Abstract:
:Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)-mutant lung cancer, which arises due to poor penetration of the brain-blood barrier by EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Although osimertinib, a third-generation EGFR-TKI, has efficacy against CNS metastases, further treatment modalities are still needed as some of these lesions do not respond to osimertinib, or undergo progression after an initial response to this drug if radiotherapy has already been conducted. Here, we investigated the efficacy of water-soluble erlotinib (NUFS-sErt) against these metastases. This agent was synthesized using a nano-particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR-TKIs. The average NUFS-sErt particle size was 236.4 nm, and it showed time-dependent dissolution in culture media. The effects of NUFS-sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR-mutant lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS-sErt produced a dose-dependent inhibition of tumor growth and enhanced survival rate. Notably, the injection of NUFS-sErt into the brain ventricle caused significant tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS-sErt is a novel, water-soluble form of erlotinib that can be administered using intraventricular or intrathecal injections. The target cases would be patients with a progressive CNS metastasis and no other therapeutic options. This drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Kim DH,Choi YJ,Sung KJ,Yoo SA,Sung YH,Kim JK,Choi CM,Yun M,Lee EY,Jin YS,Cook S,Rho JK,Lee JCdoi
10.1002/1878-0261.12394subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2182-2190issue
12eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/i) embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal-length life. Later in life, however, these mice develop spontaneous pre-tumoral lesions or solid tumors (lymphoma...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.01.001
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:Most analyses of high throughput cancer data represent tumors by "atomistic" single-gene properties. Pathifier, a recently introduced method, characterizes a tumor in terms of "coarse grained" pathway-based variables. METHODS:We applied Pathifier to study a very large dataset of 2000 breast cancer samples...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.04.006
更新日期:2015-08-01 00:00:00
abstract::The pivotal role of LYRIC/AEG-1 in malignant transformation, tumourigenesis and chemo-resistance has previously been demonstrated in different cell types and sub-cellular compartments. The localisation of LYRIC/AEG-1 appears crucial to its function and is regulated by three lysine-rich nuclear localisation signal regi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.009
更新日期:2014-05-01 00:00:00
abstract::Peritoneal dissemination is a major clinical obstacle in gastrointestinal cancer therapy, and it accounts for the majority of cancer-related mortality. Calreticulin (CRT) is over-expressed in gastric tumors and has been linked to poor prognosis. In this study, immunohistochemistry studies revealed that the up-regulati...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.009
更新日期:2015-04-01 00:00:00
abstract::Deregulation of the insulin-like growth factor (IGF) axis and dysbalance of components of the IGF system as potential therapeutic targets have been described in different tumor types. IGF2 is a major embryonic growth factor and an important activator of IGF signaling. It is regulated by imprinting in a development- an...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12164
更新日期:2018-02-01 00:00:00
abstract::Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs w...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.004
更新日期:2016-02-01 00:00:00
abstract::Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor-associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tu...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12095
更新日期:2017-07-01 00:00:00
abstract::Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2012.07.001
更新日期:2012-10-01 00:00:00
abstract::Modern technologies enable detection and characterization of circulating tumor cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as markers for therapeutic response in breast cancer. First studies have incorporated CTC analyses to guide therapeutic interventions and stratification of breast ca...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.07.005
更新日期:2016-10-01 00:00:00
abstract::CDC25 (cell division cycle 25) phosphatases are essential for cell cycle control under normal conditions and in response to DNA damage. They are represented by three isoforms, CDC25A, B and C, each of them being submitted to an alternative splicing mechanism. Alternative splicing of many genes is affected in response ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2012.06.003
更新日期:2012-10-01 00:00:00
abstract::Although mutations in the phosphoinositide 3-kinase catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA-mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12053
更新日期:2017-05-01 00:00:00
abstract:PURPOSE:DNA analysis by NGS has become important to direct the clinical care of cancer patients. However, NGS is not successful in all cases, and the factors responsible for test failures have not been systematically evaluated. MATERIALS AND METHODS:A series of 1528 solid and hematolymphoid tumor specimens was tested ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.004
更新日期:2015-11-01 00:00:00
abstract::In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to io...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12635
更新日期:2020-03-01 00:00:00
abstract::The elevated expression and activation of human telomerase reverse transcriptase (hTERT) is associated with the unlimited proliferation of cancer cells. However, the excise mechanism of hTERT regulation during carcinogenesis is not well understood. In this study, we discovered cleavage and polyadenylation specific fac...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.02.001
更新日期:2014-05-01 00:00:00
abstract::The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.03.004
更新日期:2016-06-01 00:00:00
abstract::Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms rema...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12765
更新日期:2020-10-01 00:00:00
abstract::Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring p...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.09.005
更新日期:2010-12-01 00:00:00
abstract::Thyroid transcription factor-1 (TTF-1, encoded by the NKX2-1 gene) is highly expressed in small-cell lung carcinoma (SCLC) and lung adenocarcinoma (LADC), but how its functional roles differ between SCLC and LADC remains to be elucidated. Here, we compared the genome-wide distributions of TTF-1 binding regions and the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12608
更新日期:2020-02-01 00:00:00
abstract:PURPOSE:To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients. PATIENTS AND METHODS:Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
abstract::ERBB2 amplification and overexpression are strongly associated with invasive cancer with high recurrence and poor prognosis. Enhanced ErbB2 signaling induces cysteine cathepsin B and L expression leading to their higher proteolytic activity (zFRase activity), which is crucial for the invasion of ErbB2-positive breast ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.07.004
更新日期:2014-12-01 00:00:00
abstract::Breast cancer is a heterogeneous disease that can be divided in subtypes based on histology, gene expression profiles as well as differences in genomic aberrations. Distinct global DNA methylation profiles have been reported in normal breast epithelial cells as well as in breast tumors. However, the influence of the t...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.11.004
更新日期:2011-02-01 00:00:00
abstract::Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be 'BRCA1-like' or 'non-BRCA1-like', which refers to resembling a BRCA1-mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.03.002
更新日期:2015-08-01 00:00:00
abstract::Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX® -i120 platform to facilitate negative enrichment, immunofluorescent labelin...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12876
更新日期:2020-12-10 00:00:00
abstract::Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are kno...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.011
更新日期:2016-02-01 00:00:00
abstract::It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have gener...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12799
更新日期:2020-09-13 00:00:00
abstract::Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next-generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real-time representation of a tumor and its molecular heterogeneity than tissue. Howe...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12791
更新日期:2021-01-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract::Endocytosis is an important regulator of cell-cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial orga...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::In order to secure high-quality cancer care for increasing numbers of cancer patients in the upcoming decades, the complete continuum of cancer research and cancer care needs a thorough overhaul, with more emphasis on prevention and early detection, and a greater focus on the development of innovative treatments that ...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12441
更新日期:2019-03-01 00:00:00
abstract::Current hypotheses suggest that tumors originate from cells that carry out a process of "malignant reprogramming" driven by genetic and epigenetic alterations. Multiples studies reported the existence of stem-cell-like cells that acquire the ability to self-renew and are able to generate the bulk of more differentiate...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2012.10.006
更新日期:2012-12-01 00:00:00