergoes apoptosis. Altogether, cisplatin enriches cancer stem cells properties in SP fraction, which is evident from increased levels of pluripotency gene OCT4/SOX2/NANOG expression. Disruption of PIK3CA-NF-κB loop by Wortamannin reduces SP fraction by 1.4-1.6 fold in control and treated cells. CONCLUSION:Together, our study signifies an active role of NF-κB-TNFα-PIK3CA bi-modal loop in cisplatin-mediated promotion and maintenance of CSC-like population in platinum-resistant cells.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Thakur B,Ray Pdoi
10.1186/s13046-017-0636-8subject
Has Abstractpub_date
2017-11-23 00:00:00pages
164issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-017-0636-8journal_volume
36pub_type
杂志文章abstract::The aim of this study was to assess the nuclear/cytoplasmic (N/C) ratio using computerized image analysis of cervical smears with intraepithelial neoplasia (CIN) grade I to III associated or not with cellular changes of human papillomavirus (HPV) in an attempt to determine if this method is more sensitive for the esti...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::Seventeen adult urologic sarcomas treated at the Oncology Hospital of Ankara in the last ten-year period are described. There were six cases of paratesticular rhabdomyosarcoma (RMS), four cases of liposarcoma (LS), three cases of leiomyosarcoma (LMS); two cases of Kaposi sarcoma limited to glans penis, and only one pr...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) is the major histological type of liver cancer with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNA) has been proved to be associated with various cancer types, while its regulation in HCC is largely unknown. METHODS:To figure out the specific role of lncRN...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1128-9
更新日期:2019-04-10 00:00:00
abstract::We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Axillary lymphadenectomy is a very important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. On the other hand, using early diagnosis we can see a high number of cases where the lymph nodes are negatives. With the intention of avoiding unnecessary axilla...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::Doxorubicin (DOX) has a wide spectrum of antitumor activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from the generation of oxygen-free radicals. The objective of the present study was to investigate the influence of the antioxidant, thymoquinone (TQ) on...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Circulating tumor cells (CTCs) hold great potential in both clinical application and basic research for the managements of cancer. However, it remains to be an enormous challenge to obtain efficient detection of pancreatic CTCs. New detection platforms for the detection of pancreatic CTCs are urgently requir...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0340-0
更新日期:2016-04-12 00:00:00
abstract::Radiofrequency Thermal Ablation (RFA) of liver tumors is done by percutaneous, laparoscopic and open surgical approach. Selection criteria for percutaneous or open surgical ablation of 65 hepatic lesions are here evaluated in 45 patients treated in a two-years period. Twenty-five patients were males and 20 females, ag...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Peroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI) in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-93
更新日期:2009-06-30 00:00:00
abstract::Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis. In the present study, we investigated the efficacy of Emblica officinalis (E. officinalis) polyphenol fraction (EOP) on the induction of apoptosis in mouse and human carcinoma cell lineses an...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract::The aim of the study was to investigate the blood supply of the normal nipple areola complex (NAC) and the spared areola complex after a nipple-sparing mastectomy using the analysis of the fluorescence from the indocianine green dye (ICG) injection. Between December 2002 and July 2003 we performed the ICG analysis in ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients. METHODS:Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were randomly assigned to epirubicin/vinorelbine (a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1756-9966-30-39
更新日期:2011-04-12 00:00:00
abstract:PURPOSE:To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. METHODS:A meta-analysis of randomized controlled trials (RCT)...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,meta分析
doi:10.1186/1756-9966-28-1
更新日期:2009-01-06 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells wh...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Elucidating mechanisms in oncogenes and epigenetic modifiers are needed to gain insights into the etiology and treatment of cancer, regulation of oncogene by chromatin modifiers at post-transcriptional level is critical and remains unclear. We have investigated the role of GINS4 in NSCLC. METHODS:The expres...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1276-y
更新日期:2019-06-28 00:00:00
abstract:BACKGROUND:The histone methyltransferase G9a has recently been identified as a potential target for epigenetic therapy of acute myeloid leukemia (AML). However, the effect of G9a inhibition on leukemia stem cells (LSCs), which are responsible for AML drug resistance and recurrence, is unclear. In this study, we investi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01565-3
更新日期:2020-04-15 00:00:00
abstract::The aim of this study was to assess the efficiency of the radioguided localization and excision technique using radiopharmaceuticals injected directly or close to occult breast lesions. We studied thirty-two consecutive patients with thirty-six occult breast lesions detected mammographically or ultrasonically categori...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND:Agonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0126-9
更新日期:2015-02-05 00:00:00
abstract:BACKGROUND:Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-014-0119-0
更新日期:2015-01-16 00:00:00
abstract:BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of tumors, with aggressive clinical course that renders prognostication and choice of treatment strategy difficult. Chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) is the current first-line trea...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0768-5
更新日期:2018-05-02 00:00:00
abstract:BACKGROUND:The signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosstalk between two pathways is not completely understood. METHODS:The expression of STAT1 protein was ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0773-8
更新日期:2018-05-11 00:00:00
abstract:BACKGROUND:The transcription factor HOXD9 is one of the members of the HOX family, which plays an important role in neoplastic processes. However, the role of HOXD9 in the growth and metastasis of gastric cancer (GC) remains to be elucidated. METHODS:In vitro functional role of HOXD9 and RURY3 in GC cells was determin...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1399-1
更新日期:2019-09-23 00:00:00
abstract:BACKGROUND:Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Nevertheless, its effects on colorectal cancer (CRC) remain poorly defined. In this study, we aim to demonstrate the biological function of ANGPT...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0548-7
更新日期:2017-06-12 00:00:00
abstract:BACKGROUND:The chemokine receptors CXCR4 and CCR7 play an important role in cancer invasion and metastasis. This study investigated the expression of CXCR4, CCR7, CXCL12, CCL21, and EGFR to illustrate the role of these biomarkers in breast cancer metastasis and prognosis. METHODS:The CXCR4, CCR7, CXCL12, CCL21, and EG...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-16
更新日期:2010-02-24 00:00:00
abstract::Tumor ablation by radiofrequency (RFA) is an appealing therapeutical strategy for the treatment of liver tumors (hepatocarcinoma and metastatic lesions) to be used as valid alternative to the surgical resection that often is appropriate and feasible in only a minority of patients. RFA induces the localised and control...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract::The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA seq...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-020-01706-8
更新日期:2020-09-17 00:00:00
abstract::The role of viruses in the etiology of human oral cancer is critically reviewed. Available evidences show a positive correlation for human oral cancer with human papilloma virus (HPV), herpes simplex virus (HSV) and human herpes virus type-6 (HHV-6), having strongest association with HPV. These viruses may act alone o...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND:Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-45
更新日期:2011-04-26 00:00:00
abstract::Patients with ulcerative colitis (UC) have a higher incidence of colorectal cancer. UC-associated colorectal cancer is thought to develop in patients with preexisting UC-associated dysplasia. It is crucial to diagnose UC-associated dysplasia and early stage of cancer in patients with long-standing UC for the purpose o...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB d...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/1756-9966-30-115
更新日期:2011-12-29 00:00:00